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Management of Extravasation of Chemotherapeutic Agents – Adult/Pediatric – Inpatient/Ambulatory

Management of Extravasation of Chemotherapeutic Agents – Adult/Pediatric – Inpatient/Ambulatory - Clinical Hub, UW Health Clinical Tool Search, UW Health Clinical Tool Search, Clinical Practice Guidelines, Oncology


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UWHC Guidelines for the Management of Extravasation of
Chemotherapeutic Agents - Adult/Pediatric - Inpatient/Ambulatory
Clinical Practice Guideline
Table of Contents
EXECUTIVE SUMMARY ......................................................................................................................... 3
SCOPE......................................................................................................................................................... 3
METHODOLOGY ..................................................................................................................................... 3
DEFINITIONS1,2 ....................................................................................................................................... 4
INTRODUCTION...................................................................................................................................... 5
TABLE OF DRUGS EVALUATED ......................................................................................................... 6
RECOMMENDATIONS FOR EXTRAVASATION MANAGEMENT: ............................................... 6
a. Anthracyclines .................................................................................................................................................. 6
b. Alkalayting Agents ............................................................................................................................................ 8
c. Vinca Alkaloids .................................................................................................................................................. 9
d. Platinums ........................................................................................................................................................ 10
e. Other vesicants/irritants ................................................................................................................................ 11
f. Photosensitizing Agents ................................................................................................................................. 11
UW HEALTH IMPLEMENTATION .................................................................................................... 12
REFERENCES: ........................................................................................................................................ 13
APPENDIX A: INTRAVENOUS CHEMOTHERAPEUTIC AGENTS EVALUATED FOR
EXTRAVASATION RISK ...................................................................................................................... 15
CPG Contact for Changes:
Name: Philip Trapskin, PharmD, BCPS, Drug Policy Manager
Phone Number: 608-263-1328
Email address: ptrapskin@uwhealth.org
CPG Contact for Content:
Name: Mary Mably, RPh, BCOP
Phone Number: 608-263-1263
Email address: mmably@uwhealth.org
Copyright © 2014 University of Wisconsin Hospitals and Clinics Authority
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Guideline Authors: Kari Caldwell, NP; Bethaney Campbell, RN, MN, AOCNS; Kate Croegaert, PharmD;
Susan Hanauer, RN, MSN; Sarah Lentz, RPh, BCOP; Mary Mably, RPh, BCOP; Dan Mulkerin, MD; Andy
Pulvermacher, PharmD; Tammy Troester, PharmD, BCOP
Coordinating Team Members: Mary Mably, RPh, BCOP and Sara Shull, PharmD, MBA, BCPS
Review Individuals/Bodies: Chemotherapy Council, Oncology Practice Committee
Committee Approvals/Dates:
Oncology Practice Committee—September 2014
Chemotherapy Review Council –October 2014
Pharmacy and Therapeutics Committee- December 2014
Original Release Date: June 1999
Previous Revision Dates: June 2009
Next Scheduled Review Date: September 2016
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A. Executive Summary
Guideline Overview:
This guideline is intended to provide reference for the prevention and treatment of phlebitis and
extravasation of chemotherapeutic agents. A comprehensive list of intravenous (IV)
chemotherapeutic agents is included with classification of extravasation risk. Recommendations for
documentation and follow-up of an extravasation event are also included.
Key Practice Recommendations:
1. Take prompt action to stop infusion of offending chemotherapy immediately.
2. Application of heat or cold is specific to type of chemotherapy extravasated. Follow
instructions carefully.
