SHORT REVIEW

Reguli pentru manipularea citostaticelor folosite în boala canceroasă

 Rules for the manipulation of cytostatic agents used in cancerous disease

First published: 30 martie 2020

Editorial Group: MEDICHUB MEDIA

DOI: 10.26416/OnHe.50.1.2020.2962

Abstract

The manipulation of cytostatic drugs used in the treatment of cancer is a matter of knowing and following strict rules of transport, dilution and administration. Also, ac­ci­dents that may occur through leakage of cytostatic solu­tions (contamination) must be prevented and de­con­ta­mi­na­tion maneuvers must be known. Disposal of waste re­sul­ting from the administration of chemotherapy, as well as bio­lo­gical products from the patients treated with cy­to­sta­tics should also be known by those who mani­pu­late the cy­to­sta­tics. Another point of interest in the ma­ni­pu­la­tion of the cytostatics is the use of the hood, the working mode with the hood and the rules imposed in the room where the hood is located. In this article, in addition to the above, I present some aspects related to the de­con­ta­mi­na­tion of medical personnel in case of accidental con­ta­mi­na­tion and the procedure in case of extravasation of the cytostatics.

 

Keywords
cytostatic, handling, protection and decontamination measures

Rezumat

Manipularea citostaticelor utilizate în tratamentul can­ce­­ru­lui incumbă cunoaşterea şi respectarea unor reguli stric­te de transport, diluţie şi administrare. De asemenea, ac­ci­den­tele care pot apărea prin scurgeri ale soluţiilor de cito­sta­ti­ce (contaminarea) trebuie prevenite, iar manevrele de decontaminare trebuie cunoscute. Aruncarea deşeurilor rezul­ta­te după administrarea chimioterapiei, precum şi a produselor bio­lo­gice provenite de la pacientul tratat cu citostatice trebuie de asemenea cunoscută de către cei care manipulează cito­sta­ti­ce­le. Alte puncte de interes în manipularea citostaticelor le reprezintă utilizarea hotei, modul de lucru cu hota şi regulile impuse în încăperea în care se află hota. În acest articol, pe lângă cele amintite, am prezentat şi câteva aspecte legate de decontaminarea personalului medical în caz de contaminare accidentală şi procedura în caz de extravazare a citostaticului.

 

Guidelines

There are numerous guides for the manipulation of cytostatics. We will look at the guide published by A.C. Easty and collaborators.

The medical personnel dealing with the administration of cytostatic drugs should be educated for this activity and should participate annually in courses and information on this subject. Personal protective equipment is mandatory. The regulations in force must also be observed.

Description of protective equipment

Gloves

The gloves used to handle cytotoxic drugs must comply with the asthma standard D-6978-(05)-13 and should not contain any powder (talc). Gloves are recommended to be nitrile, polyurethane, neoprene or latex. Latex is a known allergen, a factor that must be considered for glove selection. Vinyl gloves should not be used. The frequency of glove changes can be adjusted according to the level of exposure at each step in the medication circuit. For example, when administering reconstituted drugs, workers should change their gloves immediately if the gloves are broken, perforated, or visibly contaminated with a cytotoxic drug and should ensure that routine practices are followed. The gloves are put before putting the lot.

Gowns used to handle cytotoxic drugs should be disposable; they should be made of lint-free and waterproof fabric; should have long sleeves, with cuffs fastened; and it should close in the back. Dresses should be changed in case of contamination, spillage or breakage. For the preparation of medicines, the robes should be changed at half a turn or every 3.5 hours. The supplier should be able to certify that the robe protects against cytotoxic drugs(1).

Face protection

Mask should be worn whenever there is a risk of spraying (for example, during certain drug administration procedures). It is preferable to use a full face shield. If wearing goggles, these must be worn together with a fluid-resistant mask.

Caps are required only in the sterile preparation room and are worn to prevent microbial contamination of the sterile field.

Shoe covers (boots)

The disposable boots are worn to prevent the contamination of the footwear of the health workers, in the sterile training room or in case of spillage. The shoe covers must be removed immediately at the exit of the sterile preparation room to avoid contamination of other areas.

Handling containers for delivery
of cytotoxic drugs

Packaging may have high levels of contamination. In the pharmacy there should be a packing area to limit the risks of exposure. The packing area should be a separate space, separated from the dining areas and preferably a separate room (SR). There should be adequate ventilation in the area, negative pressure and preferably vented outwards.

Preparation of cytotoxic drugs

The oncology pharmacy must comply with the relevant norms from the Romanian Pharmacy Society and with the AMCS accreditation standards. In Romania, in most medical units where chemotherapy is performed, the cytostatics are prepared on the medical oncology sections, unfortunately, and not in the hospital pharmacy.

