3.

1 Safe Handling, Administration

and Disposal of Chemotherapy
Agents
Introduction
There have been increasing numbers of reports in the literature describing the possible
effects of chemotherapy drugs on health care professionals (Fuchs et al., 1997; Grummt
et al., 1993; Selevan et al., 1985; Valanis et al., 1997). It has therefore become
imperative that staff is knowledgeable regarding the safe handling of
chemotherapy drugs. The risk to health care professionals from handling a hazardous
drug stems from its inherent toxicity and the extent to which workers are exposed to the
drug. The primary routes of exposure are through direct skin contact and through
inhalation of aerosolized drug products. Other potential exposure occurs during the
disposal of the drugs, disposal of the items used in drug preparation and administration,
and when caring for patients who have received these drugs.
Although the absolute risk cannot be eliminated, much can be done to reduce the
relative risks associated with the handling of chemotherapy agents (Mayer, 1992).
Health care professionals who handle chemotherapy are advised to be well informed of
the potential health hazards, be familiar with safe handling and disposal of these
agents, utilize appropriate protective equipment and adhere to available written policies,
procedures and guidelines.

The information related to health risks to fetuses due to the handling of chemotherapy
agents during pregnancy is limited. The risks involved can be reduced significantly if
one adheres to standard safety precautions while handling chemotherapy agents. This
risk of exposure can be minimized by personal protective equipment (PPE), a needle-
less system, and ventilation cabinets. Please refer to your institution’s policy on
Pregnancy and exposure to chemotherapy agents.

This evidence based document is intended to facilitate the standardization of

institutional practice guidelines for the safe handling of chemotherapy agents across the
Province of Ontario. Following these guidelines will assist in minimizing unnecessary
exposure and maximizing safety. These recommendations do not differentiate between
high- and low-risk situations, as there is no known minimum safe exposure and always
the potential for contamination.

Receiving of Chemotherapy Agents
Handling procedures need to begin with safely receiving these products into the
hospital.
 Institutional policies for accidental exposures must be in place.
 Please refer to the Occupational Safety and Health Administration (OSHA) and the
American Society of Hospital Pharmacists (ASHP) guidelines.
  As there is a risk of broken vials, individuals receiving packaged cytotoxic agents should
be protected to the same degree recommended for those preparing and administering
chemotherapy.
 Chemotherapy spill kits should be available in the Institutional Receiving Department
and departments where chemotherapy is being prepared, dispensed and administered.
 In the event of a spill or untoward exposure, notify appropriate authorities, e.g.
Occupational Health & Safety, Environmental Services, as per institutional policies.
Education
All pediatric oncology nursing orientation programs should include a review of hospital
policy, procedures and guidelines for administrating oral chemotherapy, for monitoring
chemotherapy infusions, caring for patients receiving chemotherapy and the risk of
occupational exposure.
 Parenteral chemotherapy should only be administered by health care professionals who
have been specially trained in parenteral chemotherapy administration.
 Standardized courses and curricula for chemotherapy administration should be developed
at each tertiary institution. If satellite centres do not have a pediatric oncology orientation
program, satellite nurses are to be trained and tested in chemotherapy administration at a
tertiary centre.
Preparation of Chemotherapy Agents
It is recommended that all pharmacies follow the OSHA guidelines when preparing and
dispensing of chemotherapy. All Cytotoxic drugs and containers should have an appropriate
label to alert handler of special precautions needed for handling.
As a reference, click here to link to CCO guidelines for Safe Handling.
Unpacking and Storage
Packaging can have high levels of contamination; therefore it is strongly recommended
that:
 there be an unpacking area in the pharmacy limiting exposure risks
 the unpacking area be a separate dedicated space, separate from eating areas
 there be a receptacle for cytotoxic waste in the unpacking area
 workers at risk of exposure wear a protective gown and two (2) pairs of gloves when
unpacking and cleaning cytotoxic drugs, from the opening of the external packaging to
the placing of the secondary and/or primary packaging in their storage space.
 workers check the integrity of all packaging at every step of the unpacking process
 damaged contents be treated as a spill
 the primary and or secondary packaging be cleaned prior to being placed in storage
 a regular cleaning protocol be in place
 all drug containers be cleaned to reduce external contamination; ensure that this does not
interfere with the integrity of the container or with reading of the label.
  procedures be in place to minimize the risk of contamination of surfaces during the
cleaning of vials (e.g. use of a disposable, plastic-backed, absorbent pad)
 all surfaces be cleaned when the task is complete
 when removing or transporting drugs out of the storage area, one pair of gloves and a
gown be worn.
It is regulated that there be adequate ventilation in the area, negative pressure and
preferably vented to the outside.  Establish a dedicated negative-pressure storage area
for cytotoxic drugs that minimizes the risk of contamination.

