INTRODUCTION

Cytotoxic drugs are toxic compounds and are known to be carcinogenic, mutagenic and/or teratogenic. On direct contact, they may cause skin, eyes, and mucous membranes irritation, as well as tissue ulceration and necrosis. The toxicity of cytotoxic drugs makes it necessary to minimise the exposure of health-care workers to these drugs. The handling and administration of cytotoxic drugs should not be carried out by pregnant staff. At the same time, aseptic conditions should be maintained.

In order to highlight the danger of cytotoxic materials, the following signs are used:

• In some countries, it is mandatory that cytotoxic drugs and their waste are properly identified with the capital “C” symbol and, under it, the words “CYTOTOXIC /CYTOTOXIQUE “ in capital letters, and the both words and the symbol should appear on a dark grey rectangle.
• This sign will be added to the cytotoxic drugs in the MSF catalogue.

• Cytotoxic materials can also be identified by a purple symbol representing a cell in the late phase of division know as telophase. The labels are dark purple and bear the telophase symbol.

CYTOTOXIC DRUGS IN THE MSF STANDARD LIST (ACCORDING WHO CLASSIFICATION)

http://www.whocc.no/atc_ddd_index/?code=L01D&showdescription=no

GENERAL RULES

• Safety measures: ensure that safety equipment, protocols, and instructions are available in all areas where cytotoxic drugs are stored, handled, prepared, administered and disposed of.
• Minimise handling and movement of cytotoxic drugs from reception to preparation.
• Medicines should remain in their original secondary or tertiary packaging (sealed plastic bag and/or cartons), as the outside of many commercial vials may be contaminated, presenting an exposure risk to anyone handling them.
• Cytotoxic vials are usually well-packaged by pharmaceutical companies, so no specific Personal Protective Equipment (PPE) is required for staff transporting cytotoxic agents, as long as the original packaging is intact and there are no signs of damage or leakage.
• For vials that have not been opened but are no longer in their original packaging, use protective gloves (nitrile, powder-free).
• As damage or leakage can only be detected by handling the product, wearing gloves is advisable when handling cytotoxic agents.
• Centralise the preparation of cytotoxic agents:A
• One single person should transport all cytotoxic drugs needed for the next 24 hours from the pharmacy to preparation area at one time.
• Prepare the drugs in one place.
• Provide safety equipment (see below) in all areas where cytotoxic drugs are stored, handled, prepared or administered.
• Easily visible posters with protocols/instructions describing how to manage cytotoxic drug spills should be available on the wards and are part of nursing care.
• The following materials should be present (or readily available):
• Cytotoxic Spill Kit containing all PPE and materials needed to clean up spills.
• Running water supply + soft soap.
• Device for eye wash (EMEQEYEW7++) (or alternatively 1l of 0.9% NaCl with a 60ml Luer syringe (SINSSYDL60-) or infusion set (SINSSETI2-).
• Movement of cytotoxic drugs should be limited and rationalised. All transports should be coordinated from departure up to the arrival. The TREM card (transport emergency card) and MSDS (material safety data sheet) sheet should be prepared and given to the driver to facilitate transport through customs or by air.

RECEPTION AND STORAGE OF CYTOTOXIC DRUGS

• Ensure that the cytotoxic drugs are stored according to the manufacturer's specific requirements. Be aware that storage conditions may vary between from manufacturers for the same.
• Store cytotoxic drugs centrally in the main pharmacy, avoid storing them in the preparation room.
• Cytotoxic drugs should NOT be stored near or on top of other medicines or medical equipment. They must be stored securely to minimise the risk of breakage and contain any spillage. Ensure clear, visible labelling for easy identification.
• The best storage option is a closed cupboard. Lower shelves mat be used as an alternative, but the storage area should limit the risk of contamination or exposure.
• Labelling and storage directions:
• Mark boxes with arrows on the outside to indicate the box proper storage orientation (to prevent the box from being turned upside down).
• Apply a "hazardous" sticker to the box.
• Ensure that all labels are clear and understandable for all staff involved in handling of the cytotoxic products.
• Reception: visually inspect cytotoxic drugs upon receipt to check for any damage or leakage during transport. In damage or leakage is detected, appropriate PPE should be worn, and proper actions must be taken immediately.

CYTOTOXIC SPILL KIT

A Cytotoxic Spill Kit must be available in all areas where cytotoxic substances are used. All staff handling cytotoxic drugs and waste should be trained in spill management and decontamination. A ready-to-use cytotoxic spill kit can be ordered (SDDCCYTTS2-).

• PPE
• 1 surgical cap (ELINCADS1S-)
• 1 pair of shoe covers (ELINSHOC001)
• 4 pairs of of long-sleeved nitrile examination gloves (SMSUGLEN1+++): inner and outer pair, for 2 persons
• 2 respirators FFP2 (ELINMASP+++)
• 2 protective glasses (SPPEGOGPR++)
• 1 non-woven surgical gown (ELINGOWS+++)
• Pean forceps (ESURFOAP14S) or standard dressing forceps (ESURFODR14-) for collecting glass from broken ampoules or vials.
• Single-use plastic sharps container (SINSCONT2P-).
• Disposable absorbent material such as cotton rolls, compresses, toilet paper, or kitchen paper. Enough to absorb up to 1 litre.
• Absorbent towel with a waterproof layer (ELINDRAW6D-)
• Disposable cleaning cloths (towels).
• Liquid soap (for cleaning the floor).
• 3 plastic bags:
• one for contaminated absorbent material and cleaning materials
• one for disposable protective clothing
• one for protective goggles, which should be washed after use.
• 1 biohazardous waste bag (ELABBAGR001) to place the first two bags.
• Instruction card for safely mopping up spills on surfaces.
• Instruction card for wearing / removing PPE.

