Cyclophosphamide

Full Profile

General Information

Cyclophosphamide is a drug used in chemotherapy and exists as a white crystalline powder.^[2] It may also be referred to by its trade names, such as Cytoxan or Neosar.^[3] There are numerous other synonyms and product names; see HSDB for more information.^[3]

Cyclophosphamide has been classified by IARC as Group 1, carcinogenic to humans,^[4] with a well established link to leukemia and bladder cancer in humans.^[2] A recent review of Class 1 carcinogens by IARC reaffirmed this classification.^[9] Other health effects experienced by patients taking cyclophosphamide can include digestive problems and nausea, hair loss, temporary sterility, and bone marrow suppression.^[3]

Cyclophosphamide has been ranked by CAREX Canada as a Group A (immediate high priority) for occupational settings, targeting people who may be exposed to the drug at work (i.e. nurses and pharmacists), rather than those who are prescribed the drug for therapeutic use. Prioritization for pharmaceuticals was based on the carcinogenicity of the substance – only IARC Group 1 and 2A drugs were considered – and whether the drug is registered for use in Canada.

Regulations and Guidelines

Occupational Exposure Limits (OEL)

No occupational exposure limits for Canada or any other international bodies were located.

Canadian Agencies/Organizations

Agency	Designation/Position	Year
Health Canada	DSL – high priority substance (added under the Food and Drug Act)*	2004[5]

Cyclophosphamide was not included in other Canadian government chemical listings reviewed.^[6]

Main Uses

Cyclophosphamide is an antineoplastic and immunosuppressive drug used to treat cancer and autoimmune disorders.^[2] It may be used alone or in combination with other medications.^[2]

Occupational Exposures

Occupational exposure to cyclophosphamide may occur via inhalation or dermal exposure.^[2]

Probable exposure scenarios in Canada are in hospitals and are limited to handling in wholesale pharmacies, patient handling, sanitary and similar services, research, and education.^[8]

Nurses

In 2006, the Canadian Institute for Health Information (CIHI) estimated that 68 Licensed Practical Nurses (LPNs) and 2,975 Registered Nurses (RNs) worked in the oncology areas of Canadian hospitals^[10] and thus may have been exposed to chemotherapeutic drugs (including cyclophosphamide). The number of nurses potentially exposed to cyclophosphamide by province is shown in the table below.

Nursing Oncology Workforce by Province/Territory 2006[10]
	RN	LPN
Canada	2,975	68
NL	63	0
PE	**	*
NS	206	**
NB	128	12
QC	1,345	0
ON	0	0
MB	139	0
SK	174	18
AB	511	8
BC	396	15
YT	*	0
NT	0	0
NU	^	..

Pharmacists and Pharmacy Technicians

Pharmacists and pharmacy technicians are potentially exposed to chemotherapeutics when they prepare the drugs for patient use.

A report by Eli Lilly on hospital pharmacies in Canada (for 2005/06) reports the number of hospitals with in-house pharmacies performing hematology and oncology functions for the whole country.^[11] This data is presented in the table below. There were 94 pharmacists working in outpatient pharmacies with hematology/oncology, and 91 in inpatient pharmacies.

Inpatients are patients who are admitted to hospital. Outpatients visit the hospital for treatment, but are not admitted. There could be minor differences in the types of drugs prepared by workers in these different pharmacies (i.e. IV drugs are likely used more for inpatients), therefore we differentiate this information in the table.

Number of Hematology/Oncology Clinical Pharmacy Services 2005/6[11]
	All	BC	Pr.	ON	QC	Atl.
Hospitals (total n)	142	20	20	45	42	15
Outpatient pharmacy (n)	118	17	14	32	40	15
Inpatient pharmacy (n)	116	16	15	34	39	12

Pharmacy technicians compose approximately 47% of the average hospital pharmacy staff (pharmacists compose 40%).^[11] The number of pharmacy technicians exposed to chemotherapeutic drugs can therefore be estimated as being slightly higher than the number of pharmacists.

Sources

1. Wikimedia Commons Photo: Cyclophosphamide
2. NTP 12th Report on Carcinogens for Cyclophosphamide (2011) (PDF)
3. Hazardous Substances Data Bank entry for Cyclophosphamide (Search term: ‘cyclophosphamide’)
4. IARC monograph summary, Volume 26 Supplement 7 (1987) (PDF)
5. Health Canada’s Prioritization of the DSL (2004)
6. CEPA List of Toxic Substances (1999)
7. Health Canada Drug Product Database (Search term: ‘cyclophosphamide as active ingredient’)
8. Ward et al. 2007. Mortality and Cancer Incidence in a cohort of Registered Nurses From British Columbia, Canada. American Journal of Industrial Medicine. 50:892–900.
9. IARC Monograph Volume 100: A review of human carcinogens—Part A: pharmaceuticals (2011)
10. CIHI, 2006. 2006 Workforce Trends Health Human Resources Database
11. Eli Lilly Canada. 2007. 2005/06 Hospital Pharmacy in Canada Report. (PDF)

Other Resources

1. BC Cancer Agency, Cancer Drug Manual, Cyclophosphamide (2006) (PDF)
2. Cancer Research UK Website, Cyclophosphamide