Cytotoxic Drug Preparation

It is strongly recommended that:
 the oncology pharmacy be in compliance with relevant guidelines from the Canadian
Society of Hospital Pharmacists (CSHP) and Accreditation Canada standards. While the
specific details of oncology pharmacy planning is beyond the scope of this document,
details and some important considerations may be found in the Canadian Standard
Association document CSA Z8000-11 (19)
 special requirements for heating, ventilation and air-conditioning (HVAC) systems in
health care facilities be taken into consideration
 all mixing, and preparation of administration sets with a cytotoxic drug be performed in
one centralized area in a specially designated class II type B biological safety cabinet that
(18):
(a) is exhausted through a HEPA filter to the outside atmosphere in a manner that
prevents recirculation into any inside area

(b) has exhaust and ventilation systems that remain in operation for a sufficient period
of time to ensure that no contaminants escape from the biological safety cabinet into the
workplace

(c) is equipped with a continuous monitoring device to permit confirmation of adequate

airflow and cabinet performance.

 airlocks be considered if there are particular concerns about the propagation of airborne
cytotoxic drugs.
 the layout facilitate the unimpeded cleaning of all surfaces (walls, floors, ceilings, doors,
diffusers, windows)
 the furniture and equipment in the sterile preparation room be kept to a bare minimum
 there be a visual link (e.g. a window as a way to communicate between the sterile
preparation room and the pharmacy, in order to view the work in progress)
 access to the sterile room be limited to trained and authorized workers.
  the biological safety cabinets remain in operation 24 hours a day, 7 days a week, as
recommended by the manufacturers.
It is legislated that the facilities include an emergency eyewash that may or may not be
hooked up to the airlock sink. As a minimum, that emergency eyewash should be able
to provide 15 minutes of flushing to both eyes. It is strongly recommended that a full
shower be accessible nearby.

Closed-drug transfer systems (e.g., PhaSeal®) are not a substitute for class II type B
biological safety cabinets.

In the non-sterile drug preparation process (e.g., oral preparations), it is strongly

recommended that the same level of worker protection be adhered to.

Establish policies and procedures regarding preventive maintenance, monitoring,

certification and the optimal use of facilities and equipment.

Drug Preparation
The following recommendations apply to the preparation of all cytotoxic medications
including parenteral, oral and topical, both sterile and non-sterile preparations. It is
strongly recommended that:
 policies and procedures include the use of appropriate PPE, the equipment for preparation
including appropriate ventilation, and other automated equipment for packaging and a
dedicated work area.
 workers (pharmacists or pharmacy technicians) wear PPE, a cap, surgical/procedure
mask, shoe covers, a protective gown and two (2) pairs of gloves to make sterile
preparations of cytotoxic drugs in preparation cabinets.
 Organize the work to limit microbial and environmental contamination.
 workers cover the work surface with a disposable, absorbent, sterile, plastic-backed pad
to absorb any liquid contamination that may occur. The pad should not cover the front
and rear grilles of the preparation cabinet and should be changed after 3.5 hours of
continuous work; for a new batch of preparations or in the event of a spill or
contamination.
It is legislated that the pad be disposed of in a cytotoxic waste receptacle. Limit the
quantity of supplies and cytotoxic drugs in the cabinet, to avoid adversely affecting the
laminar flow and to facilitate regular cleaning of the work surface; place the sterile
products in the centre and the non-sterile products (e.g., waste receptacle) along the
sides of the cabinet.

Remove the packaging, when applicable, and clean all of the drug containers before
taking them into the preparation cabinet. For sterile preparations, adhere to aseptic
technique for sterility. Use handling techniques that limit the risk of injury or accidental
exposure. It is strongly recommended that:
  spiking of bags and priming of tubing occur before the addition of the cytotoxic drug
unless the clinical protocol requires otherwise.
 cytotoxic drugs be reconstituted in the pharmacy.
 the drug containers not be overfilled to avoid compromising their integrity.
 air never be removed from the IV tubing with a solution containing the drug.
 IV tubing is primed and air removed in the pharmacy, prior to adding the cytotoxic
drug(s) to the infusion solution.
It is legislated that cytotoxic drugs be labeled to inform those handling these
preparations of the nature of the drugs and the precautions to be taken. Cytotoxic drugs
must display the “Cytotoxic” hazard symbol or the word “Cytotoxic”.

Transport and Storage Following Preparation

Transport cytotoxic drugs using a method that will prevent contamination of the
environment in the event of breakage. It is strongly recommended that:
 cytotoxic drugs be placed in a closed, leak-proof plastic bag (e.g., Ziploc® type).
 transport of the cytotoxic drug in a closed, leak-proof plastic bag from the pharmacy be
done in a rigid, shock-resistant, leak-proof container made of a material that can be easily
cleaned and decontaminated.
 the bottom be covered with an absorbent, plastic-backed cloth.
 mechanical transport systems, such as pneumatic tubes, not be used because of the stress
they put on the contents, and the whole transport system would be compromised if a leak
occurred.
It is legislated that the transport container be identified with the “Cytotoxic” hazard
symbol and be cleaned regularly.

