Vesicant & irritant chemotherapy

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Always double check information at the primary references linked below.
==Chemotherapy vesicant & irritant properties and suggested management for extravasation==
Always stop infusion of the causative medication first and, if appropriate, elevate the affected extremity. The venous access should not be removed immediately, since it can be used to attempt aspirating extravasated fluid and for administration of an antidote, if clinically appropriate. If an antidote is not going to be used, the venous access can be removed after aspiration of the extravasated fluid has been attempted. In general--aside from the exceptions listed below--keeping the extravasation cold is preferable to cause vasoconstriction, to prevent spread of the medication, and to decrease inflammation/pain. Some medications are more likely to have vesicant properties in high concentrations or large volumes.
In order from most likely to least likely to cause damage when extravasation occurs: vesicants (most likely), exfoliants, irritants, inflammitants, and neutrals (least likely). Some references primarily classify drugs as vesicants or irritants, so those categories will preferentially be used below over classifying as inflammitants and exfoliants. It is also important to note that some medications are classified differently by different references.
The following information is a compilation from the various resources listed below.Chemotherapy extravasation injury (UpToDate)Beth Israel Deaconess Medical Center. Administration and Extravasation Management of Vesicant Chemotherapy Agents. 11/2010 revision.Polovich M, Whitford JM, Olsen M. Chemotherapy and biotherapy guidelines and recommendations for practice, 3rd ed, Oncology Nursing Society, Pittsburgh, PA, 2009. Section V: Immediate Complications of cytotoxic therapy, p.105.ONS (Oncology Nursing Society) chemotherapy extravasation FAQsWengström Y, Margulies A; European Oncology Nursing Society Task Force. European Oncology Nursing Society extravasation guidelines. Eur J Oncol Nurs. 2008 Sep;12(4):357-61. link to original article EuroPMCFiras Y Kreidieh, Hiba A Moukadem, and Nagi S El Saghir. Overview, prevention and management of chemotherapy extravasation. World J Clin Oncol. 2016 Feb 10; 7(1): 87–97. link to original article EuroPMCBeatson West of Scotland Cancer Centre Chemotherapy extravasation guideline (locally hosted backup)West Suffolk Hospitals extravasation guideline (locally hosted backup)
Drug 	Vesicant or Irritant 	Apply Heat or Cold 	Additional treatment/antidote
Aclarubicin (Aclacinomycin) 	Irritant 	Cold (different suggestions for anthracyclines depending on reference):
*Apply cold pack initially for 30 to 60 minutes, then repeat every 15 minutes on day 1 only. Remove cold pack at least 15 minutes before dexrazoxane therapy.
*Apply cold pack intermittently for 15 minutes at a time, four times per day for 3 days	(off-label, based on general management strategies for anthracyclines) Dexrazoxane (Totect): Dexrazoxane should be administered over 1 to 2 hours IV at the recommended doses below, daily for 3 consecutive days. Site of administration should be in a large vein away from the extravasation. The first infusion should be initiated as soon as possible and within the first six hours after extravasation.
*Day one: 1000 mg/m2
*Day two: 1000 mg/m2
*Day three: 500 mg/m2
If cooling techniques are being used, withhold cooling 15 minutes before and after the infusion. Infuse in an extremity or area other than the one affected by extravasation. Reduce dose by 50% for patients with creatinine clearance less than 40 mL/min.