Remark on gloves

All gloves have some degree of permeability to cytotoxic drugs, and this permeability increases over time. Vinyl and latex surgical gloves should not be used, as they do not provide the required level of protection.

Gloves specifications:

• Gloves should be made from materials that minimise drug permeability, such as nitrile, polyurethane, or neoprene.
• Gloves must be powder-free, as powder can absorb contaminants, increasing the risk of aerosolization and contact contamination
• Gloves should be long enough to cover the gown sleeves when the wearer's arm is fully extended

SPILL MANAGEMENT

A system must be in place to promptly report spills or contamination of staff. The incident report should include the following information:

• type of incident
• actions taken to manage the spill
• actions taken to prevent recurrence

PROCEDURE FOR LARGE SPILLS

• Alert and notify:
• Alert people in the immediate vicinity that a hazardous spill has occurred and direct them to stay clear.
• Request assistance from an additional person to provide materials, read the instruction cards, and handle the waste bag.
• Secure the area:
• Cordon off the spill area and, if possible, close windows and doors to contain the spill.
• Turn off any fans or ventilation system that may spread the spill or aerosolised particles.
• Open the Cytotoxic Spill Kit and display hazard signs around the perimeter of the spill area.
• Don PPE in the following order:
• respiratory protection
• goggles
• cap
• first pair of gloves
• gown
• overshoes
• second pair of gloves
• the assistant should also wear two pairs of gloves, goggles, and respiratory protection
• Contain the spill:
• For a liquid spill: cover the spill with an absorbent waterproof plastic-lined towel.
• For a powder spill: cover the spill with absorbent towels to minimise dust production. Carefully wet the towel with water (without flooding the pill), allowing the powder to dissolve and be absorbed by the towel.
• Collect and dispose of the spill:
• Use the scoop and scraper to gather the absorbed material and any broken glass.
• Discard the collected cleaning materials into the first plastic bag held by the assistant.
• Do NOT handle sharps/glass with your hands. Use forceps or tweezers to carefully dispose of needles and glass into the sharps container.
• Clean the area:
• Wash the area several times with water and detergent, rinsing thoroughly each time with water. Always work from the outside of the spill toward the centre.
• Remove PPE in the following order:
• outer gloves
• overshoes
• gown
• goggles
• cap
• respiratory protection
• inner gloves
• place used disposable items into the secondplastic bag.
• place the protective glasses into the third bag for cleaning.
• The assistant (still wearing PPE) closes the first two plastic bags and places them into the "biohazard" bag.
• The assistant removes his PPE and adds the single-use PPE into the "biohazard" bag.
• Wash hands with soap and water.
• Wash goggles in hot, soapy water while wearing non-sterile gloves, then dry with paper towels (discard paper towels into the "biohazard" bag).
• Place the "biohazard" bag into the appropriate hazardous waste bin.
• Contact the waste or Watsan manager responsible for the transport and disposal of the biohazard bag.
• Ensure the Cytotoxic Spill Kit is replaced and fully stocked for future use.

PROCEDURE FOR SMALL SPILLS:
DROPS OR SPLASHES ON EQUIPMENT, FURNITURE, OR FLOOR

• If not already done, don the appropriate PPE as described above.
• Immediately cover the affected area with absorbent material.
• If the spill involves a powder, gently cover with it an absorbent towel to minimise dust production. Wet the towel to dissolve the powder and allow it to absorbed by the towel.
• Carefully collect the absorbed material, making sure to use forceps to pick up any broken glass.
• Discard the collected waste into the appropriate waste bin (solid container dedicated to cytotoxic waste, such as vials, needles etc.).
• Wash the affected area with water and detergent, then rinse thoroughly several times with water.
• Dry the cleaned area using absorbent towels or cloths.
• Discard the waste into the cytotoxic waste bin.
• Remove and dispose of gloves safely, then replace them with clean ones.

MANAGEMENT OF ACCIDENTAL EXPOSURE TO CYTOTOXIC SUBSTANCES

• Inhalation of drug aerosols, dust, powder, or droplets:
• When opening the vial or handling the drug, inhalation of large quantities is unlikely due to the small vial size. If respiratory symptoms occur, move the victim away from the source into fresh air.
• Skin exposure:
• If splashes, drops, or contaminated surface come into contact with healthy skin or a wound, irritation, allergic reaction, itching, burning, and skin lesions (particularly with vincristine) may occur.
• Remove any contaminated clothing or shoes immediately.
• Flush the affected area with a large volume of water for 10-20 minutes, then wash thoroughly with soap and rinse with running water.
• If the skin is damaged, apply a clean dressing.
• Eye contact:
• Flush the eyes with a large volume of water or normal saline eye drops for at least 15-20 minutes.
• Seek immediate medical attention.
• If gloves are worn, remove them before flushing the eyes, as they may be contaminated.
• If contact lenses are worn, remove them immediately before flushing.
• Ingestion (unlikely via splashes, contaminated food, drink, or hand-to-mouth contact).
• Do not induce vomiting.
• Clothing contamination:
• All contaminated clothing should be removed and discarded in the "biohazard" waste bag if it is to be disposed of.
• For clothing that is not to be discarded, wash separately in hot water, and repeat washing.

See also: Hazardous waste management of health structures within low-income Countries, MSF, 2013, 3rd edition.

Contact your section pharmacist for more details.