Preparation for the Administration of Chemotherapy

Protective Clothing Recommendations
For all protective clothing and equipment (gowns, gloves, goggles, face shields), the
manufacturer must provide documented evidence of the impermeability to
chemotherapy agents. Research has shown that gowns made of high-density
polyethylene provide the most protective barrier against spillage or aerosolization of
cytotoxic drugs (ONS, 1997, pg.6).
Gowns Must Be:

 Worn wherever chemotherapy agents are being manipulated and administered.

 Disposable, impermeable/low permeability fabric, lint-free, with back closure and long
cuffed sleeves, which should be tucked into the gloves.
 Changed in the event of an obvious spill (time to permeability of a vesicant is one hour).
 Single use (ONS, 2003) or according to the manufacturer’s recommendations.
Gloves:

 Use gloves that have been tested to protect against permeations by chemotherapy agents
and are strongly recommended to comply with ASTM standard D-6978-(05)-13 (CCO
guidelines).
 Hand washing should occur before donning gloves and after removing gloves.
 The minimum acceptable standard is powder-free surgical latex gloves (0.007 inches).
Some newer products may be thicker and provide more protection. Other suitable
materials include polyurethane, neoprene or nitrile.
 In the event of latex sensitivity, equivalent surgical nitrile gloves should be used.
 Gloves should be changed after each administration, OR if contamination or puncture
occurs, OR every 60 minutes.
Masks:

 Must be worn throughout the process of chemotherapy drug manipulation and

administration.
 Surgical masks are not acceptable.
 Masks that are designated to protect against aerosolized particles by the manufacturer
should be used. It is strongly recommended that fit tested respirators such as NIOSH
certified N95 or N100 be used to protect against airborne powder or aerosolized particles.
 The literature is unclear as to how long each mask offers protection. Masks should be
changed with obvious contamination as well as when it no longer seals to face.
Eye and Face Protection:

 Plastic Face Shields must be worn wherever chemotherapy agents are being manipulated
and administered.
 It is recommended that contact lenses should not be worn because of risk of absorption.
 Safety glasses or regular eye glasses are not adequate.
 Eye protectors should be cleaned after each use according to manufacturer’s
recommendations.
 In the event of contamination, appropriate spill procedures must be followed (OSHA
guideline).
Drug Preparation Area for Nursing Personnel
A dedicated area with restricted access and that is free of food and drink is required.
Chewing of gum in this area should not be allowed.
 This designated area should not be heavily trafficked.
 Signs that restrict access to authorized personnel only should be displayed.
  Appropriate warning labels must be placed on all chemotherapy drug storage areas
(OSHA guideline)
 A sink, an eyewash station and a spill kit should be available in this space. A less
desirable alternative is the availability of large volumes of saline solution for eye washing
purposes.
 A plastic-backed absorbent pad should be used under tubing, syringe or sites of potential
leak.
 Leak-proof and puncture-proof biohazard containers should be present. All needles,
syringes and other disposable items should be disposed of in these.
Preparation for the Administration of Oral Chemotherapy : 1

Examples: Mercaptopurine, Thioguanine.

It is recommended that all health care professionals administering oral
chemotherapy adhere to the protective clothing guidelines as outlined above (Protective
Clothing Recommendations).

Handling Precautions:

1. Transfer chemotherapy tablets/powder into empty syringe barrel without touching them
(wear gloves).
2. Open capsules in a biohazard hood.
3. It is preferable to dissolve tablets in water instead of crushing them (see below).
4. Prepare each dose on an absorbent pad on an uncluttered surface.
5. Discard materials that have been in contact with the tablets/capsules (medicine cups, oral
syringes, absorbent pad, etc) as hazardous waste.
6. Wash your hands after preparing medication.
Tablets
For children who cannot swallow tablets, methotrexate, mercaptopurine and thioguanine
can be dissolved in water according to the following procedure:

Manipulate the required number of tablets into a liquid formulation immediately prior to
dose time as follows:

1. Remove the plunger of a 10 mL oral syringe.

2. Place the required number of tablets into the barrel of the oral syringe.
3. Replace the plunger and draw up 5-7.5-10 mL of tap water (not hot water) into syringe.
4. Cap oral syringe with blue syringe tip
5. Wait 5-15 minutes to allow the tablets to disintegrate (gently rock back and forth; shake
syringe occasionally)
6. Give the dose in usual manner.
7. Draw up another 5 mL of tap water into oral syringe. Cap syringe and shake well to
dislodge any remaining particles. Give dose in usual manner.
8. Rinse the dissolve and dose device after each use.
Capsules
For children who cannot swallow capsules or where the dose is less than one capsule,
the contents of the capsule can be emptied into a Dissolve and Dose (TM) container
and made into a solution using the following procedure. This should be performed in a
biohazard hood if possible. Examples include procarbazine, temozolomide,
hydroxyurea:

1. Knock the powder down into one end of the capsule.

2. Take the top off the capsule and empty the contents into the Dissolve and Dose device.
3. Add 10 mL of tap water (not hot)
4. Cap the device, shake well and allow to sit for 2 minutes.
5. Measure the appropriate dose using an oral syringe.
For children who cannot swallow capsules where the dose is one or more capsules the
contents of the capsule may be removed and mixed with food or liquid immediately prior
to dose time as follows. This should be performed in a biohazard hood if possible.