Hoods should be used to prevent air recirculation in the cabinet. There is evidence to suggest that some robotic devices that prepare cytotoxic drugs improve the accuracy of drug preparation and reduce potential harmful staff events. All mixing and preparation of administration kits with a cytotoxic drug should be performed in a centralized area in a special office.

In order for the preparations to be sterile, workers should cover the work surface with a sterile pad with plastic absorbent support to absorb any contamination with the fluid that may occur during handling. The gasket must not cover the front and rear grilles of the preparation hood. The swab should be changed after 3.5 hours of continuous work or for a new batch of preparations.

Air should never be removed from the infusion tube with a solution containing the drug. The infusion tubes should be primed and the air removed to the pharmacy before the cytotoxic drug or drug is added to the solution for infusion. Glass containers are not recommended because of the increased risk of breakage and exposure.

Labeling and final packaging

Cytotoxic drugs should be labeled to inform the person handling these preparations about the nature of the medicines and the precautions to be taken. The danger symbol “Cytotoxic” or the words “Cytotoxic/Cytotoxique” must be displayed on the containers containing cytotoxic drugs. Place each container of cytotoxic drugs (e.g., syringe, bag), as well as administration supplies (e.g., tubing) in a clear, leak-proof plastic bag.

After final verification, the plastic bags containing the cytotoxic drugs must be placed in a rigid (ideally opaque) transport container, appropriately identified with “Cytotoxic/Cytotoxique”.

Administration of drugs

Luer-lock connectors should be used for intravenous administration. Closed systems can provide additional protection. Disposable plastic support pads should be used on work surfaces and placed under tube or bag connections and ports when attaching any tube, bag or syringe that has been exposed to a cytotoxic drug. If a closed system is not used, never unplug the tube from cytotoxic drugs. Dispose of the bag with the tube attached to a suitable waste bin as a single unit. Needles designed for safety must be used in accordance with the Needle Safety Regulation. Do not clean the needle air before administering the cytostatics.

Oral cytotoxins should be handled in such a way as to avoid contact with the skin, release of aerosols or powders into the air, and cross-contamination with other medicines. Solid oral preparations (tablets) of cytotoxic drugs should be crushed or cut in the cabinet. Biological security. If patients are not able to take a solid format, the pharmacy should provide these drugs in an oral syringe, in an oral form ready for liquid administration.

Waste management

Workers dealing with biological fluids, droppings, contaminated litter and dirty equipment of patients who have received cytotoxic drugs should wear one pair of gloves and a protective gown. Face protection should be worn when there is a risk of splashing.

Waste cytotoxic drugs

The term “cytotoxic waste” includes any material that comes into contact with cytotoxic drugs during storage, handling, preparation, administration and disposal – for example, packaging material, protection equipement, syringes, tube-bag, medicine bags.

Other wastes (soft items such as tubing, protective equipment etc.) should be placed in leak-proof and tear-resistant containers, identified with the risk symbol “Cytotoxic/Cytotoxique”.

For final disposal outside the institution, all cytotoxic waste must be in rigid containers that do not leak, identified with the risk symbol “Cytotoxic/Cytotoxique” and scheduled for transport outside the institution.

Accidental exposure

Any accidental leakage of cytostatics must be reported. If a cytotoxic drug accidentally comes into contact with the skin or clothing of a worker, the worker should immediately remove the contaminated cloth, thoroughly wash the skin of the affected area with soap and water and rinse further.

If appropriate, the contaminated worker should take a shower. A dilution shower should be available nearby (for example, in clinics or oncology units). All contaminated fabrics should be disposed of in cytotoxic waste. If a cytotoxic drug comes into contact with the worker’s eyes, the worker should wash his or her eyes at an eye wash station. Alternatively, workers can use an isotonic solution (e.g., sterile 0.9% NaCl) to rinse their eyes. The eyes should be washed for at least 15 minutes. If the contact lenses are worn, they must be removed immediately before redness. In case of pricking with a needle or sharp wound, allow the wound to bleed freely. Under the jet of water, gently and thoroughly wash the area with soap.

Figure 1. Inspecţia Muncii Romania (Work Inspection Romania)
Figure 1. Inspecţia Muncii Romania (Work Inspection Romania)


 

Figure 2. Recommendations of the European Society of Oncology Pharmacy(3)
Figure 2. Recommendations of the European Society of Oncology Pharmacy(3)

The present guide must review the methodological guide to prevent risks related to exposure of carcinogens, mutagens and toxins for reproduction elaborated by the World Inspection in 2002 in the twinning project RO99/IB/OT01“Designing a protection system for works exposed to dangerous agents in the workplace”(2).

