Cytotoxic Drug Reconstitution

Background

 The pharmacist  all medication preparation:

- non-sterile creams, ointments;
- sterile compounds e.g. eye drops;
- sterile products e.g. TPN, IV admixtures and Cytotoxic drugs.

 The pharmacist  knowledge of:

- ingredients,
- equipment,
- compatibility,
- stability,
- technique needed to compound sterile and non-sterile
extemporaneous prescriptions.
 Background

 Personnel
- proficiency in the art of compounding,
- knowledge,
- experience,
- ability to assume the responsibility.
- continuing competency and training programs.

 Apparel
- clean clothing.
- protective apparel, e.g. lab coats/jackets, apron or gloves.
- to protect drug products from contamination during processing or
packaging.
- to help protect employees.
 Background

 Area
- specifically designated area.
- adequate lighting and ventilation.
- the compounding area for sterile products shall be
separate and distinct from the area used for
compounding of non-sterile drug products.

 Equipment
- appropriate design, composition, size and suitably
located.
- cleaned and sanitized to prevent contamination.
 Background

 Packaging
- containers used in compounding shall be stored in a manner
to prevent contamination.
- bagged or boxed containers shall be stored off the floor.
- containers shall not be reactive, additive or absorptive.
- containers shall provide adequate protection against
foreseeable external factors in storage.

 Expiration date
- Expiration dates should be derived using any of the following:
a) the manufacturer’s expiry date of the product with the shortest expiration,
b) pharmaceutical compendia,
c) professional literature,
d) in-house stability and/or sterility studies.
 Cytotoxic Drug Preparation

 Personnel
- All pharmacy personnel involved in any aspect of Cytotoxic
agent handling shall be trained in:
- appropriate handling techniques,
- preparation,
- reconstitution,
- administration,
- disposal of Cytotoxic agents.

- All pharmacy staff shall be informed:

- health hazards of working with Cytotoxic agents,
- handling of Cytotoxic agents by pregnant, breastfeeding women or
individuals actively try to conceive should be prohibited.
- the effect of exposure to hazardous drugs on human reproduction is
not fully understood.
 Cytotoxic Drug Preparation

 Apparel
- wear protective clothing “special clean, low particulate generating
disposable garments, with a back closing, long sleeves, tight fitting cuffs
and neck”.
- remove wristwatches, and jewelry.
- wash hands and arms up to the elbows with antimicrobial skin cleanser.
- wash hands before and after the preparation session.
- wear sterile, powder free gloves and disinfect regularly with 70% isopropyl
alcohol.
- change the disposable gloves every 30-60 minutes or when contaminated
or punctured.
- wear head and facial hair coverings, covering the ears and all the hair to
minimize particulate shedding.
- wear face mask.
- wear garments prior to entering the aseptic preparation area, and remove
upon exiting the area.
Cytotoxic Drug Preparation
 Cytotoxic Drug Preparation

 Area
- dedicated solely to the preparation of sterile products.
- limited access.
- secluded from general traffic to minimize air turbulence.
- well lit.
- nonporous washable floors, walls and counters.
- untrained personnel shall not enter the aseptic
preparation area unless they are supervised .
- an eyewash station should be located within 7 meters of
the work area.
 Cytotoxic Drug Preparation

 Equipment
laminar air flow hood equipped with a HEPA filter to prevent
contamination with microorganisms and particulate matter.
- the hood should be kept running continuously.
- if turned off, it should not be used for at least 30 minutes after
being turned on, or as specified by the manufacturer.
- a qualified technician shall certify the hood at least annually.
Biological Safety Cabinets shall be cleaned and disinfected
before and after each preparation session:
- water for injection or irrigation and a small amount of cleaner,
- 70% isopropyl alcohol.
Cytotoxic Drug Preparation
Cytotoxic Drug Preparation
 Cytotoxic Drug Preparation

 Definition of Hazardous Drugs:

Carcinogenic
Teratogenic
Reproductive toxicity
Organ toxicity at low doses
Genotoxic

 By definition; a drug is deemed hazardous if it causes

harm to organs:
Liver damage was reported in the literature on three nurses
(working 6, 8 and 16 years) with chemotherapeutic agents.
Cardiotoxicity related to the use of anthracyclines.
 Cytotoxic Drug Preparation

 Cancer Risk in Workers

Leukemia in nurses (Skov et al, 1992)
Cyclophosphamide (Sessink et al, 1993)
NHL & skin cancer (Hansen & Olsen, 1994
Overall increased cancer risk (Martin, 2005)

 Reproductive Risks in Workers

Fetal abnormalities (Hemminki et al, 1985)
Spontaneous Abortions (Stucker, 1990)
Infertility (Valanis et al, 1997)
Miscarriages (Valanis et al, 1999)
Infertility, premature labor, low-birth weight, learning disabilities in offspring
(Martin, 2005)
Infertility (Fransman, 2007)

 Teratogenicity
Conflicting opinion on exposure during 2nd and 3rd trimesters.
Greatest danger during 1st trimester.
Cytotoxic Drug Preparation

Modes of Contact for Drug Exposure

to Healthcare Worker
Hazardous Drug Reconstitution
 Cytotoxic Drug Preparation
 Policies and Procedures
- Ensuring Cytotoxic ampoule heads are clear of liquid.

- Wrapping the ampoule neck with an alcohol swab before cracking.

- Dissolving powders in ampoules and vials by introducing diluents slowly

down the wall (wetting minimizes dusting) “but it’s not always possible”.

- Measuring final volumes before removing the needle from the vial.

- Wrapping the needle and vial top with an alcohol swab before withdrawing
the needle to minimize aerosol escape and removes last drop from needle
tip.
 Cytotoxic Drug Preparation

- Using syringes and IV infusion administration sets with luer-loc fittings.

- Attaching and priming IV infusion administration sets prior to adding Cytotoxic

agent.

- Needles shall not be recapped or clipped after use, but discarded directly into a
designated Cytotoxic sharps container to prevent accidental skin punctures.

- Using a negative pressure technique by injecting a small amount of air into a vial
permitting the removal of the required volume.
 Cytotoxic Drug Preparation

- All cases of exposure to Cytotoxic agents must be reported and documented.

- An incident report must be completed documenting the cause and corrective action taken.
- Detailed treatments shall be developed and available in the event of Cytotoxic exposure via skin
puncture, skin or eye contact or inhalation.

- A clearly defined, formal procedure for handling Cytotoxic agent spills must be developed.
- Clearly labeled spill kits must be kept in or near all preparation, administration and storage
areas.
- All broken containers, contaminated packaging and cleanup materials must be disposed of
appropriately in Cytotoxic waste containers.
 Cytotoxic Drug Preparation

 Vinca Alkaloid Administration

- In setting where a patient has an order for a lumbar puncture and a
combination of intrathecal and intravenous therapy, the following
procedures must be in place:

a) ensure that vinca alkaloids (vincristine, vinblastine, vindesine, etc..) are NEVER in the same
treatment area where a lumbar puncture is being performed.
b) prevent cross labeling in the pharmacy by physically separating intrathecal and intravenous
doses during all stages of preparation and labeling.
c) clear the hood of all intravenous medications prior to mixing drugs for intrathecal use.
d) prominently warn that vincristine and other vinca alkaloids are fatal if given intrathecally.
Ensure the warning label is affixed DIRECTLY to the label on the syringe barrel (i.e.
WARNING: FATAL IF GIVEN INTRATHECALLY).