Chemotherapic drugs

Due to the remarkable toxicity of antiblastic drugs, particular attention is recommended both when manipulating them and when employing personal protective devices.

Manoeuvres at risk

The preparation of antiblastic drugs involves the carrying out of numerous procedures that may entail both fumes and/or aerosol formation and the spread of the preparation as drops especially during the following phases:

• opening of the drug vial,
• filling of the syringe,
• expulsion of air from the syringe when dosing the drug,
• removal of needle from the drug phial,
• transfer of the drug to the phleboclysis phial.

When administering the drug the manoeuvres at highest risk for the operator are as follows:

• expulsion of air from the syringe before administrating the drug,
• drug leakage in the syringe's joints as well as in the valve of the air filter.

A further phase of possible contamination not only for doctors and nurses but also for the general services personnel is represented by the disposal of such drugs and of the materials employed for their preparation (gloves, white coats, syringes, etc.). Special care must be paid to the excretions of the treated patients, as they may contain high levels of antiblastic drugs and, therefore, they may represent a further source of exposure during the assistance service.
In general, the highest concentrations of the drugs in the excretions are found during the first and the second day after administration (except cisplatin whose t1/2 is longer: about 6-8 days).

Antiblastic drugs preparation

The preparation of antiblastic drugs should be concentrated as much as possible in one single centralized centre. The preparation must be carried out in a laminar air flow (from the top downwards) fume cupboards located in rooms expressely meant for the preparation of drugs, with a good natural air exchange and without transiting and/or stopping of other personnel. Such equipment must be periodically overhauled (at least yearly), particularly as far as filters are concerned, by qualified technical personnel.
In the case of decentralized preparation, exposure of the personnel should be definitely incidental if both correct procedural rules and proper personal protective devices are strictly adopted. In this case, if the preparation operations are carried out on a free plane, the drugs must be prepared in an isolated working area, specifically designated for the purpose, far from heat sources or draught. Furthermore, before starting the preparation operations, the working plane should be covered with a disposable absorbent length of material, waterproof on the back to reduce the chance of dispersion in the case of an accidental leaking of the drug.
To reduce the risk of contamination, the operator must wear:

• white coat,
• gloves,
• mask,
• spectacles,
• hair-containing cap.

The contemporaneous employment of all these protective devices is necessary when the preparation is carried out on a free plane; when the operations are carried out under the laminar air flow fume cupboard, the employment of the white coat and gloves is enough. As far as gloves are concerned, they must be disposable and made of polyvinyl chloride (PVC): in fact, some antiblastic drugs (nitrogen mustard) may pass both through latex and polyethylene gloves.
In the case of continuative contact with the antiblastic drugs, gloves must be replaced every 30 minutes. Both before wearing the gloves and especially after having removed them, it is necessary to accurately wash the hands with water and soap, because gloves may originally present faults that allow the passage of drugs.

Recommended procedures for antiblastic drugs preparation

During the preparation of lyophilized antiblastic drugs contained in phials with pierceable rubber stopped, it is necessary to follow these directions:

• Open the solvent vial by winding a sterile gauze round the vial's neck.
• Aspirate the contents of the solvent vial according to the usual modality.
• Perforate the rubber stopped of the phial, containing the lyophilized drug, with a 1 ml insulin syringe, with the needle but without the piston. The syringe must be positioned on the outer margin of the rubber stopped to create a valve-system to prevent an increase in pressure inside the phial when the solvent is introduced. Such increase in pressure, in fact, could allow either the detaching of the needle from the syringe or the emission of the liquid from the phial during the pulling out of the needle.
• Introduce the solvent in the phial perforating the centre of the rubber membrane, directing the diluent towards the phial's walls to make sure that all powder is wet before shaking it.
• Remove from the phial the syringe and the needle employed to introduce the solvent, leaving in place the insulin syringe.
• Aspirate the diluted drug without introducing air in the phial, leaving in place the insulin syringe. After the desired quantity of drug has been aspirated, remove the syringe with the inserted needle from the phial and then expel any residual air from the syringe, by positioning a sterile gauze at the top extremity of the needle to avoid contamination of the operator in the case of an accidental leakage of the drug.
• At the end of the preparation, the drug phial with the insulin syringe must be disposed of in a rigid container with irreversible hermetic sealing and sent to disposal as special hospital waste.
• During the administration of the drug, it is necessary to put a protective waterproof length of material under the patient's arm to avoid spilling of the drug over the bed linen.