Examples include lomustine, temozolomide, hydroxyurea, procarbazine:

1. Put the food or liquid you will mix the drug with in a small medication cup.
2. Knock the powder down into one end of the capsule.
3. Take the top off the capsule and empty the contents into the medication cup.
4. Mix the powder and the food/liquid that is in the cup.
5. Draw liquid mixed with drug into a syringe.
Administration and Disposal of Chemotherapy Agents
There should be no open food in patient room when the IV system is opened for the
purpose of administering chemotherapy agents, as there is a potential for the food to be
contaminated. In cases where food is used to help with taste aversions or as a comfort
measure, exceptions can be made by the administering RN to give the
chemotherapy agents with caution as per her/his discretion.
 PPE, as outlined above, should be used.
 Plastic-backed absorbent pads should be placed under tubing and syringes.
 Only syringes and tubing with Luer-Lok connections should be used.
 Infusion bags should be changed at waist level (Brown et. al, 2001).
Disposal of Equipment /Personal Protective Equipment used to Administer Chemotherapy
Agents:
 All syringes and needles should be discarded in containers that are puncture-resistant,
leak-proof, that have a lid that seals securely, and that are appropriately labeled.
 Bags and solution administration sets should be discarded intact in appropriately labeled
resealable containers that are both leak-proof and puncture-proof.
 PPE used during handling and administration should be disposed of in appropriately
labeled container.
Nursing Care and Management of Patients Who Have Received Chemotherapy Agents
Potential duration of excretion of chemotherapy agents and their metabolites are not
well defined. While there is some data derived from the adult population, the extent to
which this is applicable to children is unclear. Therefore, there is a real potential risk to
health care professionals and parents who are caring for children following the
administration of chemotherapy agents. It is suggested that PPE should be worn up to
48 hours post administration of intravenous (IV) chemotherapy agents and for up to 7
days post oral chemotherapy agents administration.
Personal Protective Equipment (PPE)
PPE must be worn when handling any patient’s blood or body fluids.
 Plastic Face Shields should be worn when there is a risk of splash, e.g., flushing toilet,
changing diapers, frequent or unpredictable vomiting.
 Parents must be gloved when handling excreta and diapers up to 7 days post treatment.
 Gloves should be discarded after each patient use, and when soiled or contaminated with
body fluids, in appropriately labeled containers.
 Gloves and gowns should not be worn outside of the drug administration area.
Flushing of Toilets
 All toilets should be flushed twice, as recommended in the literature but not evidence
based (Brown et. al, 2001, p.70).
 The toilet bowl (seat up) should be covered with a plastic-lined, absorbent pad (absorbent
side facing down) prior to flushing. These pads should be disposed of in biohazard
containers after each use.
Disposal of Diapers
 Diapers should be disposed of in a biohazard container for up to 7 days after
chemotherapy administration.
Disposal of Contaminated Linen
 Contaminated, non-disposable, linen should be handled with gloves and gowns and
should be dealt with in a manner consistent with institutional policies regarding handling
and disposal of infectious linens.
 Parents should not clean up contaminated linens or clothing. This should be done by
gowned and gloved health care personnel.
Patients who go to Other Areas of the Hospital
 Personnel in other areas of the Hospital (e.g., Diagnostic Imaging, Echocardiography)
should observe these safe handling guidelines when handling patients who have received
chemotherapy agents.
 These guidelines should be disseminated to all hospital personnel who may care for
oncology patients in other areas.
Disposal of Biohazardous Contaminated Materials
As per OSHA guidelines – Section IX, all areas where chemotherapy drugs are handled
should have specific disposable containers close at hand for easy and safe disposal.
 Needles and syringes should be disposed intact.
 Sharps and breakable items e.g. vials, ampoules should be disposed of in leak proof,
puncture resistant containers with labels indicating chemotherapy (cytotoxic) waste.
  Non-sharp chemotherapy drug waste, e.g. plastic IV bags and tubing, personal protection
equipment, should be sealed in leak proof, puncture resistant containers with appropriate
labels.
 These containers should be of a different colour from regular disposal of hazardous waste
containers.
Accidental Contamination and Chemotherapy Spills
Every institution should have policy and procedures in place for the management of
accidental contamination and chemotherapy spills. All health care professionals who
handle chemotherapy agents should be oriented and familiar with these policy and
procedures.
It is strongly recommended that a spill management kit be readily available within the
work area.

