11 Oncologic Drug Exposure Risks

KITJAR RUANGTHAI M.D.

Oncologic drug Exposure Risks and Prevention Guidelines

19 June 2014


สิ่งคุกคามซ่ึงอาจเป็นอันตรายต่อสุขภาพ

HAZARD?

HAZARD


Substitution

ENCLOSURE

สิ่งคุกคามซึ่งอาจเป็นอันตรายต่อสุขภาพ


ADMINISTRATION

สิ่งคุกคามซ่ึงอาจเป็นอันตรายต่อสุขภาพ


Anticipation (การคาดการณ)์ Recognition (การตระหนัก) Evaluation (การประเมิน)

Control (การควบคุม)

Ind

ustr

ial H

yg

ien

e M

an

ag

em

en

t S

yste

m

• Health Risk Assessment

Policy Organization

Planning and Implementation

• Industrial Hygiene Survey • Hazard Inventory & Tracking

• Report

BEI

Prioritize Risk

IH Management Exposure assessment

Prioritize Risk

Engineering control Administration - Training - Risk Communication - Chem Info System

Specific hazard, HCP PPE, Respirator

Medical Surveillance Evaluation

Action for Improvement

Toxicology review Health effects

KITJAR RUANGTHAI M.D. 6



Hazard of Risk factors

Understand material use to determine

“ TOXICITY ”

Understand situation of use to estimate

“ EXPOSURE ”

HAZARD = TOXICITY X EXPOSURE


Source of Standard values

OSHA

NIOSH

ACGIH

IARC

MSDS

Chemical fact Sheets

: Occupational Safety and Health Administration

: National Institute for Occupational Safety & Health

: American Conference of Governmental Industrial Hygienists

: International Agency for Research on Cancer

: Material Safety Data Sheet


Abbreviations

TLV

TLV-C

TWA

PEL

REL

BEI

STEL

AL

IDLH

: Threshold Limit Value

: Threshold Limit Value-Ceiling

: Time-Weighted Average

: Permissible Exposure Level

: Recommended Exposure Level

: Biological Exposure Index

: Short Term Exposure Limit (15 min)

: Action Level

: Immediately Dangerous to Life or Health


Characteristics That Define Hazardous Drugs

•Carcinogenicity • Teratogenicity or other developmental toxicity •Reproductive toxicity •Organ toxicity at low doses •Genotoxicity • Structure & toxicity that mimics

existing hazardous drugs

Adapted from the National Institute for Occupational Safety and Health (NIOSH), the Occupational Safety and Health Administration (OSHA), and

the American Society of Health-System Pharmacists



Antineoplastic Agents That are Classified as Known or Probable Human Carcinogens

IARC Group 1 (Human Carcinogens) IARC Group 2A (Probable Human Carcinogens)

Arsenic trioxide Azacitidine Azathioprine BCNU Chlorambucil CCNU Chlornaphazine Chlorozotocin Cyclophosphamide Cisplatin Myleran Doxorubicin HCl Melphalan N-Ethyl-N-nitrosourea Semustine Etoposide Tamoxifen Mechlorethamine HCl Thiotepa N-Methyl-nitrosourea Treosulfan Procarbazine HCl Mustargen-Oncovin-Procarbazine-Prednisone Teniposide (MOPP) Etoposide-Cisplatin-Bleomycin (ECB) Adapted from the International Agency for Research on Cancer (IARC).

The majority of antineoplastic drugs are nonselective in their action: they exhibit their effects in both cancerous and noncancerous cells in most organs and body tissues.



Antineoplastic Agents That are Classified as Pregnancy Category D* or X†16 Drug Pregnancy Category Drug Pregnancy Category Arsenic trioxide D Imatinib mesylate D Azathioprene D Interferon alfa-2b X Bleomycin D Irinotecan HCl D Capecitabine D Leflunomide X Carboplatin D Lomustine D Carmustine D Mechlorethamine HCl D Chlorambucil D Melphalan D Cisplatin D Mercaptopurine D Cladribine D Methotrexate X Cyclophosphamide D Mitoxantrone HCl D Cytarabine D Oxaliplatin D Dactinomycin D Paclitaxel D Daunorubicin HCl D Pipobroman D Docetaxel D Procarbazine D Doxorubicin HCl D Tamoxifin D Epirubicin D Temozolomide D Etoposide D Teniposide D Floxuridine D Thalidomide X Fludarabine D Thioguanine D Fluorouracil D Thiotepa D Gemcitabine D Topotecan D Hydroxyurea D Tositumomab X Ibritumomab tiuxetan D Vinblastine sulfate D Idarubicin D Vincristine sulfate D Ifosfamide D Vinorelbine tartrate D

15

Adapted from the US Food and Drug Administration Center for Drug Evaluation and Research.

