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Safety and Cost: Are They Mutually Exclusive with Closed System Drug Transfer Technology?

noemail@statce.com — Wed, 01 Jun 2011 13:00:00 GMT

Objectives:

• Investigate the presence of hazardous drugs in the workplace;

• Evaluate the health risk associated with long term exposure to small amounts of hazardous drugs;

• Review the application of closed system transfer device technology for enhanced protection from hazardous drug exposure;

• Evaluate reasons for not utilizing a closed system transfer device;

• Challenge the issue of closed system transfer device cost;

• Analyze the use of a closed system transfer device to extend the beyond use dating for high cost single use drug products.

Instructor: James A. Jorgenson, RPh, MS, FASHP

Release Date: 1-Jun-11 8:00 AM
Expiration Date: 1-Jun-14 8:00 AM

Please click here to view this program content:

Jim Jorgenson - Safe Handling Webinar 6.2011 from Laura De La Rosa on Vimeo.

Safe Handling Boot Camp - Nursing

noemail@statce.com — Wed, 20 Apr 2011 18:00:00 GMT

Objectives:

At the completion of this activity, the participant will be able to:

• Describe the evidence for the genotoxicity of anti-cancer chemotherapy in patients;

• Relate the specific chromosomal targets that have been associated with various chemotherapy drug classes;

• Discuss the sufficiency of current safe-handling policies in light of recent evidence of worker exposure;

• Identify the concerns associated with handling hazardous medications;

• Discuss pertinent aspects of the policy and procedure UNC Hospitals utilizes for handling hazardous medications;

• Review future research opportunities around hazardous medications;

• List ONS guidelines for safe handling;

• Describe nursing basics for safe handling;

• Describe proper donning of personal protective equipment (PPE).

Instructor: Melissa A. McDiarmid, MD, MPH, DABT, Stephen F. Eckel, Pharm.D., M.H.A., BCPS, Kristie Howlett, MS,

Release Date: 20-Apr-11 1:00 PM
Expiration Date: 20-Apr-12 1:00 PM

Safe Handling Boot Camp - Pharmacy

noemail@statce.com — Wed, 20 Apr 2011 13:00:00 GMT

Objectives:

At the completion of this activity, the participant will be able to:

• Describe the evidence for the genotoxicity of anti-cancer chemotherapy in patients;

• Relate the specific chromosomal targets that have been associated with various chemotherapy drug classes;

• Discuss the sufficiency of current safe-handling policies in light of recent evidence of worker exposure;

• Identify the concerns associated with handling hazardous medications;

• Discuss pertinent aspects of the policy and procedure UNC Hospitals utilizes for handling hazardous medications;

• Review future research opportunities around hazardous medications;

• List ONS guidelines for safe handling;

• Describe nursing basics for safe handling;

• Describe proper donning of personal protective equipment (PPE).

Instructor: Melissa A. McDiarmid, MD, MPH, DABT, Stephen F. Eckel, Pharm.D., M.H.A., BCPS, Kristie Howlett, MS,

Release Date: 20-Apr-11 8:00 AM
Expiration Date: 20-Apr-14 8:00 AM

Safe Handling Boot Camp - Health Risk Management

noemail@statce.com — Wed, 20 Apr 2011 13:00:00 GMT

Objectives:

At the completion of this activity, the participant will be able to:

• Describe the evidence for the genotoxicity of anti-cancer chemotherapy in patients;

• Relate the specific chromosomal targets that have been associated with various chemotherapy drug classes;

• Discuss the sufficiency of current safe-handling policies in light of recent evidence of worker exposure;

• Identify the concerns associated with handling hazardous medications;

• Discuss pertinent aspects of the policy and procedure UNC Hospitals utilizes for handling hazardous medications;

• Review future research opportunities around hazardous medications;

• List ONS guidelines for safe handling;

• Describe nursing basics for safe handling;

• Describe proper donning of personal protective equipment (PPE).

Instructor: Melissa A. McDiarmid, MD, MPH, DABT, Stephen F. Eckel, Pharm.D., M.H.A., BCPS, Kristie Howlett, MS,

Release Date: 20-Apr-11 8:00 AM
Expiration Date: 20-Apr-14 8:00 AM

Chemotherapy Safety Guidelines: Why We Need Them

noemail@statce.com — Fri, 28 May 2010 13:00:00 GMT

Objectives:

Goal:
This monograph was developed to explain the risks of handling chemotherapy and identify the key components of the published guidelines that should be the basis of current professional practice.

Objectives:

Specify the risks of exposure to nurses when administering hazardous drugs, such as chemotherapy.
Categorize hazardous drugs according to their opportunity for exposure.
Describe accepted procedures for handling hazardous drugs as published in selected professional guidelines.

IMPORTANT: Please complete the evaluation form at the conclusion of this program by clicking here.

Instructor: Kerry Mahar, RN, MSN, AOCN

Release Date: 28-May-10 8:00 AM
Expiration Date: 28-May-11 8:00 AM

Background
The risks of exposure to hazardous drugs have been documented for over 4 decades. Guidelines to protect patients, staff and the environment have been in place for more than 25 years. Despite the fact that this information has been incorporated into numerous versions of guidelines and institutional policies and procedures, there still remains incomplete understanding of risk and inconsistent application of the standards.

Introduction
Since the 1970’s it has been reported that the very agents used in the treatment of cancer can incur unwanted effects on those preparing and administering them. In particular, a study in Finland revealed that nurses who handled chemotherapy had that agent in their urine. (Falck, 1979) Subsequent reports revealed nurse complaining of many of the symptoms their patients, who had received full doses, experienced. These symptoms included nausea, vomiting, hair loss and mouth sores.

Through the 1980’s and 1990’s numerous studies have confirmed the genotoxic effect on nurses and pharmacists exposed to antineoplastic agents (National Institute for Occupational Safety and Health, NIOSH, 2004).   Fetal loss, abnormalities, and low birthweight have been related to length of maternal exposure (Hemminki, 1985). The risk of cancer in nurses who have handled chemotherapy was reported from leukemia data collected among Danish oncology nurses between 1943 and 1987. In addition, there seemed to be a relationship between leukemia rates and physicians working in the same department at that time. (Skov, 1992)

The 2004 NIOSH Alert cites several examples of healthcare provider symptoms and injuries related to direct exposure.   Skin contact and fume inhalation of carmustine led to severe GI distress in a nurse a few hours after exposure. Another nurse appeared to have developed allergic asthma after 3 years of work-related exposure to hazardous drugs. Lastly, a nurse’s aide, who had worn personal protective equipment (PPE) while handling urinals of patients who had received chemotherapy, developed skin irritation and a rash.

The term hazardous drug was first used by the American Society of Health-System Pharmacists (ASHP) in 1990. A hazardous drug is defined as any chemical that is a physical hazard or health hazard. A physical hazard relates to combustibility or reactivity (i.e. solvents, some cleaning agents, etc.). A health hazard, the focus of this report, is a chemical that has shown to incur acute or chronic health effects in exposed individuals. (NIOSH, 2004.) Hazardous drugs are identified by having one or a combination of the following characteristics: genotoxic, teratogenic, carcinogenic, which cause fertility changes and result in organ toxicities even at low levels of exposure. (NIOSH, 2004)

The International Agency for Research on Cancer (IARC) has identified numerous agents as either carcinogenic, probable carcinogenic and possible carcinogenic to humans. Alkylatings agents including cyclophosphamide and melphalan are some of the most carcinogenic agents. Other established carcinogens include arsenic trioxide, tamoxifen and thiotepa. Probable carcinogens include azacitadine, cisplatin, carmustine, etoposide and doxorubicin. Examples of possible carcinogens are dacarbazine, bleomycin and daunorubicin.

Opportunity for Exposure
The risk of a healthcare worker’s exposure to hazardous drugs (HDs) begins from the time a delivery arrives at the loading dock to the time the IV materials, syringes, and related safety equipment are discarded in the hazardous waste receptacle. The highest risk is related to the amount of drug one can be potentially exposed to and the amount of time one is open to exposure. Therefore, the highest rates of exposure are related to preparation and administration of antineoplastic agents.

Exposure to HDs most often occurs from ingestion or inhalation of aerosolized prepared medication, dust or powder (pure drug or dried prepared medication), and less commonly accidental injection. Other mechanisms of exposure include contact with contaminated surfaces, and improper disposal or spill management.   It is important to consider that improper handling at any point can lead to exposure to those who are unaware of the exposure at all.

Preparation of antineoplastic agents involves the reconstitution and withdrawal of drug from vials, and transferring the drug to a syringe or IV bag.   Administration involves connecting (and disconnecting) syringes or IV tubing to patient IV access. Any of these activities can result in an accidental spill or splash, splattering, spraying or aerosolization. Once an agent is outside of a closed system (aerosolized, spray, etc.) it can be ingested or inhaled or come into contact with skin or mucous membranes. Once ingested, inhaled or in contact with membranes, absorption can and does occur.

Less obvious, and many may argue, far more prevalent, is contact and repeated exposure to minute amounts of drug in the treatment area. Such surfaces include desks and tables where chemotherapy may briefly be placed, keyboards used with gloved hands that handled a syringe or bag, patient treatment chairs, bedside tables, urinals and bed pans that have contained waste that may have excreted drug in it.

After an individual exposure, measures must be taken to remove any product from skin, clothing and the immediate environment. Material Safety Data Sheets (MSDS) should be available to allow the best management of an exposure and the subsequent cleanup. Personal management usually involves removal of contaminated clothing and washing with soap and water. Mucosal contact must be dealt with immediately. Eye rinsing or use of an eyewash station is necessary for even the slightest exposure to the face. If ingestion occurs, it is not recommended that vomiting be induced. Emergency treatment should be sought immediately. Unfortunately, any drug that is absorbed by ingestion, inhalation or mucosal exposure cannot be removed. The amount of agent absorbed will most likely be very small, but the individual must be prepared to experience some type of effect (either local or systemic).

In general there are no defined safe limits of exposure to hazardous drugs, according to NIOSH, the Occupational Safety and Health Administration (OSHA) or the American Conference of Government Industrial Hygienists (ACGIH).

Guidelines
In 1986, OSHA published guidelines for antineoplastic drugs. US Environmental Protection Agency (EPA) standards for the handling of hazardous waste have been in existence since 1976. OSHA (1999) and ASHP (1990) recommend hazardous drug waste be handled in the same fashion. Hazardous drug waste includes partially filled vials, undispensed products, unused IVs, needles and syringes, gloves gowns, underpads, contaminated materials from spill cleanups, and containers such as IV bags or drug vials that contain more than trace amounts of hazardous drugs and are not contaminated by blood or other potentially infectious waste.

In 1998, the Department of Labor established the following hierarchy of hazard controls.

Eliminate the hazard – not necessarily achievable as the drugs need to be prepared and administered
Substitute – utilizing a less toxic substance
Engineering controls – isolate the hazard by using equipment that is designed to protect from exposure
Administrative controls – this includes educational and training standards, limiting personnel who come into contact with hazardous agents
Personal Protective Equipment (PPE) – the individual’s use of the available barriers to protect oneself

In 2004, NIOSH issued an alert identifying specific recommendations for the handling of antineoplastic agents. Keeping in mind the US Department of Labor’s hierarchy, the recommendations include practices related to:

Receiving and Storage
Drug Preparation and Administration
Ventilated Cabinets
Routine Cleaning
Decontamination
Housekeeping
Waste Disposal
Spill Control

Additional guidelines that address hazardous drugs or the equipment in which they are manipulated have been developed by The Centers for Disease Control (CDC), National Institute of Health (NIH), International Society of Oncology Pharmacy Practitioners (ISOPP), ASHP, Oncology Nursing Society (ONS), United States Pharmacopeia (USP), and The National Sanitation Foundation.

Profession-based guidelines like USP, ONS and ISOPP are all based on the recommendations of the 2004 NIOSH Alert. Each group has expanded on those practice areas pertinent to their roles. First and foremost, education and training that is required is outlined in all of these guidelines. Any worker who may be at risk of exposure to a hazardous drug must receive the appropriate amount of training to both perform the tasks correctly and to protect themselves. For instance, ISOPP, outlines the training required for anyone preparing or administering chemotherapy. In addition, the preparation of parenteral cytotoxic drugs should be undertaken only by pharmacy personnel. ONS guidelines address in detail the use of PPE during handling, administration and disposal of waste products.

The following table summarizes the recommendations, components and implementation guidelines of the 2004 NIOSH Alert.

Recommendation	Components	Guideline Implementation
Assess the hazards of the workplace	1. Evaluate the workplace to identify and assess hazards before anyone begins work with hazardous drugs.	Physical layout Equipment Decontamination process Potential points of exposure
	2. Regularly review the current inventory of HDs, equipment, and practices	Institutional Safety Committee
	3. Conduct regular training reviews with all potentially exposed workers	Include employees in discussions related to effectiveness or issues concerning the program
Handle drugs safely	1. Implement a program for safely handling HDs at work and review this program annually on the basis of the evaluation	Policies and Procedures for: labeling, storage, spill control
	2. Establish procedures and provide training for handling HDs safely, cleaning up spills, and using all equipment and PPE properly	Make spill kits and PPE available and easy to access.
	3. Establish work practices related to both drug manipulation techniques an to general hygiene practices.	Policy on food items in the work area.
Use and maintain equipment properly	1. Develop workplace procedures for using and maintaining all equipment that functions to reduce exposure.	Policy on use of ventilated cabinets, closed system transfer devices, closed IV systems, PPE

The Resource Conservation and Recovery Act - commonly referred to as RCRA - is the primary law governing the disposal of solid and hazardous waste. Congress passed RCRA on October 21, 1976 to address the increasing problems the nation faced from our growing volume of municipal and industrial waste. RCRA, which amended the Solid Waste Disposal Act of 1965, set national goals for:

Protecting human health and the environment from the potential hazards of waste disposal.
Conserving energy and natural resources.
Reducing the amount of waste generated.
Ensuring that wastes are managed in an environmentally-sound manner.

The following sections highlight the detailed recommendations for preparation, administration and disposal of chemotherapy. These guidelines were selected from the ISOPP Journal of Oncology Pharmacy, Preventing Occupational Exposure to Antineoplastic and Other Hazardous Drugs in Health Care Settings Practice by the NIOSH and the 2009 Oncology Nursing Forum.

Preparation

All cytotoxic medications should be prepared in a central location within a sterile environment. A Biologic Safety Cabinet (BSC) must be used for all reconstitution and preparation of cytotoxic medications for administration.
Personal protective equipment (PPE) will include a non-linting and non-absorbent polyethylene gown with cuffs gripped at the wrist. Disposable sleeve covers may also be used to protect the wrist and lower arm. If in a cleanroom, hair covering, overshoes and surgical mask must be worn. Gloves should be powder-free and proven resistant to chemotherapy. Latex, nitrile and neoprene are the only materials validated for handling of chemotherapy. Double gloving is recommended and gloves should be changed after 30 minutes of use.
The use of special devices to protect the handler, preparer and administrator of cytotoxics should be implemented. This includes a closed system transfer device that prevent spraying and aerosolization (ISOPP 2007).

Use of a Closed System Transfer Device (CSTD)
NIOSH defines a CSTD as a device that mechanically prohibits the transfer of environmental contaminants into the system and the escape of hazardous drug or vapor concentrations outside the system (NIOSH 2004). ISOPP further states that the devices need to be leak proof and airtight. While there are numerous marketed devices currently, there is a paucity of published literature supporting their benefits. One of the early studies demonstrated the reduction of both surface contamination and urinary presence of chemotherapy six months after the implementation of a closed system transfer device. Another study evaluated five different marketed devices to determine if they met the NIOSH and ISOPP definitions of a CSTD.

Following a two-part evaluation, only one of the devices was successful in meeting these definitions of a CSTD. Many hospitals are either currently using or evaluating the CSTD products on the market. It is recommended to undertake your own evaluation to ensure that it meets the NIOSH and ISOPP definitions and has peer-reviewed data to supports its claims.

Administration
(ONS 2009)

It is recommended that a pharmacist attach and prime IV tubing to the cytotoxic agent to be administered.
All chemotherapy should be labeled to indicate its hazardous nature. Storage of these agents should be in specified containers in a location that limits exposure (i. e. on a specific shelf in the medication preparation area).
IV set up should be closed and all connections should be luer-locked.
Utilization of closed system transfer devices is recommended.
PPE will include a non-linting and non-absorbent polyethylene gown with cuffs gripped at the wrist. Gloves should be powder-free and proven resistant to chemotherapy. Double gloving is recommended. If there is a risk of splash, eye and face protection should be used. A respirator (such as a non-powered, air-purifying, particulate –filter respirator) should be worn when administering an aerosolized HD. PPE should be worn for administration of HDs by any route, spiking IV bags containing HDs and changing IV tubing, priming IV tubing, handling leakage from tubing, syringe and connections sites. PPE should also be worn when disposing of HDs and items contaminated by HDs. (ONS 2004)
Dispose of the gown after each use or if it becomes soiled. Remove the gown and outer gloves and place into the hazardous waste receptacle. Then remove the second pair of gloves and dispose. (NIOSH, 2004)
Wash hands with soap and water.

Disposal of Waste
(NIOSH 2004)

Waste Disposal

Trace waste (those that contain less than 3% of the original quantity of HD) which consists of used syringes, IV tubing, gowns, gloves, empty vials should be placed in a yellow chemotherapy waste container.
Disposal of arsenic trioxide and any bulk amounts (3% original quantity) should be in an RCRA-rated container.

Housekeeping

Wear two pairs of gloves and a disposable gown when handling soiled linen, stool or urine from patients who have received HDs within the last 48 hours. Wear a face shield if a splash risk (NIOSH 2004).
Linen may be placed in a leak-proof laundry bag for usual cleaning (ONS, 2009).
Dispose of the gown after each use or if it becomes soiled. Remove the gown and outer gloves and place into the hazardous waste receptacle. Then remove the second pair of gloves and dispose.
Wash hands with soap and water. Do not use a hand sanitizer (NIOSH 2004).

Spill Management

All institutions should have a specific policy and procedure for spill clean up.
Spills and the clean up is considered high risk for aerosolization and splash. In addition to double gloving and gowning, face shield and respirator use is required (NIOSH 2004).

Most recently, in 2009, ONS and the American Society of Clinical Oncologists (ASCO) developed a joint set of Chemotherapy Administration Standards. The joint ASCO/ONS guidelines are a unique and comprehensive approach to standardizing the entire process of chemotherapy treatment. Multidisciplinary standards were developed regarding the flow of chemotherapy administration:

The review of clinical information and regimen selection
Treatment planning and informed consent
Order/prescription writing
Drug Preparation
Treatment compliance
Administration and monitoring
Response and toxicity monitoring

There are eight standards. They include staffing, planning, practice, ordering, preparation, administration, patient consent and education, and monitoring/assessment (Jacobson et al., 2009). There is no specific standard related to safe handling but these standards speak to adequate training of personnel, education of patients and monitoring and re-assessment of the plan of care and response to treatment.

Discussion
The availability and specificity of the guidelines for safe handling of chemotherapy are undisputed. Unfortunately, there are many who do not have enough knowledge of the risks or of the guidelines which has resulted in less than optimal adherence to the recommendations. Barriers to adherence include lack of clear institutional policies, denial or dismissal of risks and inconvenience (Mahar, 2008). Raising the awareness of risks and how to protect oneself is one way to improve adherence. The establishment of practice-based organization position statements and creating a Safe Handling Awareness Day has certainly raised awareness, but has there been a change in practice?

Increasingly, non-providers or indirect caregivers are also at risk of exposure. Oral chemotherapy is taken by the patient or administered by a family member. These therapies are also taken for extended periods of time, so that bottles and pills are more commonplace outside of the clinical area. Family, assistive personnel and pets can be exposed. As more agents are used in the clinical setting for non-oncology diseases (i.e. neurology, rheumatoid arthritis, organ transplant) clinicians who may not have the education and training that oncology nurses receive. Ensuring this group of clinicians receives that education and training is the responsibility of the employer.

References

American Society of Health-Systems Pharmacists. ASHP Guidelines on Handling Hazardous Drugs. 2006, 63:1172-1191.
Cass, Yaakov and Setton, Isaac. 25 Years of Safe Handling of Cytotoxics (Antineoplastics) in Israel. Journal of Oncology Clincal Practice. 2006, Vol 12, pp. 83-90.
Falck K., Grohn P, Sorsa M. et all Mutagenicity in Urnine of Nurses Handling Cytostatic Drugs. Lancet. 1979. 1:1250-1251.
Gambrell, J and Moore, S. Assessing Workplace Compliance with Handling of Antineoplastic Agents. Clinical Journal of Oncology Nursing. 2006,Vol 10, No. 4. Pp 473 – 477.
ISOPP, ISOPP Standards of Practice: Safe Handling of Cytotoxics, Journal of Oncology Pharmacy Practice (Suppl) Vol 13, pp. 1-81.
Jacobson, J. O., Polovich, M., McFiff, K. K., LeFebvre, K. B., Cummings, C., Galioto, M., Bonelli, K. R., and McCorkle, M. R.. Ameirica Society of Clinical Oncology/Oncology Nursing Society Chemotherapy Administratin Safety Standards. Oncology Nursing Forum. Vol. 36, No. 6, Nov 2009.
Martin, S. and Larson E. Chemotherapy Handling Practices of OUtpaitent and Office-Based Oncology Nurses. ONF, 2003, Vol 30, No. 4. Pp 575-581.
Mahar K. Practical Applications: Overcoming Barriers to Chemotherapy Safety in Nursing. The Oncology Nurse. Vol. 1 No. 5, Oct/Nov 2008. (suppl).
National Institute for Occupational Safety and Health. Preventing Occupational Exposure to Antineoplastic and Other Hazardous Drugs in Health Care Settings. Sept 2004.
Polovich, Martha. Safe Handling of Hazardous Drugs. Online Journal of Issues In Nursing. Sept 30, 2004.
US Pharmacopeial Convention, USP 797. Guidebook to Pharmaceutical Compounding Sterile Preparations, 2008.
United States Department of Labor, OSHA Technical Manual, Section 4, Chapter 2
Vanchieri, C., Health Hazards to Community Practice Nurses: The Big Worry, Community Oncology, 2005, May/June Vol 2,, No 2. Pp 277-279
Valanis, B. G, Vollmer W. M., Labuhn K. T, et al. Acute Symptoms Associated With Antineoplastic Drug Handling among Nurses. Cancer Nursing, 1993, 15:288-295.
Martin S., The Adverse Health Effects of Occupational Exposure to Hazardous Drugs Community Oncology, 2005. 2: 397-400.
Ritchie, MA, McAdams C, and Fritz, N. Exposure Risk in the Handling and Administration of Chemotherapy Agents: A Review and Synthesis of the Literature. Online Journal of Knowledge Synthesis in Nursing, 2000,Vol 7, No. 4

Regulations and Recommendations of Safe Handling

noemail@statce.com — Mon, 26 Apr 2010 13:00:00 GMT

Objectives:

At the conclusion of the knowledge-based activity, pharmacists should be able to:

evaluate current risk associated with exposure to hazardous drugs
review national recommendations and standards related hazardous drugs
outline strategies to reduce the potential exposure to hazardous drugs

At the conclusion of the knowledge-based activity, certified pharmacy technicians should be able to:

evaluate current risk associated with exposure to hazardous drugs
review national recommendations and standards related hazardous drugs
outline strategies to reduce the potential exposure to hazardous drugs

Instructor: Stephen Eckel, PharmD, MHA, BCPS & Scott W. Savage, Pharm.D., M.S.