Trastuzumab emtansine (Kadcyla) 	Irritant 	Cold - 15 to 20 minutes at a time for at least four times per day for 24 hours 	None known
Amsacrine (Amsidine) 	Vesicant 	Cold - 15 to 20 minutes at a time for at least four times per day for 24 hours 	None known
Arsenic trioxide (Trisenox) 	Irritant 	Cold - 15 to 20 minutes at a time for at least four times per day for 24 hours 	None known
Bendamustine 	Irritant (usually)Vesicant (rare) 	Cold - for 6 to 12 hours 	None known
Bleomycin (Blenoxane) 	Irritant or neutral, depending on reference 	Cold - 15 to 20 minutes at a time for at least four times per day for 24 hours 	None known
Bortezomib (Velcade) 	Irritant 	Cold - 15 to 20 minutes at a time for at least four times per day for 24 hours 	None known
Busulfan (Myleran) 	Irritant 	Cold - 15 to 20 minutes at a time for at least four times per day for 24 hours 	None known
Carboplatin (Paraplatin) 	Irritant 	Cold - Every 8 hours for 3 days; if using sodium thiosulfate, apply cold pack for 6 to 12 hours after administration of sodium thiosulfate	Sodium Thiosulfate: Mix 4 mL of 10% sodium thiosulfate with 6 mL sterile water (yields 10 mL of 1/6 molar sodium thiosulfate). Inject 5 mL subcutaneously using a 25 gauge needle, changing needles between each injection, into affected area in a pinwheel fashion.OR DMSO (Dimethylsulfoxide) 99%: 4 drops per 10 square centimeters of skin surface applied topically over area twice the size affected every 8 hours for 7 days. Allow to air dry.
Carmustine (BCNU) 	Vesicant/Irritant (depending on reference) 	Cold - 15 to 20 minutes at a time for at least four times per day for 24 hours 	Manage conservatively as first line option with supportive non-pharmacologic strategies. Hyaluronidase may be used in extreme scenarios such as large volume extravasation or severe irritation.Hyaluronidase: Inject a total of 1 mL (200 units) divided into 5 to 10 subcutaneous injections of 0.1 to 0.2 mL in a pinwheel fashion using a 25 gauge needle, changing needles between each injection, into affected area. May use up to 250 units if symptoms persist.
Cisplatin (Platinol) 	Vesicant (in concentrations ≥0.5 mg/mL)Irritant (in concentrations less than 0.5 mg/mL)	Cold - Every 8 hours for 3 days; if using sodium thiosulfate, apply cold pack for 6 to 12 hours after administration of sodium thiosulfate	Sodium Thiosulfate: Mix 4 mL of 10% sodium thiosulfate with 6 mL sterile water (yields 10 mL of 1/6 molar sodium thiosulfate). Inject 5 mL subcutaneously using a 25 gauge needle, changing needles between each injection, into affected area in a pinwheel fashion.OR DMSO (Dimethylsulfoxide) 99%: 4 drops per 10 square centimeters of skin surface applied topically over area twice the size affected every 8 hours for 7 days. Allow to air dry.
Cladribine (Leustatin) 	Irritant or neutral, depending on reference 	Cold - 15 to 20 minutes at a time for at least four times per day for 24 hours 	None known
Cyclophosphamide (Cytoxan) 	Irritant or neutral, depending on reference 	Cold - 15 to 20 minutes at a time for at least four times per day for 24 hours 	None known
Cytarabine (Ara-C) 	Irritant or neutral, depending on reference 	Cold - 15 to 20 minutes at a time for at least four times per day for 24 hours 	None known
Cytarabine liposomal (DepoCyt) 	Irritant 	Cold - 15 to 20 minutes at a time for at least four times per day for 24 hours 	None known
Dacarbazine (DTIC) 	Irritant 	Cold - If using sodium thiosulfate, apply cold pack for 6 to 12 hours after administration of sodium thiosulfate 	Manage conservatively; shield exposed tissues from light.OR Sodium Thiosulfate: Mix 4 mL of 10% sodium thiosulfate with 6 mL sterile water (yields 10 mL of 1/6 molar sodium thiosulfate). Inject 5 mL subcutaneously using a 25 gauge needle, changing needles between each injection, into affected area in a pinwheel fashion. NOTE: Sodium thiosulfate is recommended only when concentrated dacarbazine is extravasated. There are no clinical reports of the use of sodium thiosulfate following dacarbazine extravasation. Its use for dacarbazine extravasation is based on evidence that it has worked as an antidote for dacarbazine-induced skin toxicity.