D = Clear evidence of risk to the human fetus.

X = Clear evidence that medication causes abnormalities in the fetus.


Potential for Worker exposure

• Throughout its life cycle

•These workers include

• receiving personnel,

•pharmacists and pharmacy technicians,

•nursing personnel,

•physicians,

•operating room personnel,

•environmental services personnel, and

•housekeeping workers


Adapted from the National Institute for Occupational Safety and Health.

List of Hazardous Drug Handling Activities in Workers Activity Primary Group of Workers Exposed Handling drug - contaminated vials Pharmacists, pharmacy technicians Reconstituting powdered or lyophilized drugs and further diluting

either the reconstituted powder or concentrated liquid forms of hazardous drugs

Expelling air from syringes filled with hazardous drugs Compounding potent powders into custom-dosage capsules Administering antineoplastic drugs by intramuscular, subcutaneous, Nursing personnel

or intravenous (IV) routes Generating aerosols during the administration of drugs, either by

direct IV push or by IV infusion Priming the IV set with a drug-containing solution at the patient

bedside Handling body fluids or body-fluid-contaminated clothing,

dressings, linens, and other materials Handling contaminated wastes generated at any step of the

preparation or administration process Counting out individual, uncoated oral doses and tablets from Pharmacists, pharmacy technicians,

multi-dose bottles and nursing personnel Unit-dosing uncoated tablets in a unit-dose machine Crushing tablets to make oral liquid doses


List of Hazardous Drug Handling Activities in Workers

Activity Primary Group of Workers Exposed Contacting measurable concentrations of drugs present on drug Pharmacists, pharmacy technicians,

vial exteriors, work surfaces, floors, and final drug products nursing personnel, (bottles, bags, cassettes, and syringes) housekeeping personnel

Handling unused antineoplastic drugs or antineoplastic drug contaminated waste

Decontaminating and cleaning drug preparation or clinical areas Performing certain specialized procedures (such as intraoperative, Physicians, nursing personnel, and

intra-peritoneal chemotherapy) in the operating room operating room personnel Transporting infectious, chemical, or hazardous waste containers Nursing, housekeeping and waste disposal personnel Removing and disposing of personal protective equipment after Pharmacists, pharmacy technicians,

handling hazardous drugs or waste nursing & housekeeping personnel Performing repairs or maintenance on biological safety cabinets or Maintenance, biological safety

isolators used to prepare antineoplastic drugs cabinets certification personnel

Adapted from the National Institute for Occupational Safety and Health.


CONDITIONS FOR EXPOSURE •Both clinical and nonclinical workers may be

exposed to hazardous drugs when they create • aerosols, • generate dust, • clean up spills, or • touch contaminated surfaces

during the preparation, administration, or disposal of hazardous drugs. • The following list of activities may result in

exposures through inhalation, skin contact, ingestion, or injection:


Occupational exposures to hazardous drugs

can lead to -

• Acute effects: headache, dizziness, nausea,

allergic reaction (asthma & skin rashes).

•Chronic effects:

- increased genotoxic effects

- Developmental & reproductive events

- possibly cancer (leukemia)


Recent evidence summarized that

• Worker exposure to hazardous drugs is a persistent problem.

• The sampling methods used in the past have come into

question and may not be a good indicator of contamination

in the workplace.

• Surface contamination of the workplace is common and

widespread.

• A number of recent studies have documented the excretion

of several indicator drugs in the urine of healthcare workers.

• Results from studies indicate that worker exposure to

hazardous drugs in health care facilities may result in adverse

health effects.


Hierarchy of Industrial Hygiene Control

• Elimination of the hazard or substitution with a less

hazardous chemical (this is not feasible in health care)

• Engineering controls (the use of biological safety cabinets,

isolators, or closed systems)

• Administrative controls (training and education programs;

availability of material safety data sheets; established work

practices, policies, and surveillance)

• Personal protective equipment (the use of protective gloves,

gowns, respiratory protection, and eye protection)

Adapted from Soule RD. Industrial Hygiene Engineering Controls


NIOSH recommends

NIOSH is currently conducting studies to further

identify potential sources of exposure and methods

to reduce or eliminate worker exposure to these drugs.

To minimize these potentially acute (short-term) and

chronic (long-term) effects of exposure to hazardous

drugs at work, that at a minimum, employers and

health care workers to follow.


Summary of NIOSH Recommended Procedures 1. Assessment the hazards in the workplace. - Evaluate the workplace to identify & assess hazards.

- Regular review the current inventory of hazardous drugs, equipment and practices, seeking input from affected workers.

- Conduct regular training reviews with all potential exposure workers in workplaces where hazardous drugs are used.