 SAMPLE WARNING LABEL

 References
1. Brown KA, Esper P, Kelleher LO, O’Neill B, Polovich M, White JM. (2001)
Chemotherapy and biotherapy guidelines and recommendations for practice. Oncology
Nursing Society.
2. Fuchs J, Hengstler JG, Jung D, Hilti G, Konietzko J, Oesch F. DNA damage in nurses
handling antineoplastic agents. Mutation Research. 342(1-2):17 – 23, 1995 Mar.
3. Gullo, SM. (1995). Safe handling of cytotoxic agents. Oncology Nursing Forum, 22 (3),
523.
4. Grummt T, Grummt HJ, Schott G. Chromosomal aberrations in peripheral lymphocytes
of nurses and physicians handling antineoplastic drugs. Mutation Research. 302(1):19-
24, 1993 May.
5. Mayer DK. Hazards of chemotherapy. Implementing safe handling practices. Cancer.
70(4 Suppl):988- 992, 1992 Aug 15.
6. Occupational Safety and Health Administration. (1995). Work practice guidelines for
personnel dealing with cytotoxic (antineoplastic) drugs. Washington, DC: Office of
Occupational Medicine.
7. Occupational Safety and Health Administration Instruction TED 1.15, (1995). Section V:
Chapter 3, Controlling Occupational Exposure to Hazardous Drugs, 1 – 32.
8. Oncology Nursing Society. (1997). Safe Handling of Cytotoxic Drugs. 2nd Edition.
9. Polovich M, Blecher CS, Glynn-Tucker EM, McDiarmid M, Newton SA. Safe Handling
of Hazardous Drugs. Pittsburgh (PA): Oncology Nursing Society (ONS); 2003. 56 p
 10. Ritchie MA, McAdams C, Fritz N. Exposure Risk in the Handling and Administration of
Chemotherapy Agents: A Review and Synthesis of the Literature. The Online Journal of
Knowledge Synthesis for Nursing, 7 (4).
11. Selevan SG, Lindbohm, ML, Hornung RW, Hemminki K. A study of occupational
exposure to antineoplastic drugs and fetal loss in nurses. The New England Journal of
Medicine. 313(19):1173 – 1178, 1985 Nov 7.
12. https://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=293473.Easty A,
Coakley N, Cheng R, Cividino M, Savage P, Tozer R, White R, Safe handling of
cytotoxics . Toronto (ON): Cancer Care Ontario; 2013 December 4. Program in
Evidence-Based Care Evidence-Based Series No.: 16-3.
13. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3990661/ Ecancermedicalscience. Is it
safe for pregnant health-care professionals to handle cytotoxic drugs? A review of the
literature and recommendations. 2014 Apr
14. http://jop.ascopubs.org/content/5/5/245/T2.expansion.html Journal of Oncology Practice.
Safe Handling of Parenteral Cytotoxics: Recommendations for Ontario. JOP September
2009 vol. 5 no. 5 245-249.
15. Griffin E.  Safety Considerations and Safe Handling of Oral Chemotherapy Agents.  Clin
J Oncol Nurs 2003;7(Suppl 6):25-9.
Bibliography
1. Association of Pediatric Oncology Nurses. (1998). Cancer Chemotherapy Handbook. 2.
Canadian Association of Nurses in Oncology. (1995). Standards for Nursing Practice and
Education related to the Administration of Cancer Chemotherapy.
2. Canadian Society of Hospital Pharmacists Official Publication 2000. Guidelines for the
Handling and Disposal of Hazardous Pharmaceuticals (Including Cytotoxic Drugs), 99 –
110.
3. Connor TH. Permeability testing of glove materials for use with cancer chemotherapy
drugs. Oncology. 52(3):256-259, 1995 May-Jun.
4. Kevekordes S, Gebel TW, Hellwig M, Dames W, Dunkelberg H. Human effect
monitoring in cases of occupational exposure to antineoplastic drugs: A method
comparison. Occupational & Environmental Medicine. 55(3):145-149, 1998 Mar.
5. Laidlaw JL, Connor TH, Theiss JC, Anderson RW, Matney TS. Permeability of four
disposable protective clothing materials to seven antineoplastic drugs. American Journal
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Biomonitoring of nurses handling antineoplastic drugs. Mutation Research. 322(3):203-
208, 1994 Sep.
7. Mahon SM, Casperson DS, Yackzan S, Goodner S, Hasse B, Hawkins J, Parham J,
Rimkus C, Schlomer M, Witcher V. Safe handling practices of cytotoxic drugs: The
results of a chapter survey. Oncology Nursing Forum. 21(7):1157-1165, 1994 Aug.
8. McDevitt JK, Lees PS, McDiarmid MA. Exposure of hospital pharmacists and nurses to
antineoplastic agents. Journal of Occupational Medicine. 35(1):57-60, 1993 Jan.
9. Nieweg RMB, de Boer M, Dubbleman RC, Gall HE, Hesselman GM, Lenssen PC, van
Maanen LW, Majoor PW, Ouwerkerk J, Slegt JH. Safe handling of antineoplastic drugs:
Results of a survey. Cancer Nursing. 17(6):501-511, 1994 Dec.
 10. Skov T, Maarup B, Olsen J, Rorth M, Winthereik H, Lynge E. Leukaemia and
reproductive outcome among nurses handling antineoplastic drugs. British Journal of
Industrial Medicine. 49(12):855- 861, 1992 Dec.
11. Undeger, U, Basaran, N, Kars, A, Guc D. (1999). Assessment of DNA damage in nurses
handling antineoplastic drugs by the alkaline COMET assay. Mutation Research, 439,
277 – 285.
12. Valanis BG, Vollmer WM, Labuhn KT, Glass AG. Acute symptoms associated with
antineoplastic drug handling among nurses. Cancer Nursing. 16(4):288-295, 1993 Aug.
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Primary authors Mr. Kaniska Young-Tai, The Hospital for Sick Children, Toronto and
Ms. Sylvie Kozlowskyj, Health Sciences North, Sudbury. Reviewed by POGO Satellite
Manual Review Nursing Group, 2016 and the POGO Satellite Manual Review
Pharmacy Working Group, 2016.