Dactinomycin (Cosmegen) 	Vesicant 	Cold - 15 to 20 minutes at a time for at least four times per day for 24 hours 	None known
Daunorubicin (Cerubidine) 	Vesicant 	Cold (different suggestions depending on reference):
*Apply cold pack initially for 30 to 60 minutes, then repeat every 15 minutes on day 1 only. Remove cold pack at least 15 minutes before dexrazoxane therapy.
*Apply cold pack intermittently for 15 minutes at a time, four times per day for 3 days	Dexrazoxane (Totect): Dexrazoxane should be administered over 1 to 2 hours IV at the recommended doses below, daily for 3 consecutive days. Site of administration should be in a large vein away from the extravasation. The first infusion should be initiated as soon as possible and within the first six hours after extravasation.
*Day one: 1000 mg/m2
*Day two: 1000 mg/m2
*Day three: 500 mg/m2
If cooling techniques are being used, withhold cooling 15 minutes before and after the infusion. Infuse in an extremity or area other than the one affected by extravasation. Reduce dose by 50% for patients with creatinine clearance less than 40 mL/min.
Daunorubicin liposomal (DaunoXome) 	Irritant 	Cold - 15 to 20 minutes at a time for at least four times per day for 24 hours 	No additional treatment, e.g. Dexrazoxane (Totect), is recommended.
Docetaxel (Taxotere) 	Irritant (usually)Vesicant (rare) 	Cold (different suggestions depending on reference):
*Apply cold pack 15 to 20 minutes at a time for at least four times per day for 24 hours 
*Apply ice to the area for 15 to 20 minutes each hour for 4 hours. Caution: excessive cold can cause tissue damage.	Hyaluronidase: Inject a total of 1 mL (200 units) divided into 5 to 10 subcutaneous injections of 0.1 to 0.2 mL in a pinwheel fashion using a 25 gauge needle, changing needles between each injection, into affected area. May use up to 250 units if symptoms persist.
Doxorubicin (Adriamycin) 	Vesicant 	Cold (different suggestions depending on reference):
*Apply cold pack initially for 30 to 60 minutes, then repeat every 15 minutes on day 1 only. Remove cold pack at least 15 minutes before dexrazoxane therapy.
*Apply cold pack intermittently for 15 minutes at a time, four times per day for 3 days	Dexrazoxane (Totect): Dexrazoxane should be administered over 1 to 2 hours IV at the recommended doses below, daily for 3 consecutive days. Site of administration should be in a large vein away from the extravasation. The first infusion should be initiated as soon as possible and within the first six hours after extravasation.
*Day one: 1000 mg/m2
*Day two: 1000 mg/m2
*Day three: 500 mg/m2
If cooling techniques are being used, withhold cooling 15 minutes before and after the infusion. Infuse in an extremity or area other than the one affected by extravasation. Reduce dose by 50% for patients with creatinine clearance less than 40 mL/min.
Pegylated liposomal doxorubicin (Doxil) 	Irritant 	Cold - 15 to 20 minutes at a time for at least four times per day for 24 hours 	No additional treatment, e.g. Dexrazoxane (Totect), is recommended.
Epirubicin (Ellence) 	Vesicant 	Cold (different suggestions depending on reference):
*Apply cold pack initially for 30 to 60 minutes, then repeat every 15 minutes on day 1 only. Remove cold pack at least 15 minutes before dexrazoxane therapy.
*Apply cold pack intermittently for 15 minutes at a time, four times per day for 3 days	Dexrazoxane (Totect): Dexrazoxane should be administered over 1 to 2 hours IV at the recommended doses below, daily for 3 consecutive days. Site of administration should be in a large vein away from the extravasation. The first infusion should be initiated as soon as possible and within the first six hours after extravasation.
*Day one: 1000 mg/m2
*Day two: 1000 mg/m2
*Day three: 500 mg/m2
If cooling techniques are being used, withhold cooling 15 minutes before and after the infusion. Infuse in an extremity or area other than the one affected by extravasation. Reduce dose by 50% for patients with creatinine clearance less than 40 mL/min.