3. Administration of antidote is specific to type of chemotherapy extravasated. Follow instructions
carefully.
4. Prevent future sun exposure of extravasated tissue.
Pertinent UWHC Policies & Procedures:
1. Hospital Administrative Policy 8.59: Chemotherapy Process: Informed Consent, Ordering,
Verification, Administration, Documentation and Education
2. Appendix A: Hospital Administration Policy 8.59: Medications Defined as Chemotherapy at
UWHC
B. Scope
Intended Users
This guideline is intended for use by hematology, oncology and bone marrow transplant physicians,
pharmacists, nurses and other health care providers involved in the delivery of IV chemotherapeutic
agents to adult and pediatric patients in the inpatient and ambulatory settings.
CPG Objective
The purpose of this guideline is to prevent chemotherapy extravasation events and provide
recommendations to manage chemotherapy extravasation events that do occur, including
appropriate interventions, documentation and monitoring.
Target Population:
Adult or pediatric patients being treated with an IV chemotherapeutic agent in either the inpatient
or ambulatory setting.
Guideline metrics:
Annual number of extravasation events as a proportion of the annual number of administered doses
(% of doses resulting in extravasation); annual number of extravasation events that result in tissue
damage. Compare UW Health extravasation rate to benchmark institutions or national rate.
C. Methodology
A modified Grading of Recommendations Assessment, Development and Evaluation (GRADE)
developed by the American Heart Association and American College of Cardiology has been used to
assess the Quality and Strength of the Evidence in this Clinical Practice Guideline (Figure 1.)
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Figure 1. Quality of Evidence and Strength of Recommendation Grading Matrix
D. Definitions1,2
a. Extravasation – the unintentional administration of a potential vesicant medication or
solution into tissue surrounding the intended vascular system
b. Vesicant – an agent that can produce local irritation, necrosis and sloughing of tissues
when inadvertently injected into subcutaneous or muscle tissues during intravenous
administration
c. Irritant (non-vesicant) – an agent that can cause injection site pain, burning and
phlebitis, but NOT tissue necrosis. Care should be taken to avoid venipuncture sites in
area that may have compromised circulation.
d. Chemical Phlebitis – chemical irritation affecting the innermost layer of a vein resulting
in cell destruction, infiltration and inflammation
e. Chemotherapy: For a list of medications defined as chemotherapy, see Appendix A of
Hospital Administrative Policy 8.59.
f. Investigational Drug: The vesicant potential of investigational drugs may not be known
during clinical trials. Investigational drugs known to be vesicants will be clearly identified
with extravasation procedures outlined. Regardless of vesicant properties, any
extravasation involving investigational drugs must be brought to the attention of the
study group immediately for determination of appropriate action.
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E. Introduction
Extravasation of chemotherapeutic agents can result in permanent damage or disability.
Numerous chemotherapeutic medications have the potential to cause tissue damage if
extravasated. Intravenous chemotherapy agents are defined as vesicant, irritant, or non-
vesicant based on their potential to cause tissue damage when extravasated. A thorough
understanding of agent-specific extravasation risk and prevention techniques can help to reduce
the risk for extravasation events. If an extravasation event occurs, knowledge of the procedure
for management can help to limit tissue damage.
There is no centralized reporting system for documenting extravasation events, and the
reported incidence of chemotherapy extravasation events varies widely with estimated ranges
between 0.01-7%2. Improvements in infusion techniques and monitoring have reduced the
incidence of extravasation events.
Risk factors for extravasation of chemotherapy using a peripheral IV include1,2:
ξ Small or fragile veins (elderly patients, long-term steroid use)
ξ Obesity, which may obscure view of peripheral veins
ξ Hard/sclerosed veins (previous chemotherapy administration or history of IV drug
abuse)
ξ Diseases causing impaired circulation (Raynaud Syndrome, diabetes, peripheral vascular
disease)
ξ Patients with limited vein selection (lymphedema, amputation, dialysis fistula)
ξ Patients with communication difficulties/somnolence which may reduce ability to
report signs or symptoms of extravasation
ξ Patients with sensory deficits which may impair ability to sense pain at administration
