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Safe handling of cytotoxic drugs

Several clinical and laboratory studies have proved that most cytotoxic agents have carcinogenic, teratogenic and/or mutagenic effects.(1)

Authors reported acute and chronic reactions associated with occupational exposure of healthcare workers (pharmacists, pharmacy technicians and nurses) during preparation and administration of these drugs: skin diseases, such as contact dermatitis, eczema and urticaria, but also nausea and obstetrical side-effects.(2)

Trace concentrations of antineoplastic agents have been detected in the urine of staff handling these drugs, suggesting a real exposure.(3,4) However, in many of these studies, the authors did not say whether staff received specific training on drug handling practices, whether a suitable system of protection (downward-airflow biological safety cabinet or isolator) was used for the preparation of these agents or if special guidelines were established and followed in the hospitals.

This article briefly reviews the most important recommendations for the safe handling of cytotoxic agents during their preparation.

Standard operating procedures for drug preparation
The preparation of cytotoxic drugs involves the use of either a downward-airflow biological safety cabinet or an isolator. When they are correctly used, these two devices provide the same efficiency for staff protection.(5)

Air from the preparation room and from the HEPA (high-efficiency particulate air) filter of the downward-airflow biological safety cabinet must be exhausted outside the working area. This system avoids occupational exposure of staff by inhalation. The use of a closed-system device with or without a biological safety cabinet, such as PhaSeal® (Carmel Pharma) or Tevadaptor® (Teva Pharmaceuticals Europe), offers a solution to reduce contamination as far as possible.

When using a downward-airflow biological safety cabinet or an isolator, these recommendations must be followed:

  • Gloves offer the first line of protection when handling cytotoxic drugs and are frequently in contact with these agents.(6) Double-gloving is recommended for preparation inside a downward-airflow biological safety cabinet. Gloves should be changed at least every 30 minutes, although every 15–20 minutes is better.(7) They must be removed immediately if torn or punctured. The permeability of several glove materials has been tested. Results showed that neoprene, natural rubber latex and nitrile gloves display the highest resistance to permeation. Vinyl, which is the most permeable material, should never be used. Inside isolators, ­operators must wear three pair of gloves. The first pair, under the neoprene gloves (second pair), is directly in contact with the skin. The third pair, whose material can be neoprene, natural rubber latex or nitrile, is put above neoprene gloves. As in downward-airflow biological safety cabinets, gloves should be changed every 30 minutes.
  • Venting devices with hydrophobic filters should be used in order to reduce internal pressure in vials during the reconstitution of powders. This system allows for limited leakage of cytotoxic agents by aerosolisation. The closed devices described above include a pressure equalisation system, which ensures that there is neither overpressure nor vacuum when air or fluid is injected into, or aspirated from, the vials.
  • The inside of downward-airflow biological safety cabinets and isolators must be decontaminated every day. Decontamination consists of surface cleaning, first with water in order to eliminate potential contamination with cytotoxic agents, then with a detergent such as isopropyl alcohol. Surfaces must be dried with compresses between these two steps. The back of removable trays, if those are present, must be cleaned at least every week using the same decontamination agents. Cleaning should always proceed from least to most contaminated areas.

Training and evaluation of operators
Training and regular evaluation of operators involved in the preparation of antineoplastic drugs are essential to improve compliance with general handling procedures and, thus, to reduce occupational exposure. The training method using a fluorescent dye solution as a safe simulated liquid cytotoxic allows to assess each operator’s preparation technique. Pharmacists ask pharmacy technicians to prepare several fluorescein solutions. At the end of each preparation, an ultraviolet (UV) light lamp (365nm) is used to estimate surface contamination (by ­counting the number of projections on several surfaces, such as work trays, absorbent papers, gloves and gowns).

Despite the publication of several safety standards for the handling of cytotoxic drugs during the past decade, awareness of the potential risks of exposure is not universal.

The only way to implement the recommended guidelines is to set up training and evaluation programmes for operators.


Bertrand Favier

Laurence Gilles
Pharmacy Department
Centre Régional de Lutte Contre le Cancer Léon Bérard
E:[email protected]

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