3.3 Extravasation Management

The following procedures outline recommendations for the prevention and treatment of
extravasation of chemotherapy agents. Chemotherapy should only be administered by
an Association of Pediatric Hematology/Oncology Nurses (APHON) certified personnel
with demonstrated knowledge of and clinical skills in the administration of
chemotherapy. Maintain provider status as per APHON standards. Extravasation can
occur with either peripheral intravenous (PIV) or central line intravenous
administrations.

Definitions
Extravasation is the inadvertent leakage of vesicant drug or solution into the tissues
surrounding an intravenous (IV) site.
Vesicant is an agent that can cause blistering or tissue necrosis when extravasated.
Irritant is an agent that can cause a local inflammatory reaction but does not cause
tissue necrosis when extravasated.
None refers to an agent that is considered not to be a vesicant or an irritant.
Signs of extravasation include the following:
 Pain and/or burning in the infiltrated area
 Swelling near the IV injection site or along venous tract
 Erythema in the infiltrated area
 Poor or absent blood return from the IV catheter
 Increase in IV pump pressures
Signs of irritant or vesicant extravasation:

 Aching and tightness along vein

 Full length of vein may become erythematous and/or discolored
 Swelling unlikely
 Usually able to get blood return
Flare Reaction
 No pain
 Immediate blotches or streaks along vein which usually subside within 30 minutes with
or without treatment
 Swelling unlikely, wheals may appear along vein line
 Usually able to get blood return
Signs and Symptoms Associated with Vesicant Extravasation, Venous Irritation and Flare
Reaction
SIGN/SYMPTOM VESICANT IRRITANT FLARE

Pain + + –

Swelling + – –

Erythema + + –
 Pump pressure + – –
increase

Poor or absent blood + +/- –

return

Ulceration + (delayed) – –
Below is a list of antineoplastic vesicants and irritant drugs classified into the following
categories:
(See Section ‘Guidelines for Management of Extravasation of Vesicant Antineoplastic
Drugs’ below)
Vesicant Nonvesicant

Irritant None

Amsacrine Arsenic trioxide Aldesleukin

Busulfan Bortezomib Asparaginase

Carmustine CISplatin Bacillus Calmette–Guérin vaccine

(BCG)

Dactinomycin Dacarbazine Bevacizumab

DAUNOrubicin (DAUNOmycin) DOCEtaxel Bleomycin

DOXOrubicin (Adriamycin) Etoposide (VP-16) Brentuximab

Epirubicin Mesna (undiluted) Buserelin

IDArubicin MitoXANTRONE CARBOplatin

Mechlorethamine (Nitrogen Mustard) 1

Oxaliplatin Cladribine
Melphalan 2
PACLitaxel Clodronate

Mitomycin Teniposide (VM-26) Cyclophosphamide

Streptozocin Temozolomide Cyproterone

VinBLAStine   Cytarabine

VinCRIStine   Dexrazoxane

Vindesine   Fludarabine

Vinorelbine   Fluorouracil

    Gemcitabine

    Ifosfamide

    Interferon

    Irinotecan

    Leucovorin

    Methotrexate

    Pentostatin

    Raltitrexed
     RiTUXimab

    Thiotepa

    Topotecan

    Trastuzumab

1, 2  
Treat like a vesicant

Adapted from the BCCA Cancer Drug Manual, BC Cancer Agency, November 2014

Adapted from Chemotherapy Extravasation guidelines LHSC, revision June 2015

Guidelines for Prevention of Extravasation

Vesicant antineoplastic agents should be administered by qualified personnel.
Vesicant/irritant drugs should be administered via Central Venous Catheters (CVCs)
whenever possible.  

