Principles of Cytotoxic drug preparations

CYTOTOXIC DRUG PREPARATION PRINCIPLES

1

1. What is cancer ?

Term cancer refer to a heterogeneous group of diseases caused by anImpairment of the normal functioning of genes, which lead to genetic damage

Cancer cells also known as tumors, or neoplasms.

2. Give me the characters of cancer?

They arise from a single abnormal cell, which continues to divide indefinitely.Uncontrolled growth, ability to invade local tissues, and ability to spread, or metastasize, are charecteristics of Cancer.

2S.Aravinth Vijay Jesuraj,

M.Pharm,DPMM,(PhD)

Types

BenignMalignant

MalignantSolid tumors-carcinomas is of epithelial cellsEg. Lung, colon, breast.Sarcomas-connective tissue, eg bone- osteosarcomaEg muscle-leiomyosarcoma Hematological malignancies-LymphomasEg.Hodgkin and non-Hodgkin lymphomasLeukemias-tumors of blood forming elementsClassified as acute or chronic, myeloid or lymphoid


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Cells are dividing in higher proportion

Local invasiveness

Tendency to spread to other parts of the body

Less differentiated cell morphology

Tendency to retain some characteristics of the tissue of origin


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Viruses: Including Epstein-Barr virus (EBV), Hepatitis B virus (HBV) and Human papillomavirus (HPV)

Environmental and occupational exposures: Eg: Ionizing and ultraviolet radiation, exposure to chemicals (Vinyl chloride, benzene and asbestos)

Lifestyle factors: Eg: High-fat, low fibre diets, tobacco, ethanol use

Medication: Alkylating agents and immunosuppressant Genetic factors: Inherited mutations, cancer causing genes

(oncogenes), defective tumor-suppressor genes


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WARNING SIGNS1. Change in bowel or bladder habits2. A Sore that does not heal3. Unusual bleeding or discharge4. Thickening or lump in the breast or

elsewhere5. Indigestion or difficulty swallowing6. Obvious change in a wart or mole7. Nagging cough or hoarseness


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Guidelines for screening: Because many cancers do not produce signs or symptoms until they have become large the goal of screening is to detect cancers early, when the disease is curable and to reduce mortality


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CYTOTOXIC DRUGS

Cytotoxic drugs are the therapeutic agents intended for but not limited to the treatment of cancer. These drugs are known to be highly toxic to cells, mainly through their action on cell reproduction. Many have proved to be carcinogens, mutagens or teratogens

Cytotoxic drugs are increasingly being used in a variety of healthcare settings, laboratories and vertinary clinics for the treatment of cancer and other medical conditions such as rheumatoid arthritis, multiple sclerosis and auto-immune disorders


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OCCUPATIONAL EXPOSURE

Drug preparation Pharmacist Drug administration Nurses and medical officers Handling patient waste Transport and waste disposal Laboratory staff, Spills Cleaning

Maintenance waste disposal staff


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Health effects attributed to cytotoxic drugs exposure among people preparing and administering cytotoxic drugs include:

Abnormal formation of cells and mutagenic activityAlterations to normal blood cell countFoetal loss in pregnant women and malformations in the offspring of pregnant womenAbdominal pain, hair loss, nasal sores and vomitingLiver damage


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RISK CONTROL

Following risk control measures can be implemented for reducing the risk to the employee

Establishment of written policies and protocols to ensure the safe handling of cytotoxic drugsEffective planning and design of the workplaceUse of best practice control measures and specialised equipment such as cytotoxic drug safety cabinetsThe implementation of stringent handling proceduresTraining and education of employees


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Outsource cytotoxic drug preparation work from a company that specializes in that sort of work

Purchase cytotoxic drugs in ready to use form such as pre-filled syringes

Purchase cytotoxic drugs in the safest form available Review health and safety information about cytotoxic

drugs before making a decision to purchase Use facilities that meet recommended technical and

safety standards


M.Pharm,DPMM,(PhD)

ESTABLISHING CYTOTOXIC PREPARATION FACILITY

Cytotoxic clean room that houses a laminar flow cytotoxic drug safety cabinet or pharmaceutical isolator for drug preparation

