Employee Safety in Chemopreparation Unit

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‫الرحيم‬ ‫الرحمن‬ ‫ا‬ ‫بسم‬
Employee’s Safety with Cytotoxic
Drugs
Ph. Areeb Ahmed Abbasi
Pharmaceutical Care Department
King Abdullah Medical City

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What are Cytotoxic drugs?
•Drug that inhibits or prevents the function of cells.
•Used to treat cancer and other benign conditions as indicated.
•CD preparations are available in oral, IV, and other dosage forms.
•Also used to treat psoriasis, Rheumatoid Arthritis & Juvenile RA, Steroid
resistant muscle conditions.
•CD cannot distinguish between normal and malignant cells. As a result of the
treatment, many normal cells such as hair follicles and the lining of the digestive
system are damaged along with the cancer cells.

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The American Society of Hospital Pharmacists (ASHP) considers CDs to be:
•Genotoxic – a substance that damages DNA. Such damage can lead to the growth of
a malignant tumor.
•Carcinogenetic – a substance that may cause mutations leading to the development of
tumors in healthy cells.
•Mutagenic – a substance that alters the DNA of a living being, increasing the
likelihood of a mutation.
•Teratogenic – a substance that may cause malformations of an embryo or fetus
(birth defects).
•Contact with CD can cause immediate problems such as dermatitis, dizziness, nausea
and headache.
•(Mutation is a natural process that changes a DNA sequence.)

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•Physicians
•Nurses
•Pharmacists
•Assistants
•Patients
•Patient family members
•Stores and receiving personnel
•Housekeeping and maintenance
•Any person who interact with CDs…

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When are we at risk???
Anyone who works with patients receiving
cytotoxic drugs are at risk of exposure, and
must be protected at all times while
working with cytotoxic drugs. Exposure
may occur when
•Preparing,
•Administering,
•Storage,
•Transporting drugs,
•Handling patient waste,
•Disposing of waste, and
•Cleaning spills.

