Safe handling of cytotoxic drugs

- Preventing occupational exposures

 TOPICS
• Rules and regulations for health personnel and
work environment

• Exposure and possible health risks

• Management of use of alcohol, drugs and chemicals
• Pregnancy and breast feeding

• Personal Protective Equipment

Topics cont.

• Waste management

• Management of cytotoxic spills

• Needle accidents

• Repetative strain injuries

3 important considerations when
handling cytostatics:

• Protect the operator

• Protect the surroundings/environment

• Protect the product (sterility)

 International recomendations
”Law on Health personnel”:

•Purpose: contribute to the safety of patients and the quality of the

health care services.

• Gives all health workers an independent responsibility for the

tasks they perform.
• Obligated by law to report incidents that has influenced or
could influence patient safety
“Law on work environment” cont.

• Purpose: make sure the employees work in a safe

environment

• Employers responsibilities:

• Identify potential risk areas (risk analysis)

• Provide technical aid/equipment (safety benches)
• Provide PPE (Personal Protective Equipment)
• Provide SOPs (Standard Operating Procedures)
• Training of personnel, regular updates
• Training includes temporary help, cleaning personnel,
etc.
 “Law on work environment” cont.

• The employees responsibilities:

• Responsible for own health and safety and the health

and safety of colleagues who can be influenced by
ones work-routines
• Participate in training and retraining offered by
employer
• Follow guidelines/SOPs provided
• Use PPE provided
International recomendations
”Regulation on handling drugs in businesses providing
health care”:
•Purpose: Secure correct and good drug handling
• Includes necessary knowledge and training
•Business leader is responsible for the drug handling, and that it is
handled justifiable and according to existing laws and regulations
•Health personnel should make sure that the correct drug is given
to the correct patient, in the correct dose, at the correct time and
in the correct way
• A double control of drug and dose calculation is
recommended for drugs for injection/infusion.
• Calculation and setting infusion rate is also recommended to
have a double control
The need for guidelines and risk
management
• Cytotoxic drugs have the potential to kill or reduce the growth
of living cells.
• Increasing use, also as immunomodulating therapy
• Potentially increasing exposure for health personnel handling
the drugs and patients
• Health personnel have been signalizing worries about effects of
exposure during preparation, administration and waste
handling
• Contamination of drugs have been found in pharmacies, in
wards and toilets used by patients and in urine samples of
health personnel
Training of personnel: knowledge, skill
and attitude
• Management need to show that they are serious about health and
safety and that they follow existing laws and guidelines

• SOPs (Standard Operating Procedures) should exist for all aspects of

cytotoxic handling

• Relevant training must be given in existing procedures

• The training must secure that the employee develops the desired
attitude, and that the importance of health and safety is understood
Retraining of personnel
• Just as important as the training is regular retraining

• Theoretical and practical

• Visual control

• Making sure the employees follow existing guidelines

• Reading procedures over again – sign after reading

• Needs to be put in a system.

What must we protect us against?

• Cytotoxics
• Other cleaning chemicals
– Ethanol
• Antibiotics
• Injuries from overuse (repetetive strain injury).

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Health effects
• Cytotoxic drugs do not distinguish between normal and cancerous
cells

• Targets rapidly growing cells;

• Bone marrow cells
• Hair follicles
• Mucous cells
• Genital cells

• All well known and acceptable risks in the treatment of cancer

patients

• Unacceptable risk for health personnel dealing with these drugs every
day
Ways of exposure
Inhalation of gases, aerosols and particles
•During preparation:
• opening ampoules
• Spills from syringes and needles
•Broken vials of freeze-dried cytotoxic drugs
•Evaporation at room temperature

Absorption
•direct contact with skin, eyes, mucous membranes
•contamination on hands
•not wearing PPE
•spills
•touching contaminated surfaces
•removing PPE the wrong way
Ways of exposure cont.

Oral intake
• Direct contact between contaminated hands and food,
drinks, tobacco, chewing gum, make up
• Body fluids from patients
• PS! Wash hands thoroughly after handling and before eating
Injection
• Skin punctures from contaminated needles
• During preparation
For how long does a cytotoxic drug
remain in the body?
• Theoretically 87,5 % of the cytotoxic drug is excreted after 3 times
the drugs half life (t ½ = the period of time required for the
concentration or amount of drug in the body to be reduced by one-
half)

• Excretion time depends on:

• Dose
• Administration time
• Multiple infusions, multiple drugs
• Kidney and liver function

• General rule: 72 hours after administration

Effects of exposure
• Acute effects
• Well documented
• Typically large spill situations or preparing cytotoxic drugs in
unventilated areas; nausea, headache, dizziness

• Long term effects

• Source of worry
• Coherence between the handling of cytotoxic drugs and
fertility impairment, spontaneous abortions, low birth
weights, fetal loss and fetal abnormalities
• Cancer; some report an increasing risk of leukemia for
health workers
Dealing with Pregnancies
• If the work environment provides ”zero exposure” there should be no
higher risk for pregnant women handling cytotoxic drugs

• HOWEVER; in a normal work situation spills will occur and that is an

unacceptable risk.

