02 safe handling of cytotoxic drugs

8/4/2019 02 Safe Handling of Cytotoxic Drugs

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Lee Sing Chet

Oncology PharmacistTaiping Hospital


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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

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A drugs is considered hazardous if it exhibits 1 or more ofthe following 5 characteristics in humans or animals:

1. Carcinogenicity2. Teratogenicity or other developmental toxicity3. Reproductive toxicity4. Organ toxicity at low doses

5. GenotoxicityASHP

ASHP = American Society of Health-System Pharmacists

Hazardous Drugs


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List of Cytotoxic Drugs Available in HTPG

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

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

Injection Forms

Bleomycin HCl 15mg/vial

Carboplatin 150mg/15ml,450mg/45ml

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


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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


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Potential Hazard From Cytotoxic Drugs

Since 1970s, a growing concern on the safety aspect ofhandling cytotoxic drugs

Acute Effects

- Severe soft tissue injury

- Dizziness, light-headedness, nausea

- Eye irritaion


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Chronic Effects

- Little is known of the long-term effects of exposureto small quantities of cytotoxic drugs over anextended period of time

- No exposure limits set for CDs

- Carcinogenic

- Teratogenicity

- Reproductive toxicity

- Genotoxicity

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- should be made aware of the potential risks

- where possible, be offered alternative duties

Pregnant Breast Feeding Planning Parenthood


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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 thelength of exposure [Hemminki et al. 1985]

: low birth weight and congenital abnormalities[Peelen et al. 1999]

: infertility [Valanis et al. 1999]


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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 patientswere treated with antineoplastic drugs [Skov et al. 1990]

Estimated cyclophosphamide causes an additional1.4-10 cases of cancer per million workers each year.[Sessink et al. 1995]


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Who is at risk?

Manufacturers and shipping personnel

Pharmacists and pharmacy assistants

Doctors, medical assistants and nurses

Hospital attendants

Housekeeping

Family members and caregivers11

Everyone involved in handling CDs


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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

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needlestick


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Reconstitutingpowdered CDs and further dilutingeither the reconstituted powder or concentratedliquid forms of CDs

Crushing tablets to make oral liquid doses

During the administration of drugs, either by directIV push or by IV infusion

Touch the outer vial of un-opened cytotoxic drugs

Will These Conditions Increase Risk of Exposure?

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Handlingpatientsbody 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

Will These Conditions Increase Risk of Exposure?


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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


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Guidelines

2004, NIOSH (National Institute

Of Occupational Safety & Health)

: NIOSH Alert: recommendations for the

safe handling of hazardous

drugs


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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


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A. front opening

B. sash

C. exhaust HEPA filter

D. supply HEPA filter

E. negative pressureexhaust plenum

F. blower

Biological Safety Cabinet (BSC) Type II

Carbon Filters


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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


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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

N95 mask

Chemo gloves

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Others

Hair cover, eg bouffant cap or tudung cap

Boot cover or shoe cover

Eye and face protection

Should be used whenever there is a possibility

of exposure from splashing

Face shield is preferred over safety

glasses/goggles

Shoe cover Boot cover Bouffant cap

Safety goggles

Face shield

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Other specific methods of control

Luer-lock syringe Chemo Spike0.2 micron air venting filter

To ensure betterconnection of syringe

and needleTo capture aerosolization

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Special Device

"A device that mechanically prohibits the transfer ofenvironmental contaminants into the system and the

escape of hazardous drug or vapor concentrationsoutside the system.

......NIOSH

(closed system drug-transfer device, CSTD)

NIOSH = National Institute Of Occupational Safety & Health


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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


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CLAVE connector


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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


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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


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Drug packaging & transport

Protected from light (not all but most)

Visually examine before removing it from theplastic bag/container

The transport container

- dedicated for cytotoxic drugs only- clearly labelled For Cytotoxic Drugs Only

Drug collection by well trained personnel only


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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 :


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Hydroxyurea 500mg

Letrozole 2.5mg

Methotrexate 2.5mg

Tamoxifen 20mg

Thioguanine 40mg

Oral Cytotoxic Drugs

Anastrozole 1mg

Bicalutamide 50mg

Capecitabine 500mg

Clodronate 800mg

Cyclophosphamide 50mg

Cyproterone 50mg


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Administration of Oral CDs

Wear gloves

Non-touch technique

: tablets/capsules are tipped from their container orenvelope 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) Supplementto 13: 1-81

NIOSH Alert (CDC) : Preventing occupational exposures toantineoplastics & other hazardous drugs in health care settings 2004

Guide 2008: Cytotoxic drugs and related waste, Workcover New SouthWales, Australia

ASHP (US) Guidelines on Handling Hazardous Drugs, Am J Health-SystPharm. 2006; 63:1172-93

OSHA (US) Technical Manual Section VI: Chapter 2 Controlling

Occupational Exposure To Hazardous DrugsHealth 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 AssessmentReport. 2008. Medical Development Division, MOH Malaysia.


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Thank you!

02 safe handling of cytotoxic drugs

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