Etoposide (Vepesid) 	Irritant 	Heat (different suggestions depending on reference):
*15 to 20 minutes at a time for at least four times per day for 24-48 hours 
*warm compresses for 30 to 60 minutes, then alternate off/on every 15 minutes for 1 day	Hyaluronidase: Inject a total of 1 mL (200 units) divided into 5 to 10 subcutaneous injections of 0.1 to 0.2 mL in a pinwheel fashion using a 25 gauge needle, changing needles between each injection, into affected area. May use up to 250 units if symptoms persist.
Floxuridine (FUDR) 	Irritant 	Cold - 15 to 20 minutes at a time for at least four times per day for 24 hours 	None known
Fluorouracil (5-FU) 	Irritant 	Cold - 15 to 20 minutes at a time for at least four times per day for 24 hours 	None known
Gemcitabine (Gemzar) 	Irritant 	Cold - 15 to 20 minutes at a time for at least four times per day for 24 hours 	None known
Idarubicin (Idamycin) 	Vesicant 	Cold (different suggestions depending on reference):
*Apply cold pack initially for 30 to 60 minutes, then repeat every 15 minutes on day 1 only. Remove cold pack at least 15 minutes before dexrazoxane therapy.
*Apply cold pack intermittently for 15 minutes at a time, four times per day for 3 days	Dexrazoxane (Totect): Dexrazoxane should be administered over 1 to 2 hours IV at the recommended doses below, daily for 3 consecutive days. Site of administration should be in a large vein away from the extravasation. The first infusion should be initiated as soon as possible and within the first six hours after extravasation.
*Day one: 1000 mg/m2
*Day two: 1000 mg/m2
*Day three: 500 mg/m2
If cooling techniques are being used, withhold cooling 15 minutes before and after the infusion. Infuse in an extremity or area other than the one affected by extravasation. Reduce dose by 50% for patients with creatinine clearance less than 40 mL/min.
Ifosfamide (Ifex) 	Irritant or neutral, depending on reference 	Cold (different suggestions depending on reference):
*60 minutes every 8 hours for 3 days
*15 to 20 minutes at a time for at least four times per day for 24 hours	DMSO (Dimethylsulfoxide) 99%: 4 drops per 10 square centimeters of skin surface applied topically over area twice the size affected every 8 hours for 7 days. Allow to air dry.
Irinotecan (Camptosar) 	Irritant 	Cold - 15 to 20 minutes at a time for at least four times per day for 24 hours 	None known
Ixabepilone (Ixempra) 	Irritant 	Cold - 15 to 20 minutes at a time for at least four times per day for 24 hours 	None known
Mechlorethamine (Mustargen) 	Vesicant 	Cold - for 6 to 12 hours after administration of sodium thiosulfate 	Sodium Thiosulfate: Mix 4 mL of 10% sodium thiosulfate with 6 mL sterile water (yields 10 mL of 1/6 molar sodium thiosulfate). Administration varies depending on reference:
*Inject 5 mL subcutaneously using a 25 gauge needle, changing needles between each injection, into affected area in a pinwheel fashion.
*For every 1 mg of mechlorethamine suspected to have extravasated, inject 2 mL of the 1/6 molar sodium thiosulfate solution subcutaneously into the extravasation site using a 25 gauge or smaller needle.
Melphalan (Alkeran) 	Irritant or neutral, depending on reference 	Cold - 15 to 20 minutes at a time for at least four times per day for 24 hours 	None known
Mitomycin (Mutamycin) 	Vesicant 	Cold - 15 to 20 minutes at a time for at least four times per day for 24 hours 	Sodium Thiosulfate: Mix 4 mL of 10% sodium thiosulfate with 6 mL sterile water (yields 10 mL of 1/6 molar sodium thiosulfate). Inject 5 mL subcutaneously using a 25 gauge needle, changing needles between each injection, into affected area in a pinwheel fashion.