Release Date: 26-Apr-10 8:00 AM
Expiration Date: 26-Apr-13 8:00 AM

In 1917, mustard gas (CH2ClCH2)S was a feared chemical weapon that caused a myriad of symptoms frequently resulting in death. However, by the late 1920s a topical form of mustard gas showed promising effects alleviating pain associated with superficial tumors.(1) By 1946, nitrogen mustard (also known as chlormethine or mechlorthamine) , an agent once intended to end life, had become a pivotal agent in lymphoma cancer treatment. (2)

Although surgery and radiation continue to be a mainstay in the cooperative efforts of the mulitdisplanary healthcare team to treat cancer, medicinal treatment options continue to expand available treatment modalities. With continued scientific advances, chemotherapy and biologic therapy is now commonly administered with curative intent, as adjuvant or neoadjuvant therapy, or palliative symptom relief in advanced disease.(3)

In the United States, the American Cancer Society estimates almost 1.5 million new cancer cases and roughly 600,000 deaths from cancer in 2009.(4) The National Cancer Institute forecasts a doubling of this figure by 2050 with the growing and aging population.(5) With treatment not only is the patient at risk, but the health care professionals caring for the patient have a high risk of being exposed to these hazardous drugs. Considering this risk, coupled with growing patient volumes, it is paramount to have a clear understanding of the exposure risk, the national recommendations and standards related to hazardous drugs, and strategies to reduce exposure risk.

Hazardous Drugs and Exposure Effects:

Hazardous drugs are drugs that possess qualities presenting the risk of unwanted health effects to those handling these drugs. The term hazardous drug, first used within the American Society of Health-System Pharmacist (ASHP)’s “Technical Assistance Bulletin (TAB) on Handling Cytotoxic and Hazardous Drugs”, was further expanded in 2004 by the National Institute for Occupational Safety and Health (NIOSH).(6)

In the NIOSH Alert, drugs considered hazardous are identified by exhibiting one of the following six criteria: carcinogenicity, teratogenicity or developmental toxicity, reproductive toxicity in humans, organ toxicities at low doses in humans or animals, genotoxicity, or new drugs that mimic existing hazardous drugs in structure or toxicity. (Table 1).(7,8) Health care workers are at an exposure risk throughout the medication use process, not only during the preparation, distribution, and administration phases, but also during the subsequent disposal process of the used hazardous drug. Potential routes of exposure include inhalation, dermal contact, ingestion, or injection. In fact, it is estimated that roughly 5.5 million U.S. health care workers, including physicians, nursing, pharmacy, environmental services, research, and shipping/receiving personnel, will be exposed to hazardous drugs annually at some point throughout the process.(7)

Health hazards associated with hazardous drug exposure were initially reported in the 1970s, when patients were diagnosed with secondary malignancies post-treatment with hazardous drugs for their primary neoplasm. Additionally, historical laboratory data compiled by the International Agency for the Research of Cancer (IARC) supported these observations and lead to the classification of certain hazardous drugs as human carcinogens (Group1) and probable human carcinogens (Group 2A). (Table 2)(9,10)

Falck et al., first reported occupational exposure to hazardous drugs. Nurses caring for patients receiving a cyclosphosphamide based regimen had higher mutagenic markers in their urine. The mutagencity measure was less remarkable after a “duty-free” weekend indicating potential correlation of exposure frequency to cumulative occupational exposure.(11) From a pharmacy perspective, personnel preparing hazardous drugs in a horizontal, laminar airflow work bench (LAFW) had detectable mutagenic markers. However, personnel using a vertical, biological safety cabinet (BSC) had non-detectable mutagenic markers.(12) Additional evidence has validated acute health effects associated with hazardous drug exposure in nursing and pharmacy personnel including hair loss, hypersensitivity, headaches, adverse reproductive effect, increased risk of neoplasm, and chromosomal abnormalities.(13-19)

Table 1: NIOSH Alert Hazardous Drug Classification (7,8)

Characteristic		Result
Carcinogenicity		Causes cancer
Teratogenicity		Damages developing fetuses
Reproductive toxicity		Impairs fertility
Organ toxicity		Impairs organ function
Genotoxicity		Damages DNA
Mimic existing hazardous drugs in structure and toxicity		Any of the above

Sources of Exposure:

Exposure of health care professionals to hazardous drugs is varied in route as previously mentioned. Surface contamination is evident in all phases of the medication use process. During the preparation, administration and distribution phase, contamination has been documented within pharmacy and nursing areas.(20-22) Dermal contamination can be a direct result of the external contamination of hazardous drug vials which can subsequently lead to surface contamination of other areas. In 1999, six cancer treatment centers in Canada and the United States were evaluated for the level of contamination of hazardous drugs. Measurable amounts of contamination were detected in 75% of the pharmacy area samples and 65% of the administration area samples.(20) Additional studies have presented consistent results to other published data showing surface contamination within primary engineering controls (e.g. LAFWs, BSCs, compounding aseptic isolators, and cleanrooms), equipment used for preparation and administration of hazardous drugs (e.g. intravenous bags and tubing), and general work surfaces (e.g. desk, floors, countertops, and cabinets).(10,22-24) Such diverse contamination of work surfaces only increases the risk of personnel exposure.

Measureable indicators of hazardous drug exposure in the urine of health care workers are documented in over 19 studies worldwide. A majority of these studies detected one or more hazardous constituent. Additionally of the 19 studies, four of them described secondary exposure to health care personnel that had no direct contact with the patient.(10) Based on the expected excretion of some of the measured hazardous drugs, in particular cyclophosphamide, inference was possible correlating an increased risk of cancer in those with systemic exposure.(20,25)

Inhalation and ingestion exposure are also a potential risk. Although minimal data supports a complete understanding of the effects of these types of exposure, studies report little to no detectable contamination to significant contamination indicated by particulate air sampling. Ingestion serves as an alternative route to dermal absorption due to the combination of surface contamination transferring from the hands to the mouth.(10) This exposure data validated the incidence and risk of hazardous drug contamination and has garnered a response from governmental and health care professional bodies. These efforts, as detailed in the next section, all intend to reduce the occupational exposure risk of personnel.

Safe Handling Guidelines and Standards:

Guidelines to minimize exposure to hazardous drugs were first published by the Society of Hospital Pharmacists of Australia in 1981.(26) Today, there are multiple guidelines or references that guide the management of hazardous drugs.(7,27-31)

Occupational Safety and Health Organization (OSHA)

OSHA, whose mission is to assure safe and healthful working conditions for working men and women, first released guidelines for safe handling of hazardous drugs in 1986. Under OSHA standards, material safety data sheets (MSDS) for any hazardous drug must be available to the health care worker. Subsequent updates, reinforced prior findings that personnel exposure to hazardous drugs is an increasingly serious health concern promoting updated guidelines in 1995.(27,28)

National Institute for Occupational Safety and Health (NIOSH)

Although guidelines had been released from both governmental and professional organizations prior to 2004, data indicated that contamination and exposure to hazardous drugs within the workplace continued.(20-22) The NIOSH Alert, representing the recommendations of governmental and non-governmental thought leaders, intended to increase the awareness among the employers and the front-line health care workers. It applies to all workers who handle hazardous drugs and provides tools for preventing exposure that can be implemented by the employee or employer in their daily activities.

ASHP Guidelines on Handling Hazardous Drugs

Originally published in 1990, the updated guidelines intend to characterize the reoccurring and new concerns associated with the handling of hazardous drugs.(6) Additionally, it discusses specific recommendations concerning development of a safety program, general work practices, processes related to labeling and packaging, benefits of protective equipment, and containment and disposal of hazardous drugs.(29)

American Society of Clinical Oncology (ASCO) and Oncology Nursing Society (ONS)

The Oncology Nursing Society (ONS), originally established by nurses working in research settings involved with medical oncologist, released guidelines in 1982.(30) Updates to ONS’s guidelines, focuses on the knowledge base necessary to reduce risk associated with hazardous drugs including safe handling and administration.(31)

Additionally, ASCO released guidelines intended for application at physician’s offices, infusion centers, free-standing cancer-centers, and any other treatment site, except a hospital outpatient department.(32) The updated ASCO guidelines include minimum level of services necessary to provide hazardous drug therapy.(33) Recently, ASCO and ONS jointly released standards encompassing seven domains of which preparation and administration practices are discussed. ASCO and ONS intend adoption should be the goal for best practice implementation in ambulatory care setting.(34)

United States Pharmacopeia

The Food, Drug, and Cosmetic Act of 1938 recognized the United States Pharmacopeia-National Formulary (USP-NF) as the official compendia of drug standards with the Food and Drug Administration (FDA) responsible for enforcement. USP Chapter <797>, based on its chapter number, is considered an enforceable regulation; however, the FDA looks to individual states to regulate pharmacy practice.(35,36) Within the most recent version, hazardous drugs as compounded sterile preparations has a distinct section with specific details related to the engineering and facility controls along with personnel training and attire required to prevent injury and illness associated with hazardous drug exposure.

United States Environmental Protection Agency (EPA)

The discovery of pharmaceuticals in surface, ground, and drinking waters around the United States has been a direct way for the everyday citizen to have an awareness of the risk associated with hazardous drugs. Established in 1976, the Resource Conservation Recovery Act (RCRA), sought to address the disposal of hazardous chemicals. The list of regulated chemicals include a variety of commonly used hazardous drugs. Failure to comply with the RCRA regulations can result in potential EPA violations and associated monetary fines.(37)

The Joint Commission

Created in 1951, this accreditation body is the oldest and largest health care standard-setting and accrediting body in the United States. In order to earn and maintain, The Joint Commission’s approval, an organization must undergo on-site survey. Within the Hospital Accreditation requirement, Medication Management and Environment of Care standards related to hazardous drugs. These standards and associated Elements of Performance (EP) guide the management, disposal, and minimization of risk associated with hazardous drugs. Non-compliance with these standards can result in non-accreditation for an organization.(38)

Strategies to Reduce Potential Exposure:

Knowing that there is a potential for exposure in your workplace to chemotherapy products is not enough. It is important to develop strategies for reducing contamination for employees. Some recommendations are easy to achieve and many places already complete them. However, others will require time to develop, resources to purchase, and organizational approval to implement.

Determining and classifying medications as hazardous – NIOSH recommends a written inventory of all hazardous medications that will be used to be developed(7). This list needs to also come with a process to keep it updated and active, as new medications are added to the formulary. While the IARC provides carcinogenicity classifications of hazardous medications (table 2), this information is not current with all of the existing medications in the workplace. This table provides a good start for an organization in determining classification for medications they use, it should not be an end of itself. Medications that need to be reviewed for hazardous includes biologics, oral cancer medications, and medications that are teratogenic (but not used for the treatment of cancer). Another required recommendation is to have MSDS sheets available to all employees who could come into contact with the medication. These provide needed information to employees.

Table 2: International Agency for the Research of
Cancer Hazardous Drug Classifications (9)

Group 1:

(Carcinogenic to Humans)

Group 2:

(Probably Carciongenic to Humans)

Arsenic trioxide

Azathioprine

Chlorambucil

Chlornaphazine

Cyclophosphamide

Myleran

Melphalan

Semustine

Tamoxifen

Thiotepa

Terosulfan

Mustarge-Oncovin-Procarbazine-Prednisone (MOPP)

Etoposide-Cisplatin-Bleomycin

Azacitidine

BCNU

CCNU

Chlorozotocin

Cisplatin

Doxorubicin

N-Ethyl-N-nitrosurea

Etoposide

Mechlorethamine

N-Methyl-nitrosourea

Procarbazine

Teniposide

Implement policies and procedures for handling chemotherapy – After the list is determined, explicit policies and procedures need to be developed surrounding the handling of these medications. Each employee that has the potential for interacting with the chemotherapy needs to be evaluated for risk potential. This evaluation should start all the way from the receipt of medications to the administration of them. It has been studied that the outside of chemotherapy vials have trace contamination on them(22). This develops through the manufacturing process and could pose a concern for those handling medications on the loading dock. Issues to be discussed revolve around whether they should handle these medications while wearing gloves and should chemotherapy be stored in a separate area so as to not contaminate other medications. After the medication is in the pharmacy, USP <797> recommends that the medications be stored in a negatively pressured room. Another overlooked employee group is housekeeping. Many times they will enter the pharmacy to clean and not take the appropriate steps to protect themselves.
Training employees – all employees need to be educated about the concerns with handling chemotherapy products. This should be done at the point of orientation, but should not end there. Continual education should be implemented as a part of the culture of the workplace. Part of the training should include the various steps that the organization uses to protect the worker. Simple steps include double-gloving with chemotherapy-approved gloves, use of a lint-free gown, hair nets, masks, shoe protection, and when needed, an eye shield. Other required steps in the training are the utilization of the appropriate environmental controls: either a barrier isolator or a biological safety cabinet. These procedures should both be taught and explained to the employee, but also observed to ensure compliance.
Environmental controls – NIOSH and USP 797 have recommendations on the appropriate environmental controls that need to be used in the pharmacy. These are established to protect both the product from microbial contamination and the employee from exposure to hazardous drugs. Many of the recommendations are associated with airflow, hood placements and selection, and filtration of the air.
Monitoring chemotherapy contamination – USP <797> recommends that an organization undertakes a surface wipe study to detect contamination of chemotherapy every 6 months(35). This will allow you to monitor over time the level of chemotherapy on surfaces in order to determine if exposure levels increase or decrease. In addition, there is also a recommendation from NIOSH to undertake medical surveillance of your employees(7).
Cleaning procedures – at the end of the shift or day, the organization needs to develop a plan for cleaning the work surfaces of both the preparation and the checking areas. One area to discuss is the use of a decontamination product as a part of this process. There is currently one marketed for use that uses sodium hypochlorite. This product would be used in addition to the routine sterilization that occurs.
Handling chemotherapy spills – it is imperative that each location that prepares and administers hazardous medications to store a chemotherapy spill kit. Each employee working in those areas should be knowledgeable about location and how to use it in the event of a spill.
Disposal of hazardous medications – this is an area that is receiving significant national attention. The RCRA regulation provides some direction on disposal of medications(37), but each organization needs to develop policies that provide for disposal of chemotherapy vials and for chemotherapy infusions.
Use of a closed system transfer device (CSTD) – over the past few years, there has been a significant growth of technology in this area. NIOSH defies a device that mechanically prohibits the transfer of environmental contaminants into the system and the escape of hazardous drug or vapor concentrations outside the system(7). ISOPP further states that the devices need to be leak proof and airtight(39). While there are numerous marketed devices currently, there is a paucity of published literature supporting their benefits. One of the early studies demonstrated the reduction of both surface contamination and urinary presence of chemotherapy six months after the implementation of a closed system transfer device(21). Another study evaluated five different marketed devices to determine if they met the NIOSH and ISOPP definitions of a CSTD(40). Following a two-part evaluation, only one of the devices was successful in meeting these definitions of a CSTD. Many hospitals are either currently using or evaluating the CSTD products on the market. It is recommended to undertake your own evaluation to ensure that it meets the NIOSH and ISOPP definitions and has peer-reviewed data to supports its claims.

Conclusions:

Chemotherapy and hazardous drug preparation is not without risk. While these medications have been demonstrated to be effective at treating cancer and other disorders, they also have side effects not only for the patient, but also for the healthcare worker. The most important issue is to be aware of the concerns and risks present with handling hazardous drugs. There are also many regulations and guidelines to assist in providing recommendations on how to protect healthcare workers from exposure to chemotherapy. Reviewing these statements and instituting a few processes have been demonstrated to reduce the exposure to hazardous drugs.

Bibliography

1. Joensuu G. Systemic chemotherapy for cancer: from weapon to treatment. Lancet Oncol 2008;9:304.

2.   Goodman LS, et al. Nitrogen mustard therapy. JAMA 1946;132:126-32.
3.   Medina PJ and Fausel C. Cancer treatment and chemotherapy. In Dipiro JT, eds. Pharmacotherapy: A Pathophysiologic Approach , 7th ed. New York, 2008: 2085-119.
4.   Jamel A, et al. Cancer statistics, 2009.CA Cancer J Clin 2009;59:225-49.
5.   Edwards BK, et al. Annual report to the nation on the status of cancer, 1973-1999, feature implications of age and aging on U.S. cancer burden. Cancer 2002;94;2766-2792.
6.   American Society of Hospital Pharmacists. ASHP technical assistance bulletin on handling cytotoxic and hazardous drugs. Am J Hosp Pharm. 1990;47:1033-49.
7.   National Institute for Occupational Safety and Health. NIOSH alert: preventing occupational exposure to anti-neoplastic and other hazardous drugs in health care settings.
         http://www.cdc.gov/niosh/docs/2004-165/pdfs/2004-165.pdf (accessed 2010 Mar 9).
8.   Power L and Jorgenson J. Safe handling of hazardous drugs: video training program. American Society of Health-System Pharmacists. Maryland, 2006.
9.   International Agency for the Research of Cancer. IARC monographs database on carcinogenic risks to humans. http://monographs.iarc.fr/ENG/Classification/index.php (accessed 2010 March 9).
10.   Connor TH and McDiarmid. Preventing occupational exposures to antineoplastic drugs in health care settings. CA Cancer J Clin 2006;56;354-365.
11.   Falck K, et al. Mutagenicity in urine of nurses handling cytostatic drugs. Lancet 1979;1:1250-1.
12.   Anderson RW, et al. Risk of handling injectable antineoplastic agents. Am J Hosp Pharm 1982;39:1881-87.
13.   Valanis BG et al. Acute symptoms associated with antineoplastic drug handling among nurses. Cancer Nurs 1993;16:288-95.
14.   Dranistsaris G , et al. Are health care providers who work with cancer drugs at an increased risk for toxic events? A systemic review and meta-analysis of the literature. J Oncol Pharm Pract                            2005;11:69-78.
15.   Selevan SG, et al. A study of occupational exposure to antineoplastic drugs and fetal loss in nurses. N Engl J Med 1985;313:1173-78.
16.   Valanis BG, et al. Association of antineoplastic drug handling with acute adverse effects in pharmacy personnel. Am J Hosp Pharmacy 1993;50:455-62.
17.   Skov T, et al. Leukaemia and reproductive outcome among nurses handling antineoplastic drugs. Lancet 1990;336:1446.
18.   Sessink PJM, et al. Drugs hazardous to healthcare workers, a review article. Drug safety 1999;20(4);347-59.
19.   Sessink PJM, et al. Urinary cyclophosphamide excretion and chromosomal aberrations in peripheral blood lymphocytes after occupational exposure to antineoplastic agents. Mutation research                               1994;309:193-99.
20.   Connor TH, et al. Surface contamination with antineoplastics agents in six cancer treatment centers in Canada and the United States. Am J Health-Syst Pharm 1999;56:1427-32/
21.   Wick C, et al. Using a closed-system protective device to reduce personnel exposure to antineoplastic agents. Am J Health-Syst Pharm 2003;60:2314-20.
22.   Connor TH, et al. Surface contamination of chemotherapy drug vials and evaluation of new vial-cleaning techniques: results of three studies. Am J Health-Syst Pharm. 2005;62:475-84.
23.   Harrison BR, et al. Comparison of surface contamination with cyclophosphamide and flurouracil using a closed-system transfer device versus standard preparation techniques. Am J Health-Syst Pharm.             2006;63:1736-44.
24.   McDevitt JJ, et al. Exposure of hospital pharmacists and nurses to antineoplastic agents. J Occup Med. 1993;35:57-60.
25.   Bos RP and Sessink PJM. Biomonitoring of occupational exposure to cytotoxic anticancer drugs. Reviews on environmental health. 1997;12(1):43-58.
26.   Harrison BR. Developing guidelines for working with antineoplastic drugs. Am J Hosp Pharm. 1981;38:1881-87.

27. United States Department of Labor, Occupational Safety and Health Administration. Hazard Communication. 29 CFR Part 1910.1200.

http://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=standards&p_id=10099 (accessed 2010 March 10).

28.   United States Department of Labor, Occupational Safety and Health Administration. Controlling occupational exposure to hazardous drugs. OSHA technical manual, TED 01-00-15. Section VI. Chapter 2.             http://www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2.html (accessed 2010 March 11).
29.   American Society of Health-System Pharmacists. ASHP guidelines on handling hazardous drugs. Am J Health Syst Pharm. 2006;63:1172-93.
30.   Oncology Nursing Society: Outcome standards for cancer nursing education. Pittsburgh, 1982.
31.   Polovich M, et al. Chemotherapy and Biotherapy Guidelines and Recommendations for Practice. 3rd edition. Pittsburgh, 2009.
32.   American Society of Clinical Oncology: Criteria for facilities and personnel for the administration of parenteral systemic antineoplastic therapy. J Clin Oncol. 1997;15:3416-17.
33.   American Society of Clinical Oncology: Criteria for facilities and personnel for the administration of parenteral systemic antineoplastic therapy. J Clin Oncol. 2004;22:4613-15.
34.   Jacobson JO, et al. American society of clinical oncology/oncology nursing society chemotherapy administration safety standards. 2009;99:1-7.
35.   USP General Chapter <797>. The current United States Pharmacopeia and the National Formulary and Supplements. Rockville, Md: The United States Pharmacopeial Convention, 2007.

36. US Food and Drug Administration. Compliance Policy Guides Manual; CPG Sec. 460.200 Pharmacy Compounding.

http://www.fda.gov/ICECI/ComplianceManuals/CompliancePolicyGuidanceManual/ucm074398.htm (accessed 2010 March 11).

37.   US Environmental Protection Agency. Hazardous Waste Regulations. http://www.epa.gov/epawaste/laws-regs/regs-haz.htm (accessed 2010 March 12).
38.   The Joint Commission E-dition. Hospital Accreditation Requirements. http://amp.jcrinc.com/Frame.aspx (accessed 2010 March 12).
39.   Special devices. J Oncol Pharm Pract.2007;13:27-30.
40.   Jorgenson JA, Spivey SM, Au C, et al. Contamination Comparison of Transfer Devices Intended for Handling Hazardous Drugs Hosp Pharm—2008;43:723–727

Looking at the Safe Handling of Drugs a Whole New Way

noemail@statce.com — Tue, 08 Dec 2009 17:30:00 GMT

Objectives:

Upon completion of the program, the participant will be able to:

Define a “closed-system transfer device”;
Identify at least two (2) examples of how to monitor for hazardous medication exposure;
State recommendations for environmental sampling;
Describe at least three (3) risks associated with occupational exposure to hazardous drugs, as described by the 2004 NIOSH Warning;
List at least three (3) examples of acute effects and three (3) examples of long term effects of hazardous drug exposure in healthcare workers;
Identify the three (3) primary routes of exposure to hazardous drugs;
List at least three (3) common features described in the major national Guidelines for safe handling of hazardous drugs (NIOSH, ASHP, ONS, and USP 797).