The preparation of drugs contained in vials must be carried out according to the following modalities:

• Open the phials containing the drug, after verification that no liquid is present in their upper part, by winding a sterile gauze round the vial's neck up to the line of demarcation of the breaking point; this device allows both to contain the aerosol dispersion of the drug on opening the vial and to avoid the risk of injury to the worker.
• Aspirate the drug contained in the vial according to the usual modality.
• Expel the air from the syringe protecting the needle with a sterile gauze to avoid contamination in the case of an accidental leakage of the drug.

When preparing the phleboclysis, it is necessary to follow these directions:

• Introduce the drug in the phleboclysis' vial, perforating the centre of the rubber stopped membrane with the needle of the syringe. When removing the syringe from the phleboclysis' vial, protect the point of exit of the needle with a gauze to avoid spilling.
• The syringe employed to introduce the drug in the phleboclysis must be immediately disposed of, with the inserted needle, in the appropriate rigid containers with irreversible hermetic sealing for special hospital waste.
• Fill the connection tube as usual; to avoid leakage of the drug, it is necessary to employ both tubes that prevent trickling of the solutions and a sterile gauze to protect the extremity of the tube.
• Protect photosensitive drugs contained in the phleboclysis with a protective covering made of either cloth or aluminium sheet that must be maintained during administration.
• If the drug needs to be administered to a confused and/or poorly cooperating patient, in order to avoid the risk of accidental self-inoculation, it is better to get assistance from another operator.

Disposal of material employed for the preparation

• Once the preparation of the drug is finished, it is necessary to clean the inner part of the fume cupboard with 70% alcohol and a disposable paper cloth.
• When tidying up the material employed for therapy, it is always necessary to wear PVC gloves.
• All employed material (syringes always with the inserted needle, phials, tubes, gloves, gauzes, cotton wool, etc.) must be placed in appropriate cartons marked as special hospital waste.
• At the end of the operations working surfaces, floors and surfaces exposed to contamination must be cleaned with a 10% solution of sodium hypochlorite.

General behavioural rules for the personnel

The following are forbidden:

• entry to the preparation area of the antiblastic drugs to non-authorized personnel,
• use of make-up in the working areas: in fact, if contaminated, it may represent a prolonged source of exposure,
• eating, drinking, using chewing-gum, smoking and keeping food where cytotoxic substances are manipulated,
• wearing protective clothes outside the working area.

Health surveillance of the personnel

The operators assigned to the preparation and administration of antiblastic drugs must be subject to periodical medical examinations.
These examinations aim at supervising the general health condition of the personnel assigned to the manipulation or administration of antiblastic drugs, in order to point out any biological damage as soon as possible.
In the working history it is necessary to note down the average quantity of manipulated drugs, the average duration of exposure, any episode of accidental exposure, any injury and needle-stick injury during work.
At present, no methodology specific enough for the periodical monitoring of the exposed subjects exists.
Some investigations exist that allow to point out the presence of genotoxic damage (assessment of the exchange of sister chromatids, assessment of the frequency of chromosomic aberrations, observation of the frequency of micronucleus). They are highly sensitive but aspecific and, furthermore, they take a long time and are very difficult to carry out.
The tests that assess the magnitude of the mutagenic power of the exposed subjects' urine are not specific enough because strongly influenced both by dietetic and environmental factors, as well as by personal habits (such as smoking).
If it is necessary to monitor the absorption of the antiblastic drugs in the exposed subjects, it is possible to dose the drug in the urine.
During pregnancy, especially during the first three months, workers must not be appointed to tasks entailing exposure to antiblastic drugs.
Although the passing of cytotoxic substances in the maternal milk has not been yet documented, it is better, as a precaution, to avoid appointing breast-feeding workers to the manipulation of cytotoxic substances.

	Ambulatories
	Pharmacy
	Clinical wards

	Ambulatories
	Pharmacy
	Clinical wards

Chemotherapic drugs