Mitoxantrone (Novantrone) 	Irritant (usually)Vesicant (rare) 	Cold - Apply cold packs for 15 to 20 minutes four times per day for 1 to 2 days. 	None known
Oxaliplatin (Eloxatin) 	Irritant (usually)Vesicant (rare) 	Heat - Apply warm compresses to extravasation site for 1 hour. Caution: excessive heat can cause tissue damage. 	Sodium Thiosulfate: Mix 4 mL of 10% sodium thiosulfate with 6 mL sterile water (yields 10 mL of 1/6 molar sodium thiosulfate). Inject 5 mL subcutaneously using a 25 gauge needle, changing needles between each injection, into affected area in a pinwheel fashion.Corticosteroids: For large extravasations, Dexamethasone (Decadron) 8 mg PO twice per day for up to 14 days is recommended to help mitigate the local inflammatory reaction.
Paclitaxel (Taxol) 	Irritant (usually)Vesicant (rare) 	Cold generally recommended (different suggestions depending on reference):
*Apply cold pack 15 to 20 minutes at a time for at least four times per day for 24 hours 
*Apply ice to the area for 15 to 20 minutes each hour for 4 hours. Caution: excessive cold can cause tissue damage.
Controversial use of heat: EONS (European Oncology Nurses Society) suggests application of heat to encourage circulation and to dilute & diffuse the chemotherapy.	Hyaluronidase: Inject a total of 1 mL (200 units) divided into 5 to 10 subcutaneous injections of 0.1 to 0.2 mL in a pinwheel fashion using a 25 gauge needle, changing needles between each injection, into affected area. May use up to 250 units if symptoms persist.
Paclitaxel, nanoparticle albumin-bound (Abraxane)	Irritant 	Cold (different suggestions depending on reference):
*Apply cold pack 15 to 20 minutes at a time for at least four times per day for 24 hours 
*Apply ice to the area for 15 to 20 minutes each hour for 4 hours. Caution: excessive cold can cause tissue damage.	None known
Plicamycin (Mithracin) 	Vesicant/Irritant (depending on reference) 	Cold - 15 to 20 minutes at a time for at least four times per day for 24 hours 	None known
Raltitrexed (Tomudex) 	Irritant 	Cold - 15 to 20 minutes at a time for at least four times per day for 24 hours 	None known
Streptozocin (Zanosar) 	Irritant 	Cold - 15 to 20 minutes at a time for at least four times per day for 24 hours 	None known
Teniposide (Vumon) 	Irritant 	Cold - 15 to 20 minutes at a time for at least four times per day for 24 hours 	Hyaluronidase: Inject a total of 1 mL (200 units) divided into 5 to 10 subcutaneous injections of 0.1 to 0.2 mL in a pinwheel fashion using a 25 gauge needle, changing needles between each injection, into affected area. May use up to 250 units if symptoms persist.
Thiotepa (Thioplex) 	Irritant or neutral, depending on reference 	Cold - 15 to 20 minutes at a time for at least four times per day for 24 hours 	None known
Topotecan (Hycamtin) 	Irritant 	Cold - 15 to 20 minutes at a time for at least four times per day for 24 hours 	None known
Trabectedin (Yondelis) 	Vesicant 	Cold - 15 to 20 minutes at a time for at least four times per day for 24 hours 	None known
Vinblastine (Velban) 	Vesicant 	Heat - 15 to 20 minutes at a time for at least four times per day for 24 to 48 hours 	Hyaluronidase: Inject a total of 1 mL (200 units) divided into 5 to 10 subcutaneous injections of 0.1 to 0.2 mL in a pinwheel fashion using a 25 gauge needle, changing needles between each injection, into affected area. May use up to 250 units if symptoms persist.
Vincristine (Oncovin) 	Vesicant 	Heat - 15 to 20 minutes at a time for at least four times per day for 24 to 48 hours 	Hyaluronidase: Inject a total of 1 mL (200 units) divided into 5 to 10 subcutaneous injections of 0.1 to 0.2 mL in a pinwheel fashion using a 25 gauge needle, changing needles between each injection, into affected area. May use up to 250 units if symptoms persist.