Instructor: Byron Peters B.S. Pharm., R.Ph., E. Thomas Carey, Pharm D

Release Date: 8-Dec-09 11:30 AM
Expiration Date: 8-Dec-12 8:00 AM

Risky Business: Understanding & Preventing Hazardous Drug Exposure

noemail@statce.com — Fri, 13 Nov 2009 14:00:00 GMT

Objectives:
Instructor:

Release Date: 13-Nov-09 8:00 AM
Expiration Date: 13-Nov-13 8:00 AM

Risky Business: Understanding & Preventing Hazardous Drug Exposure

noemail@statce.com — Fri, 13 Nov 2009 12:00:00 GMT

Objectives:
Instructor:

Release Date: 13-Nov-09 6:00 AM
Expiration Date: 13-Nov-13 6:00 AM

An Overview of Swine Influenza A (H1N1)

noemail@statce.com — Tue, 28 Apr 2009 13:00:00 GMT

Objectives:

At the conclusion of this program, participants should be able to:

1. Define and describe swine influenza A (H1N1)
2. List the signs and symptoms of swine influenza A (H1N1)
3. Outline the pharmaceutical treatment recommendations for confirmed and suspect ill cases of swine influenza A (H1N1)
4. Outline information to provide and/or discuss with patients regarding swine influenza A (H1N1)

Instructor: Wendy Meigs RPh/ Mike Johnston, CPhT/

Release Date: 28-Apr-09 8:00 AM
Expiration Date: 28-Apr-12 8:00 AM

Important Note:
The development of this continuing pharmacy education program was expedited with approval of the Accreditation Council on Pharmacy Education (ACPE) in response to a nationally declared public health emergency by the US Department of Health and Human Services (HHS). This program was developed with the latest information available as of April 26, 2009, but since this topic is undergoing constant updates and revisions by the CDC and HHS, some information provided could possibly be outdated or revised. We strongly recommend that you obtain the latest information available directly from the CDC or HHS in addition to, and as a verification of, the information presented. The majority of this program utilizes content developed and originally published by the CDC, with permission.

INTRODUCTION
Swine Influenza A (H1NI), known as swine flu, is a respiratory disease of pigs caused by type A influenza viruses that causes regular outbreaks in pigs. Over the years, different strains of swine flu viruses have emerged. At this time, there are four main influenza type A virus subtypes that have been isolated in pigs: H1N1, H1N2, H3N2, and H3N1. However, most of the recently isolated influenza viruses from pigs have been H1N1 viruses.U.S. cases of human infection with swine influenza A (H1N1) viruses were first reported in Southern California and near San Antonio, Texas, in late March 2009. The Centers for Disease Control and Prevention (CDC) has determined that swine influenza A (H1N1) is contagious, but is unsure how easily the virus spreads between people. Like seasonal flu, swine flu in humans can vary in severity from mild to severe. According to the CDC, 12 human cases of swine flu were detected in the U.S. with no deaths occurring between 2005 and January 2009. Swine flu infection, however, can be serious and even fatal. In September 1988, a previously healthy 32-year-old pregnant woman in Wisconsin was hospitalized for pneumonia after being infected with swine flu and died 8 days later. A swine flu outbreak in Fort Dix, New Jersey occurred in 1976 that caused more than 200 cases with serious illness in several people and one death.Certain groups might be more likely to develop a severe illness from swine flu infection, such as persons with chronic medical conditions. Additionally, bacterial infections may occur at the same time as or after infection with influenza viruses and lead to pneumonias, ear infections, or sinus infections.

SWINE INFLUENZA A (H1N1)
Human cases of swine influenza A (H1N1) virus infection have been identified in several states, as well as in other countries. This is a novel influenza A virus that has not been previously identified in humans, and human-to-human transmission of the virus appears to be ongoing.

Unlike the experience in Mexico, the United States is currently observing a less severe clinical spectrum of disease with infection by the identical virus strain. As of April 26, 2009, of the confirmed cases of swine influenza A (H1N1) virus infection, only two confirmed case-patients were hospitalized and there had been no reported fatalities in the United States. Mexican health officials have reported several hundred suspect cases, including several deaths associated with confirmed swine influenza A (H1N1) virus infection. In Mexico, many patients have experienced rapidly progressive pneumonia, respiratory failure requiring mechanical ventilation and acute respiratory distress syndrome (ARDS). Therefore, the impact of this virus on the two countries has been strikingly different to date.

Novel influenza A virus infections in humans, including swine influenza A (H1N1) virus, represent a pandemic threat. Recognizing the historical precedent for the emergence of a pandemic influenza virus, which could have waves of disease with different morbidity and mortality and epidemiologic profiles, public health departments in the United States must remain vigilant.

Swine influenza A (H1N1) virus is thought to spread in the same way as seasonal influenza. The virus is spread mainly from person to person through coughing or sneezing of infected individuals, however some people may become infected by touching a contaminated object and then touching their mouth or nose. Infected individuals may be able to infect others as early as 24 hours prior to the onset of symptoms and up to 7 or more days after becoming infected.

SIGNS & SYMPTOMS
The symptoms of swine flu in people are similar to the symptoms of regular human influenza and include:

·Fever
· Cough
· sore throat
· body aches
· headache
· chills
·fatigue
· diarrhea
· vomiting

DIAGNOSIS

Official diagnosis of swine influenza A infection requires a respiratory specimen, collected while the infected person is still shedding virus, typically within the first 4 to 5 days of illness. Some individuals, especially children, may shed virus for 10 days or longer. Identification as a swine flu influenza A virus requires sending the specimen to CDC for laboratory testing.

The infectious period for a confirmed case of swine influenza A (H1N1) virus infection is defined as 1 day prior to the case’s illness onset to 7 days after onset.

SWINE INFLUENZA A (H1N1) VIRUS DEFINITIONS

A confirmed case of swine influenza A (H1N1) virus infection is defined as an individual with an acute febrile respiratory illness with laboratory confirmed swine influenza A (H1N1) virus infection at CDC by one or more of the following tests:

· real-time RT-PCR
· viral culture

A probable case of swine influenza A (H1N1) virus infection is defined as a person with an acute febrile respiratory illness who is:

· positive for influenza A, but negative for H1 and H3 by influenza RT-PCR, or
· positive for influenza A by an influenza rapid test or an influenza immunofluorescence assay (IFA) plus meets criteria for a suspected case

A suspected case of swine influenza A (H1N1) virus infection is defined as an individual with acute febrile respiratory illness with onset:
· within 7 days of close contact with a person who is a confirmed case of swine influenza A (H1N1) virus infection, or
· within 7 days of travel to community either within the United States or internationally where there are one or more confirmed swine influenza A(H1N1) cases, or
· resides in a community where there are one or more confirmed swine influenza cases.

Close contact is defined as within about 6 feet of an ill person who is a confirmed or suspected case of swine influenza A (H1N1) virus infection during the case’s infectious period.

VACCINATIONS
There is no vaccine currently indicated for swine influenza in humans. The seasonal influenza vaccine will likely help provide partial protection against swine H3N2, but not swine H1N1 viruses.The H1N1 swine flu viruses are antigenically different from human H1N1 viruses and, therefore, vaccines for human seasonal flu would not provide protection from H1N1 swine flu viruses.

PHARMACEUTICAL TREATMENT
There are four different antiviral drugs that are licensed for use in the US for the treatment of influenza: amantadine (Symmetrel), rimantadine (Flumadine), oseltamivir (Tamiflu) and zanamivir (Relenza). While most swine influenza viruses have been susceptible to all four drugs, the most recent swine influenza viruses isolated from humans are resistant to amantadine and rimantadine. At this time, CDC recommends the use of oseltamivir or zanamivir for the treatment and/or prevention of infection with swine influenza viruses.

Suspected Cases
Empiric antiviral treatment is recommended for any ill person suspected to have swine influenza A (H1N1) virus infection. Antiviral treatment with either zanamivir alone or with a combination of oseltamivir and eitheramantadine or rimantadine should be initiated as soon as possible after the onset of symptoms. Recommended duration of treatment is five days. Recommendations for use of antivirals may change as data on antiviral susceptibilities become available. Antiviral doses and schedules recommended for treatment of swine influenza A (H1N1) virus infection are the same as those recommended for seasonal influenza. (Table 1)

http://www.cdc.gov/flu/professionals/antivirals/dosagetable.htm#table

Confirmed Cases
For antiviral treatment of a confirmed case of swine influenza A (H1N1) virus infection, either oseltamivir or zanamivir may be administered. Recommended duration of treatment is five days. These same antivirals should be considered for treatment of cases that test positive for influenza A but test negative for seasonal influenza viruses H3 and H1 by PCR.

Special Considerations for Pregnant Women
Oseltamivir, zanamivir, amantadine, and rimantadine are all “Pregnancy Category C" medications, indicating that no clinical studies have been conducted to assess the safety of these medications for pregnant women. Only two cases of amantadine use for severe influenza illness during the third trimester have been reported. However, both amantadine and rimantadine have been demonstrated in animal studies to be teratogenic and embryotoxic when administered at substantially high doses. Because of the unknown effects of influenza antiviral drugs on pregnant women and their fetuses, these four drugs should be used during pregnancy only if the potential benefit justifies the potential risk to the embryo or fetus; the manufacturers' package inserts should be consulted. However, no adverse effects have been reported among women who received oseltamivir or zanamivir during pregnancy or among infants born to such women.

Special Considerations for Children
Aspirin or aspirin-containing products (e.g. bismuth subsalicylate – Pepto Bismol) should not be administered to any confirmed or suspected ill case of swine influenza A (H1N1) virus infection aged 18 years old and younger due to the risk of Reye syndrome. For relief of fever, other anti-pyretic medications such as acetaminophen or non-steroidal anti-inflammatory drugs should be recommended.

ANTIVIRA CHEMOPROPHYLAXIS
For antiviral chemoprophylaxis (pre-exposure or post-exposure) of swine influenza A (H1N1) virus infection, either oseltamivir or zanamivir are recommended. Duration of antiviral chemoprophylaxis is 7 days after the last known exposure to an ill confirmed case of swine influenza A (H1N1) virus infection.

PATIENT CONSULTATIONS
Pharmacy technicians should refer any patient considered a suspected case or describing any of the previously mentioned signs and symptoms to the pharmacist for consultation.

According to CDC recommendations, pharmacists should consult confirmed cases to stay home and avoid contact with other people as much as possible to keep from spreading your illness to others.

Suspect cases should be advised to contact their physician to report illness, by telephone or other remote means, before seeking care at a clinic, physician’s office, or hospital, with the following exceptions for when immediate medical attention required.

Immediate Medical Attention Required
Persons who have difficulty breathing or shortness of breath or are believed to be severely ill should seek immediate medical attention

Individuals who become ill and experience any of the following warning signs, seek emergency medical care.

In children emergency warning signs that need urgent medical attention include:

· Fast breathing or trouble breathing

· Bluish skin color

· Not drinking enough fluids

· Not waking up or not interacting

· Being so irritable that the child does not want to be held

· Flu-like symptoms improve but then return with fever and worse cough

· Fever with a rash

In adults, emergency warning signs that need urgent medical attention include:

· Difficulty breathing or shortness of breath
· Pain or pressure in the chest or abdomen

· Sudden dizziness
· Confusion

· Severe or persistent vomiting

For More Information
Pharmacy professionals or patients needing additional information should contact The Centers for Disease Control and Prevention (CDC) Hotline (1-800-CDC-INFO), which is available in English and Spanish, 24 hours a day, 7 days a week.

References & Resources

http://www.cdc.gov/swineflu/

http://www.hhs.gov/

http://www.who.int/csr/disease/swineflu/en/

Safe Handeling:Recommendations & Best Practices

noemail@statce.com — Mon, 20 Apr 2009 13:00:00 GMT

Objectives:

At the completion of this program, the participant will be able to :

- Evaluate the emerging data on the potential health risks of handling hazardous drugs and the recommendations/guidelines for safe handling:

- Analyze the effectiveness of closed-system drug transfer devices;

- Outline the scope and effectiveness of medical surveillance and staff training related to hazardous drugs at your institution compared to current recommendations;

- Identify key factors to be considered when selecting a closed-system drug transfer device system

Instructor:

Release Date: 20-Apr-09 8:00 AM
Expiration Date: 20-Apr-12 8:15 PM

Overcoming Barriers to Chemotherapy Safety in Nursing

noemail@statce.com — Thu, 31 Jul 2008 13:00:00 GMT

Objectives:

Goal/Purpose:
Despite evidence dating back to the 1970's, there continues to be resistance by healthcare professionals to use or properly use safe handling systems, including protective personal equipment (PPE), closed IV sets, and closed system drug transfer devices (CSDTDs). The purpose of this program is to outline barriers to the appropriate use of protective equipment and devices during the preparation, administration, and disposal of chemotherapeutic agents, and to review strategies for removing or overcoming these barriers.

Objectives:

1. Describe the rationale supporting the use of a safe handling system while preparing, administering, and discarding chemotherapy.

2. Describe the common barriers to the use of protective equipment and devices.

3. Describe two strategies for overcoming or removing these barriers.

4. Describe the current recommendations for use of CSDTDs in chemotherapy handling and administration.

Instructor: Kerry A. Mahar, RN, MSN, AOCN

Release Date: 31-Jul-08 8:00 AM
Expiration Date: 31-Jul-10 8:00 AM

Introduction
The first reported risk to humans handling antineoplastics was published in 1979 by The Lancet medical journal, in a study that found mutagenic activity in the urine of nurses working in oncology units. (Falck, 1979) This finding led to the proposal that merely handling chemotherapeutic agents led to exposure and absorption. Some years later, Valanis and colleagues reported an association between the degree of skin contact or exposure and the presence of acute symptoms experienced by nurses. (Valanis, 1993) Inadvertent exposure to these drugs has serious health consequences; common acute symptoms include nausea, vomiting, headache, dizziness, hair loss, and liver damage. Furthermore, long-term effects have been uncovered, such as increased chromosomal alternations, hepatotoxicity, and abnormal reproductive outcomes. (Martin, 2005)

Susan Martin, RN, of SUMART Healthcare Consulting, surveyed approximately 3700 members of the Oncology Nursing Society (ONS) who handled chemotherapy on a regular basis. Her survey revealed the occurrence of infertility, miscarriage, and pre-term labor and births among nurses who handled more than 9 doses of chemotherapy in a day. In addition, developmental issues among the children born to this group were noted, including Attention Deficit Hyperactivity Disorder (ADHD), speech delays, and learning disabilities.

The National Institute for Occupational Safety and Health (NIOSH) defines recommended exposure limits (RELs) as concentrations of substances that are without adverse effect. Currently, there are no identified threshold limits for workplace exposure of hazardous drugs. According to the American Society of Health-System Pharmacists (ASHP), hazardous drugs include chemotherapy, hormones, anesthetic agents, and antiviral agents that have one or more of the following attributes:

1. Carcinogenicity
2. Teratogenicity or other developmental toxicity
3. Reproductive toxicity
4. Organ toxicity at low doses
5. Genotoxicity
6. Structure and toxicity profiles of new drugs that mimic existing drugs determined
hazardous by the above criteria

Despite the increasing awareness of known exposures and adverse outcomes, there continues to be resistance to the use of safe handling systems or their components. This resistance may be based on denial of risk, insufficient information, lack of enforcement of policy or regulation, or lack of provision of safe handling devices. An exploration of barriers such as these may be helpful in allaying some myths and misconceptions, and empower nurses to take more responsibility for their own safety and that of others.

Risk of Exposure
In general, the exposure risks for nurses are related to the preparation, transport, administration, disposal of chemotherapy waste and of bodily fluids. Except for needle sticks given by IM or SC route, accidental injection is much rarer due to the universal use of needle-free administrations. The highest risk of exposure for nurses is associated with preparation and administration, primarily through inhalation of aerosolized drug, direct contact (eyes, skin, mucosa), and ingestion of an improperly handled drug.

In her 2008 article regarding the safe handling of hazardous drugs, Martha Polovich highlights the 1999 report by the Department of Commerce estimating that 5.5 million healthcare workers have the opportunity for exposure to hazardous drugs in the workplace. This estimate includes employees who directly purchase, store, prepare, deliver, administer, and discard chemotherapy, as well as those who risk exposure by working in the vicinity of the drugs.

Certainly, a spill is the exposure risk one thinks of when needing/utilizing PPE and other safety devices as protection. However, unseen actual or potential small exposures should also be of concern. Even with needleless and some closed systems, the risk of exposure persists during attachment and detachment of connections. These “releases” of drug are miniscule, often inadvertent or unintentional, and can occur on a counter or at the patient’s bed or chair. Because they go undetected, these small exposures put not only the administering nurse at risk, but also co-workers, patients, visitors, and others.

Current Guidelines
The Occupational Safety and Health Administration (OSHA) first published guidelines for safe handling in 1986. The following outlines the current NIOSH recommendations for Preventing Occupational Exposure to Antineoplastic and Other Hazardous Drugs in Health Care Settings (NIOSH Publication No. 2004-165):

1. Assess the hazards in the workplace – this includes the physical layout of the treatment/work area, volume of agents handled, spill response, and waste management. It also includes reviewing employee training on a regular basis.

2. Handle drugs safely – this includes the establishment of safe handling practices, labeling, establishing training programs and establishing work practices related to both drug manipulation techniques and to general hygiene practices

3. Use and maintain equipment properly – develop procedures for use and maintaining equipment

The NIOSH recommendations also provide more detailed guidelines for appropriate use of PPE, receiving and storage of drug, drug preparation and administration, use and maintenance of ventilated cabinets, waste disposal, spill control, and medical surveillance. According to NIOSH, "…it is known that exposures to even very small concentrations of certain drugs may be hazardous for workers who handle them or work near them," and "…evidence indicates that workers may be exposed to hazardous drugs and are experiencing serious health effects despite current work practice guidelines."

The use of CSTDs should be considered whenever available, as they limit the potential for generating aerosols and exposing preparers to needle sticks. NIOSH defines a CSTD as a device that mechanically prohibits the transfer of environmental contaminants into the system and the escape of hazardous drug or vapor concentrations outside the system (NIOSH 2004). There are a variety of drug preparation and administration systems available today, however before using any products, it is important to make sure, as recommended by the International Society of Oncology Pharmacy Practitioners (ISOPP) and ASHP, that peer-reviewed, independent studies can be provided for each component of the system to validate it's effectiveness. A device cannot be semi-closed. The PhaSeal® system is the only documented closed-system drug transfer device on the market. This system is designed to prevent leakage of drugs into the environment during preparation and administration (2005, Polovich M et al).

The most current ONS guidelines (2003) are built upon OSHA and NIOSH recommendations. Specific guidelines regarding the preparation, administration by various routes, waste management, and handling of bodily fluids, spills, and accidental exposure are included. In particular, emphasis is placed on the use of closed system drug transfer devices (CSTDs and y-site administration sets) for IV administration and proper use of PPE. The ONS Chemotherapy and Biotherapy Guidelines and Recommendations for Practice, 2nd Edition, incorporates NIOSH 2004, OSHA 1999, and American Society of Hospital Pharmacists 1990 recommendations.

These guidelines bring to light the need to properly utilize various components which, used properly, will provide the extent of protection intended to maximize the safety of the individual. No one device alone will ensure safety. In addition to the tangible components, the system must also include proper education and training.

Persistent Barriers to Proper Handling
Despite the fact that many institutions have created safety guidelines, some nurses continue to follow old or unsafe practices. Several studies have found a lack of standardization with regard to written procedures and guidelines, as well as significant inconsistencies in actual practices (Ritchie, et al). In these studies, the predominant practice was the use of gloves only. Most respondents reported they thought they were doing what was required.

The Myth of “It Can’t Happen To Me”
Often, nurses who handled and administered chemotherapy before safe handling guidelines existed are those who fail to adequately follow the current guidelines. Gather a few of them together and common stories will abound: when they first began treating patients, they mixed and prepared chemotherapy in the medication room; they recall preparing doxorubicin for IVP by squirting drug to the tip of the needle (and beyond), resulting in visible red spots on counters, walls and ceilings; food and drinks were placed in the same area as these medications. Most will report that they have not been harmed by these practices, and some still feel these agents pose no or little danger given (1) whatever exposure there is, it is “nothing” compared to what the patient receives, or (2) the perceived lessened opportunity for exposure as chemotherapy is now prepared in the pharmacy, under a hood. Their contact with the bag, syringe, tubing, and subsequent waste is minimal in comparison to past practice.

Mindset of Inconvenience
As noted previously, actual physical contact with chemotherapy administration items (bag, syringe, tubing, and waste) is often brief. Consider the following: How long does it take to disconnect an IV set and put it in a waste container? That IVP vincristine only takes a few minutes, right? Changing the bag on a continuous infusion? The gown is bothersome to don, and hot and uncomfortable to wear. Inconvenience is an unfortunate way to look at PPE, but it is true that PPE takes time. The gowns in particular are cumbersome and make many users warm over time. Some nurses report that the use of the gown and face shield is disrespectful, or may give the patient the impression that they are toxic, making them feel more isolated or alienated than they already are.

Lack of or Limited Access to Information
To many nurses, especially in the acute care setting, new and updated policies and procedures are generated at record pace, making it difficult to stay abreast of current policy. From institution to institution, the method of introducing new policies and procedures can range from a general email to all nursing staff, handouts that highlight updates/changes, to one on one updates by a nurse educator.

The use of chemotherapy in the non-oncology setting (RA, neurology, etc.) is increasing. The staff required to administer these medications may not be privy to the extensive resources available to designated oncology ambulatory clinics, and standard drug reference books do not address handling.

Lack of Policies
Chemotherapy is being administered in ever more diverse settings. IM methotrexate has been utilized in the homecare setting for years, and patients now receive both IV and oral chemotherapy in nursing homes and group residential homes (mentally ill or developmentally delayed clientele).

In some settings, more so in non-academic sites, the lack of guidelines can cause non-adherence to NIOSH or ONS guidelines. Community sites, of course, can range from a small office with one nurse and no pharmacist to a franchise of practices under one umbrella with dedicated laboratory and a chemotherapy pharmacist available all day. Implementation of practice change can be a challenge, and PPE is a cost that is not necessarily recouped in the billing process.

Noncompliance
The enforcement or validation of competency related to these guidelines and policies is also a factor. Initial education and declaration of standards may have no follow up or review, and it is difficult to change a person’s practice; often, nurses will receive and acknowledge the newer information but return to what they are accustomed to doing. This may be tied to awareness of risk, resistance to change due to the added burden additional tasks, or merely failing to recall the policy.

Overall, the underlying theme of these factors is awareness, or more exactly, lack of awareness. Educational requirements for the establishment and maintenance of competency chemotherapy administration are as varied as patient care environments. In some cases, nurses administer chemotherapy with a bare minimum of education regarding the drugs. Nurses practicing outside the acute hospital setting are at higher risk of not getting at least the basic information required to safely administer chemotherapy and maintain their own personal protection. Finally, nurses who know the toxicities related to particular drugs do not always realize the risks to themselves or others in handling those agents.

Overcoming the Barriers to Proper Handling
Oncology nurses are one of the most well represented groups of specialty nurses in terms of identifying and addressing educational needs. The ONS provides live, electronic, and written forums for basic and continuing education on chemotherapy administration. The ONS Chemotherapy and Biotherapy Course provides an evidence-based foundation for the understanding of the toxicities and risks associated with the administration of antineoplastic agents. Proper preparation and administration techniques are reviewed and the substantiating guidelines are presented. This type of educational program, in tandem with institution-defined clinical orientation, is very often the basic structure of ensuring initial chemotherapy administration competency.