site (stroke, peripheral neuropathy)
ξ Prolonged chemotherapy infusion time
ξ Untrained/inexperienced staff
ξ Bolus injections
ξ Poor cannula fixation or unfavorable cannulation site
Use caution when administering a known vesicant via a peripheral line. Please refer to Hospital
Administrative Policy 8.59 Chemotherapy Process: Informed Consent, Ordering, Verification,
Administration, Documentation and Education for complete guidelines regarding the
administration of chemotherapeutic agents and appropriate venous access device (VAD) use.
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F. Table of Drugs Evaluated
Prior to administering a chemotherapy agent, consult the following alpha index to determine
the extravasation risk. Click on the first letter of the generic drug which will direct you to the
table. Within the table, click on the drug name to review complete treatment information. If a
drug is not found within this table, consult your unit pharmacist or standard drug information
references.
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
G. Recommendations for Extravasation Management:
a. Anthracyclines:
i. The anthracycline class of chemotherapy (daunorubicin, doxorubicin, idarubicin
and epirubicin) is known to cause significant tissue damage when extravasated,
possibly requiring surgical intervention.
ii. Dexrazoxane has a protective effect against anthracycline-induced tissue
necrosis by binding to iron and preventing the formation of tissue-damaging
free radicals. Both animal studies and case reports have demonstrated the
beneficial effects of dexrazoxane in preventing anthracycline-induced
extravasation damage3-8 (Class I, Level B).
1. Dexrazoxane must be administered through the IV route within 6 hours
of the extravasation event.
2. Administer in a vein away from extravasation site (i.e. opposite arm)
3. Remove cold compress/ice packs 15 minutes before and during
administration
iii. Dimethyl sulfoxide (DMSO) is an organic solvent able to penetrate tissue when
applied topically. It functions to neutralize free radicals and facilitate removal of
extravasated vesicants from affected tissues1,9,10.
1. There is mixed evidence regarding the use of DMSO for anthracycline
extravasation1. Some reports demonstrate effective prevention of
extravasation injury when DMSO 99% was applied topically every 6-8
hours for 1-2 weeks9,11.
2. DMSO 99% used in studies demonstrating positive results is not
available in the United States2. Due to its limited availability at this
concentration, DMSO cannot be recommended for the treatment of
anthracycline extravasation. (Class III, Level B)
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Chemotherapeutic
Agent(s)
Recommendation for Extravasation Management
and Monitoring3-8
What to Avoid
Anthracyclines:
Daunorubicin
Doxorubicin
Idarubicin
Epirubicin
1. Stop injection immediately. Disconnect IV tubing and
keep IV device/port needle in place. (Class I, Level C)
2. Aspirate residual vesicant using a small syringe (3 mL)
then remove peripheral IV device/port needle. (Class I,
Level C)
3. Apply ice for 60 minutes; then every six (6) hours for 20
minutes for 48 hours. (Class I, Level C) If dexrazoxane is
ordered, remove ice packs 15 minutes prior to
administration. (Class I, Level B)
4. Notify fellow and/or staff physician responsible for
patient to decide if further measures are to be taken.
5. Obtain necessary orders for antidote medications if
physician decides they are necessary.
Treatment to be considered:
Dexrazoxane (Class I, Level B)
a) Administer dexrazoxane within six hours of
extravasation.
b) Dexrazoxane treatment duration: 3 days
c) Dexrazoxane dose is based on body surface area.
i. Day 1: 1,000 mg/m2 ; maximum dose 2,000
mg
ii. Day 2: 1,000 mg/m2 ; maximum dose 2,000
mg
iii. Day 3: 500 mg/m2; maximum dose 1,000
mg
d) The dose of dexrazoxane should be reduced by 50%
if creatinine clearance is <40 mL/minute.
e) Infuse dexrazoxane intravenously over 2 hours into
the opposite extremity of where the extravasation
took place. The rate of dexrazoxane infusion may be
decreased if infusion site burning occurs.
f) Dexrazoxane is stocked in the Sterile Products Area
(SPA) in Central Pharmacy.
6. The physician responsible for the patient should evaluate
the site as to the need for further therapy and
consultation with plastic surgery.
7. Site of extravasation will always be sensitive to sunlight.
Sunlight exposure to the area must be avoided in the
future. (Class I, Level C)
8. Follow documentation procedures outlined below.
Do NOT apply
warm/hot
compress which
can exacerbate
the
extravasation
area. (Class III,
Level C)
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8
b. Alkalayting Agents:
i. Mechlorethamine is an alkalyating agent known to cause severe and prolonged
skin toxicity and necrosis upon extravasation.
ii. Animal studies have demonstrated a protective effect of sodium thiosulfate
when given by intradermal or subcutaneous administration immediately after
mechlorethamine extravasation12. This protective effect was not observed when
given by the intravenous route.12 Sodium thiosulfate is believed to inactivate
mechlorethamine through nucleophilic reaction while also functioning as a free-
radical scavenger to reduce production of hydroxyl radicals that cause tissue
damage2,12.
Chemotherapeutic
Agent(s)
Recommendation for Extravasation Management
and Monitoring1,10,12,13
What to Avoid
Alkylating Agents
Mechlorethamine
1. Stop injection immediately. Disconnect IV tubing and
keep IV device/port needle in place. (Class I, Level C)
2. Aspirate residual vesicant using a small syringe (3 mL)
then remove peripheral IV device/port needle. (Class I,
Level C)
3. Apply ice continuously for six (6) hours. (Class I, Level C)
4. Notify fellow and/or staff physician responsible for
patient to decide if further measures are to be taken.
5. Obtain necessary orders for antidote medications if
physician decides they are to be used.
Treatment to be considered:
Sodium thiosulfate 4% (1/6 molar) Solution (Class IIb, Level C)
a) Inject subcutaneously or intradermally into the site
of the extravasation.
b) The number of injections should correspond to the
size of the lesion. Suggested dosing: Prepare 5-20
separate injections of 0.2 mL each of sodium
thiosulfate.
c) Inject subcutaneously or intradermally into the site
of the extravasation.
d) Change needle with each injection. A 25-gauge or
smaller needle is recommended.
6. The physician responsible for the patient should
evaluate site as to the need for further therapy and
consultation with plastic surgery.
7. Site of extravasation will always be sensitive to sunlight.
Sunlight exposure to the area must be avoided in the
future. (Class I, Level C)
8. Follow documentation procedures outlined below.
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c. Vinca Alkaloids:
i. Vinca alkaloids (vinblastine, vincristine, vinorelbine, vindesine) are plant-based
alkaloids known to cause tissue damage and necrosis upon extravasation.
ii. Hyaluronidase is an enzyme which functions to degrade hyaluronic acid. This
degradation of hyaluronic acid promotes drug diffusion and improves
absorption of extravasated drugs.
1. Limited clinical studies and case reports have demonstrated a reduction
in skin necrosis with administration of hyaluronidase following
extravasation of vinca alkaloids14,15
2. A total volume of 1-6 ml of 150 U/mL solution is typically injected in
divided doses subcutaneously into the area of extravasation. The usual
dose is 1 mL of solution for 1 mL of extravasated drug1,2.
Chemotherapeutic
Agent(s)
Recommendation for Extravasation Management
and Monitoring14-16
What to Avoid
Vinca Alkaloids
Vinblastine
Vincristine
Vindesine
Vinorelbine
1. Stop injection immediately. Disconnect IV tubing and
keep IV device/port needle in place. (Class I, Level C)
2. Aspirate residual vesicant using a small syringe (3 mL)
then remove peripheral IV device/port needle. (Class I,
Level C)
3. Apply a WARM compress for 30-60 minutes, then apply
a WARM compress for 15-20 minutes at a time at least 4
times per day for the first 24-48 hours. (Class I, Level B)
4. Elevate involved extremity for one day and continue as
appropriate to decrease swelling. (Class I, Level C)
5. Notify fellow and/or staff physician responsible for
patient to decide if further measures are to be taken.
6. Obtain necessary orders for antidote medications if
physician decides they are to be used:
Treatment to be considered:
Hyaluronidase 150 units/mL Injection (Class IIa, level B)
a) The volume and number of injections should
correspond to the size of the lesion. Suggested
dose: Prepare five separate injections of 0.2 mL.
hyaluronidase (total volume 1 mL).
b) Inject subcutaneously or intradermally into the site
of the extravasation. Administer using a 25-gauge
needle or smaller.
c) Hyaluronidase (refrigerated medication) is stocked
in the Sterile Products Area (SPA) in Central
Pharmacy.
7. The physician responsible for the patient should
evaluate site as to the need for further therapy and
consultation with plastic surgery.
8. Site of extravasation will always be sensitive to sunlight.
Sunlight exposure to the area must be avoided in the
future. (Class I, Level C)
9. Follow documentation procedures outlined below.
Do NOT apply
cold
compress/ice
which can
exacerbate the
extravasation
area. (Class III,
Level B)
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10
d. Platinums:
i. Oxaliplatin is a platinum chemotherapy agent known to bind to DNA nucleic acid
for a prolonged time period creating the potential for tissue irritation and
damage17.
ii. Several case reports have described tissue damage and irritation with peripheral
administration of oxaliplatin17-19. A few case reports have even described tissue
necrosis, although consensus recommendations classify oxaliplatin as an irritant
vs. a vesicant.
iii. There is no clear recommendation for the management of oxaliplatin
extravasation. Some case reports describe the use of cold compress, however,
manufacturer recommendations dictate to avoid application of ice or cold
compresses as they may exacerbate neuropathy caused by the drug. Due to this
risk for neuropathy, the use of cold compress for oxaliplatin extravasation is not
recommended. (Class III, level C).
Chemotherapeutic
Agent(s)
Recommendation for Extravasation Management
and Monitoring17-19
What to Avoid
Oxaliplatin 1. Stop injection immediately. Disconnect IV tubing and
keep IV device/port needle in place. (Class I, Level C)
2. Aspirate residual vesicant using a small syringe (3 mL)
then remove peripheral IV device/port needle. (Class I,
Level C)
3. Notify fellow and/or staff physician responsible to
decide if further measure are to be taken.
4. There are no well-defined procedures for an oxaliplatin
extravasation.
5. The physician responsible for the patient should
evaluate site as to the need for further therapy and
consultation with plastic surgery.
6. Site of extravasation may be sensitive to sunlight.
Sunlight exposure to the area must be avoided in the
future. (Class I, Level C)
7. Follow documentation procedures outlined below.
Do NOT apply ice
or cold
compresses.
Application of
cold results in
advancement of
known
neuropathic
effects (Class III,
level C).
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e. Other vesicants/irritants:
Chemotherapeutic
Agent(s)
Recommendation for Extravasation Management
and Monitoring
What to Avoid
Other Vesicants or
Irritants
1. Stop injection immediately. Disconnect IV tubing and
keep IV device/port needle in place. (Class I, Level C)
2. Aspirate residual vesicant using a small syringe (3 mL)
then remove peripheral IV device/port needle. (Class I,
Level C)
3. For all medications in the class, except vinca alkaloids,
apply ice for 60 minutes; then every six (6) hours for 20
minutes for 48 hours. (Class I, Level C)
4. Do not apply ice/cold compress for extravasation of
vinca alkaloids) (Class III, Level B)
5. Notify fellow and/or staff physician responsible to
decide if further measures are to be taken.
6. Currently there are no well-defined measures to be
taken for extravasation. Consult the primary literature
for the most up-to-date information.
7. The physician responsible for the patient should
evaluate site as to the need for further therapy and
consultation with plastic surgery.
8. Site of extravasation may be sensitive to sunlight.
Sunlight exposure to the area must be avoided in the
future. (Class I, Level C)
9. Follow documentation procedures outlined below.
f. Photosensitizing Agents:
Chemotherapeutic
Agent(s)
Recommendation for Extravasation Management
and Monitoring
What to Avoid
Photosensitizing
Agents
Porfimer
1. Tissue damage is due to irritation by photodynamic
effects.
2. Immediately protect extravasation area from all light for
a minimum of 30 days (Class I, Level C)
3. No antidote necessary (Class III, Level C)
g. Documentation of Extravasation:
i. Complete Patient Safety Net (PSN) Report per Hospital Administrative Policy
8.20.
ii. Extravasation events should be reported as adverse drug events and not as
medication use errors within the Patient Safety Net reports.
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12
iii. The incident should be documented as a progress note in the patient’s medical
record by the nurse administering the medication and by the prescribing
physician. The nursing documentation note should include the following
information:
1. Date and time of occurrence
2. Site of administration and condition of the vein
3. Description of apparatus used and method of administration
4. Patient complaint and statements
5. Agent responsible for incident and other medications administered into
the same timeframe of the suspected agent
6. Treatment measures taken for extravasation (e.g. cold packs, antidote,
etc.)
7. Further recommendations and plans for follow-up care
h. Extravasation Follow-up:
i. A physician or registered nurse from the service/unit where the extravasation
occurred will contact and evaluate the patient within 24-36 hours of the
incident, by telephone if necessary.
ii. The patient should be advised to contact his/her physician if any signs of
increased redness or tissue sloughing are noted, or if the area becomes more