Vincristine liposomal (Marqibo) 	Vesicant/Irritant (depending on reference) 	Heat - 15 to 20 minutes at a time for at least four times per day for 24 to 48 hours 	No formal recommendation, but depending on clinical condition could consider extrapolating from management of other vinca alkaloids: Hyaluronidase: Inject a total of 1 mL (200 units) divided into 5 to 10 subcutaneous injections of 0.1 to 0.2 mL in a pinwheel fashion using a 25 gauge needle, changing needles between each injection, into affected area. May use up to 250 units if symptoms persist.
Vindesine (Eldisine) 	Vesicant 	Heat - 15 to 20 minutes at a time for at least four times per day for 24 to 48 hours 	Hyaluronidase: Inject a total of 1 mL (200 units) divided into 5 to 10 subcutaneous injections of 0.1 to 0.2 mL in a pinwheel fashion using a 25 gauge needle, changing needles between each injection, into affected area. May use up to 250 units if symptoms persist.
Vinorelbine (Navelbine) 	Vesicant 	Heat - 15 to 20 minutes at a time for at least four times per day for 24 to 48 hours 	Hyaluronidase: Inject a total of 1 mL (200 units) divided into 5-10 subcutaneous injections of 0.1 to 0.2 mL in a pinwheel fashion using a 25 gauge needle, changing needles between each injection, into affected area. May use up to 250 units if symptoms persist.
===Neutrals===
These medications are generally considered to be unlikely to cause injury when extravasation occurs:
*Alemtuzumab (Campath)
*Bevacizumab (Avastin)
*Bleomycin (Blenoxane) (irritant or neutral, depending on reference)
*Cetuximab (Erbitux)
*Cladribine (Leustatin) (irritant or neutral, depending on reference)
*Clofarabine (Clolar)
*Cyclophosphamide (Cytoxan) (irritant or neutral, depending on reference)
*Cytarabine (Ara-C) (irritant or neutral, depending on reference)
*Fludarabine (Fludara)
*Gemcitabine (Gemzar) (irritant or neutral, depending on reference)
*Ifosfamide (Ifex) (irritant or neutral, depending on reference)
*Melphalan (Alkeran) (irritant or neutral, depending on reference)
*Nelarabine (Arranon)
*Pegaspargase (Oncaspar)
*Pemetrexed (Alimta)
*Pentostatin (Nipent)
*Rituximab (Rituxan)
*Thiotepa (Thioplex) (irritant or neutral, depending on reference)
*Trastuzumab (Herceptin)
===Inflammitants===
These medications are generally described as causing mild to moderate inflammation when extravasation occurs. Due to some references not using this classification, the only drugs listed in this section are ones which were unclassified by some resources, yet classified by others as inflammitants.
*Azacitidine (Vidaza)
*Methotrexate (MTX)
=="Localize and neutralize" or "disperse and dilute"==
The 2008 European Oncology Nursing Society extravasation guidelines<ref name=EONS2008%3E</ref> recommend this management for the following medications:
==="Localize and neutralize"===
*Amsacrine (Amsidine)
*Carmustine (BCNU)
*Dacarbazine (DTIC)
*Dactinomycin (Cosmegen)
*Daunorubicin (Cerubidine)
*Doxorubicin (Adriamycin)
*Epirubicin (Ellence)
*Idarubicin (Idamycin)
*Mechlorethamine (Mustargen)
*Mitomycin (Mutamycin)
*Streptozocin (Zanosar)
==="Disperse and dilute"===
*Vinblastine (Velban)
*Vincristine (Oncovin)
*Vindesine (Eldisine)
*Vinorelbine (Navelbine)
==Definitions==
*Extravasation: Leakage of a medication into tissue or extravascular space around the infusion site. May be due to direct leakage from the venous access device or from elsewhere in the vessel (such as from previous phlebotomy).
*Flare reaction: A skin reaction to a medication which is an allergic response. 
*Vesicant: Medication that may causes severe and/or irreversible tissue injury and necrosis.
*Irritant: Medication that can cause local inflammatory reactions at the infusion site, which may include: burning, swelling, pain, inflammation, tightness, or phlebitis. Clinical exam may reveal warmth, erythema, or tenderness.
==Reference==
Category:Supportive oncology