Lee Sing Chet Oncology Pharmacist Taiping Hospital

What is Cytotoxic Drugs (CDs)? Antineoplastic, anticancer or cancer chemotherapy drugs Ability to kill or arrest the growth of living cells

(both cancer cells and normal cells)

Hazardous drugs

Hazardous Drugs
A drugs is considered hazardous if it exhibits 1 or more of the following 5 characteristics in humans or animals: 1. 2. 3. 4. 5. Carcinogenicity Teratogenicity or other developmental toxicity Reproductive toxicity Organ toxicity at low doses Genotoxicity

ASHP

ASHP = American Society of Health-System Pharmacists

List of Cytotoxic Drugs Available in HTPG

Injection Forms
Bleomycin HCl 15mg/vial Carboplatin 150mg/15ml,
450mg/45ml

Fluorouracil (5-FU)
250mg/5ml, 1g/20ml

Cisplatin 10mg/ml, 50mg/50ml Cyclophosphamide 200mg/vial,

1g/vial

Docetaxel 20mg/vial, 80mg/vial

Doxorubicin 10mg/5ml Epirubicin 10mg/5ml, 50mg/25ml Etoposide 100mg/5ml

Gemcitabine 200mg/vial, 1g/vial Ifosfamide 1g/vial Methotrexate 50mg/2ml Mitomycin-C 10mg/vial Paclitaxel 30mg/5ml,
100mg/17ml, 250mg/41.7ml

Vincristine 1mg/1ml Oxaliplatin 50mg/25ml

Non-Cytotoxic Drugs
Injection Filgrastim (Neupogen) 300mcg/1ml

(30IU/1ml)
Injection Folinic Acid (Leucovorin) 50mg/5ml
Injection Granisetron (Kytril) 3mg/3ml Injection Ondansetron (Zofran) 8mg/4ml

Injection Pamidronate 30mg/vial

Injection Zoledronic acid 4mg/ml

Potential Hazard From Cytotoxic Drugs

Since 1970s, a growing concern on the safety aspect of handling cytotoxic drugs Acute Effects - Severe soft tissue injury - Dizziness, light-headedness, nausea - Eye irritaion

 Chronic Effects - Little is known of the long-term effects of exposure to small quantities of cytotoxic drugs over an extended period of time - No exposure limits set for CDs - Carcinogenic - Teratogenicity

- Reproductive toxicity
- Genotoxicity
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Pregnant

Breast Feeding

Planning Parenthood

- should be made aware of the potential risks

- where possible, be offered alternative duties

Evidence For Health Effects

Developmental & Reproductive Effects A review of 14 studies : - exposure to antineoplastic drugs & adverse reproductive effects association [Harrison 2001] - major reproductive effects : fetal loss [Selevan et al. 1985; Stcker et al. 1990] : congenital malformations depending on the length of exposure [Hemminki et al. 1985] : low birth weight and congenital abnormalities
[Peelen et al. 1999]

: infertility [Valanis et al. 1999]

Evidence For Health Effects

Cancer A significantly risk of leukemia among oncology nurses - in the Danish cancer registry 1943-1987 [Skov et al. 1992] A significantly risk of leukemia - among physicians employed for at least 6 months in a department where patients were treated with antineoplastic drugs [Skov et al. 1990] Estimated cyclophosphamide causes an additional 1.4-10 cases of cancer per million workers each year.
[Sessink et al. 1995]

Who is at risk? Everyone involved in handling CDs Manufacturers and shipping personnel Pharmacists and pharmacy assistants Doctors, medical assistants and nurses Hospital attendants Housekeeping Family members and caregivers
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Exposure Routes Inhalation of aerosols, particulates and droplets Dermal contact/absorption

Unintentional ingestion from

hand to mouth contact Unintentional injection through a needlestick injury

needlestick
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Will These Conditions Increase Risk of Exposure?

Reconstituting powdered CDs and further diluting either the reconstituted powder or concentrated liquid forms of CDs Crushing tablets to make oral liquid doses
During the administration of drugs, either by direct IV push or by IV infusion Touch the outer vial of un-opened cytotoxic drugs

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Will These Conditions Increase Risk of Exposure? Handling patients body fluids, clothing, dressings, linens, and other materials
Handling used IV line & branula Expelling air from syringe filled with hazardous drugs Removing and disposing of personal protective equipment (PPE) after administration of chemotherapy Sharing the toilet with chemotherapy patients

Guidelines
1990, ASHP (American Society of Health-System Pharmacists) : technical assistance bulletin (TAB) : handling cytotoxic and hazardous drugs in 1990

1995, OSHA (Occupational Safety and Health Administration)

: new guideline : occupational exposure to hazardous drugs

Guidelines 2004, NIOSH (National Institute

Of Occupational Safety & Health)