painful.
iii. The patient should be advised to avoid any future exposure of the area of
extravasation to the ultraviolet rays of the sun by covering the area or using a
sun block cream. Sun block cream may only be used if the skin surface is intact.
(Class I, Level C)
H. UW Health Implementation
Potential Benefits: Use of the guideline should result in fewer extravasation events. When
extravasation occurs, following these guideline recommendations should limit tissue damage.
Potential Harms: Pharmacologic interventions may be administered incorrectly despite clear
recommendation, resulting in tissue damage.
Qualifying Statements: None
Implementation Plan/Tools
1. Guideline will be housed on U-Connect in a dedicated folder for CPGs.
2. Release of the guideline will be advertised in the Clinical Knowledge Management Corner within
the Best Practice newsletter.
3. Links to this guideline will be updated and/or added in appropriate Health Link or equivalent
tools, including: medication records for the chemotherapy and antidotes included in the guideline
4. Education about revisions for prescribers, nurses, pharmacists, and other relevant stakeholders
will be provided.
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13
Disclaimer
CPGs are described to assist clinicians by providing a framework for the evaluation and treatment of
patients. This Clinical Practice Guideline outlines the preferred approach for most patients. It is not
intended to replace a clinician’s judgment or to establish a protocol for all patients. It is understood
that some patients will not fit the clinical condition contemplated by a guideline and that a guideline
will rarely establish the only appropriate approach to a problem
I. References:
1. Perez Fidalgo JA, Garcia Fabregat L, Cervantes A, Margulies A, Vidall C, Roila F. Management of
chemotherapy extravasation: ESMO-EONS Clinical Practice Guidelines. Ann Oncol. 2012;23 Suppl
7:vii167-173.
2. Schulmeister L. Extravasation management: clinical update. Semin Oncol Nurs. 2011;27(1):82-90.
3. Langer SW, Sehested M, Jensen PB. Dexrazoxane is a potent and specific inhibitor of
anthracycline induced subcutaneous lesions in mice. Ann Oncol. 2001;12(3):405-410.
4. Langer SW, Sehested M, Jensen PB. Treatment of anthracycline extravasation with dexrazoxane.
Clin Cancer Res. 2000;6(9):3680-3686.
5. Mouridsen HT, Langer SW, Buter J, et al. Treatment of anthracycline extravasation with Savene
(dexrazoxane): results from two prospective clinical multicentre studies. Ann Oncol.
2007;18(3):546-550.
6. Langer SW, Thougaard AV, Sehested M, Jensen PB. Treatment of experimental extravasation of
amrubicin, liposomal doxorubicin, and mitoxantrone with dexrazoxane. Cancer Chemother
Pharmacol. 2012;69(2):573-576.
7. Hasinoff BB. The use of dexrazoxane for the prevention of anthracycline extravasation injury.
Expert Opin Investig Drugs. 2008;17(2):217-223.
8. Kane RC, McGuinn WD, Jr., Dagher R, Justice R, Pazdur R. Dexrazoxane (Totect): FDA review and
approval for the treatment of accidental extravasation following intravenous anthracycline
chemotherapy. Oncologist. 2008;13(4):445-450.
9. Bertelli G, Gozza A, Forno GB, et al. Topical dimethylsulfoxide for the prevention of soft tissue
injury after extravasation of vesicant cytotoxic drugs: a prospective clinical study. J Clin Oncol.
1995;13(11):2851-2855.
10. de Wit M, Ortner P, Lipp HP, et al. Management of cytotoxic extravasation - ASORS expert
opinion for diagnosis, prevention and treatment. Onkologie. 2013;36(3):127-135.
11. Olver IN, Aisner J, Hament A, Buchanan L, Bishop JF, Kaplan RS. A prospective study of topical
dimethyl sulfoxide for treating anthracycline extravasation. J Clin Oncol. 1988;6(11):1732-1735.
12. Dorr RT, Soble M, Alberts DS. Efficacy of sodium thiosulfate as a local antidote to
mechlorethamine skin toxicity in the mouse. Cancer Chemother Pharmacol. 1988;22(4):299-302.
13. Baxter. Mustargen official prescribing information. Lebanon, NJ: Recordati Rare Diseases Inc.;
2013.
14. Cicchetti S, Jemec B, Gault DT. Two case reports of vinorelbine extravasation: management and
review of the literature. Tumori. 2000;86(4):289-292.
15. Bertelli G, Dini D, Forno GB, et al. Hyaluronidase as an antidote to extravasation of Vinca
alkaloids: clinical results. J Cancer Res Clin Oncol. 1994;120(8):505-506.
16. Laurie SW, Wilson KL, Kernahan DA, Bauer BS, Vistnes LM. Intravenous extravasation injuries:
the effectiveness of hyaluronidase in their treatment. Ann Plast Surg. 1984;13(3):191-194.
17. de Lemos ML, Walisser S. Management of extravasation of oxaliplatin. J Oncol Pharm Pract.
2005;11(4):159-162.
Copyright © 2014 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 12/2014CCKM@uwhealth.org