The proposal of the Order of the Medical Assistants in Romania generally contains the same recommendations as those listed before, but a more elaborate protocol should be developed(4).

Personal protective equipment (PPE)

The European Union has issued several directives to ensure a high quality of personal protection equipment (Directive 2016/425). Guidelines for personal protective equipment – version 24 August 2017 aims to facilitate a common interpretation and application of the PPE Directive. Personal protective equipment must meet European compliance (EC) standards and be specified in risk assessment. Personnel must wear safety equipment. Adequate personal protection is needed in each area identified as being at risk. Depending on the area of work, personal protective equipment is composed of:

  • protective suit (can be combined with cuffs)

  • protective gloves

  • protective respiratory equipment

  • caps

  • glasses for visual protection

  • shoe covers (boots).

Requirements of the prescription form
and its verification

The prescription of the anticancer drug by the doctor is sent to the pharmacy in an electronic format and/or on paper. The prescription should contain at least the following information:

  • Patient’s name, date of birth, sex and identification number.

  • Weight, height and/or body surface.

  • The hospital section, the outpatient unit or the medical office.

  • Prescribed drug (trade name or international common name).

  • Dose calculated based on body surface area, weight or single dose.

  • A prescribed dose – reduced in case of failure of an organ or of the parameters to be specified.

  • Route and duration of administration.

  • The type and volume of the solvent in which the substance is diluted.

  • Diagnosis.

  • The dates and/or days and time of administration.

  • The date and signature of the prescribing physician or in the case of the electronic signature the clear identification of the prescribing physician, for a safe release.

Extravasation

Extravasation represents a serious complication of anticancer drugs administered intravenously without the knowledge of risk factors, preventive measures, immediate detection and appropriate treatment. An extravasation kit for immediate treatment should be easily accessible in each ward.

Specific decontamination

In this regard, we cite a significant study. The purpose of this study was to examine the elimination and deactivation of cytotoxic contamination on the surfaces of a pharmaceutical isolation workstation (a room where the hood or dilution plant is placed). Three cytotoxic drugs were evaluated in three phases. Using the decontamination technologies currently available in the pharmaceutical and medical environments, Phase I investigated the physical elimination of contamination by detergents, Phase II and III investigated the effectiveness of detergents and vaporized hydrogen peroxide (VHP) in cytotoxic degrading drugs 5-flurouracil, doxorubicin and cyclophosphamide were removed from the surface by removal with detergents. VHP and alkaline detergents caused doxorubicin degradation. The effect observed with HPV is pH dependent, but none of the technologies applied had any effect on the chemical stability of 5-flurouracil and cyclophosphamide under the conditions tested(5).

Safe working practices when handling cytostatics should include the following:

The hands should be washed before dressing and after dilution activity. Then the equipment is removed and thrown away.

Employees must work below eye level to reduce the risk of eye exposure.

Gloves should be changed immediately. After use, gloves and gowns should be disposed of in designated waste containers.

The place of connection of the syringe and i.v. tubes must be provided with locking connections. Infusion sets and pumps should be checked for leakage during use. Use an absorbent field below the area where the dilution is done manually in the hood. Sterile typhoon should be placed around the syringe connection sites.

The removal of air from i.v. infusion tubes must be done in the hood. If priming is done at the administration site, an adapter will be used to minimize leakage, and i.v. sets should be primed with a solution that does not contain drugs using a discharge method. Needles and syringes should not be crushed or cut. These should be placed in a puncture resistant container, then in a toxic waste disposal bag. Sharps contaminated with blood or other infectious materials should be placed in puncture-proof, tightly sealed containers and properly labeled as soon as possible after use and stored in such containers until reprocessed accordingly. I.v. administration kits should be discarded intact. Unused medicines must be returned to the pharmacy.

I.v. pumps should be removed from any drug contamination after use(6).

Care of patients receiving cytostatics

Patient droppings that are contaminated should be handled in such a way as to protect health workers from exposure.

Personal protective equipment. All personnel responsible for handling excretions, including urine, vomiting or faeces, from patients who have received cytostatic therapy in the past 48 hours, must wear personal protective equipment, as described before. Eye and face protection should be worn when spraying is possible. Protective equipment should be disposed of after each use or as soon as it is known to be contaminated, as detailed in Waste Disposal. The hands should be washed with soap and water after removing the gloves or immediately after contact with the above substances.