• Women who are pregnant or are planning to be pregnant should be

protected against cytotoxics and take necessary precautions

• It is safe for breast feeding mothers and men that are planning
children to work with cytotoxics- according to normal procedures
Dealing with pregnancies cont.
• Pregnant women should pay extra attention when:
• Prepare cytotoxic drugs
• Administrate cytotoxic drugs
• Handle cytotoxic waste, spills or body fluids
• Draw blood or perform any other invasive procedures on
patients receiving cytotoxic drugs

• Pregnant women can:

• Work in ward where cytotoxic drugs are administered
• Work in pharmacy as normal
• Participate in patient care that does include contact with
cytotoxic drugs, i.v. sets or body fluids from patients.
• Women who are nursing/breastfeeding can handle cytotoxic
drugs as long as PPE is used and guidelines are followed
Effects of exposure
• Exposure occurs during
- preparation
- transport
- administration
- waste handling
- handling body fluids from patients
- spill handling

• Probability of negative effects increase with:

- The amount of handling and frequency of exposure
- Bad routines or lack of routines
Alcohols
• Drinking:
– Most healthy individuals tolerate a little ethanol
• Fire hazard:
• Do not store more than necessary in each room
• Large quantities should be stored in a fire
cupboard

• Toxic effects of isopropanol = 2 x Ethanol, both in

amount and length of exposure

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 What about antibiotics?
• Attack micro organisms by stopping growth or
killing them
• Micro organisms distinguish themselves from
human cells in different ways, but some
antibiotics can be toxic and can give allergic
reactions to different people (penicillin)
• Antibiotics can harm both the inner and outer
environment

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Cytotoxic and antibiotic exposure

• Using proper aseptic working technique, the

probability of harmful exposure of cytostatics
and antibiotics are small
• Proper working technique minimizes free
aerosols and droplets during production and
in addition the bench and the room design
provides protection of staff
• Accidents like liquid spills, broken vials and
needle stick injuries can still happen
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Personal Protective Equipment (PPE)
• “Clothes and equipment designed to
protect the carrier and reduce or
eliminate risk of damage or illness”

• Clothes, plastic apron, plastic sleeves.

• Gloves; always wear gloves handling

cytotoxic drugs
• Double pair of gloves in preparation
and spill handling

• Eye- and respiratory protection; goggles,

mask P2

• Removing PPE must not cause further

contamination
Extra equipment for protection during
production of antibiotics and cytotoxics

• 2 sets of gloves, inner glove should be made

of nitrile
• Cytotoxic production  safety bench situated
in a clean room.
• Bench coat
• Swabs

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 Hazardous waste and waste disposal
• ”Waste that can cause or contribute to an increased mortality or serious
disease, or is a potential risk for humans or environment if handled,
stored, transported or destroyed the wrong way”

• Should be handled separately from other waste and according to specific

procedures

• Risk waste containers must be available where cytotoxic drugs are

prepared and administered

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Risk waste in handling cytotoxic
drugs

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 Risk waste in handling cytotoxic drugs
• Equipment used in preparation (syringes, needles, swabs, vials, bench
coat ect.)
• Infusion sets and empty bags from given infusions
• Expired vials/ infusion bags of cytotoxic drugs
• Unused infusion bags returned from ward
• Any used service material (HEPA-filters)
• PPE and cleaning cloths used in cleaning safety benches and production
facilities
• Outer packaging from vials of cytotoxic drugs

• Leaking infusion bags  leak-proof containers (bucket with lid) 

handled as risk waste
• Broken glass and used needles  hard plastic boxes eliminating the risk of
cuts with contaminated material  handled as risk waste
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Management of spills

• Cleaned up immediately by trained personnel

• Spills on skin, eyes or clothes or skin punctures should have top priority
• All waste generated in cleaning spills is to be handled as risk waste
Spill kits

