Vesicant & irritant chemotherapy

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.

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.