Handling of underwear. Linens contaminated with cytostatics or excrement from patients who have received chemotherapy within the last 48 hours should be carefully handled to reduce employee exposure and environmental contamination. Lingerie contaminated with cytostatics should be placed in specially marked laundry bags and then inserted into a labeled and waterproof bag. The laundry bag and its contents must be washed beforehand, and then the linen added to other laundry for a second wash. Laundry staff should wear gloves and dresses while handling pre-washed materials.

Reusable item. Glassware or other contaminated reusable items should be washed twice with detergent by a trained employee wearing personal protective equipment(7).

  • Destruction of doxorubicin and daunorubicin using potassium permanganate/sulfuric acid:

  • Doxorubicin or daunorubicin, 30 mg, dissolved in 3 mol/liter sulfuric acid, 10 ml, is destroyed by potassium permanganate, 1 g, in 2 hours.

  • Destruction of methotrexate and dichloromethotrexate using potassium permanganate/sulfuric acid:

  • Methotrexate, 50 mg, or dichloromethotrexate, 10 mg, solid compound, dissolved in 3 mol/liter sulfuric acid, 10 ml, is destroyed by potassium permanganate, 0.5 g, in 1 hour.

  • Destruction of cyclophosphamide and ifosfamide using alkaline hydrolysis in the presence of dimethylformamide:

  • Cyclophosphamide or ifosfamide, 100 mg, in dimethylformamide, 20 ml, is destroyed by 12 g/100 ml sodium hydroxide solution, 10 ml, when re-fluxed for 4 hours.

  • Destruction of vincristine sulfate and vinblastine sulfate using potassium permanganate/sulfuric acid:

  • Vincristine sulfate or vinblastine sulfate, 10 mg, in 10 ml of 3 mol/liter sulfuric acid is completely destroyed by 0.5 g of potassium permanganate in 2 hours.

  • Destruction of cisplatin by reduction with zinc powder:

  • Cisplatin, 30 mg, dissolved in 2 mol/liter sulfuric acid, 50 ml, is destroyed by zinc powder, 1.5 g, in 10-12 hours.

  • Methods of degradation of cytostatic drugs in hospital formulations:

  • Degradation by sodium hypochlorite, degradation by hydrogen peroxide, Fenton reagent.

  • Chemical destruction methods for cytostatic drugs(8):

  • Use a liquid-resistant absorbent mat.

The airflow is vertical, therefore no objects can be located above the work surface (for example, shelves or containers hung on the wall).

Figure 3. Handling cytostatic drugs(9)
Figure 3. Handling cytostatic drugs(9)

 Inside the hood, the quality of the airflow may not be the same in all regions. Therefore, work at least 10-15 cm from all side edges.

Always leave the hood on (24 hours a day, 7 days a week); if no one works there for longer periods, such as at night and on weekends, reduce, but do not turn off the airflow.

Cover the ventilation slots.

Before you start operating, make sure all necessary equipment is available on the work surface.

During the maintenance of the hood, especially when changing the filter, cytostatic drug particles can reach the environment. Therefore, clean the room completely after maintenance(10).

Conflicts of interests: The author declares no conflict of interests.

Bibliografie

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4324350/pdf/conc-22-e27.pdf
  2. https://www.inspectiamuncii.ro/documents/66402/264079/Ghid+metodologic+pentru+prevenirea+riscurilor+legate+de+expunerea+la+agen%C5%A3i+cancerigeni%2C+mutageni+%C5%9Fi+toxici+pentru+reproducere/c09a8c32-e5fd-46f7-bf6a-c26bd29ca983
  3. https://www.esop.li/downloads/QuapoS%206.pdf
  4. https://www.oamr.ro/wp-content/uploads/2014/02/Protectia-assistentilor-medicali-in-oncologie.pdf
  5. Roberts S, Khammo N, McDonnell G, Sewell GJ. Studies on the decontamination of surfaces exposed to cytotoxic drugs in chemotherapy workstations. J Oncol Pharm Pract. 2006 Jun; 12(2):95-104.
  6. https://www.osha.gov/SLTC/hazardousdrugs/controlling_occex_hazardousdrugs.html#drug_admin
  7. https://www.osha.gov/SLTC/hazardousdrugs/controlling_occex_hazardousdrugs.html#drug_admin
  8. https://www.who.int/docstore/water_sanitation_health/wastemanag/ch21.htm
  9. https://www.bms.com/assets/bms/us/en-us/pdf/handling-cytostatic-drugs.pdf
  10. https://www.bms.com/assets/bms/us/en-us/pdf/handling-cytostatic-drugs.pdf