• Should contain all of the materials needed to clean up spills

• Should be available in all areas where cytotoxic drugs are handled;
hospital ward, pharmacy
• Every employee should know where the nearest spill kit is kept, and
should be trained in how to use it
• Can be purchased pre-made
• Can easily be assembled/made by pharmacy
Spill kit Inventory
• Guideline on how to use the kit
• Plastic bags
• Risk waste bags
• Face masks, P2
• Goggles
• Plastic apron or other protective clothing
• Shoe covers
• Gloves, minimum 4 pairs (preferably nitrile gloves)
• Absorbent material, swabs, sanity pads/diapers/absorbent bed
sheet
• Demonstration - www.oncolex.com
• Disposable caps
• Arm protectors
• Warning signs
• Soap, preferable liquid soap
Handling spills – general principles
• Ask for help if necessary!!!
• Identify the spill area.
• Fluids should be covered with dry swabs or absorbent material
(diaper).
• Dry spills should be covered with moist swabs before covered with
absorbent material
• No fluids should be left before cleaning
• Clean with soap and water
• Start in the cleanest areas and work your way to the centre of the spill
• Do NOT return cloths to wash solution/bucket – change cloth
• Throw away used cloths in a plastic bag
• Replace used spill kit immediately
 Principles – spillage management
• Protect yourself using the right clothing
– Spill kit must always be available
• Be calm
– You manage spillage better when you can think clearly
– Sudden movements can stir up particles
• Soap (not alcohol) can dissolve cytotoxics and
remove the spillage from surfaces.
• Never spray soap directly on a spillage because this
can cause aerosols

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 Principles – spillage management
• Powders must carefully be wetted with soap before
being dried up
– Powders are easier to swirl up than drops, liquid
– Soap works better than just water
• Soak up as much liquid as possible before washing
with soap
• Wash in the direction of least spillage to most
• Wash a bigger area than the original spillage
• Treat all cloths and equipment as hazardous waste
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Small spills
• Drops and liquid less than 5 ml
• Production surfaces or bags
• Spillage on the bench coat alone, roll up the coat carefully
and dispose it.
• Use sterile swabs to soak up all visible liquid
• Use soap cloths or soap saturated swabs to wash the
surface or the infusion bag.
– Change the cloths often
• Change gloves

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Large spills
• Powder spillage or liquids greater than 5 ml
• Large spills are managed by the minimum of
people all other people should leave the room
– Get help if you are alone
– Get help with the spill kit and get up a warning
sign.

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Management of large spills
• Liquid must be covered carefully with an absorbent sheet
• Powders must be covered with a soap moisted absorbent
sheets
– Place new absorbent sheets on top until the top layer is
dry
– Repeat until all visible spill is removed
• Pick up any glass pieces with a tweezers
• Some cytotoxics can be deactivated with special solutions
• Wash ultimately from the periphery to the centre, from top
to bottom

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Large spills- management
• Take off gloves and other protective clothing
carefully turning them inside out, wash hands
and put on new gloves
• Fold up work clothes and put them in a plastic
bag and send them to be washed.
• If the clothes are really soiled throw them
away as hazardous waste
• Wash hands again

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Spills on skin, eyes and clothes
• In most cases spills on unharmed skin and clothes
presents little risk
• Employees with open sores on hands or face should
not work in clean rooms. All sores should be covered
with a plaster
• Some cytotoxics irritate the skin more than others
and can give skin reactions.
• Cytotoxics can irritate the eyes
• Spillage in the eyes could give an exposure risk for
the throat (through the tear canal)
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 Inactivation
Drug Management
Amsakrin Aceton + sodium hypochlorite solution 3-5%
Wash with soap and water.
Cisplatin Rinse with lots of water. Some people are
allergic to platina so a skin reaction can occur

Etoposid and Etoposid Exposure to etopisid can give skin reactions.

phosphate Wash well with soap and water.
Metotrexat Wash with water. Use a hand cream
afterwards.
Mitomycin Very skin irritating. Rinse with large amounts of
water followed by soap and water. Do not use
hand cream

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 Spills in the eyes
• Following rules applied to spillage of cytotoxics, other drugs
 soap and alcohol
• Rinse the eyes immediately including the lower and upper
eyelid with large amounts of water.
– Isotonic NaCl stings less, but tap or bottled water can be
used
• Keep rinsing for at least 15 minutes
• Contact the doctor when:
– Spillage of particularly tissue irritating or tissue toxic
substances.
– Suspected damage or irritation
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 Spills on bare skin
• Rinse quickly with large amounts of tap water
or with bottled water for at least 15 mins.
• Wash the area thoroughly with soap and
water
– Amsakrin: Use inactivation solution first
• Contact the doctor with persistent discomfort
or allergic reactions