Institutional Level
Employers are not required to abide NIOSH guidelines, but are charged with establishing safe handling precautions. Organizations that provide care to patients that required the use of hazardous materials should - and often do - demonstrate that safety is an institutional value to which there is a commitment. Administrators need to prioritize implementation and compliance. The generation of policies and procedures should be paired with a comprehensive and realistic educational plan. Managers and supervisors must provide staff with the amount of time needed to review information or attend training. Training with regard to safe handling and disposal should also include data related to risks of exposure. Competency and compliance with policy and procedure should be evaluated on a regular basis, and remediation to ensure competency should be provided as needed. Interventions for non-adherence to policy should be communicated to all staff. The appropriate equipment for safe handling should be readily accessible. And at all times, staff should have ready access to the necessary guidelines/policies.

The use of both environmental and biological monitoring may be utilized to increase awareness of risk as well as measure compliance with safe practice; NIOSH, ASHP and ONS recommend the use of biologic monitoring (urine testing) as part of a comprehensive safe handling system.

Professional Level
All personnel dealing with patients receiving chemotherapy have a stake in ensuring chemotherapy is administered safely. Unsafe chemotherapy preparation and administration poses exposure threat to others. Countertop contamination, aerosolization, spills and improper disposal can impact the patient, visitors, nursing aides, housekeepers, and other health providers. Therefore, adherence to safe handling procedure and embracing an institution’s values is demonstrates respect for coworkers, patients, and community.

Peer-to-peer demonstration and expectation of adherence to policy and procedure, including the use of proper equipment is important in maintaining the “safety culture” generated by an institution’s commitment to patient and staff safety. The role of the preceptor is key to ensuring that new employees adopt the practices prescribed by the institution. Selection and preparation of preceptors is often the responsibility of the Nurse Manager and the Clinical Nurse Specialist or Clinical Educator, and a definitive preceptor preparation and selection process should include affirmation of competency, teaching skills, communication and feedback skills, and the proper utilization of resources.

Individual Level
Ultimately, all nurses are responsible for ensuring their own protection. Knowing the hazards and how to protect oneself is primary to practice. Individuals should have the proper resources (clinical support, policies and procedures, equipment, time) before preparing and administering chemotherapy. Despite the institution’s definition of competency, each individual has his or her idea of what makes them competent to practice. Maintaining membership in groups such as ONS and a local chapter can help an individual connect with others who have similar practices and concerns about practice. Networking and sharing experiences can lead to questioning practice and empowering one to address concerns with others within their institution.

Gambrell and Moore (2005) suggest using the SOLVE® 5 Step Problem-Solving Process (Action Services LLC, Rock Hill SC), which is very similar to the nursing process, to implement change in practice in the use of safe handling procedures. The SOLVE method relies on personnel to expose organizational procedures, tools, and training that empower personnel to act. This is a nonpunitive process that allows anyone within a system to look at problem and provide direct input. The involvement of those from all areas can lead to more open communication and comprehensive understanding of issues (pharmacy, nursing, materials management, etc.), and subsequently provide a better outcome with respect to increased use of safety equipment or safe handling practices.

Summary
No one knows what the “safe” limit of exposure to various carcinogenic or mutagenic agents might be. At this time, there is no device or test which can satisfactorily monitor the degree of exposure to cytotoxic drugs. The goals should be to minimize or remove the risk of exposure at every opportunity during the shipping, delivery, preparation, transport, administration, and disposal of chemotherapy. Establishing and maintaining competency around the safe handling and administration of chemotherapy is dependent on both the individual’s understanding of the risks and the support of the organization.

Decisions to practice safe handling of antineoplastic agents among nurses appear to be related to knowledge of risk of exposure and institutional guidelines (Ritchie, et al). It seems that in addition to the establishment of guidelines for safe handling, a mechanism for enforcement or evaluation is required for program effectiveness. Institutions must provide the tools for staff to perform their duties in the safest possible manner, and the staff must be willing to use these tools.

As discussed, OSHA, NIOSH and ONS provide complete and detailed recommendations for the safe handling of chemotherapeutic agents. Employers refer to these guidelines to create policies and procedures for nurses, pharmacists, physicians, environmental services, etc. The creation, dissemination and enforcement of these policies are then delegated to managers, boards and committees, and many institutions incorporate members of these groups into other organizational bodies. Including nurses and pharmacists in the development of policies and procedures that affect their adoption is a key factor in the generation of a sensible policy that is feasible in practice.

References
Falck K, Grohn P. et al. (1979). Mutagenicity in urine of nurses handling cytostatic drugs. The Lancet. 1(8128):1250-1251.

Gabrell, J. and Moore, S. Assessing Workplace Compliance With Handling of Antineoplastic Agents. Clinical Journal of Oncology Nursing Volume 10 Number 4 (2006), pp. 473-477.

Martin, S. and Larson, E. Chemotherapy-Handling Practice of Outpatient and Office-Based Oncology Nurses. Oncology Nursing Forum Volume 30, Number 4, 2003.

Martin, Susan. The adverse health effects of occupational exposure to hazardous drugs. Community Oncology, Sept/Oct 2005 pp. 397-400.

NIOSH Publication No. 2004-165: Preventing Occupational Exposure to Antineoplastic and Other Hazardous Drugs in Health Care Settings

Oncology Nursing Society, Safe Handling of Cytotoxic Drugs. (2004 update of 1997 original)

Polovich M. Safe Handling of Hazardous Drugs. 2008 American Nurses Association. The Online Journal of Issues in Nursing. ISSN: 1091-3734.

Polovich M., Blecher CS, Glynn-Tucker EM, McDiarmid, M and Newton, SA. Safe handling of hazardous drugs. Pittsburgh PA: ONS; 2003.

Ritchie, M. A., McAdams, C. and Fritz, N. Exposure Risk in the Handling and Administration of Chemotherapy Agents: A Review and Synthesis of the Literature. The Online Journal of Knowledge Synthesis for Nursing. Feb 2000, 7(4)

Shaner-McRae, H. McRae, G. and Jas, V. The Online Journal of Issues in Nursing 2007; 12(2).

Valanis, B. Vollmer, W. Labuhn, K, and Glass A. Acute symptoms associated with anitneoplastic drug handling among nurses. Cancer Nursing (1993) Volume 16: 288-295.

Vanchieri, C. Health Hazard to Community Practice Nurses: The ‘Big Worry’ Community Oncology May/June 2005, 2(3) pp. 277 – 279.

The Basics of Safe Handling Hazardous Drugs

noemail@statce.com — Fri, 11 Jul 2008 13:00:00 GMT

Objectives:

Program Goal: To bring the reader up to date on the background in the safe handling of hazardous drugs and review the options currently available.

Program Objectives:
At the conclusion of this program, participants should be able to:
1. identify and define terms in the safe handling of hazardous drugs
2. inform pharmacists, nurses and technicians on the reasons why we
handle hazardous drugs the way we do
3. categorize the data available directly and indirectly involving safe handling
4. review containment options as they are available and understood today
5. express the differences and limitations of current system containment

Instructor: Timothy Tyler, PharmD

Release Date: 11-Jul-08 8:00 AM
Expiration Date: 11-Jul-11 8:00 AM

The safe handling of hazardous drugs is a subject that is as relevant today to the medical oncology community as it was when the dialogue sprouted in the literature three decades back. There is little else that has the potential to so dramatically impact not only the work lives but downstream health of nurses, pharmacists and technicians in the oncology setting as how therapeutic agents are received, stored, inventoried, managed, mixed, delivered, administered and disposed. Since this is a well worn subject that has been reported on numerous times in the literature it may be of benefit to use the basic principles of journalism to make this education piece serviceable. For those who do not recall the basics, they consist of asking the five W’s: Who, What, Where, Why and When. We will endeavor to answer all of these as we review this topic.

Why? Why do we care about the safe handling of drugs deemed by others to be hazardous? The simple answer is because the majority of these hazardous drugs are cytostatic or cytotoxic agents used in cancer chemotherapy that are widely in use in physicians offices, outpatient clinics and hospitals all across North America. To date we have not come up with a definition of safe exposure – we assume that any level of exposure is bad. We do not know at present if this is accurate but it is what we currently have to face in the realm of working with hazardous drugs. Here we need to define terms to explain plainly the safety concerns that are widely acknowledged.

According to the HCS (Hazard Communication Standard) from The Occupational Safety and Health Administration (OSHA), a branch of the federal government, the term “hazardous” refers to any chemical/agent/drug that is a physical or health hazard. This seems fairly simple and straightforward. A health hazard is further delineated as something for which evidence in at least one study provides statistically significant evidence that acute or chronic health effects may occur in those exposed. (1)

There have been numerous terms used and defined over the decades but the most recent stem from the 1990 Technical Assistance Bulletin (TAB) from (then) American Society of Hospital Pharmacists (ASHP) (2) that proposed criteria which were adopted by OSHA in their 1994 guidance in the form of a HCS and further refined in the National Institute for Occupational Safety and Health (NIOSH) alert of 2004. (3) This brings us back to the TAB that was updated and published most recently by ASHP in 2006. As a caution, if the reader is searching for the 2006 updated TAB it entitled the ASHP Guidelines on Handling Hazardous Drugs. (4)

For our purposes we will define Hazardous Drugs (HD) as those that possess toxic properties and may therefore cause and one or combination of the following [NIOSH 04 Alert – Appendix A]:
1) carcinogenicity
2) teratogenicity or other developmental toxicity
3) reproductive toxicity
4) organ toxicity (at low doses)
5) genotoxicity (mutagenicity)
6) structure and toxicity profiles of new drugs that mimic existing drugs determined to be hazardous by the above criteria

So the answer in a nutshell as to “why” we care is listed as items one through six. To be clear about a subject that is viewed with much fear but little in the way of concrete answers to questions of down stream, long term risk, it helps to further review these and explain these terms.

Carcinogenicity refers to anything that is directly involved in the genesis and promotion of cancer. Carcinogens can be of drug, radioactive substance, asbestos or even tobacco smoke origins. The action is clear but the mechanism can be varied. A carcinogen may cause direct harm or it can simply impair the multiple redundant repair mechanisms in an organism to prevent going down the path of developing a cancer.

We refer to any agent or drug that can induce genetic damage in offspring as being teratogenic as it extends beyond the current generation. In this expanded definition note that the term includes harm that ranges from not being readily apparent to so harmful that miscarriage is the inevitable result. Examples of this would be high, ionizing radiation from multiple sources, viral infections, certain syndromes involving poison and similar situations where the “poison” is a drug or pharmacologic agent actually intended to treat or cure disease. Examples of such agents would be cis-retinoic acid or diethylstilbestrol; where there is a therapeutic benefit to be had for the patient but still risk to the unborn.

When the term reproductive toxicity is included with teratogenicity the implication is that sterility or reduced capacity for reproduction are likely outcomes. This can be either acute or delayed. It can be insidious in that it reduces the reproductive window to an artificially low mark while not causing out and out sterility.

Organ toxicity is dependant on the organ system referred to. For example the lungs can be the initial problem with inhaled substances but then when absorbed; the agent may go on to cause further harm in other or added organ systems. The single largest organ in the human body is the skin and as such is a likely avenue of intake into the body. It can be either the organ system affected as in the case of a rash or other dermal eruption or as we saw with the example of the lungs, a means to another toxic ends. Since the distinction takes on elements of adverse reactions from drugs dosed at therapeutic levels the addendum “at low doses” brings about the concern that this occurs with even trace contact or contamination.

When an agent is mutagenic it refers to changes in genetic information of life. Literally it means a change in information stored at the DNA level. Recently the newer term genotoxicity has come to somewhat supplant the term mutagenic which is probably more familiar to the reader. While mutagens induce mutations there are other sources and indeed scientists believe there to be a background level found in nature. Unfortunately we do have evidence to suggest that mutations lead to cancer which is of paramount concern when it comes to handling drugs that can cause directly or indirectly, this effect. Mutagens are typically considered to be carcinogens – implying that the changes to the genetic material are making cancer a likely outcome.

Lastly, we have been able to make class assumptions as our ability to better define agents has improved. In the current era we have computer modeling and better analytical equipment to study new agents as they are commercially produced. In the not so distant past a drug would have years and perhaps a decade or more of study before becoming an agent approved for human use. While this was without the aid of much of our modern technology, it did allow for better classification and understanding of a drugs toxicity profile. Currently we have a much more rapid progression of agents into the common, commercial use. We now rely more on our ability to classify agents and as such we can predict that if a new agent from an existing class is produced it is a simple matter to lump it into the same profile as existing agents in that class until proven otherwise. The ultimate goal here is to protect from occupational exposure and as such it was designed to err on the side of caution.

While this gives us a pressing reason for caring “why” we care, there is also the more mundane answer which involves regulatory compliance and ultimately ethical standards. Agents that can cause mutagenic, carcinogenic or teratogenic effects must be contained and there have been multiple attempts to categorize a uniform approach to their safe handling which the balance of this continuing education exercise will be exploring.

Now that we understand why these agents are of concern and interest, the next question in the journalistic vain is “what”? What data do we have to support the concern? In truth there is slim data that answers objectively what we currently know for certain many years after exposure to a HD. In many cases the answers will require several decades of time after exposure to know exactly what the risks are. In order to answer “what” completely we need to skip ahead to who or whom? Who is it that determines whether or not a drug is a potential problem?

The concern comes from linking what we know for certain and what we suspect. This is best done by either the government agency with resources or the professional societies, which have membership with the requisite expertise. Several organizations have been leading the charge as it where in the dissemination of information and they are OSHA, NIOSH, and ASHP.

In 2004, the National Institute for Occupational Safety and Health (NIOSH) “urged health care workers, employers, and safety professionals to take immediate action to reduce the risks from a newly identified occupational hazard: exposure to antineoplastics and other hazardous drugs.” (6) Consider that chemotherapy in some form has been around since the 1950’s so this alert might appear to be about half a century late. Still, there was comparatively little known about cellular biology in the middle of the 20th century compared with the current modern era and even now we admit that some useful information still eludes us.

NIOSH was established by the Occupational Safety and Health Act of 1970 which also established the Occupational Safety and Health Administration (OSHA). Although NIOSH and OSHA were created by the same Act of Congress, they are two distinct agencies with separate responsibilities. NIOSH is in the U.S. Department of Health and Human Services and is primarily a research agency. OSHA is in the U.S. Department of Labor and is responsible for creating and enforcing workplace safety and health regulations. NIOSH and OSHA often work together toward the common goal of protecting worker safety and health. (7)

NIOSH is moreover, a part of the Centers for Disease Control and Prevention which is funded under the Department of Health and Human Services. It has the power to issue advisory statements but is not vested with executive authority. NIOSH is probably more familiar to healthcare workers for its standards on respiratory fit testing for masks. This has become a requirement in the hospital provider community not because of it’s origin with NIOSH but because it has been adopted as a standard by the Occupational Safety and Health Administration (OSHA) which does have executive authority.

So to reiterate, NIOSH researches and makes advisory statements and OSHA, when a statement needs to be enforced for worker safety, enacts it into statutory regulation. We find ourselves with an advisory statement in the 2004 alert but it has yet to be made into a statutory regulation by OSHA, although some might argue that the United States Pharmacopoeia (USP) Convention has taken some elements of the 2004 NIOSH alert seriously enough to revise USP797 in late 2007 to incorporate elements of hazardous drug storage, preparation and management. (8)

Now that “who” has been fleshed out, let us return our gaze to the question of “what” posed earlier. What data is available and what recommendations are there? The NIOSH alert was a 93-page document with specific warnings and lists of relevant suggestions to workers and employers on exposure prevention of the 138 drugs listed as a sample in Appendix A of the alert. The specific verbiage of the NIOSH alert is excerpted as follows: “Health care workers who prepare or administer hazardous drugs (e.g., those used for cancer therapy, and some antiviral drugs, hormone agents, and bioengineered drugs) or who work in areas where these drugs are used may be exposed to these agents in the workplace.” (9) This is very relevant to any discussion on the topic of safe handling of hazardous drugs. The current website for the entire document in PDF format is found at http://www.cdc.gov/niosh/docs/2004-165/pdfs/2004-165.pdf That listing was compiled from multiple sources but for those who have followed this subject, it merely reinforces the 1994 OSHA HCS (hazard communication standard) requiring all employers to create or develop an inventory of all hazardous chemicals in the workplace. As a reminder in the hospital setting this is managed or made possible by the exhaustive Material Safety data Sheets (MSDS) in big binders throughout the work environment or even now possibly available in wider distribution as electronic documents. It is prudent to mention at this point that those where never intended to be static but living in the sense that they are continually being updated with new data sheets if a listing is amended or for new agents as they become commercially available and are stocked or even can include investigational agents if a MSDS sheet is available. (10)

About 5.5 million U.S. health care workers are potentially exposed to hazardous drugs, including pharmacy and nursing personnel, physicians, environmental services workers, workers in research laboratories, veterinary care workers, and shipping and receiving personnel. While it may seem ironic that the very health care team, whose mission is caring for the sick, is itself a "high-hazard" industry for the workers it employs. In fact, published studies have shown that workplace exposures to hazardous drugs can cause both acute and chronic health effects such as skin rashes, adverse reproductive outcomes (including infertility, spontaneous abortions, and congenital malformations), and possibly leukemia and other cancers. (11) The health risk depends on how much exposure a worker has to these drugs and how toxic they are.

Additionally but not really explained in the literature is that every worker brings a unique genetic predisposition and exposure history of other assaults on their genome such as high ionizing radiation and viral exposures that may have been sub clinical. The result is that it is impossible to predict with any certainty what can be expected. Workers can be protected from exposures to hazardous drugs through engineering, administrative controls, and proper protective equipment. NIOSH had an update meeting in August of 2007 to update the list of hazardous drugs as well as discuss issues that have yet to be resolved.

The U.S. health care industry is one of the fastest growing sectors, with over 14 million workers in 2006 with another 3 million jobs estimated to be created between 2006 and 2016. (12) Again, today there are an estimated five and a half million of these health care workers potentially exposed to hazardous drugs or drug waste and that aside from the expected cast of characters, including pharmacists, nurses, physicians, maintenance workers, operating room personnel; others who may come into contact with these drugs while performing their job could include secretaries, drug representatives, shipping and receiving personnel in addition to family and friends that many times accompany patients into the treatment areas for moral support while the patient is receiving therapy.

We have already determined that hazardous drugs are those that have been determined through research studies to have a potential for causing harm to healthy individuals, including potential risks of cancer, skin rashes, birth defects, and reproductive toxicity. These same drugs also play a critical role in treatment of patients with serious illnesses like cancer and HIV infection. Although the potential therapeutic benefits of hazardous drugs outweigh the risks of side effects for ill patients, exposed health care workers risk these same side effects with no therapeutic benefit.

Health care workers can be exposed through inhalation, skin contact, skin absorption, ingestion or injection. Because of the multiple routes of potential exposure, NIOSH recommends a comprehensive approach to minimizing worker exposure. This comprehensive safety and health program should include engineering controls, good work practices, and proper personal protective equipment. In addition to these aspects of the program, NIOSH is also recommending that a medical surveillance program be used to support these efforts, collecting and interpreting data to better find out if there are changes in the health of workers. (13)

A new report from the National Institute for Occupational Safety and Health (NIOSH) recommends that employers institute medical surveillance programs for health-care workers who are occupationally exposed to hazardous drugs, and suggests practical strategies and components for such programs. The document, Workplace Solutions: Medical Surveillance for Health Care Workers Exposed to Hazardous Drugs, supplements previous NIOSH resources that highlighted potential health risks for health-care employees who are exposed to hazardous drugs.

A primary goal of any medical surveillance program would be to establishing a baseline for individuals' health and then to have in place systems for monitoring their health over time. NIOSH Director John Howard, M.D. has commented that the, ”recommendations in this document, which were developed in partnership with health care professionals, offer practical and effective measures for instituting and maintaining safe, efficient procedures for handling hazardous drugs.”

NIOSH outlines the basic elements a medical surveillance program should include to help employers establish this plan and ensure that those workers who are exposed to hazardous drugs are routinely monitored. The basic recommendations include these:
• Health questionnaires
• Laboratory tests
• Physical examination completed at the time the worker is hired, and updated periodically.
• Follow-up with those workers who have shown changes in their health or have had a significant exposure. (14)

It should be noted that no system will be perfect in scope or surveillance as long as we have imperfect understanding of the all the effects of HD were are using. Establishing a medical surveillance program does help to detect changes in workers health, allowing employers to evaluate the current practices to see if changes are needed to help protect other workers from exposure. Obviously to be of use, records for this sort of program needs to be held in perpetuity or until the person under surveillance is deceased. As an alternative, a 30 year period has often been used when trying to put a time limit on retention of records. [I know this is used but could not trace the origin of the 30 years number used frequently among management]

When? This is an interesting query, which leads us again back to the data available. While it has been stated that the first chemotherapeutic drugs were made available over 50 years ago, it was in 1979 approximately 30 year ago that a rather startling discovery was made. The journal Lancet published the report of researchers form Finland that had discovered mutagenic substances found in the urine of nurses on hospital chemotherapy wards. Those nurses were preparing and then administering doses of chemotherapy for patients. (15) (16)

While not quite the lightning bolt it would be today, it did at least provoke further study and we have seen multiple citations in the literature from that point on until the present day. Most of the work has focused on environmental controls or admixture technique and devices for further reduction of contamination. Even in these later studies there was still some contamination with multiple attempts to manage or improve outcomes have been published and republished but still they are almost never entirely free of contamination. The probable answer to the baseline contamination was first published in AJHP in a 2005 article as an exhaustive report on the extent of contamination of drug vials coming from the manufacturer. In this article we have what could be called damning evidence that no matter how many alerts or statutes were issued, nothing can take something contaminated from the beginning and hope to end up with a cleaner product in the end. At present, after the article exposed a glaring problem there has been no agency that has sprung into regulatory action and the PhRMA industry has not come forward as yet with a comprehensive plan to limit or even reduce vial contamination. Vials alone were tested and this has left all concerned to ponder the potential contamination of the package inserts and individual carton containers that the drugs are shipped inside. (17) A recent editorial in AJHP reiterated a charge to “Demand Clean Vials” (18) and while certainly the appropriate course of action, it will likely require pressure from the professional associations on PhRMA to affect a solution. The other alternative is for a governmental agency such as NIOSH to issue a separate alert and then another agency like OSHA to enact a regulatory statute and enforce it.

Regardless of the outside community’s activity, the reader should be aware that the current state of vials (and probably package inserts and the inside of shipping containers) arriving for use is to be held as highly suspect and indeed treat that receivable as a HD and use the same personal protective equipment (PPE) for its receipt as used in its admixture or administration. While many hospital providers do this, many do not and even fewer physician practices report handling HD receivables in this manner.

The question of “where” will be taken to mean where these guidelines, alerts and activities are designed for and are complied with – the HD clean room. We will therefore look at the various and sundry containment methodology available in the marketplace today and to compare and contrast them in addition to reviewing the expertise needed manipulate them and (hopefully) provide the maximal protections from HDs.