Consider the following measures to prevent extravasation:

1.
Anticipate the possibility of extravasation.
2.
Ensure extravasation treatment protocol and antidotes are readily available.
3.
Careful vein selection for PIVs.
4.
Minimize number of venipunctures in starting PIVs.
5.
Ensure good blood return from site prior to administration, during and upon completion.
If infusion is less than one hour check for blood return every 15 min.  If greater than one
hour check site and blood return every hour.
6. Ensure free flowing Intravenous fluids during administration of vesicant chemotherapy
when applicable.
7. Frequent monitoring if PIV/port needle sites or CVC site and monitor for increase in
pump pressures.
Extravasation supplies should be available.
Starting a New PIV for Administration of Vesicant Drugs
Choose PIV site carefully.  Choose the most distal position of a vein and in this order if
possible:

1. Dorsum of hand
2. Forearm
3. Wrist (potential damage to tendons and nerves should extravasation occur)
Avoid the antecubital fossa since this area is dense with tendons and nerves; damage
here can result in loss of structure and function.

If first attempt is unsuccessful, select another site preferably in another limb.  Avoid a
distal point in the same vein because of the potential for extravasation “downstream”.

Guidelines for Management of Extravasation of Vesicant

The following guidelines are recommended for the management of extravasation.  The
medical team should be notified immediately and treatment must be individualized to
each extravasation event.

*It is unclear whether injection of antidotes into area of extravasation is of benefit.  Most
small extravasations do not result in serious problems without the injection of antidotes.”
(BCCA Cancer Drug Manual, BC Cancer Agency November 2014.)

  Important Steps Key Points

1. STOP the IV infusion. Click here to access the Flowchart

Do not remove the IV/port needle yet available for quick reference.

2. Detach IV tubing/syringe from the IV/port  

needle.  Attach a new syringe to the IV/port
needle as close as possible to insertion site. 
Aspirate as much drug, blood and tissue fluid
as possible.  Remove the syringe.

3. Notify the medical team of extravasation as  

soon as possible.

4. REMOVE the original angiocatheter/port  

needle.

5 Consult section ‘Antidotes and treatments of  

extravasation’ below.

6. Continue as per table below for each drug.  

 7. Administer analgesics as ordered. Corticosteroid cream (e.g. hydrocortisone
1% cream) may reduce inflammation.

Silver Sulfadiazine cream, povidone

iodine ointment or sterile dressings may
also provide symptomatic relief or
prevent secondary infection.

8. For PIVs, restart the IV at another site,  

preferably in the opposite limb or in the same
limb proximal to the infiltrated area, if needed.
For Port-a-catheter, re-access to heparin lock.

9. Immobilize the affected limb or area.  Elevate  

the affected area to promote venous drainage
and to reduce edema.

10. Document the extravasation occurrence in the  

patient’s chart and complete your hospital
Safety Report. Photo documentation may be
helpful. Consent may be required.

11. Consult Plastics upon Medical Doctor(MD)  

/Nurse Practitioners (NP) discretion and/or no
  improvement of site in 24 hours.

12. Extravasation known:  Return to clinic in 24-
48 hours for assessment, then weekly for one
month minimum.
Extravasation suspected:  Telephone call in 24
hours by nurse to assess and then in one week
minimum.
Provide Information to patient/ family
with what to look for and when to call.
The site should be observed daily by the
patient and/or parent for one month as
there may be delayed reaction. 

Guidelines for Management of Extravasation of Irritant Drugs

The following guidelines are recommended for the management of extravasation.  The
medical team should be notified immediately and treatment must be individualized to
each patient.  While the medical team may elect to use an antidote if one exists, or
topical medications, it is important to realize that many patients recover fully with no
drug treatment at all.
  Important Steps Key Points

1. Stop IV infusion. Click here to access the Flowchart available

Do not remove angiocatheter/port needle yet. for quick reference.

2. Detach IV tubing/syringe from IV/port needle.   

Attach a new syringe to IV/port needle as close as
possible to insertion site.  Aspirate as much drug,
blood, and tissue fluid as possible.  Remove the
syringe.

3. Notify the medical team of extravasation as soon  

as possible.

4. REMOVE the original angiocatheter/port needle.  

5. Continue as per table below for each drug.  

6. Administer analgesics as ordered. Corticosteroid cream (e.g. hydrocortisone

1% cream) may reduce inflammation.

Silver Sulfadiazine cream, Povidone iodine

ointment or sterile dressings may also
provide symptomatic relief or prevent
secondary infection.

7. For PIVs, restart the IV at another site, preferably  

in the opposite limb or in the same limb proximal
to the infiltrated area, if needed.
For Ports, re-access to heparin lock or re-establish
IV.
 8. Immobilize the affected limb or area.  Elevate the  
affected area to promote venous drainage and to
reduce edema.

9. Document the extravasation of occurrence in the  

patient’s chart and complete your hospital safety
report.  Photo documentation may be helpful.
Consent may be required.

10.  Consult Plastics upon MD or Nurse Practitioners  

discretion and/or no improvement of site in 24
hours.

11. Extravasation known:  Return to clinic in 24-48
hours for assessment, then weekly for one month
minimum.
Extravasation suspected:  Telephone call in 24
hours by nurse to assess and then in one week
minimum.
Provide Information to patient/ family with
what to look for and when to call. The site
should be observed daily by the patient
and/or parent for one month as there may be
delayed reaction. Click here for sample
documents.