Employee’s Safety with Cytotoxic Drugs
Factors:
-Reported toxic effects of CD on health workers.
-Drug related factors
-Worker related factors
-Equipment related factors
-Quality management role
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-Reported toxic effects of CD on health workers
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Reported Direct Toxic Effect of CD on Health
workers
In two studies there were association between self-
reported skin contact with CD and the occurrence of
acute symptoms. Questionnaire Data: Valanis B, et al,
Cancer Nurs 16(4): 288-295, 1993 ; Valanis B, et al, AJHP,
50: 455-62, 1993
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Toxic Effect of CD-(contin.)
-In two studies higher prevalence of menstrual
dysfunction noticed in nurses who handle CD. The
highest prevalence in nurses over 30 years of age.
Questionnaire Data: Shortridge, LA, et al, Cancer Nurs
18(6): 439-44, 1995 ; Shortridge, L, Dissertation, 1977.
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Spontaneous Abortion: Three studies reported
increased rate of spontaneous abortion in female
health workers handling CD. The most recent one
was NCI-USA study involving 2976 pharmacy and
nursing personnel. Spouses of men handling CD had
the same risk. Questionnaire Data: Valanis, B, et al,
JOEM, 41(8): 632-638, 1999
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Infertility: NCI-USA funded study on 4659 nursing and
pharmacy personnel which demonstrated lower
fertility in women handling CD. Questionnaire Data:
Valanis, et al, JOEM, 39(6): 574-580, 1997
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Toxic Effects of CD( Indirect)-contin.
17 out of 27 studies found cytogenetic
abnormalities in health workers
14 out of 30 studies were (+) for urine
mutagenicity test (Ames test) on health workers
handling CD
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Toxic Effects of CD-(contin.)
83 non-smoking nurses and pharmacists:
23 pharmacists preparing CD, 28 nurses preparing
and administering CD , 32 nurses only
administering CD.
5/32 of nurses reported skin contact in the group
administering CD.
11 of 83 (13%) of scans were (+) (8 nurses and 3
pharmacists).
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- At least 15 out of 18 studies detected CD in urine of
workers (pharmacists, pharmacy technicians, nurses,
health care workers) (1975-2000)
- 13 studies detected cyclophosphamide (CP) and one
study detected ifosfamide (IFS) and two studies
detected platinum derivatives. One study 5-FU
metabolite.
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Cancer risk is difficult to assess. However, data
from patient studies were used.
Cancer risk is about 1.4-10 per million annually
after 10 years of work. This is additional risk due
to CP.
Senssink, PJM, et al, Rev Environ Health, 21(1): 43-58, 1997.
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-Reported toxic effects CD on health workers
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Drug Related Factors:
-Carcinogenic potential.
-Physicochemical characteristics.
-Pharmaceutical and manufacturing factors
-Quantity of drug handled.
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Carcinogenic Potential:
Eight antineoplastic agents are carcinogenic to humans:
Cyclophosphamide, melphalan, busulphan,
chlorambucil, treosulphan, chlornaphazine,
azathioprine, and 13909-09-6 (IARC).
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Probable carcinogenic agents: Carmustine lomustine,
cisplatin, nitrogen mustard, thiotepa, doxorubicin,
and procarbazine.
Possible carcinogenic agents: Dacarbazine,
bleomycin, daunorubicin, mitomycin C, streptozocin,
daunorubicin, and nitrogen mustard N-oxide.
Unclassiffied agents: Antimetabolites, antimitotic
inhibitors, and ifosfamide.
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Physicochemical Characteristics:
-Lipophilicity: cyclophosphamide, platinum
-Volatibility: cyclophosphamide (Sessink PJM et. al., Arch.
Environ. Health, 1997, Kiffmeyer T. et. al., Pharm. J., 2002;
Mason, H. J. et. al., Ann. Ocup Hyg, 2005)
-Aerosolization
Platinum
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Pharmaceutical and Manufacturing Factors
-Surface contamination of CP and IF packaging.
Hedmer, M., et al., Ann. Occup. Hyg., 2005).
-Cytotoxic contamination on the outside of vials
(platinum, CP, IF, MTX). Mason, H. J. et al., Ann.
Occup. Hyg., 2003).
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Quantity of Drug Handled
-The center with highest number of preparation had
more contamination with CP, IP, and 5-FU. Connor,
T.H., et. al., AJHP, 1999.
- Bulk manufacturing of Cytotoxic tablets: CP, MTX,
Hydroxyurea, 6-MP…
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-Reported toxic effects of CD agents on health workers
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Worker Related Factors:
-Susceptibility
-Seniority
-Smoking and nutritional habits
-Stress
-Gender and body mass
-Duration of exposure
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-Susceptibility
-Seniority
-Stress
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Susceptibility
Staff with family history of cancer are probably at
higher risk.
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-Susceptibility
-Seniority
-Stress
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Seniority
Handling technique may be poorer when handled by
new employee .Labuhn, K. R. N. et. al., Cancer Nurs.,
1998.
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-Susceptibility
-Seniority
-Stress
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Smoking and Nutritional Habits
-Smoking is known to predispose to lung,
nasopharyngeal, bladder------> Cancers.
-Fried meat is known to increase likelihood of (+) urine
mutagenicity. Baker, R. et. al., Cancer Lett., 1982.
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-Susceptibility
-Seniority
-Stress
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Stress
Nurses with (+) scans for contamination handled
more doses than nurses with (-) scans who handled
less doses per week. This could reflect inattention to
technique because of stress.(Also applies to
pharmacists)
More acute symptoms reported were significantly
associated with the number of doses handled. Valanis B, et
al, AJHP, 50: 455-62, 1993
There should be uniformity.
Labuhn, K. R. N. et. al., Cancer Nurs., 1998.
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-Susceptibility
-Seniority
-Stress
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Gender and body mass
Significantly more acute symptoms in females handling
chemo with higher body mass. This was not
significant in males. Valanis B, et al, AJHP, 50: 455-62,
1993
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-Susceptibility
-Seniority
-Stress
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Duration of Exposure
In one study nurses exposed for 20-31 years show
higher cytogenetic abnormalities than nurses
exposed for 1-19 years. There was no difference
between the control group and the group exposed
for 1-14 years. Kasuba , V, et al, J Appl Tox, 19(6): 401-4,
1999.
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Training and Management:
Who should be trained?
•Physicians
•Nurses,
•Pharmacists
•Assistants,
•Stores and receiving personnel,
•Housekeeping and maintenance
•Any person who interact with CDs…
•What training can be given to patients???

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These training procedures should:
•Be for the proper handling, mixing, and disposal of cytotoxic drugs
and waste by-products.
•Be written, posted, and available to all employees;
•Include how training will be developed, delivered, and evaluated;
•Include descriptions of the roles of supervisors to ensure that all
proper regulations are followed.
•Be informed about full hazards of cytotoxic drugs.
•Methods of preparation.
•Use and disposal procedures.
•Patient care.
•Protective equipment and how to use it properly.
•Spill procedures.
•Maintenance of the facilities and equipment.

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Chemo dept should maintain a record of information on the
•Toxicity,
•Exposure treatment procedures,
•Solubility,
•Stability,
•General description of the appearance for all CDs that are used in the
facility.
•This record should be easily accessible at all times of day, and
available to all staff who interact with CDs.