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 Spills on clothes
• Focus: minimise risk for skin contact
• Ordinary clothes (cotton etc)
– Try to take the clothes off before the liquid soaks through
the surface
– Cut off clothes if necessary
– Never take them off over your head
• Plastic apron/ disposable coat
– Soak up the liquid with a compress
– Cut off the apron and fold it up with the soiled side inside
• Arm protectors pulled straight off with out turning them inside
out.
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 Skin puncture –Needle/ sharp
accidents
• Some cytotoxics are more damaging than others
• Non tissue toxic or tissue irritating
– Normally no skin necrosis
• Tissue irritating
– Can give pain and inflammation in and around the injured
area
– Normally no permanent damage
• Tissue toxic
– Can give necrosis inn and around the damaged area
– Wrong treatment can give permanent damage

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 Skin puncture accidents
• Take off gloves turning them inside out, go to
the sink and press out blood from the
puncture site.
• Ask for help for further treatment
• Check if the drug is tissue toxic or irritating

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Tissue toxic, danger for
Tissue irritating Non tissue toxic or irritating
necrosis
Amsakrin Cisplatin Ifosfamid
Dakarbazin Doksorubicin liposomalt Asparaginase
Daktinomycin Estramustin Bleomycin
Docetaxel Etoposid Bortezomib
Bevacizumab, Cetuximab,
Doksorubicin, Epirubicin,
Floksuridin Rituximab , Trastuzumab,
Daunorubicin, Idarubicin
Alemtuzumab
Irinotekan Florouracil Cyklofosfamid
Mitoguazon Irinotekan Cytarabin
Mitomycin-C Karboplatin Fludarabin
Mitoxantron Karmustin Gemcitabin
Paklitaxel Oxaliplatin Melfalan
Streptozocin Pemetrexed, Ralitrexed Metotrexat
Vinblastin, Vindesin,
Teniposid Tiotepa
Vinkristin, Vinorelbin
Topotekan
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 Skin punctures
• Non tissue toxic/irritating drug
– Cover the puncture with plaster when it has
stopped bleeding

• If an ampoule breaks when being opened

some glass can puncture and be found under
the skin
– Contact doctor if you can’t or are unsure if you
have removed all the glass splinters-
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 Skin punctures
• Tissue irritating and tissue toxic drugs
– Keep pressing blood out of the puncture hole and
rinse with NaCl or water
– If the wound does not bleed it could be necessary
to make a small cut so the puncture hole can
bleed and wash out the cytotoxic
– Contact doctor
– Cover the puncture hole with a salt water
compress until a doctor is available

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 Reporting

• Large spills of cytotoxics or dangerous

chemicals are immediately reported as a
deviation to the person responsible for health
and safety, department head and the chief
pharmacist.
• Deviation form is filled out and sent to the
appropriate people including the Quality
Director.

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 Static work
• When you are taking part in a lot of static work it is
important to
• Warm up your muscles before the work shift starts
• Perform relaxing exercises during your shift
• Stretch out after your shift
• Warming up and stretching helps to prevent strain
injuries
• Training and physical activity outside of work helps
also to prevent strain injuries

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Exercises – Warm up
1: Gently roll shoulders 5
times forwards and 5
times backwards
2: Draw shoulder blades
together 5 times
3: Lift shoulders gently
upwards 5 times
4: Shake loose shoulders
and arms

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Exercises during production
1: Gently roll shoulders 5
times forwards and 5
times backwards
2: Stretch back for a min.
10 seconds
3: Stretch body

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Stretching
1: Stretch back for a
minimum 10 seconds
2: Stretch each underarm
for a minimum 10-15
seconds
3: Stretch muscles on each
side of neck for
minimum 15 seconds
4: Shake loose shoulders
and arms
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 Working, sitting position/posture
• Feet should rest on the footrest or floor
• When possible use elbow / underarm support
Minimises static muscle work
• Push the chair well into the working
surface/bench
• Regulate the chair
– Seat depth, seat angle, seat height, back support

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FINGER- OG HAND EXERCISES

Open and close

Rotate the wrist by
your fist
turning the hand up
and spread
and down.
all your fingers
Repeat
Repeat
15 x 3
15 x 3

Press thumb and Bend the wrist up

each finger and down slowly as
together. far as possible.
Spread all Repeat
fingers after each 15 x 3
thumb press.

Bedriftsfysioterapeut Live Bjørntvedt

 References
• http://www.ntnu.no/hms/ergoilab/forside/
• www.oncolex.no
• Sokrates QM for Sykehusapotekene
• Giftinformasjonen
• Cytostatikahåndboken
• NIOSH -National Institute for Occupational Safety and Health.
– Preventing Occupational Exposures to Antineoplastic and Other
Hazardous Drugs in Health Care Settings.
• OSHA Technical Manual - Occupational Safety and Health Administration
(section VI: Chapter 2):
– Controlling Occupational Exposure to Hazardous Drugs
• ASHP - American Society of Hospital Pharmacists
– Guidelines on Handling Hazardous Drugs

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