Occupational Risk of Antineoplastic Drugs

Pharmacy Seminar Phoebe C. Llamelo

Objectives
Define what are antineoplastic drugs and why
they are classified as hazardous drugs.

Identify the potential groups of workers exposed

to antineoplastic drugs, and then focus on pharmacists

Determine and describe the routes and common

sources of exposure of pharmacists to antineoplastic drugs

Objectives
Give the possible acute and chronic effect of
occupational exposure to antineoplastic drugs and the possible mode of action.

Discuss the methods for preventing exposure

of pharmacists to antineoplastic drugs

Identify the medical monitoring necessary for

health workers

Antineoplastic Drugs
- Substances that inhibit or prevent the proliferation of NEOPLASMS

Hazardous Drugs
Exhibit one or more of the following six characteristics in humans or animals 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

Antineoplastic Drugs
Alkylating agents Antibiotics Antimetabolites Biologicals Hormonal agents Monoclonal antibodies Nitrogen mustard derivatives Plant alkaloids Others

Mechanism of Action
bind directly to genetic material in the cell nucleus or affect cellular protein synthesis Interferes with cell division and/or damage (DNA), disrupt DNA replication during synthesis, or interfere with the repair of DNA. cytotoxic drugs may not distinguish between normal and cancerous cells
.

Recent concerns: More cancer patients More combinations of drugs Higher doses of drugs More potent drugs New procedures/settings antineoplastic medications expanding into other arenas

Potentially Exposed Groups

Workers in manufacturing Pharmacists and technicians Nursing personnel Physicians Operating room personnel Housekeeping and laundry personnel Veterinarians Retail pharmacists

Common Sources of Exposure

 DRUG PREPARATION
Drug dilution and transfer

Reconstitution of an IV drug
Spiking ang IV bag

Cutting, crushing, or other manipulation of coated or uncoated tablets and capsules for pediatric, geriatric

 DISPOSAL OF DRUGS AND WASTE

Emptying waste containers and cleaning contaminated areas

CONTACT WITH CONTAMINATED SURFACES

Drug vials, counter tops, keyboards, IV bags, tables, chairs, waste containers

 CONTAMINATION IN AREAS THOUGHT TO BE DRUG-FREE

Locations adjacent to work areas

POSSIBLE PASSAGE THROUGH HEPA FILTERS

Vapors

Routes of Exposure

Inhalation
drug aerosols are generated during drug compounding and transfer from one container to another.

Activities that can cause release of Hazardous Drugs aerosols: breaking open an ampule withdrawing a needle from a vial transferring drug from a vial to a syringe or other container expelling air from a syringe attaching intravenous (IV) tubing to IV containers and priming tubing powders generated during the crushing of tablets

Dermal
Accidental needle prick Most common route- contact to contaminated surfaces and objects Contact to body fluids of patients who have received the medication

Oral
hand-to-mouth after touching

contaminated surfaces

Effects of Antineoplastic Drugs Exposure

accidental needle prick of a finger with mitomycin-C has been reported to cause the eventual loss of function of that hand (Duvall and Baumann 1980).

varying degrees of local tissue necrosis upon direct contact (Knowles and Virden 1980)

Effects of Antineoplastic Drugs Exposure

increased risk of cancer exists among exposed pharmacy technicians (Hansen & Olsen, 1994) statistically significant association between fetal loss or miscarriages and stillbirths and the occupational exposure (Selevan, Lindbohm, Hornung, & Hemminki, 1985; StOcker et al., 1990; Valanis, Vollmer, & Steele, 1999) infertility (Fransman et al., 2007; Martin, 2005)

Effects of Antineoplastic Drugs Exposure

acute symptoms in nurses and pharmacists hair loss abdominal pain nasal sores contact dermatitis allergic reactions skin injury eye injury (Harrison, 2001)

 Primary concern is for the safety of the patient Drugs must be prepared aseptically Contamination can be fatal to the patient Secondary concern is the safety of the healthcare worker Exposure to hazardous drugs must be kept as low as possible Many opportunities for exposure

Prevention of Exposure

Hazardous Drug Safety and Health Plan

Establishment of a designated HD handling area. Use of containment devices such as biological safety cabinets. Procedures for safe removal of contaminated waste. Decontamination procedures. Standard operating procedures relevant to safety and health considerations to be followed when health care workers are exposed to hazardous drugs.

Work area
Restricted, centralized procedures for spills and emergencies should be available to workers, posted in the area.

Biological Safety Cabinet

Class II or III Biological Safety Cabinets (BSC) that meet the current National Sanitation Foundation Standard

Personal Protective Equipment

GLOVES- latex, with minimal or no powder GOWNS- protective disposable gown made of lint-free, low-permeability fabric with a closed front, long sleeves, and elastic or knit closed cuffs

Work Practices
Labeling Priming- within the BCS Handling of Vials- Avoid extreme + or pressure; use large-bore needles (#18 or #20) Handling ampules Cleaning spills and discarding wastes

Continuing Exposure
Antineoplastic drugs continue to contaminate the work spaces Metabolites still being found in the urine of those who handled these drugs Wipe sampling in pharmacy and preparation areas (cyclophosphamide, ifosfamide, fluorouracil, methotrexate) Air sampling (cyclophosphamide, ifosfamide, fluorouracil)

Drug reconstitution with needle and syringe

Drug transfer from syringe to I.V. bag

Possible reasons to the problem

New workers lack of awareness of the issue Lack of vigilance in work practices Poor adherence and less strict implementation of the guidelines Potential sources of contamination that have yet to be discovered.

Conclusion
Despite decades of data and on adverse effects of occupational exposure to antineoplastic drugs, and guidelines for safe handling of these drugs, direct exposure of health care professionals to these drugs still exists. Stricter implementation of the guidelines and validation of their effectiveness should be done Each new generation of health care workers need to be educated about the risk of handling antineoplastic drugs and well trained in handling them.