: NIOSH Alert
: recommendations for the safe handling of hazardous drugs

Safety procedure at work

Preparation & dispensing

Administration Storage & transport Spill management Waste management

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Preparation & Dispensing Facilities Cytotoxic cleanroom - High Efficiency Particulate Air (HEPA) filters - Ventilated biological safety cabinet (BSC)

or isolator
- On-time maintenance Restricted access & warning signs - Anteroom and pass-through hatches
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Biological Safety Cabinet (BSC)

Isolator

Biological Safety Cabinet (BSC) Type II

A. front opening B. sash C. exhaust HEPA filter D. supply HEPA filter E. negative pressure exhaust plenum F. blower
Carbon Filters

Personnel Trained and validated personnel Personnel Protective Equipment (PPE) Not to be worn outside preparation area

Stringent aseptic technique

- in conjunction with negative pressure technique

Syringe should not be more than

three-fourths full when filled with the solution

Personnel Protective Equipment (PPE) Gloves Double layer (chemo glove, powder free)

Change every 30 min and if theres a spill

Coverall or gown Chemo gown (disposable) Respiratory protective device NOT surgical mask NIOSH certified N95 or more protective respirator
Face mask
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Chemo gloves

N95 mask

Eye and face protection Should be used whenever there is a possibility of exposure from splashing Face shield is preferred over safety

glasses/goggles
Others Hair cover, eg bouffant cap or tudung cap Boot cover or shoe cover

Face shield

Safety goggles

Shoe cover

Boot cover

Bouffant cap
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Other specific methods of control

Luer-lock syringe To ensure better connection of syringe and needle

Chemo Spike 0.2 micron air venting filter To capture aerosolization

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Special Device (closed system drug-transfer device, CSTD)

"A device that mechanically prohibits the transfer of environmental contaminants into the system and the escape of hazardous drug or vapor concentrations outside the system.

......NIOSH

NIOSH = National Institute Of Occupational Safety & Health

Special Device
Protect : the operator during preparation
: the administrator during drug administration Eg. PhaSeal, CLAVE connector, TEVADAPTOR MOH recommended : use of PhaSeal system : until hospital is equipped with clean room and BSC

BSC = biological safety cabinet

CLAVE connector

Special Device
MOH Health Technology Assessment Report
: PhaSeal system - safe and effective in reducing contamination

: Training of personnel
- to ensure the correct technique : Drawback - expensive

Preparation & Dispensing

Drug packaging & transport

Tip of the syringes should be capped - with combi-stopper - not with needles in place - to prevent puncturing the leak-proof and sealed bag
Properly labelled

Sealed, leak-proof plastic bag

In a robust, hard-walled and securely closed container

Preparation & Dispensing

Drug packaging & transport Protected from light (not all but most)

Visually examine before removing it from the plastic bag/container

The transport container - dedicated for cytotoxic drugs only - clearly labelled For Cytotoxic Drugs Only Drug collection by well trained personnel only

Storage of CDs
Dedicated storage area, separate from other drugs, including fridge Clearly labelled area with warning signs

Storage must be designed in a manner that will prevent

containers of CDs from falling Storage conditions must be proper, - eg. 5-fluorouracil and etoposide may precipitate if refrigerated
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Oral Cytotoxic Drugs

Oral agents : <5% of all anticancer drugs - expected to represent up to 25% in the next decade [Pratt S. 2002] Nearly of 200 anticancer drugs in

development are oral agents [Griffin E. 2003]

Oral Cytotoxic Drugs

Anastrozole 1mg Bicalutamide 50mg Capecitabine 500mg Clodronate 800mg Cyclophosphamide 50mg Cyproterone 50mg Hydroxyurea 500mg Letrozole 2.5mg Methotrexate 2.5mg Tamoxifen 20mg

Thioguanine 40mg

Administration of Oral CDs

Wear gloves Non-touch technique : tablets/capsules are tipped from their container or envelope directly into a disposable medication cup Separate counting tray to be used Not recommended to cut/crush tablets

After administration, discard glove as cytotoxic waste

and wash your hands
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References
ISOPP Standards of Practice J Onco Pharm Practice (2007) Supplement to 13: 1-81

NIOSH Alert (CDC) : Preventing occupational exposures to antineoplastics & other hazardous drugs in health care settings 2004
Guide 2008: Cytotoxic drugs and related waste, Workcover New South Wales, Australia ASHP (US) Guidelines on Handling Hazardous Drugs, Am J Health-Syst Pharm. 2006; 63:1172-93 OSHA (US) Technical Manual Section VI: Chapter 2 Controlling Occupational Exposure To Hazardous Drugs Health and Safety Executive(HSE): Safe Handling of Cytotoxic Drugs, UK Occupational Health and Safety Division, Canada : Cytotoxic Drugs, 1999 PhaSeal System For Chemopreparation, Health Technology Assessment Report. 2008. Medical Development Division, MOH Malaysia.
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Thank you!

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