The perfect environment will probably elude most as the space, materials and design elements needed are not too complex in and of themselves but become more so when combined and forced to function in a process that still requires efficiency and real time turnarounds. By that there is no implication of a wink and a nod that these are impossible tasks and therefore it is an option to give up before even starting, but it is an acknowledgement that this is difficult. As with anything that has morphed and evolved with time most clean rooms have grown up around existing space and equipment and the options for containment and safety have become somewhat limited.

For the program starting from scratch it is important to consider location. All guidance now recommends venting ventilator cabinet air 100% to the outside and that can be fraught with difficulty if the HD clean room is buried in a basement or deep in a multi storey building. If in a hospital or attached on the campus of a hospital, the HD clean room will be reviewed by the Joint Commission, the department of health from the state and potentially the board of pharmacy and any other agency that claims dominion over the safe handling of hazardous drugs. In the private setting the surveying option is unlikely but the provisions of the new updated USP797 apply to all areas where sterile drugs are prepared and this does apply but again it is questionable what regulatory oversight will exist in an environment that requires only a business license from the municipality to set up an office practice. Still, the provisions of USP797 are all encompassing and are to govern the preparation of sterile products universally.

Containment options suggest that all HD are stored under negative pressure so as to minimize their potential for contamination. Additionally, they should be made in an environment that controls airflow and again is under negative as opposed to positive pressure as found in requirements for the preparation of sterile products. The frequency of air changes and proof that this occurs are new additions where as before proof lay with the surveyor it now is beholden on the facility to prove they are in compliance. While that is important it should also being remembered that the vast majority of these agents will also need to be sterile preparations and as such still are required to fully comply with the other points of the USP797 statute. (19)

Workers can be exposed at multiple points, such as inhalation of aerosol and particulate matter, accidental injection or exposure through accidental sharps contact, touch or dermal contamination, oral ingestion via food or oral/mucosal contamination with hands. Of these the dermal contamination does have substantial corroboration and is a common enough event in the HD preparation activity that it may account for the majority of failures.

The 2006 ASHP guidance document calls for the creation of a safety program that fully captures all of these elements and recommends a collaborative approach since a comprehensive plan encompasses various disciplines such as nursing, pharmacy and housekeeping, maintenance and human resources among others. A basic element is the MSDS that was required by the OSHA HCS from 1994. All storage areas for HD should have appropriate storage and handling procedures. The recommendation is for double gloving and sealed containers to minimize the chance of breakage or even worse, dropping of HD vials. In addition to collaboration the concern is to minimize exposure through the restriction to only necessary personnel that have been trained and are documented as competent in handing HD. (20)

The physical plant requires all surfaces to be washable and no non-wipable surfaces should be allowed (i.e. no upholstery or carpeted areas). The design is required to be that of areas that are easy to clean and to be sequestered away from break areas or common rooms to prevent unnecessary exposure. Regardless of location, the recommendations clearly cite the need for spill kits and the training of staff necessary for their appropriate use. The area should be positive pressure ISO Class 5 clean rooms with ISO Class 7 anterooms. This is now clear that the solution in the conflict between NIOSH and USP is solved by separating the clean room functions into two separated and distinct areas. (21)

Ventilation controls are required in all USP797 compliant clean areas. More importantly they can eliminate or greatly reduce possible exposure to multiple hazards. Ventilated cabinets are the most common use but now ventilation controls in the preparation room are also necessary to keep either negative pressure in the case of HD or positive pressure where simple sterile preparation is being conducted. The most common ventilated cabinet is the Class II Biologic Safety Cabinet (BSC) followed by the Barrier Isolator (BI). Class II BSCs have been in use for decades and have been shown, when used alongside proper technique, to reduce the exposure of the operator to the hazard being manipulated. The concerns stem from three limitations reported in the 2006 ASHP guidance, namely: 1) contamination on the outside of vials from manufacturers and distributors, 2) work practices required to achieve maximal use of the ventilated cabinet are either not taught or adequately adhered to, 3) potential vaporization of HD may render the high-efficiency particulate air (HEPA) filtration system less than effective. Because of these concerns many of the current requirements for hood engineering controls require the venting to the outside of 100% of the HEPA filtered air as opposed to older suggestions that preventing a certain percentage of HEPA filtered air back into the room would be acceptable. (22)

An alternative that is used far less although it is new to the US is a glove box or BI (Barrier Isolator). The BI is still a ventilated cabinet but one that allows the used to manipulate the contents via a fixed gloved access port in a seal unit. A concern exists in that these function by containment rather than use of ventilation and proper technique as stated in the National Institute for Occupational Safety & Health, NIOSH alert of 2004. To paraphrase the group Blood, Sweat and Tears (ironically the perfect name for a band reference to safe handling of HD), what goes in must come out and at some point the containment vessel can become a nidus of contamination potential. The BI has to be shown to be reproducibly decontaminated but again, technique and use will dictate how effective this procedure is. There is a concern in the containment community that the use of BIs actually take longer but as with any equipment and employee training the speed with which they are used is dictated more by safe technical acumen rather than equipment limitations de facto. That being noted, they are used in a vast minority of places in favor of the Level II BSC. (23)

In 1999, a study was published in the American Journal of Health-System Pharmacists that reported on contamination of targeted hazardous drugs (Ifosfamide, Cyclophosphamide and Fluorouracil) in pharmacy mixing cabinets and surrounding areas and drug administration areas at three hospitals in the United States and three in Canada. “Substantial levels of contamination from three antineoplastic agents were detected on a variety of surfaces in pharmacy drug preparation areas and drug administration areas in six cancer treatment centers in Canada and the United States.” (24) This demonstrated quite clearly that surface contamination was an issue regardless of resources or expertise and that something else was needed to reduce contamination.

Currently, there are multiple systems available in the marketplace to serve as an adjunct to the ventilator cabinets to contain and avoid exposure of HD. These can be further divided into systems that filter or in some means baffle or minimize contamination and those that are truly closed systems. At present there is not a distinction in the reimbursement world (none are separately reimbursable) by professional organizations but there is a difference is contamination potential. A closed system does not allow any vapor, air or particulate matter into or out of the system once introduced.

In 2000 the PhaSeal Closed System Transfer Device (CSTD) was brought to the US market. Since then it remains the only closed system drug transfer device that has demonstrated no potential for leaks or escape of aerosolized or volatile vapor.

In 2002, the Amercian Journal of Health-System Pharmacy (AJHP) also reported on another study looking at reducing contamination using very sensitive diction methodology and concluded that CSTD used in conjunction with the Level II BSC appeared to contain surface contamination for the hazardous drugs studied. (25) This was followed a year later in 2003 with very similar results on a slightly expanded scale with the only difference in this study being the analysis of urine for hazardous drug contamination in workers. The results demonstrated that before the use of the CSTD there were 5 of 8 employees with detectable levels of hazardous drug in their urine and after the implementation of a CSTD there was none. (26) Finally, in 2006 another study was published in AJHP that again looked at surface contamination and the use of CSTD in conjunction with Level II BSC and found a significantly reduced surface contamination as opposed to standard practices alone. (27)

All of the above studies were conducted using the PhaSeal CSTD as it is a closed system needed to contain any hazardous drug contamination. A poster by Jorgenson demonstrating the integrity of dry connections was done by the University of Utah and presented at the ASHP 2007 Midyear Clinical Meeting. This poster evaluated four drug-transfer devices using an alkaline liquid for transfer as a surrogate for a hazardous drug. Litmus paper was then used as an indicator of whether or not the connections were indeed dry as witnessed by no color change or wet which would transform the litmus paper anyplace it came in contact with the alkaline solution or its residue. Each system was given 10 manipulations in all. The other three had 100% litmus change documented but the PhaSeal CSTD had none in any of the 10 manipulations. (28)

A second poster from the University of Utah was presented at the 2007 ASHP Midyear Clinical Meeting by Au and Smith which evaluated nine drug-transfer devices using titanium tetrachloride (TiCl4) used as a vapor surrogate as it smokes in contact with the moisture in room air. The nine photographs of the drug-transfer devices demonstrate the release of the TiCl4 with the exception of the PhaSeal device which reinforces its distinction as the only CSTD currently available. (29) [see appendix for a list of devices that failed?]

Further, the author has been a part of a pilot study conducted in concert with several cancer center to determine if the use of a CSTD (PhaSeal) was capable of reducing the exposure of HD. We found that it did reduce the detectible contamination and this was before the publication of the ASHP seminal citation on outside vial contamination – awaiting publication with ASHP.

When reviewing the basics of Personal Protective Equipment (PPE) it is best to begin with the three “G”s: Gloves, Gowning and Goggles. In actuality, the single most important thing is for all who are involved with HD to don protective elements uniformly. If one member of the group decides for themselves that these rules are not really necessary and just a bother or a hindrance, they thereby put everyone a possible risk. Touch contamination will be a high risk for that worker indeed but in addition it will place a higher risk via touch recontamination of all others outside of the area of containment. Examples that illustrate this can be seen if an employer or risk manager uses a dye that fluoresces on exposure to ultraviolet light. Following the clean room and then all other places that the workers left traces is sometimes the best possible lesson and drives home the point dramatically. It even can have enormous peer pressure to be sure that policies and procedures are followed to the letter.

Gloves are a basic and most essential part of any program of compliance. The use of gloves is recommended in USP797 and going one further, NIOSH recommends double gloving with HD and then only using thicker latex chemotherapy gloves. Gloves are to be changed whenever they are compromised or when the user has excess perspiration or at the very minimum every 30 minutes under hazard conditions. Gloves should be powder free and of a good fit to prevent hand fatigue. Hand fatigue is something that can occur with thicker Chemotherapy gloves. A worker will be flexing their hands to the point of fatigue fighting with tight gloves or perhaps is not accustomed to working with HD after a hiatus. Regardless, the potential for accidents or loss of fine motor control should be assessed when choosing a thickness of glove, while keeping in mind the need to provide a durable barrier from the HD and that many tests of integrity have been conducted with static gloves; that is to say they were not in motion or flexing as they would be in a true hazard environment. (30)

There are multiple citations in the literature regarding the use of latex of both the thin exam variety and the thicker Chemotherapy sort and even nitrile, polyurethane and neoprene types of gloves. Regardless, the use of the gloves appears to be most important and we will not go into depth here other than to reference the body of literature for further follow-up. (31) (32)

Gowns are also recommended by both USP797 and NIOSH but are not in total confluence as to their composition. It was previously recommended that gowns be lint-free and impermeable to chemotherapy. Regardless of the gowns used the biggest barrier to their appropriate use has been that the most effective gowns are uncomfortably hot to wear. The USP in their last 2007 revision did acknowledge this and recommended a very cool climate control of less than 68 degrees farenheight for management of the HD clean room to stimulate compliance with the gowning procedure. Again, protection from the HD is a primary role of a gown. Alongside gowning is the need for hair covering and foot coverings. Because the floors may be a source of contamination, the use of gloves when removing foot coverings a recommended. (33)

Goggles are actually not used primarily because of BSCs or BIs that provide protection for the eyes of the operator. In the event that there is perceived risk the use of a face shield is now preferable to goggles in that shields more of the face when worn appropriately. The use of a respirator can also be appropriate as opposed to a surgical mask which is in no way acceptable as it is ineffective. In order for a respirator mask to be used properly it needs to be fit tested per NIOSH standards in the literature before being put into use in a hazard situation. (34)

The environment in the ventilator cabinet (be it a BSC or BI) requires several other management and operational efficiencies. The admixture of chemotherapy or other hazardous drugs should be added to intravenous (IV) bags only after the IV Bag has been spiked and the uncontaminated IV solution has been allowed to prime the tubing now attached to the IV bag. Technique for doing this still will require that this is done consistent with sterile preparation goals in mind.

In addition, the inside of either a BSC or a BI are considered contaminated and the very act of setting an IV bag with tubing attached inside the vessel and then affixing primary and auxiliary labels is fraught with problems and the possible risk of again spreading that contamination to the outside of the IV bad and or tubing and then out to the area where the administration will take place. Consider too what we established earlier that only recently have the vials themselves that are placed in the ventilated cabinet been determined to be contaminated on the outside and thus a source of contamination for the products we hope to admix and ultimately retrieve cleanly. The desire then is to clean off any IV solution bag before labeling and then sealing it in an appropriate transfer storage bag but again, the same issue remains of not contaminating it by setting it down on preparation areas that may be contaminated. (35)

The cleaning, sterilization and decontamination of ventilated cabinets and other work areas are not only required but can again spell success or disaster in that an ineffective cleaning or decontamination procedure will only expose more than it protects. The recommendations are that ventilated cabinets, internal counters and carts cleaned each shift and as needed thereafter. Workroom counters and floors to be cleaned daily and walls, ceilings, the tray in the BSC and any shelves should be cleaned monthly. The materials necessary for cleaning need to be non-shedding on that they do not generate particles that in this case would be contaminated. (36) (37)

Waste Disposal is another area that training is necessary in that housekeeping and maintenance personnel need to be trained in addition to the primary workers performing admixture of the need
to treat HD disposal with appropriate care. Waste streams can be divided into trace and bulk chemotherapy with the definition of trace often cited as not being concentrated or “raw” chemotherapy/hazardous drug(s). Bulk Chemotherapy or hazardous drug(s) are the vials of concentrated agent with no further dilution. Most states will have specific requirements as to how to separate the waste streams and what each is constituted of to be eligible for appropriate disposal. The risk of HD is primary but if a patient has contact and therefore the waste has an infectious component as well it will need to be considered as well. (38)

This brings us to training. Training is perhaps the largest element in that it involves the wildcard of the human element. All other aspects of a safety program can be perfect and a poorly trained or untrained operator can circumvent almost every safety measure without mush effort. The training should be done by supervisors who can and do demonstrate the techniques and can observe and correct in real time. Training should be documented and then competency should be assessed periodically and documented. This is a small paragraph at the end of this continuing education booklet and yet it cannot be stressed enough as to the importance for success that training will bring. Good training will empower a staff to follow procedure and “know” they are in the right by doing things as per protocol. Unfortunately bad training can leave workers confused or feeling like they are on their own to determine what is expedient rather than what is safe.

For those who read this and are daunted by the enormous amount of effort and complexity in such an undertaking the most important thing you can do is start a Hazardous Drug Safety Review if you do not have a program in place. If you have a program in place, then update it and review the program in line with the NIOSH 2004 alert and the late 2007 revision of the USP 797. Lastly the ASHP 2006 Guidance for handling hazardous drugs should be of great assistance in making sense of a complex nexus of guidance, statutes, regulation and ethical standards to protect workers. The final word is far from being written but as our understanding of HDs and their interaction in the environment of care and among the workforce grows, so too will our comfort at knowing what the best solutions will be. Ethical standards can be of some guidance here as we have less than ideal clinical data regarding safe levels of exposure to work from. Until that time when we can predict future outcomes from exposure, it is prudent to err on the side of caution and apply the tenets of risk manage which seek to avoid risk where possible. Finally the first tenet of medicine, usually applied to patients, but adapted here for the workers in medicine is most appropriate - First, do no harm.

ENDNOTES:

1) OSHA Website www.osha.gov accessed 4/30/08
2) AHJP Vol. 47 May 1990 pp 1033 - 1049
3) NIOSH Publication 2004-165 (http://www.cdc.gov/niosh/docs/2004-165/)
4) AJHP Vol. 63 June 15, 2006 pp 1172 - 1191
5) NIOSH Publication 2004-165(http://www.cdc.gov/niosh/docs/2004-165/) Appendix A
6) AJHP Vol. 61 May 15, 2004 pg 972 (pp 972-978)
7) NIOSH Website www.cdc.gov/niosh – accessed 4/23/08
8) USP 797 Revision (http://www.usp.org/pdf/EN/USPNF/generalChapter797.pdf) accessed 12/4/07
9) NIOSH Publication 2004-165 (http://www.cdc.gov/niosh/docs/2004-165/)
10) AJHP Vol. 61 May 15, 2004 pg 972 (pp 972-978)
11) NIOSH Publication 2007-117 (http://www.cdc.gov/niosh/docs/wp-solutions/2007-117/) accessed 4/28/08
12) U.S. Department of Labor Web (http://www.bls.gov/oco/cg/cgs035.htm) accessed 4/28/08
13) NIOSH Publication 2004-165 (http://www.cdc.gov/niosh/docs/2004-165/)
14) NIOSH Publication 2007-117 (http://www.cdc.gov/niosh/docs/wp-solutions/2007-117/) accessed 4/28/08
15) AJHP Vol. 62 March 1, 2005 pg 471 Luci Power, MS “Demand Clean Vials”
16) Lancet Vol. 1 1979 pp 1250-1 (letter)
17) AJHP Vol. 62 March 1, 2005 pp475-84
18) AJHP Vol. 62 March 1, 2005 pg 471 Luci Power, MS “Demand Clean Vials”
19) USP 797 Revision (http://www.usp.org/pdf/EN/USPNF/generalChapter797.pdf) accessed 12/4/07
20) AJHP Vol. 63 June 15, 2006 pp 1172 - 1191
21) USP 797 Revision (http://www.usp.org/pdf/EN/USPNF/generalChapter797.pdf) accessed 12/4/07
22) AJHP Vol. 63 June 15, 2006 pg 1188 Appendix A
23) AJHP Vol. 63 June 15, 2006 pg 1188 Appendix B
24) AJHP Vol. 56 July 15, 1999 pp 1427 - 1432
25) AJHP Vol. 59 January 1, 2002 pp 68 - 72
26) AJHP Vol. 60 November 15, 2003 pp 2314 - 2320
27) AJHP Vol. 63 September 15, 2006 pp 1736 – 1744
28) ASHP MCM 2007 Au & Smith Poster (http://www.carmelpharmausa.com/econtent/35) accessed 4/30/08
29) ASHP MCM 2007 Jorgenson Poster (http://www.carmelpharmausa.com/econtent/35) accessed 4/30/08
30) AJHP Vol. 63 June 15, 2006 pg 1188 Appendix C
31) AJHP Vol. 63 June 15, 2006 pg 1188 Appendix C
32) AJHP Vol. 56 December 1, 1999 pp 2450 – 2453
33) AJHP Vol. 63 June 15, 2006 pg 1188 Appendix D
34) AJHP Vol. 63 June 15, 2006 pgs 1175, 1180
35) AJHP Vol. 63 June 15, 2006 pp 1181-2
36) AJHP Vol. 63 June 15, 2006 pg 1183
37) USP 797 Revision (http://www.usp.org/pdf/EN/USPNF/generalChapter797.pdf) accessed 12/4/07
38) AJHP Vol. 63 June 15, 2006 pp 1183 – 4

Conjunctivits-When is self-care appropriate?

noemail@statce.com — Thu, 01 Nov 2007 13:00:00 GMT

Objectives:

The goal of this program is to educate registered pharmacists and certified pharmacy technicians regarding the various types of conjunctivitis, as well as to suggest when self-care may be an alternative.

Learning Objectives:

Upon completion of this program, the registered pharmacist and certified pharmacy technician should be able to:

1. Establish the epidemiology, prevalence and risk factors associated with mild acute conjunctivitis.

2. State the factors that differentiate mild acute conjunctivitis from other potentially more serious ophthalmic conditions.

3. Explain the meaning of bacterial resistance and identify the potential dangers to society.

4. Identify non-prescription treatments and supportive care options.

5. Discuss the role of the pharmacist in counseling patients with mild acute conjunctivitis.

Instructor: Doris E. Hinton, R.Ph.

Release Date: 1-Nov-07 8:00 AM
Expiration Date: 1-Nov-10 8:00 AM

Introduction

Acute conjunctivitis, commonly referred to as “Pink Eye”, affects one in eight school children each year1, resulting in over 5 million cases in the U.S. alone2. It is one of the most frequent reasons for office visits to ophthalmologists3. Conjunctivitis rarely leads to visual loss or permanent structural damage, yet it accounts for a significant number of lost work and school days each year3. Patients primarily present with a pink discoloration to the whites of the eyes, and may also have a discharge that ranges from clear and watery, to thick and yellow-green in color. A feeling of grittiness or a sensation that there is something in the eye may accompany the redness and discharge3. Traditionally, conjunctivitis has been treated immediately with topical antibiotics, despite the fact that the majority of cases are self-limiting and will resolve without treatment3. With the emergence of antimicrobial resistance and its eventual consequences, it is imperative that physicians and pharmacists discourage the inappropriate use of topical antibiotics. Measures for appropriate self-treatment and supportive care of viral and environmental conjunctivitis are available, while cases with bacterial origin may prove to be self-limiting as well4. A key role of the pharmacist is to educate patients about conjunctivitis and when self-care measures can be appropriate.

Prevalence and Epidemiology

Acute conjunctivitis is generally contagious, spreading quickly and easily. Although it was once thought that viral conjunctivitis is more contagious than bacterial, it is now commonly known that both forms can be spread easily5 . Left untreated, the process can last up to 10 days5.

Conjunctivitis occurs in all age groups, with the largest concentration among children under 10 years of age6 (TABLE 1). A study of conjunctivitis incidence conducted at one pediatric practice tabulated an average age of 24.3 months, with a range of 2 weeks to 16 years5. Most children who visit a physician with a pink eye end up having simple, uncomplicated conjunctivitis without any other symptoms. The majority of cases in children are bacterial or viral5. The incidence of conjunctivitis tends to surge when children return to school and come into close contact with each other after the summer break. One reason that conjunctivitis is more prevalent among younger children is the sharing of toys at daycare centers. A child with conjunctivitis will frequently rub his or her infected eyes, play with available toys, and then another child will pick up the toys. Alternatively, older children sit at desks without close physical contact. However, the availability of computer kiosks at libraries and colleges is changing this dynamic5. Conjunctivitis is significantly more prevalent among females, which account for 61% of incidence6.

The cornea, the clear membrane covering the colored iris and pupil, tends to cope well with minor injury and irritation. As an example, if dirt scratches the corneal surface, epithelial cells slide over the abrasion rapidly and patch the injury before infection or vision changes can occur7. The conjunctiva is the protective membrane that lines the eyelids and also covers the white portion of the eye called the sclera8. The term “conjunctivitis” describes a group of inflammatory conditions that can affect the conjunctiva. The most common causes of mild conjunctivitis can be separated into three classes; bacterial, viral, and environmental8. Conjunctivitis is more commonly caused by bacteria in children (50% of cases) while viral causes are more prevalent in adults3 . The common adenoviruses, which cause most colds and upper respiratory infections, are also the cause of most viral conjunctivitis. The most common cause of bacterial conjunctivitis is S. pneumoniae, with H. influenzae being a secondary causative agent5. The natural progression of the most common types of conjunctivitis is shown in TABLE 2.

Corneal infection

Complications associated with conjunctivitis are not common; a review of 5 randomized placebo-controlled trials showed no serious outcomes in patients regardless of whether they were in the treatment group or the control group3.

Diagnosis

The classic symptom of conjunctivitis is a pink discoloration and irritation of the whites of the eyes, possibly accompanied by secretions or mucous9. The type of conjunctivitis can often be differentiated on the basis of history, physical exam, the quality of eye discharge, and whether or not both eyes are affected3,5 . One study of 111 patients who were admitted to a hospital emergency room with conjunctivitis showed that a “gluey/sticky eyelid” with a mucous discharge was present in 96% of cases10.TABLE 3 shows the typical symptoms and pre-disposing factors associated with the main forms of conjunctivitis.