2. Handle drugs safely. - Implement a program for safely handling hazardous drug at

work and review this program annually.

- Establish procedures & provide training.

3. Use and maintain equipment properly.


• Evaluate the workplace to identify and assess hazards. - Total working environment

- Equipment (ventilated cabinets, closed-system drug transfer devices, glovebags, needleless systems & PPE)

- Physical layout of work areas

- Types of drugs being handled

- Volume, frequency & form of drugs handled (tablets, coated/uncoated, powder versus liquid)

- Equipment maintenance

- Decontamination and cleaning

- Waste handling

- Potential exposures during work, including hazardous drugs, bloodborne

pathogens, and chemicals used to deactivate hazardous drugs or clean drug-

contaminated surfaces

- Routine operations

- Spill response

- Waste segregation, containment, and disposal

1. Assess the hazards in the workplace.


1. Assess the hazards in the workplace

•Regularly review the current inventory of hazardous

drugs, equipment, and practices, seeking input from

affected workers.

•Conduct regular training reviews with all potentially

exposed workers in workplaces where hazardous drugs

are used. Seek ongoing input from workers and use this

input from workers to provide the safest possible

equipment and conditions for minimizing exposures.


2. Handle drugs safely. • Implement a program for safely handling hazardous drugs

at work and review this program annually on the basis of

the workplace evaluation.

Establish work policies and procedures specific to the

handling of hazardous drugs. These policies and procedures

should address and define the following:

• Presence of hazardous drugs

• Labeling

• Storage

• Personnel issues (such as exposure of pregnant workers)

• Spill control

• Detailed procedures for preparing, administering &

disposing of hazardous drugs


2. Handle drugs safely.

• Establish procedures and provide training for handling

hazardous drugs safely, cleaning up spills, and using all equipment

and PPE properly. Inform workers about the location and proper

use of spill kits. In addition, establish procedures for cleaning and

decontaminating work areas and for proper waste handling and

disposal of all contaminated materials, including patient waste.

• Establish work practices related to both drug manipulation

techniques and to general hygiene practices - such as not

permitting eating or drinking in areas where drugs are handled

(the pharmacy or clinic).


3. Use and maintain equipment properly.

• Develop workplace procedures for using and

maintaining all equipment that functions to

reduce exposure - such as ventilated cabinets,

closed-system drug-transfer devices, needle-

less systems, and PPE.


•Wear PPE while reconstituting and admixing drugs:

- The gloves are labeled as chemotherapy gloves.

- Consider latex-sensitive workers and a number of glove

materials are suitable for protecting workers from

antineoplastic drugs.

- Consider using chemotherapy gloves for other hazardous

drugs or for which no information is available.

- Use double gloving for all activities involving hazardous

drugs. Make sure that the outer glove extends over the

cuff of the gown.

- Inspect gloves for physical defects before use.

- Prefer gloves with minimal or no powder.


•Wear PPE while reconstituting and admixing drugs:

- Wash hands with soap and water before donning protective

gloves and immediately after removal.

- Change gloves every 30 minutes or when torn, punctured,

or contaminated. Discard them immediately in a yellow

chemotherapy waste container.

- Use disposable gowns made of polyethylene-coated

polypropylene. Make sure gowns have closed fronts,

long sleeves, and elastic or knit closed cuffs.

- Dispose of protective gowns after each use.

- Use disposable sleeve covers to protect the wrist area

and remove the covers after the task is complete.


NIOSH Recommendations for Safe Handling of Antineoplastic and Other Hazardous Drugs

Activity Recommendations Receiving and storage of drugs - Wear PPE* suitable for task being performed - Properly label all hazardous drugs - Store and transport drugs in proper containers Preparation and administration of drugs - Evaluate drug preparation and administration policies

- Wear suitable PPE, including double gloves for task being performed - Limit access to areas where drugs are prepared - Use proper engineering controls when preparing drugs - Wash hands with soap & water before donning and after removing gloves - Prime intravenous tubing in a ventilated cabinet - Use needleless or closed systems when preparing & administering drugs - Do not disconnect tubing from an intravenous bag containing a

hazardous drug - Dispose of used materials in the appropriate container

Ventilated cabinets - Perform all preparations with hazardous drugs in a ventilated cabinet

designed to reduce worker exposure - Do not use supplemental engineering controls as a substitute for a

ventilated cabinet - When asepsis is required, select a cabinet designed for both hazardous

drugs containment and aseptic processing - Horizontal laminar-flow clean benches should not be used for

preparation of hazardous drugs - Properly maintain engineering controls as required by the manufacturer


Ventilated Cabinets

Use of cabinets

• Mix, prepare, and otherwise manipulate, count, crush,

compound powders, or pour liquid hazardous drugs

inside a ventilated cabinet designed to prevent

hazardous drugs from being released into the work

environment.