Access only through an anteroom. A secondary barrier to prevent cytotoxic drug contamination of the outside environment should be provided by HEPA filters that supply filtered air to the clean room and the anteroom


M.Pharm,DPMM,(PhD)

WORK ORGANISATION AND LAYOUT DESIGN

The level of concentration and visual control required

Precision of movements needed

Design of equipment and availability of adjustable furniture such as chairs, stools and footrests

Storage requirements

Potential noise sources


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ADDITIONAL CONSIDERATION IN DESIGNING AND SETTING UP CLEAN ROOM

Provision of access for cleaning

Incorporation of smooth and durable work surfaces and furniture

Installation of recessed lights

Limitation of the number of surfaces and shelves, to minimize particles shedding or the accumulation of particulate matter


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Installation of an accessible emergency shower outside the anteroom

Maintenance of an effective airlock between the cytotoxic suite and external environment

Ensuring all equipment used is dedicated to the cytotoxic clean room


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Change room facilities for changing into personal protective equipment

Provision of a means of communication between the clean room and other areas

Installation of a manometer to monitor the pressure differential within the cytotoxic suite and record daily differential pressure readings


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Consideration of the installation of a manometer alarm in case of adequate pressure differentials

Installation of a spill switch that reverses the airflow, minimizing contamination to the external environment


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Use of luer-lock syringes and fittings to keep connections together

Use of luer-slip syringes [only if luer-lock connections are incompatible] such as intrathecal needles

Use of syringe to syringe connectors when transferring solution from one syringe to another


M.Pharm,DPMM,(PhD)

Use of wide bore needles to reconstitute and draw-up cytotoxic drugs

Use of filter needles only when the cytotoxic drugs has been removed from a glass ampoule, or if particulate matter is visible

Use of air venting devices to equalize pressures and to prevent the passage of powder, aerosols and liquids

METHODS OF CONTROL IN DRUG PREPARATION EQUIPMENT


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STANDARD OPERATING PROCEDURE FOR PARENTERAL PREPARATION

Standard operating procedure for parenteral preparations should be documented, and stress the need to:

Avoid using cytotoxic drugs supplied in glass ampoule. If glass ampoules must be used, open with an ampoule breaker

Use techniques that avoid the generation of pressure differentials


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SOP FOR NON-PARENTERAL PREPARATION

Specific additional standard operating procedures for non-parenteral cytotoxic drug preparations includeUsing purpose dedicated equipmentMaking mixtures by dispersing tablets in waterNot crushing tablets in an open mortarNot counting tablets or capsules my machineCleaning equipment immediately after use with a strong alkaline detergent with pH greater than or equal to 10


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PERSONAL PROTECTIVE EQUIPMENT

Coverall or gownHead coveringClosed footwear and overshoesProtective gloves-long enough to cover the elasticized

cuffs of gowns or coverallsProtective eyewearRespiratory protective device


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EQUIPMENT MAINTENANCE

Inspection of cytotoxic drug safety cabinets, isolators and high efficiency particulate air filters (HEPA) filters

Keeping test records and a summary of results in a place accessible to employees

Not using a cabinet that has failed, until the fault has been rectified

Performing microbial and air-particles testing routinely, and recording the results


M.Pharm,DPMM,(PhD)

CLEANING DRUG PREPARATION FACILITIES

Clean daily

Use a dedicated mop and bucket

Treat all equipment as potentially contaminated

Provide personal protective equipment


M.Pharm,DPMM,(PhD)

Drug packaging: Cytotoxic drugs should be packaged in a

labelled, sealed, leak-proof container, with outer bags heat-sealed where possible, ensuring the container:

Offers protection from light when required Protects the drugs from breakage in transit Contains leakage if breakage occurs Has a childproof lid


M.Pharm,DPMM,(PhD)

Containers used for transporting prepared cytotoxic drugs should be:

Hard-walled and robust

Made from molded foam or other suitable packaging material capable of protecting the product from a shock equivalent to a drop of one meter onto a concrete surface

Securely closed and labeled with cytotoxic warning


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Documents

Principles of Cytotoxic drug preparations