Despite the fact that the specific type of conjunctivitis can often be suspected on the basis of history and a physical exam, general practitioners and pediatricians express difficulty with differentiating between bacterial and viral cases. Diagnostic tests for conjunctivitis are not routinely performed in these settings3. A UK study completed in 2001 observed general practitioners’ diagnosis and management practices for acute conjunctivitis. Questionnaires were mailed to 300 GP’s, and sadly, 95% stated that they usually prescribe a topical antibiotic despite 58% of them admitting that they think at least half of the cases are viral. Only 36% believed that they could accurately discriminate between bacterial and viral cases11. It is because of the difficulty in differentiating between bacterial and viral causes that it has become standard practice to prescribe a topical antibiotic2 .

Most cases of conjunctivitis are examined by family practice and pediatric physicians, while about 30% of patients seek the advice of an ophthalmologist6 . Referral to an ophthalmologist may be warranted when there is blurred vision, persistent photophobia, severe pain, lack of response to topical treatment, or the cause is suspected to be a herpetic virus. Ophthalmologists can perform a slit lamp examination to determine if the infection is bacterial or viral, since there is a pupillary response to this exam in bacterial cases5 .
Other ophthalmic conditions that can cause symptoms that tend to be more severe than those experienced with mild conjunctivitis include the following7:

1. Keratitis-A more serious bacterial infection experienced after severe corneal damage, such as penetration by a foreign object. Symptoms include severe pain, decreased visual acuity, and discharge from the cornea. This is the most serious complication that can be encountered with contact lens wear.
2. Ocular Herpes-A recurrent viral infection, usually caused by the HSV-1 virus that leads to cold sores. Ocular herpes is controllable, but not curable, as is the case with other herpetic viruses. Prompt treatment with antiviral agents prevents viral multiplication, and can therefore shorten the duration of the process.
3. Herpes Zoster-Caused by the varicella-zoster virus, which may travel to the head and neck region, possibly leading to a corneal lesion. The process usually resolves on its own, but antiviral treatment decreases the risk of the infection penetrating deeper into the cornea and causing scarring.

Treatment and Prognosis

The treatment of conjunctivitis varies by cause. Environmental conjunctivitis is usually as a result of seasonal allergies. Topical OTC antihistamine/vasoconstrictor drops, or topical H1-histamine receptor antagonists are good choices3.

Viral conjunctivitis should never be treated with antibiotics, as they are not effective in these cases. The strategy of “watchful waiting”, which is commonly employed with acute otitis media, may be especially appropriate for adults where conjunctivitis is most often viral. Over-the-counter artificial tears can provide comfort, as may cool compresses3. One study of 200 patients observed the effect of OTC treatment versus supportive care for viral conjunctivitis. Half were given a topical antihistamine/vasoconstrictor, while the other half were told to wash their eyes with cold water and to use ice packs. Symptoms resolved for the treatment group in an average of 4.9 days while symptoms resolved in 7.86 days among the group that used supportive care. This indicates that although viral conjunctivitis is self-limiting without antibiotics, both OTC treatment and supportive care can reduce the severity and duration of the process from its natural 10-14 day course4.

If the conjunctivitis is as a result of contact lens irritation, lens wear should be discontinued for at least 2 weeks. A topical steroid to be administered for 1-2 weeks may be prescribed by the physician3.

Conjunctivitis of bacterial origin may be self-limiting without treatment in mild cases. A Cochrane Review sought to assess the benefit of antibiotic treatment for acute bacterial conjunctivitis by meta-analysis. It showed that bacterial cases resolved within 2-5 days in 64% of placebo-treated cases11. Additionally, a 2005 UK study published in The Lancet examined 326 children with conjunctivitis aged 6 months through 12 years. Half were administered chloramphenicol eye drops for 7 days, while the other half were given placebo. Results showed that the cure rate was 83% in the treatment group, and 86% in the placebo group. These results indicate that most cases of acute conjunctivitis will resolve spontaneously without antibiotic treatment1, and that the automatic prescribing of a topical antibiotic for conjunctivitis should come into question2. However, if the bacterial infection is considered more moderate, a 5-7 day course of treatment with a broad-spectrum topical antibiotic may be warranted3. The preferred choice is a fourth generation fluoroquinolone such as moxifloxacin, due to its tolerability, convenient 3 times a day dosing, and speed of eradicating the infection5.

Consequences of Antibiotic Overuse

Penicillin was first mass produced in 1943; antibiotics have dramatically reduced illness and death from bacterial infections ever since12. However, it took only 4 years for microbes to experience evolutionary changes that would make them resistant to the very life-saving drugs that once wiped them out13. Bacteria are single-celled organisms with a small number of genes. A single gene mutation can greatly affect the organism’s virulence and resistance. Because these organisms divide and reproduce quickly, the new resistant mutant can become dominant throughout the microbial population when the antibiotic is present13.

It is the widespread use of antibiotics, versus the controlled use only when absolutely necessary, that promotes antibiotic resistance. In fact, the Centers for Disease Control and Prevention (“CDC”) claim that virtually all important bacterial infections throughout the world are developing some resistance to antibiotics13. S. pneumoniae, the pathogen responsible for most AOM, is resistant to penicillin in up to 30% of cases in some areas of the U.S., and up to 11% are resistant to third generation cephalosporins15. Greater resistance has led to the use of broader spectrum antibiotics, which are generally more expensive16. This leads to even greater resistance.
It is important to note that antibiotics are not effective against viral infections such as the flu, most sore throats, the common cold, and seasonal allergies. Antibiotic use in these instances is a waste of money and further exacerbates bacterial resistance14. Parental pressure to prescribe antibiotics is a big concern; a recent study showed that pediatricians prescribe antibiotics 65% of the time when they sense that the parent expects it, but only 12% of the time when they sense the parent will not pressure them into writing a prescription14. In 2002, the Council for Affordable Quality Healthcare (CAQH) surveyed 1000 adults to determine their beliefs about antibiotics and found that misperceptions persist about their appropriate use17 (Table 4).

Until recently, it was thought that the use of topical antibiotic drops did not lead to bacterial resistance, since they are applied in small amounts, directly to the infected area8 . However, it is now recognized that some resistance to topical medications for conjunctivitis is developing 5. A 1988 study of antibiotic susceptibility to 1291 ocular bacterial isolates found that fluoroquinolones were the most effective class, yet 18% of staphylococci were resistant to them. These organisms were very resistant to other antibiotics traditionally used for conjunctivitis, such as Gentamicin, Tobramycin, and Erythromycin18.

These results suggest that physicians that prescribe fewer antibiotics for other types of infections should be considering reducing antibiotic usage for conjunctivitis as well2. Resistance to topical antibiotics can be prevented if physicians do not automatically prescribe one for every patient with a red eye. Antibiotics should never be prescribed for viral or environmental conjunctivitis and in most cases bacterial conjunctivitis may be self-limiting as well5.

Simple measures that parents can take to prevent the spread of bacterial resistance include the following:

-do not expect or demand an antibiotic prescription with every physician visit.
-do not take an antibiotic for a viral infection.
-understand that antibiotics are not appropriate for some bacterial infections.
-Unless advised otherwise by a physician, complete the full course of an antibiotic prescription.
-never save some of an antibiotic for the next time you get sick.
-never take an antibiotic prescription that was prescribed for someone else.

In 1995, the CDC launched a national campaign designed to reduce antimicrobial resistance by educating both the public and healthcare providers.14 Pharmacists can help inform the public by providing useful educational materials to patients which can be ordered from the CDC at http://www.cdc.gov.drugresistance/community/orderform.htm#bulk.

School Policies

School policies that regulate absenteeism are in some cases antiquated and are largely set by the school district versus the CDC5 .The typical school policy states that children with conjunctivitis can be sent back to school or daycare 24 hours after antibiotic treatment is started8. This policy is despite the fact that experts consider the period of infectiousness to be 7 days from the onset of symptoms; some studies suggest the infectious period may be as long as 10-14 days3.

Except where viral or bacterial conjunctivitis is accompanied by other signs of illness, children should be allowed to remain in school once therapy is started . Specifically, the Red Book does not recommend excluding children from school if their symptoms include only a red eye with a clear discharge with no other signs of systemic disease5.

Prevention

Avoiding close contact with infected individuals accompanied by frequent hand washing is the cornerstone of preventing the spread of conjunctivitis. One study showed that one school which promoted frequent hand washing or the use of hand sanitizing alcohol gel had a 50% lower absence rate versus a control school5 .

The CDC has instituted the “Ounce of Prevention” campaign, created by the National Center for Infectious Diseases, with the goal of teaching the public the benefits of cleaning, and disinfecting, and hand washing19. Pharmacists can help with this campaign by providing consumer educational brochures, which can be ordered from the CDC at http://www.cdc.gov/ounceofprevention.

Other preventive measures for reducing the spread of conjunctivitis include the following3:

1. Contact lens wearers should be instructed in proper lens care and encouraged to replace lenses frequently.
2. Eye protection should be worn when appropriate to prevent exposure to chemical and toxic irritants.
3. Daycare centers should routinely sanitize toys and surfaces that are shared by children.
4. Infected individuals should not share towels with other family members.
5. Infected individuals should never share topical eye drops with others.

Over the Counter Pain Medications

Topical eye drops specifically for viral and environmental conjunctivitis are now available OTC in the U.S and may be used as a safe, soothing alternative in patients over 2 years of age. These eye drops should not be used if the patient is experiencing eye pain, sensitivity to light, vision changes, a lesion on the cornea, or a thick white, yellow, or green discharge7. Patients with these symptoms should be referred to a physician.

Topical antihistamine/vasoconstrictors and H1-antihistamine receptor antagonists are also available for environmental conjunctivitis caused by seasonal allergens. Over-the-counter artificial tears may be a soothing alternative as well3.

Patient Counseling

Patients see their pharmacist more often than any other healthcare provider; therefore pharmacists are in an excellent position to educate patients about appropriate conjunctivitis care20. Pharmacists can play an instrumental role in advising of the dangers of antibiotic over-prescribing both to the individual and to society. Pharmacists can help parents understand when antibiotics may be appropriate and when they are not. Of particular value is the pharmacist’s ability to suggest OTC products and appropriate supportive measures that can be used in mild cases of viral and environmental conjunctivitis.

It is important for the pharmacy technician to ensure that patients with conjunctivitis who approach the pharmacy counter be counseled by the pharmacist. Suggested points for discussion include the following:

1. Inform parents that according to studies, 64% of conjunctivitis cases tend to resolve spontaneously without antibiotics.
2. Make parents aware that avoiding contact with other infected individuals will reduce the likelihood of spreading conjunctivitis.
3. Discuss that certain daycare situations may contribute to increased incidence of conjunctivitis.
4. Inform customers that they should not share towels with family members who have conjunctivitis.
5. Consider displaying educational materials provided by the CDC for parents during critical
6. Explain the dangers of antibiotic over-prescribing to parents.
7. Educate customers about illnesses where antibiotics are not effective and are therefore not appropriate.
8. Always counsel those receiving an antibiotic to take it as directed and finish the full course.
9. Advise patients never to save antibiotics for the next illness and never to share with others.
10. Be familiar with OTC topical eye drops that may be appropriate for mild cases of acute viral and environmental conjunctivitis.

Summary

Acute conjunctivitis affects over 5 million people each year, yet it is likely to resolve spontaneously in 64% of instances. Due to the alarming increase in antimicrobial resistance seen since their discovery in the 1940’s, antibiotics must be used more judiciously if we are to continue to rely upon them for life-threatening illnesses. Research has shown that the majority of cases of conjunctivitis can be managed without prescription antibiotics, making conjunctivitis a prime area for reducing antibiotic overuse. Over-the-counter treatments and supportive measures may be appropriate choices for most cases of mild viral and environmental conjunctivitis. Pharmacists can play a significant role in reducing the inappropriate use of antibiotics by educating consumers about proper conjunctivitis self-care.

References
1. Rose PW, Harnden A, Brueggeman AB, Perera R, Sheik A, Crook D, Maret D. “Chloramphenicol treatment for acute infective conjunctivitis in children in primary care: a randomized double blind placebo controlled trial.” Lancet 2005 Jul 2; 366 (9479): 37-43.
2. Nghiem HT. “Children may not need antibiotics for acute infective conjunctivitis.” Medscape Medical News. June 24, 2005. Academic search via Medscape, http://www.medscape.com/viewarticle/507276.
3. American Academy of Ophthalmology Cornea/External Disease Panel. American Academy of Ophthalmologists Preffered Practice Pattern-Conjunctivitis. 2003 pp.1-25.
4. Majeed A, Naeem Z, Khan DA, Ayaz A. “Epidemic adenoviral conjunctivitis report of an outbreak in a military garrison and recommendations for its management and prevention.” J Pak Med Assoc. 2005 Jul; 55(7): 27-35.
5. Dorfman MS, Murphy DK, Cuming GS. “Bacterial conjunctivitis in children: containing the infection.” Infectious Diseases in Children Symposium. January 2006. Academic search via Idichildren, http://www.idichildren.com/monograph/0601/intro.asp.
6. Conjunctivitis Diagnoses: Year 2003. IC9
7. Healthlink Medical College of Wisconsin website. Http://www.healthlink.mcw.edu/eye-care/index.html. (Accessed August 2007).
8. Huget, J. “Drop the Drops?. The Washington Post. 6/28/05.
9. American Academy of Family Physicians website “Eye Problems” 2005. http://familydoctor.org. (Accessed August 2007).
10. Patel P, Diaz MCG, Bennett JE, Attia MW. “Clinical features of bacterial conjunctivitis in children.” Academic Emergency Medicine. 2007, 14: 1-5.
11. Everitt H, Little P. “How do GPs diagnose and manage acute infectious conjunctivitis? A GP Survey”. Family Practice. 2002 19(6): 658-660.
12. US FDA Website. “The Rise of Antibiotic-Resistant Infections,” Academic Search via FDA, http://www.fda.gov/fdac/features/795_antibio.html . (Accessed August 2007).
13. National Institutes of Health Website. “The Problem of Antibiotic Resistance,” Academic Search, http://www.niaid.nih.gov/factsheets/antimicro.htm. (Accessed August 2007).
14. Centers for Disease Control and Prevention Website. “Background on Antibiotic Resistance,” Academic Search, http://www.cdc.gov.drugresistance/community/. (Accessed August 2007).
15. MedlinePlus Website. “Otitis Media with Effusion,” Academic search, http://www.nlm.nih.gov/medlineplus/ency/article/007010.htm. (Accessed August 2007).
16.Emedicine.com Website. “Complications of Acute Otitis Media,” Academic search, http://www.emedicine.com/ent/topic426.htm . (Accessed August 2007).
17. McCain J., “Health Plans Respond as Microbes Develop Resistance Techniques,” Managed Care Magazine. June 2004.
18. Abelson M, Smith L. “Infectious Disease and Drug Resistance.” Review of Ophthalmology. http://www.revophth.com/index.asp?page=1_119.htm. (Accessed August 2007).
19. CDC Website. “The Ounce of Prevention Campaign,” Academic search, http://www.cdc.gov/ounceofprevention.htm. (Accessed August 2007).
Rosenfeld RM, Kay D., “Natural history of untreated otitis media,” Evidence-based otitis media 2d ed. Hamilton, Ontario:Decker; 2003: 180-98.
20. Doucette WR, Mays-Holland T, Memmott H, et al., “Cancer pain management: pharmacist knowledge and practices,” J Pain Symptom Manage. 1997;5:17-31.

A Wait and See Approach to the Management of Otitis Media

noemail@statce.com — Sun, 01 Jul 2007 13:00:00 GMT

Objectives:

At the completion of this program, the participant will be able to:
1. State the epidemiology, prevalence and risk factors associated with acute otitis media.
2. Explain the meaning of bacterial resistance and identify the potential dangers to society.
3. Outline the Clinical Practice Guideline for treating uncomplicated acute otitis media.
4. Identify available over-the-counter pain relief medications.

5. Discuss the role of the pharmacist in counseling parents of patients with acute otitis media.

Instructor: Doris Hinton, RPh

Release Date: 1-Jul-07 8:00 AM
Expiration Date: 30-Jun-10 8:00 AM

Introduction
Acute otitis media (AOM), commonly referred to as middle ear infection, accounts for more than half of all antibiotic prescriptions written by pediatricians in the U.S.¹ It is the most frequent diagnosis made in physician practices for children under 15 years of age ², affecting 83% of all children by their third birthday.³ Patients primarily complain of earache and other ear symptoms (49.7%), while a small percentage (8.6%) present with fever but no pain.² In pre-verbal children, the earache is often signaled by a disruption of sleep or an increase in fussiness. Traditionally, AOM has been treated immediately with antibiotics, but several studies have shown that most cases will resolve spontaneously without them.^4,5Given this fact along with the emergence of antimicrobial resistance,⁶ the American Academy of Pediatrics (AAP) and the American Academy of Family Physicians (AAFP) have developed a Clinical Practice Guideline for treating AOM which encourages a period of observation before initiating antibiotic treatment for most children.⁷ This should have a significant impact on reducing antibiotic over-prescribing. However, it will require educating parents about the benefits to their families of following the new approach. Many parents still expect a prescription with each doctor visit.

Prevalence and Epidemiology
AOM occurs most frequently in children, although adults are occasionally affected. It is most prevalent during the winter and early spring along with other upper respiratory infections.⁸ A Boston pediatric practice observed the medical records of 498 children from birth until 7 years of age and found that 62% experienced AOM by their first birthday, with the peak incidence occurring between 6 and 12 months.⁹ Their review uncovered a significant increase in risk among male children, among those with a sibling history of AOM and in children not breast fed.⁹ Recurrent infection is not uncommon; this same study found that 46% of 3 year olds had experienced three or more incidents of AOM.⁹ Factors that are associated with increased risk of recurrent AOM are enrollment in daycare, other respiratory illnesses, having smokers in the family, using a pacifier and infant feeding with the bottle propped.¹⁰

Children are more prone to ear infections due to their Eustachian Tubes being shorter, narrower and more horizontal, making the movement of trapped fluid more difficult. (Figure 1). Bacteria becomes trapped when swelling of the Eustachian Tube occurs due to colds and allergies, which may lead to infection.¹¹ (Figure 2). The resultant buildup of fluid and pus creates pressure against the eardrum, causing swelling, earache and sometimes redness.⁸ This type of ear infection characterized by trapped fluid and uncomfortable symptoms is formally called acute otitis media. By contrast, children may present with fluid in the middle ear without signs or symptoms of an acute ear infection; this condition is referred to as otitis media with effusion (OME). The infectious state of AOM may be followed by weeks of OME where fluid is still present but not painful, thus its common name “silent ear infection”. Children may complain of not hearing well, or more commonly the condition is noticed during a physician examination for another condition or during a well child checkup. OME usually resolves on its own over a period of weeks or sometimes months.¹²

Figure 1. Anatomy of infant versus adult Eustachian Tubes

Figure 2. Normal middle ear versus otitis media.

Complications associated with AOM (hearing loss, mastoiditis, meningitis) are much rarer since the advent of antimicrobial treatment. The risk of complications generally increases if an acute episode lasts for more than 2 weeks or if symptoms recur within 2-3 weeks.²⁷

Diagnosis
The accurate diagnosis of AOM is not assured by simply notating a history of the “classic” symptoms.¹³ One study found that the classic signs of earache, fever and irritability were observed in less than 60% of children diagnosed with AOM.¹⁴(Table 1).

Table 1-SYMPTOMS OF ACUTE OTITIS MEDIA IN 363 CHILDREN ¹⁴

Symptom	% of Children
Cough or rhinitis	94
Rhinitis	90
Cough	78
Irritability	56
Fever	55
Earache	47

Another study found that fever, crying, irritability or a combination was present in 90% of children with AOM, but these symptoms were also present in 72% of children who did not have AOM.¹³

An otoscope (Figure 3) is used to perform a physical examination of the eardrum (also referred to as the tympanic membrane) for redness and bulging, but this is often difficult due to the child’s fever and crying (which may cause redness themselves) and by blockage with ear wax. Redness alone does not suggest a diagnosis of AOM. The mobility of the eardrum may be assessed using a pneumatic otoscope. Typically, AOM is characterized by a bulging, opaque, immobile eardrum. If the eardrum is in the normal position and appears to be mobile, the child is unlikely to have AOM.¹³

Figure 3-Otoscopic Examination of the Ear

Without fluid in the middle ear space, there is no acute otitis media. An acoustic otoscope (using sound waves) or a tympanogram (using pressure echoes) may be used to confirm the presence of fluid in the middle ear space if any question remains after pneumatic otoscopy. If a bacterial diagnosis is needed, this may be accomplished by tympanocentesis, using a needle to obtain a middle ear fluid sample. A culture of the fluid may determine the presence, identification and antibiotic susceptibility of bacteria. This diagnostic tool is not used on a routine basis but may be used in cases of severe, chronic or recurrent infection.¹³

Consequences of Antibiotic Overuse
Penicillin was first mass produced in 1943,¹⁶ and antibiotics have dramatically reduced illness and death from bacterial infections ever since. However, it took only 4 years for microbes to experience evolutionary changes that would cause them to be resistant to the very life-saving drugs that once wiped them out.¹⁶ Bacteria are single-celled organisms with a small number of genes. A single gene mutation can greatly affect the organism’s virulence and resistance. Because these organisms divide and reproduce quickly, the new resistant mutant can become dominant throughout the microbial population when the antibiotic is present.¹⁷

It is the widespread use of antibiotics (versus the controlled use only when absolutely necessary) that promotes antibiotic resistance. In fact, the Centers for Disease Control and Prevention (“CDC”) claims that virtually all important bacterial infections throughout the world are developing some resistance to antibiotics.¹⁵ S. pneumoniae, the pathogen responsible for most AOM, is resistant to penicillin in up to 30% of cases in some areas of the U.S., and up to 11% are resistant to third generation cephalosporins. ¹⁸Greater resistance has led to the use of more broad spectrum antibiotics, which are generally more expensive.²⁷ This leads to even greater resistance.

It is important to note that antibiotics are not effective against viral infections such as the flu, most sore throats and the common cold. Antibiotic use in these instances is a waste of money and further exacerbates bacterial resistance.¹⁵ Parental pressure to prescribe antibiotics is a big concern; a recent study showed that pediatricians prescribe antibiotics 65% of the time when they sense that the parent expects it, but only 12% of the time when they sense the parent will not pressure them into writing a prescription.¹⁵In 2002, the Council for Affordable Quality Healthcare (CAQH) surveyed 1000 adults to determine their beliefs about antibiotics and found that misperceptions persist about their appropriate use.⁴³ ( Table 2).