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18. Foo KF, Michael M, Toner G, Zalcberg J. A case report of oxaliplatin extravasation. Ann Oncol.
2003;14(6):961-962.
19. Kennedy JG, Donahue JP, Hoang B, Boland PJ. Vesicant characteristics of oxaliplatin following
antecubital extravasation. Clin Oncol (R Coll Radiol). 2003;15(5):237-239.
20. Agency BCC. Cancer Drug Manual. 2013.
21. Cancer chemotherapy manual. Facts and Comparisons Wolters Kluwer Health, Inc; 2009.
Accessed May 6, 2009.
22. Data on file. Aldesleukin (Proleukin) extravasation letter [written communication]. East Hanover,
NJ: Novartis Oncology; March 6, 2009.
23. Data on file. Vidaza (azacitidine) [written communication]. Summit, NJ: Celgene; February 27,
2009.
24. Data on file. Infiltration or extravasation of treanda (bendamustine HCL) for injection [written
communication]. Frazer, PA: Cephalon, Inc.; February 27, 2009.
25. Data on file. Avastin - general administration guidelines [written communication]. South San
Francisco, CA: Genentech; February 27, 2009.
26. Data on file. Extravasation and arranon letter [written communication]. Research Triangle Park,
NC: GlaxoSmithKline; March 19, 2009.
27. Data on file. Abraxane extravasation letter [written communication]. Los Angeles, CA: Abraxis
Oncology; January 24, 2005.
28. Photofrin (porfimer) [package insert]. Birmingham, AL: Axcan Scandipharm Inc; 2003.
29. Folotyn, (pralatrexate). [package insert]. Westminster, CO: Allos Therapeutics, Inc.; 2009.
30. Data on file. Rituxan general administration guidelines [written communication]. South San
Francisco, CA: Genentech; March 18, 2009.
31. Data on file. Occurence of extravasation or infiltration coincident with temsirolimus
administration. Madison, NJ: Wyeth Pharmaceuticals; March 19, 2009.
32. Data on file. Herceptin general administration guidelines [written communication]. South San
Francisco, CA: Genentech; March 18, 2009.
33. Zaltrap, (Ziv-aflibercept). [package insert]. Bridgewater, NJ: sanofi-aventis U.S. LLC; 2013.
Copyright © 2014 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 12/2014CCKM@uwhealth.org