• Do not use supplemental engineering or process

controls (such as needleless systems, glove bags, and closed-

system drug transfer devices) as a substitution for ventilated

cabinets.


Selection a ventilated cabinet

• Depending on the need for aseptic processing

- When asepsis is not required, a Class I BSC or an

isolator intended for containment applications

may be sufficient.

- When aseptic technique is required, use one of

the following ventilated cabinets:

a) Class II BSC (Type B2 is preferred)

b) Class III BSC

c) Isolators intended for asepsis and containment


Types of Biological Safety Cabinets (BSC) All types have downward airflow and HEPA filters

BSC

The amount of re-circulated air

within the cabinet

Exhaust to Contaminated duct pressure

room outside negative positive

Class II

Type A 70% 30% - - P

Type B1 30% - 70% P -

Type B2 - - 100% P -

Type B3 70% - 30% P -

Class III - Totally enclosed with gas tight construction. - The entire cabinet is under negative pressure

Class I - Similar a chemical fume hood, but usually has a limited fixed work

access opening and the exhaust air must be HEPA filtered, to protect the environment.

35


Air flow and exhaust

+ -


Class I: BSC Class II: BSC

Class III: BSC


Air flow and exhaust • To confirm adequate air flow before each use.

• Use a HEPA filter for the exhaust from these controls and

exhaust 100% of the filtered air to the outside.

• Install the outside exhaust so that the exhausted air is not

pulled back into the building by HVAC systems or by the

windows, doors.

• Place fans downstream of the HEPA filter so that contaminated

ducts are maintained under negative pressure.

• Do not use a ventilated cabinet that recirculates air inside the

cabinet or exhausts air back into the room environment .

• Seek additional information about placement of the cabinet,

exhaust system, and stack design from NSF/ANSI 49–2002

[NSF/ANSI 2002].



NIOSH Recommendations for Safe Handling of Antineoplastic and Other Hazardous Drugs

Activity Recommendations Routine cleaning, decontamination, - Use suitable PPE for the task being performed housekeeping, and waste disposal - Establish periodic cleaning routines for all work surfaces and

equipment used where hazardous drugs are prepared or administered

- Consider used linen and patient waste to be contaminated with the drugs and/or their metabolites

- Separate wastes according to institutional, state, and federal guidelines and regulations

Spill control - Manage spills according to written policies and procedures

- Locate spill kits in areas where exposures may occur - Adhere to Occupational Safety & Health Administration (OSHA)

respiratory protection program - Dispose of spill material in a hazardous chemical container

Medical surveillance - Participate in medical surveillance programs at work, or see your

private health care provider if one does not exist - Medical surveillance should include the following:

• Reproductive and general health questionnaires • Complete blood count and urinalysis • Physical examination at time of employment and annual health

status questionnaire review • Follow up for workers who have shown health changes


1. Assess the hazards in the workplace.


Housekeeping • Wear protective double gloves and a disposable gown if

you must handle linens, feces, or urine from patients who

have received hazardous drugs within the last 48 hours or

in some cases, within the last 7 days.

• Dispose of the gown after each use or whenever it

becomes contaminated.

• Wear face shields if splashing is possible.

• Remove the outer gloves and the gown by turning them

inside out & placing them into the chemotherapy waste

container. Repeat the procedure for the inner gloves.

• Wash hands with soap & water after removing the gloves.


Spill Control • Established written policies and procedures.

• The size of the spill - authorized person to conduct the cleanup

& decontamination and how the cleanup is managed.

• PPE required for various spill sizes, spreading of material,

restricted access to hazardous drug spills, and signs to be

posted.

• Cleanup of a large spill is handled by workers who are trained.

• Locate spill kits & other cleanup materials in the immediate

area where exposures may occur.

• Surgical masks do not provide adequate protection.

• Dispose of all spill cleanup materials in a hazardous chemical

waste container, not in a chemotherapy waste container.


The ASHP recommends that kits include:

• chemical splash goggles,

• two pairs of gloves,

• utility gloves,

• a low-permeability gown,

• 2 sheets (12" × 12") of absorbent material,

• 250-ml and 1-liter spill control pillows,

• a "sharps" container,

• a small scoop to collect glass fragments, and

• two large HD waste-disposal bags.


Q & Answer


“ตระหนัก แต่อย่า ตระหนก”


http://www.ashp.org/doclibrary/bestpractices/prepgdlhazdrugs.aspx

47


https://www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2.html

48






http://www.cdc.gov/niosh/docs/2004-165/

Documents

11 Oncologic Drug Exposure Risks