Table 2

Americans’ beliefs about antibiotics
Percent holding belief/practice	Percent
Antibiotics are effective for treating the flu	33
Have taken antibiotics for flu	36
Antibiotics are effective against colds	25
Have taken antibiotics for a cold	37
Have antibiotics left over from a prescription	34
Leftovers because patient felt better	64
Leftovers because forgot to take all medication	36
Save left over medication for next time	44
Currently have antibiotics in household	26
Have antibiotics left over from last time someone took	39
Have antibiotics because someone is currently taking	36
Are saving antibiotics for next time someone gets sick	28
Source: COUNCIL FOR AFFORDABLE QUALITY HEALTHCARE

Simple measures that parents can take to prevent the spread of bacterial resistance include the following:

do not expect or demand an antibiotic prescription with every physician visit.
do not take an antibiotic for a viral infection.
understand that antibiotics are not appropriate for some bacterial infections.
when an antibiotic is prescribed, complete the full course of medication unless advised
otherwise by the physician.
never save some of an antibiotic for the next time you get sick.
never take an antibiotic prescription that was prescribed for someone else.

In 1995, the CDC launched a national campaign designed to reduce antimicrobial resistance by educating both the public and healthcare providers.¹⁵ Pharmacists can help inform the public by providing useful educational materials to patients which can be ordered from the CDC - here.

Research Findings
Several studies suggest that most cases of AOM will resolve spontaneously without antibiotic treatment. A meta-analysis which looked at data generated between 1966 and 1992 showed that the spontaneous resolution rate of AOM is 81%.²⁵Another meta-analysis published in 2003 showed that AOM symptoms improved within 24 hours without antibiotics in 61% of children, rising to 80% improvement in 2-3 days.¹⁹ Likewise, British researchers found that symptoms resolved basically within 3 days, whether or not antibiotics were used.²⁰In the Netherlands, AOM has been treated without initially giving antibiotics for years,²² while in the U.S. over 80% received an antibiotic prescription for AOM in 1990.⁷

In light of these findings, a British medical practice decided to change their policy on routine antibiotic administration for AOM. They withheld antibiotics among children who were not particularly ill and advised them to wait and see if symptoms improved on their own. Parents were given an informational handout and a “safety net antibiotic prescription” (SNAP) to have on hand in case symptoms worsened within the 48 hour waiting period. Results were that the number of prescriptions filled in this practice fell 32% compared to national levels. The physicians found that parents welcomed the handout and felt secure having the SNAP while they waited to see if the ear infection would resolve without an antibiotic.²¹

Subsequently in 2001, a group of physicians in the Midwest set out to determine if parents in the U.S. would be comfortable utilizing a similar approach of watchful waiting. Families were given a SNAP plus acetaminophen, ibuprofen or topical otic anesthetic drops for pain control. The results were that only 31% of the parents filled the antibiotic prescription, while 69% of cases resolved without the need for antibiotics. The majority of parents (78%) reported that pain medication was effective for treating the child’s AOM and most (63%) would be willing to treat future ear infections without antibiotics while using pain medication alone.²⁴A 2004 study conducted in an emergency room setting measured parental propensity to fill a “wait-and-see” (WASP) prescription versus those who were given a standard prescription (SP) to fill. The results were that 62% in the WASP group did not fill their prescriptions versus 13% who did not fill the SP prescriptions. This translates into a 56% reduction in the use of antiobiotics by offering the WASP²⁵.

Clinical Practice Guideline
A committee of experts was assembled by the AAP and AAFP to review all of the evidence regarding AOM and to develop up-to-date practice guidelines and recommendations for the diagnosis and treatment of AOM. The Guideline development was “evidence-based”, meaning that evidence to support the recommendations was identified, appraised and summarized. The recommendations were subjected to a rigorous peer review prior to formal approval, and were published in May 2004.⁷

The Clinical Practice Guideline applies to children between 2 months and 12 years of age, because the preponderance of evidence reviewed applied to children falling in this age range. Of note is that the Guideline is applicable only to otherwise healthy children without underlying conditions that could affect the natural course of AOM. Those with recurrent AOM (within the last 30 days) or chronic OME are excluded from these recommendations and may be candidates for more aggressive treatment.⁷

The following are key recommendations mentioned in the new Guideline:⁷

DIAGNOSIS-A certain diagnosis of AOM requires all three of the following criteria:

1. recent, abrupt onset of symptoms.

2. presence of middle ear effusion (confirmed by either bulging tympanic membrane, limited
mobility of the membrane, increased fluid level behind the membrane, or ear discharge).

3. symptoms indicating middle ear inflammation (redness of tympanic membrane, distinct ear pain.

PAIN MANAGEMENT-The Guideline recommends that the physician assess whether or not pain is present, and should recommend treatment to reduce pain. Previously, many physicians looked at pain as a peripheral concern that did not require treatment. The Guideline strongly recommends that ear pain be treated, especially during the first 24 hours regardless of whether or not antibiotics are warranted. They go so far as to say that the mainstay of symptomatic relief is pain management, not antibiotics.

OBSERVATION-For selected children, observation for 48-72 hours without the use of antibiotics is an option to be considered. This method is referred to as “watchful waiting” and gives the parent and physician the opportunity to see if the child will be among the more than 80% whose AOM will resolve without antibiotic treatment. Those children whose parent can readily communicate with the physician, can easily bring the child back in for further evaluation and have a convenient means of obtaining medication are eligible for an initial period of pain management and watchful waiting without antibiotics in the following situations:

healthy children 6 months to 2 years whose illness is not severe AND the diagnosis of AOM is uncertain.
healthy children 2 to 12 years old whose illness is not severe OR the diagnosis of AOM is uncertain.

The Guidelines define non severe illness as mild ear pain and fever <39⁰C in the past 24 hours. Severe illness is moderate to severe ear pain or fever > 39⁰C. A certain diagnosis of AOM must meet all 3 criteria: 1) rapid onset, 2) physical evidence of middle ear effusion, and 3) signs and symptoms of middle ear inflammation. Children less than 6 months old or those over 6 months whose illness is severe should be treated with antibiotics immediately. (Table 3).

Table 3. Criteria for Initial Antibacterial-Agent Treatment or Observation in Children With AOM

Age	Certain Diagnosis	Uncertain Diagnosis
< 6 months	Antibacterial therapy	Antibacterial therapy
6 months to 2 years	Antibacterial therapy	Antibacterial therapy if severe illness; observation option if not severe
> 2 years	Antibacterial therapy if severe illness; observation option if not severe	Observation option

ANTIBIOTIC SELECTION-If the physician elects to treat the child with an antibiotic, amoxicillin should be used for most children because of the high benefit-to-risk ratio. It is a narrow spectrum antibiotic that is generally effective against S. pneumoniae, the most common species of bacteria that causes AOM. Amoxicillin has an excellent safety profile and is well-tolerated by most children.

In children who have a more severe illness (severe ear pain or fever 39 ⁰C or higher) and for those where H. influenzae or M. catarrhalis is suspected, amoxicillin-clavulanate should be initiated. If the patient is allergic to amoxicillin, cefdinir, cefpodoxime or cefuroxime may be used, unless the patient had urticaria or anaphylactic symptoms. Otherwise,the physician may consider azithromycin or clarithromycin. Clindamycin can be an excellent choice for a penicillin-allergic patient with a penicillin-resistant infection.

A single dose of ceftriaxone may be used in a child who cannot tolerate oral medication. Recent studies comparing different durations of therapy have been inconclusive. As such, the Guideline recommends a standard 10-day course for children 5 years old and under or in those over 5 whose illness is severe, while children 6 and over with mild to moderate illness may be treated for 5-7 days.

REASSESSMENT-If AOM does not improve within 48-72 hours, the physician must reassess the patient.

Patients who were initially observed for 48-72 hours should begin antibiotic treatment. Initiating treatment will reduce the risk of rare complications as well as treat active infection.
Patients having been started on antibiotic treatment may have another illness, or my need a different antibiotic.

PREVENTION-Physicians should promote the prevention of AOM where appropriate, by encouraging the reduction of risk factors:

reduce respiratory tract infection by changing day care to reduce the number of children to whom the child is exposed. A group size of six or fewer children results in measurably fewer infections. ^28,29
encourage breast feeding for at least the first 6 months of life.^28,30
discourage bottle propping. ³¹
reduce/eliminate pacifier usage. ³²
reduce/eliminate exposure to passive tobacco smoke. ^33,34

Over the Counter Pain Medications
The Clinical Practice Guideline emphasizes and updates the way the physician should treat a child’s ear pain. Pain relief is central to the treatment of AOM, and deserves direct attention by the clinician. Previously, many parents and healthcare professionals thought that the initiation of antibiotic therapy was the prompt way to achieve pain relief. Many are surprised to learn that there is no difference in pain level during the first 24 hours whether or not antibiotics are used. Pain treatments, not antibiotics, are central to pain relief. The physician should recommend treatment to reduce ear pain when present. The Guideline refers to a number of pain remedies, but suggests there is inadequate evidence to rank the remedies in order of desirability. Instead, the clinician should consider benefits versus risks to the patient, as well as parent/patient preferences.

Acetaminophen or ibuprofen may be used for mild to moderate pain relief, to be dosed according to package instructions for age and weight. For children under 2 years of age, the physician should be consulted. Most studies have shown similar efficacy for acetaminophen and ibuprofen for the pain of AOM, so parent/child preference may play a large role in the decision.³⁵For children experiencing fever, ibuprofen has shown to be equal to or better than acetaminophen in comparative studies.³⁶

Topical earache drops specifically for ear pain relief are now available OTC in the U.S. These drops may be used in conjunction with oral pain relievers or as a safe, soothing alternative. Ear drops should not be used if the eardrum is perforated or if there is drainage from the ear. ³⁷

Although no controlled studies have been done to prove efficacy, applying a water bottle filled with warm water to the external ear may make the child more comfortable. A towel wrapped around the bottle may ensure that is not too hot. ³⁷

Ear Tube Surgery
When a child has severe AOM that does not respond to appropriate antibiotics, has multiple ear infections that do not resolve easily or has persistent OME resulting in evidence of hearing loss or delay in speech development, the physician may recommend ear tube surgery ( myringotomy and tympanostomy). Small plastic tubes are inserted through a tiny incision into the eardrum in order to equalize the pressure and facilitate drainage from the middle ear. About 2 million of these surgeries are performed in the U.S. each year.³⁸The tubes usually remain in place for 6 months to several years, either falling out without the child realizing it, or the physician may elect to remove them at a later date.

Pneumococcal Vaccine
In the year 2000, a vaccine to prevent infection by pneumococcal bacteria (such as meningitis, pneumonia, and otitis media) was introduced in the U.S. A recent study looked at the medical records of Tennessee Medicaid and New York commercial insurance companies and found that since the introduction of the vaccine, doctor visits for otitis media dropped by 118 and 430 per 1000 visits in those states, respectively.³⁸

Children ideally should be vaccinated when they are infants, which is when they are at greatest risk of disease. The routine schedule is 4 doses, one each at 2 months, 4 months, 6 months and between 12-15 months. Children who are between 2 and 5 years of age should still receive immunization if they have risk factors for contracting pneumococcal disease, such as the following:

sickle cell disease.
damaged or no spleen.
HIV/AIDS.
Other immune system diseases.
Taking medications that reduce immune function (chemotherapy, steroids).
Chronic heart/lung disease.
Alaskan Native/American Indian/African American descent.
Attend group daycare. ⁴⁰

Patient Counseling
Patients see their pharmacist more often than any other kind of healthcare provider ⁴² and therefore pharmacists are in an excellent position to educate and advise parents about the Clinical Practice Guidelines for diagnosing and treating AOM. Pharmacists can play an instrumental role in advising about the dangers that antibiotic over-prescribing presents both to the individual children and to society. Pharmacists can help parents understand when antibiotics may be appropriate and when they are not. Of particular value is the pharmacist’s ability to suggest appropriate pain relief products and measures to be used during the 48-72 hour observation period.

It is important for the pharmacy technician to ensure that parents of children with AOM that approach the pharmacy counter be counseled by the pharmacist. Suggested points for discussion include the following:

1. Inform parents that more than 80% of AOM cases tend to resolve spontaneously without antibiotics.

2. Make parents aware that avoiding respiratory illness will reduce the likelihood of contracting AOM.

3. Discuss that certain daycare situations may contribute to increased incidence of AOM.

4. Encourage smoking parents to quit and educate them about available OTC smoking cessation products.

5. Consider displaying educational materials provided by the CDC for parents during critical winter and early spring months.

6. Explain the dangers of antibiotic over-prescribing to parents.

7. Educate customers of illnesses in which antibiotics are not effective and therefore not appropriate.

8. Inform patients of the new Clinical Practice Guidelines which encourage “watchful waiting” in certain situations.

9. Always counsel those receiving an antibiotic to take it as directed and finish the full course.

10. Advise patients never to save antibiotics for the next illness and never to share with others.

11. Be familiar with OTC oral and topical pain relief products.

Summary
AOM is the most common childhood bacterial illness, but it will resolve spontaneously in over 80% of instances. Due to the alarming increase in antimicrobial resistance we have seen since their discovery in the 1940’s, antibiotics must be used more judiciously if we are to continue to rely upon them for life-threatening illnesses. Research has shown that most cases of AOM can be managed with pain relief and a period of watchful waiting, making AOM a prime area for reducing antibiotic overuse. The Clinical Practice Guideline set forth by the AAP and AAFP in 2004 provides the basis for disciplined diagnosis and more conservative treatment. Pharmacists can play a significant role in the ultimate success of this updated treatment philosophy.

References

1. Finkelstein JA, Metlay JP, Davis RI, Rifas-Shiman SL, Dowell SF, Platt R. Antimicrobial use in defined population of infants and young children. Arch Pediatr Adolesc Med. 2000: 154: 395-400.

2. Schappert MA. Office Visits for Otitis Media: United States, 1975-90 Vital and Health Statistics of the Centers for Disease Control Number 214, Sept. 8, 1992.

3. Daly KA. Otolaryngol Clin North Am 1991;24(4):775-86.

4. Takata GS, Chan LS, Striekelle P, Morton SC, Mason W, Marcy MM. Evidence assessment of management of acute otitis media; I. The role of antibiotics in treatment of uncomplicated acute otitis media. Pediatrics. 2001;108:239-247.

5. Rosenfeld RM. An evidence-based approach to treating otitis media. Pediatr Clin North Am 1996;43:1166-1181.

6. Neu HC. The crisis in antibiotic resistance. Science. 1992;257:1064-73.

7. Subcommittee on Management of Acute Otitis Media. Diagnosis and Management of Acute Otitis Media. Pediatrics 2004;113:1451-1465.

8. Ear Infections and Earache. American Academy of Otolaryngology-Head and Neck Surgery Website. Available at: http://www.entnet.org/healthinfo/ears/earache.cfm. Accessed March 3, 2005.

9. Teele DW, Klein JO, Rosner B. Epidemiology of Otitis Media during the first seven years of life in children in greater Boston: a prospective, cohort study. J Infect Dis. 1989 Jul:160(1):83-94.

10. Otitis Media. Family Practice Notebook.com Website. Available at: http://www.fpnotebook.com/ENT37.htm. Accessed March 3, 2005.

11. Eustachian Tube. AllRefer.com Website. Available at: http://health.allrefer.com/pictures-images/eustachian-tube.html. Accessed March 3, 2005.

12. Otitis Media with effusion. MedlinePlus Website. Available at http://www.nlm.nih.gov/medlineplus/ency/article/007010.htm. Accessed March 3, 2005.

13. Pichichero M, M.D. Acute Otitis Media: Part I. Improving Diagnostic Accuracy. American Family Physician 61(7) April 1,2000:2051-6.

14. Heikkinen T, Ruuskanen O. Otitis Media:etiology and diagnosis. Pediatr Infect Dis J. 1994;13(suppl):S23-6.

15. Background on Antibiotic Resistance. Centers for Disease Control and prevention Website. Available at: http://www.cdc.gov.drugresistance/community/. Accessed March 7, 2005.

16. The Rise of Antibiotic-Resistant Infections. US FDA Website. Available at: http://www.fda.gov/fdac/features/795_antibio.html. Accessed March 7, 2005.

17. The Problem of Antibiotic Resistance. National Institutes of Health Website. Available at: http://www.niaid.nih.gov/factsheets/antimicro.htm. Accessed March 7, 2005.

18. A Public Action Plan to Combat Antimicrobial Resistance. CDC Website. Available at: http://www.cdc.gov/drugresistance/actionplan/aractionplan.pdf. Accessed March 7, 2005.

19. Rosenfeld RM, Kay D. Natural history of untreated otitis media. Evidence-based otitis media 2d ed. Hamilton, Ontario:Decker; 2003: 180-98.

20. Little P, Gould C, Williamson I, Moore M, Warner G, Dunleavey J. Pragmatic randomized controlled trial of two prescribing strategies for childhood acute otitis media. BMJ. 2001;332:336-42.

21. Cates C. An evidence-based approach to reducing antibiotic use in children with AOM: controlled before and after study. Br Med J. 1999;318:715-716.

22. Appelman CLM, Bossen PC, Dunk JHM, van de Lisdonk EH, de Melker RA, van Weert HCPM. Guideline. Dutch College of Family Doctors. Acute otitis media. Utrecht: Dutch College of Family Doctors, 1990.

23. The National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 1999. Nhiondemand.com Website. Available at: http://content.nhiondemand.com/sde/consumer. Accessed March 8, 2005.

24. Siegel RM, Kiely M, Bien JP, Joseph EC, Davis JB, Mendel SG, Pestian JP, DeWitt TG. Treatment of Otitis Media with Observation and a Safety Net Antibiotic Prescription. Pediatrics. 112(3); September 2003:527-531.

25. Spiro, DM. Tay, K, Arnold,DH, Dziura, JD, Baker, MD, Shapiro, ED,. Wait-and-See Prescription for the Treatment of Acute Otitis Media. JAMA. 2006: 296:1235-1241.

26. Rosenfeld RM, Vertrees JE, Carr J, Cipolle RJ, Uden DL, Giebink GS, et al. Clinical efficacy of ant microbial drugs for acute otitis media: meta-analysis of 5400 children from thirty-three randomized trials. J Pediatr. 1994;124:355-67.

27. Eaton DA. Complications of Acute Otitis Media. Emedicine.com Website. Available at: http://www.emedicine.com/ent/topic426.htm . Accessed March 15, 2005.

28. Daly KA, Giebink GS. Clinical epidemiology of otitis media. Pediatr Infect Dis J. 2000;19(suppl):S31-S36.

29. Adderson EE. Preventing otitis media: medical approaches. Pediatr Ann. 1998;27:101-107.

30. Paradise JL, Rockette HE, Colburn DK et al. Otitis media in 2253 Pittsburgh-area infants: prevalence and risk factors during the first two years of life. Pediatrics. 1997;99:318-333.

31. Brown CE, Magnuson B. On the physics of the infant feeding bottle and middle ear sequela; ear disease in infants can be associated with bottle feeding. Int J Pediatr Otorhinolaryngol. 2000;54:13-20.

32. Niemela M, Pihakari O, Pokka T, Uhari M. Pacifier as a risk factor for acute otitis media: a randomized controlled trial of parental counseling. Pediatrics. 2000;106:483-488.

33. Etzel RA, Pattishall EN, Haley NJ, Fletcher RH, Henderson FW. Passive smoking and middle ear effusion among children in daycare. Pediatrics. 1992;90:228-232.

34. Ilicali OC, Keles N, Deger K, Savas I. Relationship of passive cigarette smoking to otitis media. Arch Otolaryngol Head Neck Surg. 1999;125:758-762.

35. Bertin L, Pons G, d’Athis P, et al. A randomized, double blind, multicoated controlled trial of ibuprofen versus acetaminophen and placebo for symptoms of acute otitis media in children. Fundam Clin Pharmacol. 1996;10:387-392.

36. Autret-Leca E. A general overview of the use of ibuprofen inpaediatrics. Int J Clin Prac. (suppl) 135; April 2003;9-12.

37. Foley D, Nechas E, Perry S, Salmon DK. The Doctors Book oh Home Remedies for Children. Rodale Press, Inc. 1994 Emmaus, PA.

38. Middle Ear Infections and Ear Tube Surgery. Kids Health Website. Available at: http://kidshealth.org/parent/medical/ears/ear_infections.html. Accessed March 9, 2005.

39. Poehling KA, Lafleur B, Szilagyi PG, Edwards KM, Mitchel E, Barth R, Schwartz B, Griffin M. Population-based Impact of Pneumococcal Conjugate Vaccine in Young Children. Pediatrics. Sept. 2004; 114:755-761.

40. Pneumococcal Vaccine-What You Need to Know. CDC Website. Available at: http://www.cdc.gov/nip/publications/VIS/vis-PneumoConjugate.pdf. Accessed March 9, 2005.

41. Amoxicillin. MedlinePlus Website. Available at: http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a685001.html. Accessed March 9, 2005.

42. Doucette WR, Mays-Holland T, Memmott H, et al. Cancer pain management: pharmacist knowledge and practices. J Pain Symptom Manage. 1997;5:17-31.

43. McCain J. Health Plans Respond as Microbes Develop Resistance Techniques. Managed Care Magazine. June 2004.

Best Practices for Handling Hazardous Medications

noemail@statce.com — Fri, 18 May 2007 13:00:00 GMT

Objectives: The goal of this program is to provide best practice recommendations regarding the safe handling of hazardous medications in the pharmacy. Current information regarding existing and proposed standards and guidelines will be discussed as well as implications and options for best practice compliance decisions by oncology pharmacists.

Instructor: James A. Jorgenson, RPh, MS, FASHP

Release Date: 18-May-07 8:00 AM
Expiration Date: 18-May-10 8:00 AM

Introduction
Healthcare worker safety, and in particular, safe handling of hazardous medications continues to be a topic of increasing interest among healthcare professionals. The issues of healthcare worker exposure to hazardous medications and potential adverse health outcomes associated with exposure, as well as methods for prevention of exposure are of concern among medical professionals. Cytostatic medications have been the primary focus. There are literature reports documenting teratogenicity, spontaneous abortions, and stillbirths associated with the exposure of nurses and pharmacists to cytostatic agents.1-3 In addition, over 30 drugs and drug combinations appear on the International Agency for Research on Cancer (IARC) list of known or suspected carcinogens and there is growing evidence pointing toward these drugs as possible sources of cancers in healthcare workers.4

Currently there are no exposure limits established for these agents in the United States and it is unknown what amount of exposure may be required to trigger potential adverse sequalae. Can repeated exposure over long periods of time to low doses of drugs which are known carcinogens result in cancer? It would be extremely difficult to design a clinical trial that could answer this question. The length of time required for the study and the number of variables that would have to be controlled would make such a trial virtually impossible to conduct. However, prudence would dictate that if you have a known carcinogen, the safest course of action would be to prevent exposure.

Dr. Paul Sessink and colleagues from the Netherlands have designed a cancer risk assessment model based on cyclophosphamide exposure using both an animal model and data on primary and secondary tumors in cyclophosphamide treated patients.5 Data in healthcare workers with respect to urinary excretion of cyclophosphamide was used to estimate drug uptake. The estimated uptake range was 3.6 – 18 mcg daily. Based on available data, cancer risks were calculated for a healthcare worker with a body weight of 70 kg and a working life of 40 years (200 days/year). Cancer risk associated with this exposure increased by 1.4 – 10 additional cases of cancer per year per million workers. As a result of this work, the Netherlands proposed a target cancer risk per drug of 1 extra cancer case annually per million workers and no risk higher than 100 per million per year should be allowed.