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Drug preparation and reconstitution
•Trained personal.
•Centralized dedicated location. (Separate from normal medications)
1.Engineering controls
•Room specification (USP chapter 797)
•Pre room ( ISO class 8,9)
•Ante room (Buffer room) (ISO class 7)
•Vertical Hood (ISO class 5)
•Room pressure.
•A minimum of a Class II biological safety cabinet with HEPA filter exhaust
systems that does not allow air to be circulated back into the room.
•Medications should be isolated and locked.
•Puncture proof containers for the disposal of needles, syringes and vials must
be provided and available in the preparation area. Contaminated needles,
syringes, and vials should be disposed of intact.

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2. Personal Protective Equipment (PPE)
• Protective gloves made of vinyl or nitrile rubber. Gloves should be changed frequently,
or immediately if punctured, cut, or torn. (Some times 2 pairs)
• A moisture resistant, long sleeved gown with elastic cuffs.
• Chemical splash goggles, and if necessary, full-face protection.
• In cases where there is a possibility of the medication becoming airborne, a powered air
purifying respirator is recommended.
• Face mask (Sometimes n95)
• Head cover
• Shoe cover

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3. Additional controls
•Eating, drinking, smoking, or the storage of food should be
completely prohibited in the preparation area.
•Pregnant or breastfeeding women must be placed on
protective reassignment and given a position that does not
expose them to the cytotoxic drugs.
•To prevent the spread of hazard, protective clothing should
not be worn outside of the preparation area.

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4. Spill kit
A clearly labeled cytotoxic spill kit should be kept wherever cytotoxic
medications are being prepared, stored, administered or received (shipping).
The kit should contain:
•At least two sets of surgical gloves
•Disposable eye protection
•Shoe covers
•Scoop and scraper
•Sharps container
•Warning signs
•Two large plastic disposal bags (minimum of 4mm thick)
•Decontamination agent (i.e. a basic detergent of pH 8-9 and water)
•Puncture and leak resistant waste container
•Two sheets at least 30 cm square of absorbent material

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Material safety data sheets – MSDS
•Suppliers are required to provide safety data sheets for those
chemicals classified as hazardous substances if they supply to
workplaces.
•Employers must ensure that safety data sheets and other
sources of information are accessible to workers who may be
exposed to the substances.

Employee’s Safety with Cytotoxic drugs
-Reported toxic effects of CD on health workers.
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Equipment Related Factors
-Personal Protective Devices (PPE)
-Safety Cabinets
-Isolators
-Closed System
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-Safety Cabinets
-Isolators
-Closed System
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Personal Protective Equipments (PPE)
No studies found, studying this factor alone but
usually with other factors.
However, they have a major role in protecting the
worker. Selection of the proper gown and glove is
important.
Also the duration of glove in contact with skin is a
major determinant of permeation in several studies.
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-Safety Cabinets
-Isolators
-Closed System
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Safety Cabinets
In three studies the use of biological safety
cabinet (BSC) reduce chance of getting (+) urine
mutagenicity test in pharmacy technicians
In one study less cytogenetic abnormalities with
use of BSC. Jakab, et al, JTEH, 62(2):307-18, 2001
(Maintenance of BSC by deep clean and microbial
contaminations)
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-Safety Cabinets
-Isolators
-Closed System
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Isolators (Glove boxes)
The major advantage is that isolators will effectively
protect handlers from contact with
contamination inside the isolator.
Crauste-Manciet et. al. Ann. Occup. Hyg., 2005.
Isolators can reduce the exposure .There is no major
difference between positive pressure or negative
pressure isolators as far as exposure. Mason. H. J.
et. al., Ann. Occup. Hyg., 2005.
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-Safety Cabinets
-Isolators
-Closed System
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Closed System
Several studies have shown that closed system
(Phaseal®) did reduce contamination.
Closed system should be combined with other safe
handling practices. Crauste-Manciet et. al. Ann. Occup.
Hyg., 2005.
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Objectives:
-Introduction
-Reported toxic effects of CD on health workers
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Quality Management Role
-Safe Handling Guidelines Implementation
ASHP, … (including CD store areas)
Selection of staff to handle CD is important
by interview: chronic problems, smoking,.. etc.
documentation is important for future use.
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Technique
Best preparation, administration techniques
should be chosen.
Contamination of syringe plunger during
sampling of CP solution. Regular
replacement of syringes is enforced. Gilles,
F.B., et. al. J Onc. Pharm. Pract., 2005.
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Conclusion
Occupation exposure to CD is still occurring.
Some sources of contamination are unknown
and/or difficult to control.
However, implementation of the latest
recommendation for protection is essential.
Awareness of the health worker is important in
order to keep alert.
Quality Management has a big role in employee
safety.
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Immediate management:
If at any time there is skin contact with any cytotoxic drug, the
affected worker should
Wash the affected area by soap & water.
Should not scrape or abrade the skin (may increase the
exposure)
For eye contact, flush the eye with copious amount of water by
holding back the eye lids for atleast 15 mins
Seek medical evaluation by physician.
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Employee Safety in Chemopreparation Unit

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