15
Appendix A: Intravenous Chemotherapeutic Agents Evaluated for Extravasation Risk
Drug Name
(generic)
Extravasation Risk Comments Reference
Vesicant Irritant Not a known
vesicant/irritant
Ado-trastuzumab
emtansine √
20
alemtuzumab √ 1,10,20,21
aldesleukin √ 20,22
arsenic trioxide √ 20,21
asparaginase √ 1,10,20
azacitidine √ 10,20,23
belinostat √ 20
bendamustine

Case reports describe both
irritant and vesicant properties
1,10,20,24
bevacizumab √ 10,20,25
bleomycin √ 1,10,20,21
bortezomib √ Few reports describe as irritant 20,21
brentuximab
vedotin √
20
busulfan √ 10,20,21
cabazitaxel √ 20
carboplatin

Irritant at concentrations
greater than 10 mg/mL
1,10,21
carfilzomib √ 20
carmustine

Case reports describe both
irritant and vesicant properties
1,10,20,21
cetuximab √ 20,21
cisplatin

Concentrations >0.5 mg/mL may
result in tissue cellulitis, fibrosis
and necrosis
1,10,20,21
cladribine √ 1,10,20
clofarabine √ 10
cyclophosphamide √ 1,20,21
cytarabine √ 1,10,20
Copyright © 2014 University of Wisconsin Hospitals and Clinics Authority
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16
Drug Name
(generic)
Extravasation Risk Comments Reference
Vesicant Irritant Not a known
vesicant/irritant
dacarbazine √ 1,10,20,21
dactinomycin √ 1,10,20,21
daunorubicin √ 1,10,20,21
Daunorubicin
liposomal

1,10,20
decitabine √ 10,21
denileukin diftitox

Mild injection-site reactions
have been reported (8%)
21
docetaxel

Case reports describe both
irritant and vesicant properties
1,10,20,21
doxorubicin √ 1,10,20,21
doxorubicin
liposomal √
1,10,20,21
epirubicin √ 1,10,20,21
eribulin mesylate √ 20
etoposide √ 1,10,20,21
floxuridine √ 21
fludarabine √ 1,10,20,21
fluorouracil √ 1,20,21
gemcitabine

Case reports describe irritant
properties
1,10,20,21
ibritumomab Y 90

Local tissue damage may occur
depending on amount of
radioactivity present.
21
idarubicin √ 1,10,20,21
ifosfamide √ 1,20,21
ipilimumab √ 20
irinotecan √ 1,21
ixabepilone √ 1,21
leucovorin √ 20,21
mechlorethamine √ 1,20,21
Copyright © 2014 University of Wisconsin Hospitals and Clinics Authority
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17
Drug Name
(generic)
Extravasation Risk Comments Reference
Vesicant Irritant
Not a known
vesicant/irritant
melphalan

Case reports describe both
irritant and vesicant properties
1,10,20,21
mesna √ 20,21
methotrexate √ 1,10,20,21
mitomycin C √ 1,10,20,21
mitoxantrone

Case reports describe both
irritant and vesicant properties
1,10,20,21
nelarabine √ 10,26
obinutuzumab √ 1
ofatumumab √ 1
oxaliplatin

Case reports describe both
irritant and vesicant properties
1,10,20,21
paclitaxel

Case reports describe both
irritant and vesicant properties
1,10,20,21
paclitaxel protein
bound √
Case reports describe both
irritant and vesicant properties
1,10,20 27
panitumumab √ 20,21
pegaspargase √ 10
pemetrexed √ 1,10,20
pentostatin √ 10,21
pertuzumab √ 1,20
porfimer √ 28
pralatrexate √ 29
raltitrexed √ 1,10,20
ramucirumab √ 1
rituximab √ 1,10,20 30
romidepsin √ 20
streptozocin √ 1,10,21
temsirolimus √ 1,20,31
Copyright © 2014 University of Wisconsin Hospitals and Clinics Authority
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18
Drug Name
(generic)
Extravasation Risk Comments Reference
Vesicant Irritant
Not a known
vesicant/irritant
temozolomide √ 20
teniposide √ 1,10,20,21
thiotepa √ 1,10,20
topotecan √ 1,21
tositumomab and
iodine - 131

Tositumomab itself is not a
vesicant, but local tissue
damage may occur depending
on the amount of radioactivity
present.
21
trastuzumab √ 1,10,20 32
vinblastine √
1,10,20,21
vincristine √
1,10,20,21
vindesine √
1,10,20,21
vinorelbine √
1,10,20,21
ziv-aflibercept
√ 33
Copyright © 2014 University of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 12/2014CCKM@uwhealth.org