Numerous studies have demonstrated the presence of cytostatic medications in the work environment.6-9 In addition, Wick et al demonstrated the presence of cyclophosphamide and ifosphamide in the urine of oncology nurses, pharmacist and pharmacy technicians in the United States.10 It seems clear that we have room for improvement in how we protect healthcare workers from this potential health risk. This article will describe a “best practice” approach to assist with creating a system that protects both patients and healthcare workers. United States Pharmacopeia Chapter 797, the National Institute for Occupational Safety and Health’s hazardous medication alert, the European Quality Standards for Oncology Pharmacy Services, the ASHP Guidelines on Handling Hazardous Drugs, as well as personal and professional observations form the foundation for these best practice suggestions.11-15 These recommendations are not intended to be “all encompassing” but have been selected to address some of the most visible and important aspects of oncology practice.

Receipt and Storage of Hazardous Medications
Safe handling should begin with receipt of hazardous medications. These items should be shipped from the distributor or manufacturer in specially marked containers identifying the contents as hazardous. Maximum attention should be given to ensuring that the packaging protects the contents from breakage. Foam packing inserts and rigid wall containers are preferred. The drugs themselves should be in sealed over wraps or contained in sealable plastic bags to contain any contamination present from the manufacturer and to contain any potential contamination resulting from breaks or leaks.

When opening the shipments, it should be assumed that the contents are contaminated and all appropriate safety precautions employed. If possible, the cartons should be unpacked in an area separate from the normal working area that is well ventilated. PPE should be worn when unpacking and shelving the products. Upon opening the shipping container, a visual inspection should be performed to determine if there are any obvious breaks or leaks. If detected, normal procedures for spill control should be initiated. Hazardous drug inventory should be in a separate area from the rest of the normal inventory. To ensure maximum protection from any potential contamination, the hazardous storage area should be well ventilated. Ideally, this would be a negative pressure room when compared with adjacent areas.

The hazardous drugs should be stored in rigid bins with high walls and fronts of sufficient size to protect the drugs. The bins should be located on shelving that includes a “lip” or guard to help minimize any potential for falls and breakage. An additional safety measure would include placing each box containing a hazardous drug in a sealable plastic bag prior to putting the drug in the storage bins to further minimize any potential for airborne and surface contamination and to contain any potential spills resulting from breakage during storage or transport to the preparation area.

Environment
Careful consideration should be given to the overall design of intravenous sterile product preparation areas that will include the compounding of hazardous medications. While the NIOSH Alert represents guidelines only, USP Chapter 797 is an enforceable standard under the FDA. It may also be surveyed against by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) and may be adopted by state boards of pharmacy. It seems clear that the expected revisions for USP Chapter 797 will include elements of the NIOSH Alert.

When considering building a new facility or upgrading an existing facility a prudent suggestion would include “over engineering” the project against current standards. The European Standards which have been in practice for four years as well as the proposed USP Chapter 797 revisions and the ASHP Guidelines on Handling Hazardous Drugs provide a good model upon which to build.

A best practice environment should include a separate cleanroom area for compounding hazardous medications with access limited to those personnel specifically trained in the preparation of these agents. This area should meet all of the standards specified by the International Standards Organization (ISO) for ISO 7 quality air.16-18 In addition, to protect the workplace from any potential escape of hazardous medication, this area should be negative pressure, preferably 0.01 inch water column or greater when compared with surrounding areas. ISO standards specify positive pressure, however, this should be avoided to prevent the spread of any potential hazardous contamination to adjacent areas. The hazardous preparation area should also be 100% vented to the outside to minimize any potential spread of contamination to other areas of the pharmacy.

The anteroom for the buffer or cleanroom area should also be ISO 7 air quality as opposed to the expected ISO 8. This is required since the hazardous medication preparation cleanroom is negative pressure and the air quality being drawn into the room should be equivalent to the actual room air quality. Construction of a facility that provides a common ISO 7 anteroom which services both a negative pressure ISO 7 cleanroom for hazardous medications as well as an ISO 7 positive pressure cleanroom for non-hazardous medications would be an ideal design.

Construction of a traditional hard wall facility may present significant challenges in terms of facility design as well as significant expense. With many organizations facing difficult decisions in terms of allocation of limited capital dollars, consideration of a modular cleanroom design may provide a less costly opportunity to achieve a best practice environment.

Equipment
Ventilated Cabinets

When compounding intravenous sterile products containing hazardous medications, an appropriate ventilated cabinet, either a biological safety cabinet (BSC) or isolator, should be utilized. The BSC or isolator must be capable of maintaining an ISO 5 air quality environment under normal operating conditions and should be 100% vented to the outside. This contaminated air exhaust vent should be situated at least 12 feet from ground level and should not be in close proximity to any doors, windows or air intake vents. When evaluating BSCs it is important to understand the differences between Class I, Class II and Class III units.

Class I units are essentially fume hoods which protect the operator but do not ensure asepsis. They have an open front with a minimum air flow velocity of 75 ft/min and HEPA exhausted air. Class I BSCs or containment isolators could be utilized for handling hazardous drugs but are not for use when aseptic compounding of hazardous drugs is required.

Class II BSCs protect personnel as well as the product and environment. Class II BSCs have an open front inward air flow with downward HEPA filtered laminar flow and HEPA filtered exhaust. Class II units include four different types of BSCs, A1, A2, B1 and B2 units.

Type A1 units produce a minimum inflow air velocity of 75 ft/min; down flow is mixed with inflow; exhaust may be into the surrounding environment and contaminated ducts are not surrounded by negative pressure. Type A2 differs from A1 with an inflow velocity of 100 ft/min and negative pressure surrounding the plenums. Type B1 units have an inflow air velocity of 100 ft/min; the down flow is uncontaminated recirculated inflow; contaminated down flow is exhausted through a dedicated duct with HEPA filtration to the atmosphere and all contaminated ducts are under negative pressure. Type B2 units differ from B1 with down flow drawn from external air and all down flow is exhausted to the atmosphere without recirculation.

Type III BSCs are completely contained units of gas tight construction. Operation of the unit is conducted through attached rubber gloves and viewed through a non-opening window. The unit is maintained under negative pressure; intake air is HEPA filtered; exhaust air is double HEPA filtered or HEPA filtered and incinerated. A best practice recommendation for BSC use would be a Class II, Type B2 unit or a Class III.19-20

As with BSCs, it is important to select an isolator that best meets the needs of hazardous medication preparation.21 There are numerous differences between isolators including positive vs. negative pressure, air flow dynamics (turbulent flow vs. unidirectional), aseptic vs. containment and recirculation of air vs. complete venting to the outside. In general, an isolator is considered a “mini cleanroom” environment with fixed walls, floors and ceiling.

Ideally for hazardous medication preparation, a compounding aseptic isolator with unidirectional air flow that is 100% vented to the outside should be utilized. The isolator must be capable of providing and maintaining an ISO 5 environment for sterile preparation under normal working conditions. For maximum safety, this unit should be situated in the ISO 7 negative pressure cleanroom reserved for hazardous medication preparation. If this is not possible, at a minimum, it should be situated in a separate negative pressure room capable of at least 12 air exchanges per hour.

Closed System Drug Transfer Devices

An additional layer of protection which represents best practice is the deployment of closed system drug transfer devices (CSDTD). The U.S. Pharmacopoeia General Chapter 797 (USP 797) proposed revisions recommend closed-system drug-transfer devices (CSDTD) for the containment of hazardous drugs in an International Organization for Standardization (ISO) Class 5 environment. CSDTDs are also part of the hazardous drug handling guidelines from the American Society of Health-System Pharmacists (ASHP).

The National Institute for Occupational Safety and Health (NIOSH) also recommends the use of CSDTDs as additional protective measures in conjunction with Class II biological safety cabinets (BSC). Each guideline does not recommend substituting closed-system drug-transfer devices for the preparation of hazardous drugs in a ventilated cabinet but rather using closed system drug-transfer devices with a ventilated cabinet or compounding aseptic isolator. These systems are designed to prevent the release of hazardous medications into the environment.

Ideally, CSDTDs should be combined with a negative pressure cleanroom and a BSC or CAI. When considering CSDTDs it is important to review the NIOSH definition of a closed system drug transfer device: “a mechanically closed system that prevents contamination of the drug product and prevents the escape of drug or drug vapors”. This is a key definition since several commonly used drugs form volatile gas at normal conditions of room temperature and pressure and includes fluorouracil, etoposide, cyclophosphamide, cisplatin and carmustine.22

HEPA filtration or a 0.22 micron filter in a transfer device will not trap these gases. This concept was visually demonstrated by Cam Au and Bart Smith of the University of Utah.23 In their study, they tested five commercially available drug transfer systems to determine which systems met the NIOSH definition of “closed”. Titanium tetrachloride was utilized for this study to simulate the escape of vapor from a CSDTD. Titanium tetrachloride generates very visible smoke when it comes into contact with moisture in the air (hydrochloric acid, titanium dioxide and titanium hydrochloride are formed).

Simulations were conducted in a research laboratory at the University of Utah. Three milliliters of titanium tetrachloride was delivered into a glass vial and sealed. The transfer devices were assembled and each device spiked its own vial containing titanium tetrachloride. A 60 milliliter syringe was filled with 50 milliliters of air and attached to each device. The plunger of the syringe was compressed at a constant rate over 5 seconds. Photographs and a video were taken to document any escape of smoke from the transfer device. Five different products were tested. The entire filter based systems allowed smoke to move from the vial into the work area in all tests.

The PhaSeal System by Carmel Pharma was the only system tested that completely prevented the release of smoke and met the definition of a closed-system transfer device as stated in the NIOSH Alert. Systems using traditional 0.22 micron filters do not contain the release of gas, hence cannot be considered closed.

It should be noted that the newer systems on the market have not proven to meet the NIOSH definition of mechanically closed or the ISOPP guidelines on airtight and leak proof requirements. To prove the actual performance equivalence to a closed system, clinical studies must be performed and published in peer-reviewed journals as stated by ASHP Guidelines (AJHP Vol 63, June 15, 2006, p. 118).

To validate the test, an independent testing laboratory was provided with the testing materials and protocol and the test was duplicated. Results from the independent laboratory were identical to the results seen at the University of Utah with only the PhaSeal system being closed. Also to eliminate any concerns regarding filter damage from the hydrochloric gas, which would potentially contribute to escape of the smoke from the filter based systems, the same independent testing laboratory was asked to verify filter integrity. Following the test, filters were removed and coated with gold and dried and viewed under high powered electron microscopy. There were no breaches in filter integrity from the brief exposure to the hydrochloric gas that could have contributed to the observed escape of smoke. When evaluating CSDTD use, it is imperative to select a system that protects healthcare workers in all phases of the process from initial vial entry to patient administration.

Personal Protective Equipment

A “last line of defense” for personnel engaged in handling hazardous medications is the deployment of personal protective equipment (PPE). This should consist at a minimum of a gown, eye protection and gloves. PPE should be worn whenever handling hazardous medications. This includes the receipt and unpacking of these agents from distributors or manufacturers, the removal from storage and the preparation of these agents.

PPE should be used in addition to ventilated cabinets and closed system drug transfer devices. Gloves should be worn at all times when handling hazardous medications. Gloves may be made from a variety of substances such as latex, polyurethane and nitrile or neoprene rubber. For sterile compounding activities, powder free gloves are preferred. Any gloves utilized for manipulation of hazardous medications should be certified and labeled as “chemotherapy gloves”.

The American Society for Testing and Materials has standardized tests to validate the ability of medical gloves to withstand exposure to chemotherapy drugs. When working with hazardous medications it is always advisable to practice “double gloving”. This practice ensures maximum protection of the operator but is also an important tool to prevent the spread of any contamination. Upon completion of the sterile compounding and decontamination of the final product, the outer glove can be removed in the ventilated cabinet and the inner glove remains on the operator for labeling and preparation of the final product for transport. Gloves should be changed immediately if any contamination is suspected or if they are damaged in any way. Gloves should also be changed if the operator leaves the ventilated cabinet. During sustained compounding operations, gloves should be changed at a minimum of every 30 minutes.

Gowns or coveralls should also be worn when handling hazardous medications. The gowns should be disposable. They should be constructed from lint free material, have a completely closed front and have long sleeves with tight fitting wrist cuffs. Gowns should be coated with polypropylene for maximum protection.24 Spun-bond non-woven material alone provides little operator protection. As with gloves, gowns should be changed if damaged or if contamination is suspected. Following completion of handling or compounding activities, gowns should be disposed of as hazardous waste and should never be worn outside the immediate work area designated for handling the hazardous medications.

Eye protection should be utilized whenever there is a potential for splash or aerosol exposure. In cases such as spills, a full face shield is advisable for maximum protection. In these cases use of a respirator may also be advisable. If a respirator is deployed, operators must be trained in its use and they must be fit tested to ensure maximum protection. Surgical masks, hair and shoe coverings should also be worn during sterile compounding of hazardous medications just as with all sterile compounding. These items are intended for product protection and do not generally afford additional protection for the operator from the hazardous drugs. As with all other PPE, once compounding is completed, these items should be disposed of as hazardous waste.

Personnel
The emphasis on best practice in oncology cannot underestimate the importance of training and monitoring for healthcare workers who routinely handle hazardous drugs. Pharmacists and pharmacy technicians must receive competency based training and be certified in safe handling techniques. Healthcare organizations should develop competency programs that test the employee’s ability to effectively understand all oncology policies and procedures.

ASHP has developed two resources to help prepare pharmacy technicians and pharmacists in competency training; 1 – Basics of Aseptic Compounding Technique and 2 – Safe Handling of Hazardous Drugs are available through ASHP (www.ashp.org). Competency should be verified by a written test, by media fill testing to verify aseptic technique, by observation of simulated chemotherapy preparation utilizing flourescein dye as a surrogate marker for chemotherapy and by observation of compounding technique during normal working conditions. Competency should be verified for all new personnel and periodically (at least annually) for all currently certified personnel.

Administrators of the chemotherapy program should continually update participants with new information regarding medications or changes in practice. The success of a safe handling program is dependant on a collaborative approach between all disciplines. Representatives from each discipline (physicians, nurses, pharmacy, environmental health, housekeeping and safety) should be involved in developing policies and procedures. Key programmatic policies should include the safe handling of hazardous drugs and medical surveillance. These policies should establish safe standards for the preparation, dispensing, transport, administration and disposal of hazardous drugs.

Medical Surveillance
All employees that regularly come into contact with hazardous medications should be part of an organized medial surveillance program. This should include a baseline examination on hire or on assignment to an area that requires routine handling of hazardous medications. A follow-up examination should also be conducted annually or at a minimum every two years or after any incidence of acute exposure. Examinations should include a health assessment focused on systems that may indicate evidence of chemotherapy exposure such as skin, mucous membranes, lymph system and hair.

Selected laboratory tests should be conducted which may include a urinalysis, complete blood count with differential and a comprehensive metabolic panel. Additionally, as part of a comprehensive surveillance program provisions should be established to safeguard healthcare workers from the reproductive and teratogenic risks associated with exposure to hazardous drugs. For employees that are pregnant or breastfeeding or actively attempting to conceive or father a child where their normal duties involve regular handling of hazardous drugs, the organization should have policies in place that provide the employee with other duties during this time that reduce their exposure risk.

Cleaning and Decontamination
As previously mentioned, many studies have documented chemotherapy surface contamination in preparation and administration work areas. These areas which include work surfaces must be decontaminated and cleaned on a periodic basis or workers will continue to be exposed to hazardous medications.

A best practice recommendation is to clean and decontaminate work surfaces before and after each activity and at the end of each shift. A cationic soap solution followed by a dilute sodium hypochlorite solution followed by an inactivating agent such as sodium thiosulfate (to prevent discoloration of stainless steel) would be a good decontamination sequence. In addition, it has been demonstrated that many chemotherapy vials come directly from the manufacturer with surface contamination present on the vial.25-26 An additional safety measure would be decontamination of these vials.

All chemotherapy vials should be decontaminated with sodium hypochlorite wipes prior to shelving or using the product. When chemotherapy vials are initially unpacked and wiped down, full personal protective equipment should be utilized just as if chemotherapy were being prepared. It is also a best practice recommendation for all healthcare workers to regularly wash their hands thoroughly after removing personal protective equipment.

Spill Management
Chemotherapy spills may occur during preparation, transport or administration of chemotherapy. Spill kits should be located in all areas where chemotherapy is prepared and administered. The goal is to implement processes to prevent hazardous spills where possible. All staff preparing, administering or transporting chemotherapy should be trained in spill management. Once a spill has occurred, the nearest spill kit should be obtained.

Personal protective equipment should be utilized including a chemotherapy resistant gown, shoe covers, eye protection and two pair of chemotherapy certified gloves. The spill should be contained by draping a chemotherapy mat or absorbent pad over the spill area. This will limit the spread of the spill. If the spill is in a patient care area, relocate the patients away from the spill and limit access by posting a Hazardous Drug sign.

All personnel involved in clean up of a spill must be trained. If trained, spills less than 5ml may be cleaned by staff responsible for the spill. If the spill is greater than 5ml, it is generally best practice to call environmental services to handle the spill. If the spill is on a patient or staff member, remove the contaminated clothing and immediately wash the skin with soap and water for 20 minutes.

If splashed in the eyes, rinse with water for 15 minutes. An eye wash or eye bath should be located in all areas where splash risk may occur. Immediate medical attention should be provided. Spills should be cleaned with alkaline detergent and decontaminated with sodium hypochlorite and neutralized with sodium thiosulfate.

Blot or wipe the area with disposable towels and place all contaminated materials in a chemotherapy disposable bag and dispose of as chemotherapy waste. If glass is present, this should not be picked up by hand. A hard plastic scoop supplied in most spill kits should be utilized. Any contaminated linen should also be placed in a chemotherapy labeled bag for special cleaning.

Waste Handling
All hazardous drug waste must be disposed of according to guidelines published by the organization’s Department of Environmental Health and Safety as well as any applicable state and federal regulations. Hazardous waste must be handled separately from other hospital trash.

Hazardous waste includes all amounts of these agents including small or trace amounts left in syringes as well as partial vials or unused portions of intravenous solutions containing these agents, materials used in the preparation and administration of these agents, as well as any spills and material utilized to absorb the spill. It is important to review the standard options for disposing of medical waste.

Generally regulated medical waste will be collected in red sharps containers or red bags. These red containers should never be used to dispose of drugs and particularly any hazardous drugs. Often times the disposal methods for regulated medical waste involve only autoclaving, microwaving or other non-incineration methods. Chemotherapy waste should be treated as a hazardous drug and should be disposed of using yellow containers labeled as such. Chemotherapy drug waste is required to be disposed of using incineration at a regulated medical waste incinerator. Generally all empty vials, syringes, needles, IV bags and other supplies utilized in preparation and administration should be disposed of in the yellow hazardous waste containers. The ash from the incineration is sent to a non-hazardous land fill so it is important to have all agents completely incinerated to avoid any leaching into the groundwater system. It is also worth noting that additional drugs other than chemotherapy are considered hazardous.

The US EPA regulations under the Resource Conservation and Recovery Act also classify agents that are toxic, ignitable, corrosive or reactive as hazardous.27 These agents should be collected in appropriately marked containers. This category includes the P and U listed drugs which are considered hazardous when disposed of as the sole active ingredient in the preparation. These agents include: epinephrine, warfarin and nicotine as well as seven specific chemotherapy agents. In addition, other agents may be considered hazardous under the toxicity category if they contain amounts of chemicals such as mercury in the form of thimerosal or phenylmercuric acetate in excess of set limits.

A licensed medical waste contractor should be retained to remove this waste on a regular basis and to assist with proper collection and storage of hazardous drug waste.

Summary
The issue of safe handling of hazardous medications in the pharmacy to prevent exposure of healthcare workers is an important consideration. This is a complex topic with many variable components that must be addressed to provide a comprehensive safety program. It is also an area that is not static, standards and guidelines for safe handling continue to evolve, and it is imperative that healthcare professionals and organizations stay abreast of the current trends to ensure that work environments are as safe as possible.

Reference List
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21. Midcalf B et al. (eds.) Pharmaceutical isolators: a guide to their application, design, and control. London: Pharmaceutical Press, 2004.
22. Kiffmeyer TK, Kube C, OpiolkaS et al. Vapor pressures, evaporation behavior and airborne concentrations of hazardous drugs: implications for occupational safety. Pharm J. 2002; 268:331-7
23. Au C and Smith B. Evaluation of vial transfer devices for containment of hazardous drug vapors. Abstract, 2007 University Health System Consortium, Resident Poster Session presented at the UHC Pharmacy Advisory Council meeting, Anaheim, CA.
24. Connor TH. An evaluation of the permeability of disposable polypropylene-based protective gowns to a battery of cancer chemotherapy drugs. Appl Occup Environ Hyg. 1993; 8:785-9.
25. 21. Connor TH et al. Surface contamination of chemotherapy drug vials and evaluation of new vial cleaning techniques: results of three studies. Am J Health Syst Pharm. 2005 Mar 1; 62(5): 475-84.
26. Connor TH. Hazardous anticancer drugs in health care: environmental exposure assessment. Ann N Y Acad Sci. 2006 Sep; 1076: 615-23.
27. U.S. Environmental Protection Agency, Resource Conservation Act. Available online at: www.access.gpo.gov/nara/cfr/cfrhtml_00/Title_40/40cfrv23_00.html Accessed December 18, 2006.

Best Practices for Handling Hazardous Medications

noemail@statce.com — Fri, 18 May 2007 13:00:00 GMT

Equipment
Ventilated Cabinets

Closed System Drug Transfer Devices

Personal Protective Equipment

Botulinum Nuerotoxin

noemail@statce.com — Tue, 01 May 2007 13:00:00 GMT

Objectives:

Upon completion of this CE activity, participants should be able to:

Understand the molecular events triggered by botulinum neurotoxin (BoNT) uptake into the cell
Explain which neurotransmitters are affected by BoNT treatment
Review a range of clinical applications in which BoNT has been shown to have some effect

Instructor: Childers, Hallett

Release Date: 1-May-07 8:00 AM
Expiration Date: 1-May-10 8:00 AM

See printed monograph.

Focus on Muscular Pain

noemail@statce.com — Tue, 01 May 2007 13:00:00 GMT

Objectives:

Upon completion of this CE activity, participants should be able to:

Discuss the efficacy of botulinum neurotoxins (BoNTs) in the treatment of muscular pain
Describe treatment options for patients with muscular pain
Review condition-specific technique, including injection-site selection and dosing of BoNT for muscular pain
Discuss patient management, including postinjection care and patient compliance

Instructor: Ferrante, Lang

Release Date: 1-May-07 8:00 AM
Expiration Date: 1-May-10 8:00 AM

See DVD and monograph.

Muscle Overactivity in the Upper Motor Neuron Syndrome

noemail@statce.com — Tue, 01 May 2007 13:00:00 GMT

Objectives:

Upon completion of this CE activity, participants should be able to:

Recognize common patterns of limb dysfunction associated with UMN syndrome.
Describe the functional limitations and difficulties experienced by patients with limb deformities.
Identify the muscle groups that are typically affected by common limb deformities.

Instructor: Esquenazi, Mayer

Release Date: 1-May-07 8:00 AM
Expiration Date: 1-May-10 8:00 AM

See CD-Rom.