Cytotoxic drugs

Cytotoxic drugs (antineoplastic drugs) are widely used in the treatment of cancer and some non-neoplastic diseases. The main therapeutic effect to kill or to decrease the proliferation of tumour cells. However, because of their in general non-selective mode of action, normal (non-tumour) cells may also be damaged, resulting in toxic adverse effects. Pharmacists, pharmacy technicians and nurses involved in the preparation and administration, and workers employed in the production of these drugs, may face health risks.

 

Adverse effects of cytotoxic drugs

The acute adverse effects of many cytotoxic drugs, such as irritation of skin, eyes and mucous membranes, dizziness, headache, dermatitis, alopecia, nausea, vomiting, diarrhoea and menstrual problems have frequently been observed in patients treated with these drugs. More severe toxicity may occur in several tissues and organs, such as bone marrow suppression, liver, bladder, kidney and lung.

Apart from the acute effects, cytotoxic drugs may cause delayed adverse effects such effects on reproduction and cancer. Reproductive effects reported are foetal loss, congenital malformations, low birth weight, infertility and learning disabilities in the children of nurses who have handled cytotoxic drugs.

According to the International Agency for Research on Cancer (IARC), there is sufficient evidence for the carcinogenicity in humans of eight cytotoxic drugs. In addition, eight drugs are considered as probably carcinogenic to humans and eight drugs as possibly carcinogenic to humans.

 

Occupational exposure to cytotoxic drugs

During the preparation and administration of cytotoxic drugs there are several potential events that may result in environmental contamination and exposure of healthcare workers.

To protect the workers handling cytotoxic drugs, protective measures were taken and safety guidelines were developed and implemented.  Special attention was given to the effective use of personal protective equipment (PPE) such as protective clothes, masks, gloves and gowns and the use of biological safety cabinets and isolators. More recently, closed-system drug transfer devices and robotic systems were introduced.

Despite the widespread promulgation of safety guidelines all over the world, and the subsequent adoption of standard protective measures, healthcare workers involved in the preparation and administration of cytotoxic drugs continue to be exposed to these drugs.

Many studies have shown environmental contamination with cytotoxic drugs in the healthcare setting. Drugs were detected in the air and on work surfaces in drug manufacturing areas, administration area and preparation areas even though drug preparation was carried out in biological safety cabinets and isolators. In addition, cytotoxic drugs or their metabolites were detected in the urine of pharmacists, pharmacy technicians, nurses and workers in drug production and manufacturing. Based on these data, an additional cancer risk was calculated for pharmacy technicians and nurses involved in the preparation and administration of cyclophosphamide. In many studies, the additional cancer risk was above the strive risk level.

 

Monitoring occupational exposure

Despite the use of protective measures and implemented guidelines, it is still necessary to check whether healthcare workers are exposed. Environmental monitoring and biological monitoring are used to measure environmental exposure and uptake (dose), respectively.

 

Environmental monitoring

Determination of air concentrations of cytotoxic drugs (aerosols) is used for the quantification of external exposure to these drugs.

More popular is the use of so-called wipe tests to measure environmental contamination. With wipe tests, potential contaminated surfaces are pre-wetted and wiped with a tissue. The tissue is then analysed for the drugs to be monitored. Finally the amount is calculated for the area wipe and expressed per cm2. By taking wipe samples, contaminated surfaces can be traced and ranked according to the level of contamination. The causes of the contamination can then be attempted to be elucidated. Wipe tests can be used to evaluate preparation and administration procedures, to check outside contamination of drug vials, to test devices, and to check cleaning procedures.

Taking wipe samples has become very popular and, nowadays, many hospitals perform these tests on a regular basis to evaluate their procedures and routines.

Contamination of gloves can be measured to check spillage during handling of the drugs and to evaluate handling procedures. Skin contamination can be measured to establish potential exposure by skin and to check the effectiveness of personal protective equipment.

 

Biological monitoring

Several methods have been developed for biological monitoring of occupational exposure to cytotoxic drugs. The best validated and most specific and sensitive method is the determination of cyclophosphamide and ifosphamide in urine. In addition, exposure to 5-fluorouracil can be assessed by analysis of the metabolite α-fluoro-β-alanine in urine. An additional cancer risk can be calculated by measurement of cyclophosphamide in urine.

 

To make environmental and biological monitoring easily available for routine practise, Exposure Control has developed the CYTO WIPE KIT and the CYTO URINE KIT. Both kits have been used for many years in 200-250 hospitals all over the world.


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