Antidotes and Treatments of Extravasation

  Compress Actions Rationale
Required
Amsacrine COLD 1.  Remove the IV/port DMSO speeds up
needle. removal of the
Dactinomycin drug from the
2.  Apply 50% DMSO tissue and is a
DAUNOmycin (Dimethyl sulfoxide) free-radical
topical solution to an scavenger.
(DAUNOrubicin) area twice that affected
by extravasation Air-drying is
(approximately 1.5 required as DMSO
DOXOrubicinEpirubicin
mL). may cause blisters
with occlusions.
IDArubicin
3.  Allow DMSO to air
dry. Do not cover and  
Mitomycin repeat QID for at least
7 days. Cold compresses
cause
4.  Elevate limb and vasoconstriction
apply gentle pressure and decrease fluid
to site. absorption.

5.  Apply ice pack

wrapped in towel or
cold compresses to the
extravasation site for 1
hr; continue cold
compresses x 15-20
min, qid for 24-48 hrs. 
Care must be taken to
avoid tissue injury
from excessive cold.
VinBLAStine WARM 1.  Remove IV/port  
needle
VinCRIStine  
2.  MD to administer
Vindesine antidote*:  
hyaluronidase 1500
Vinorelbine units dissolved in 1 mL Cooling may have
of either sterile water adverse effect
for injection or normal
saline injection
infiltrated into affected
area subcutaneous  in a
clockwise fashion in
divided doses around
the site ( as soon as
possible after
extravasation).14

3.  Elevate limb and

apply pressure to site

4.  Apply warm

compresses to
extravasation site for 1
hr; continue warm
compresses 15-20 min
qid for 24-48 hrs.  Care
must be taken to avoid
injury from excessive
heat.
Mechlorethamine (Nitrogen COLD Administer antidote: 2  
Mustard) mLsodium thiosulfate
4% solution for each 1
mg of drug via same
IV/Port needle or use
25 gauge needle to
inject subcutaneously. 
(to prepare mix 1.6 ml
sodium thiosulfate
25% solution with 8.4
mL sterile water for
injection to give 10 mL
of a 4 % solution.

1.     Remove the IV/

Port needle

2.     Elevate limb and

apply gentle pressure
to site

3.     Apply ice pack

wrapped in towel or
cold compresses to the
extravasation site for 1
hr; continue cold
compresses for 15-20
min, QID for 24-48
hours.  Care must be
taken to avoid tissue
injury from excessive
cold
 Busulfan COLD 1.  Remove IV/port  
needle.
Carmustine  
2.  Elevate limb and
DOCEtaxel apply gentle pressure Cold compresses
to site. cause
Melphalan vasoconstriction
3.  Apply ice pack and decrease fluid
PACLitaxel wrapped in towel or absorption
cold compresses to the
extravasation site.
Streptozocin
Continue cold
compresses for 15 to
20 minutes QID for 24
to 48 hours. Care must
be taken to avoid tissue
injury from excessive
cold.

Adapted from the BCCA Cancer Drug Manual, BC Cancer Agency, November 2014.

Supply of Antidotes
A supply of antidotes should be readily available and maintained in areas where
chemotherapy is administered for easy access. 
Hyaluronidase (See Antidote table above)* 1500 units’ injection is a Special Access
Medication.  A future use supply should be kept in the Pharmacy so that doses may be
administered as soon as they are ordered.  A Special Access request form must be
submitted within 24 Hours.

NOTE: For drugs and antidotes not listed please consult Pharmacy. For non-vesicant/irritant
antineoplastic drugs please refer to your hospital guidelines on the treatment for extravasation.
The superiority of dexrazoxane over DMSO has not been established. Dexrazoxane is
  

not included in this policy and DMSO remains the standard of care for anthracycline
extravasation. References are provided for a situation where dexrazoxane use may be
deemed warranted.
References
1. C. Cancer Agency Policy III-20, Extravasation of Chemotherapy, Prevention and
Management of, Revised November 2014, Approved by Provincial Systemic Program
Committee.
2. Cancer Care Ontario, Appendix 2 – Extravasation of Chemotherapy (Revised October )
Retrieved from https://www.cancercare.on.ca/cms/one.aspx?
portalId=1377&pageId=10760
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23(4):229-31.
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14. Olver IN, Aisner J, Hament A. et al. A prospective study of topical dimethyl sulfoxide for
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Primary author Ms. Julie Dowler, Children’s Hospital, London Health Sciences Centre,
London with input from Ms. Denise Reniers, Children’s Hospital, London Health
Sciences Centre Ms. Mary Jo Decourcy, Children’s Hospital, London Health Sciences
Centre, and Ms. Anne Chambers,  Children’s Hospital, London Health Sciences Centre,
London.  Reviewed by POGO Satellite Manual Review Nursing Group, 2016 and the
POGO Satellite Manual Review Pharmacy Working Group, 2016.