Vesicant & irritant chemotherapy

Definitions

• Extravasation: Leakage of a medication into tissue around the infusion site.
• Flare reaction: A skin reaction to a medication which is an allergic response.
• Vesicants: Medications that may cause severe and/or irreversible tissue injury and necrosis.
• Irritants: Medications that can cause local inflammatory reactions at the infusion site, which may include: swelling, pain, inflammation, or phlebitis.

Vesicant chemotherapy

Some medications have vesicant properties in higher concentrations or large volumes.

• Amsacrine (Amsidine)
• Carmustine (BiCNU) (listed by some references as irritant)
• Cisplatin (Platinol) (concentration >=0.5 mg/mL)
• Dactinomycin (Cosmegen)
• Daunorubcin (Cerubidine)
• Docetaxel (Taxotere) (rare; also listed as an irritant)
• Doxorubicin (Adriamycin)
• Epirubicin (Ellence)
• Idarubicin (Idamycin)
• Mechlorethamine (Mustargen)
• Mitomycin (Mutamycin)
• Mitoxantrone (Novantrone) (rare; also listed as an irritant)
• Oxaliplatin (Eloxatin) (rare; also listed as an irritant)
• Paclitaxel (Taxol) (rare; also listed as an irritant)
• Streptozocin (Zanosar)
• Trabectedin (Yondelis)
• Vinblastine (Velban)
• Vincristine (Oncovin)
• Vindesine (Eldisine)
• Vinorelbine (Navelbine)

Irritant chemotherapy

• Arsenic trioxide (Trisenox)
• Bleomycin (Blenoxane)
• Bortezomib (Velcade)
• Busulfan (Myleran)
• Carboplatin (Paraplatin)
• Carmustine (BiCNU) (listed by some references as vesicant)
• Cisplatin (Platinol) (concentration <0.5mg/mL)
• Cladribine (Leustatin)
• Cytarabine liposomal (DepoCyt)
• Dacarbazine (DTIC)
• Daunorubicin liposomal (Daunoxome)
• Docetaxel (Taxotere) (also listed as a rare vesicant)
• Doxorubicin liposomal (Doxil)
• Etoposide (Vepesid)
• Fluorouracil (5-FU)
• Gemcitabine (Gemzar)
• Ifosfamide (Ifex)
• Irinotecan (Camptosar)
• Melphalan (Alkeran)
• Mitoxantrone (Novantrone) (also listed as a rare vesicant)
• Oxaliplatin (Eloxatin) (also listed as a rare vesicant)
• Paclitaxel (Taxol) (also listed as a rare vesicant)
• Paclitaxel, nanoparticle albumin-bound (Abraxane)
• Plicamycin (Mithracin)
• Teniposide (Vumon)
• Thiotepa (Thioplex)
• Topotecan (Hycamtin)
• Vincristine liposomal (Marqibo)

Suggested management of chemotherapy extravasation

Always stop infusion of the causative medication first and, if appropriate, elevate the affected extremity. 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.

Drug	Vesicant or Irritant	Apply Heat or Cold	Known Antidote	Treatment
Arsenic Trioxide	Irritant	Cold	None	None
Bleomycin	Irritant	Cold	None	None
Bortezomib	Irritant	Cold	None	None
Busulfan	Irritant	Cold	None	None
Carboplatin	Irritant	Cold – every 8 hours for 3 days	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	Irritant	Cold	Manage conservatively	Manage conservatively as first line option with supportive non-pharmacologic care measures. Hyaluronidase maybe used in extreme cases such as large volume extravasation, severe irritation, etc.
			Hyaluronidase	Inject a total of 1 mL (200 units) divided into 5-10 subcutaneous injections of 0.1-0.2 mL in a pinwheel fashion using a 25 gauge needle, changing needles between each injection, into affected area up to 250 units or until symptoms resolve.
Cisplatin	Irritant (in concentrations of <0.5 mg/mL)	Cold – 60 minutes every 8 hours for 3 days	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 afftected 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	Irritant	Cold	None	None
Dacarbazine	Irritant	Cold	Manage Conservatively	Manage conservatively with attention to protect exposed tissues from light following drug administration
			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 afftected 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	Vesicant	Cold	None	None
Daunorubicin	Vesicant	Cold	Dexrazoxane	Dexrazoxane once daily for 3 consecutive days. The first infusion should be initiated as soon as possible and within the first six hours after extravasation. Recommended dose: (Maximum daily dose) Day one: 1000 mg/m² (2000 mg) Day two: 1000 mg/m² (2000 mg) Day three: 500 mg/m² (1000 mg) 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 the extravasation. Reduce dose by 50% for patients with creatinine clearance <40 mL/min.
Docetaxel	Irritant	Cold	Hyaluronidase	Inject a total of 1 mL (200 units) divided into 5-10 subcutaneous injections of 0.1-0.2 mL in a pinwheel fashion using a 25 gauge needle, changing needles between each injection, into affected area up to 250 units or until symptoms resolve.
Doxorubicin	Vesicant	Cold - Apply intermittently for 15 minutes, 4 times daily for 3 days	Dexrazoxane	Dexrazoxane once daily for 3 consecutive days. The first infusion should be initiated as soon as possible and within the first six hours after extravasation. Recommended dose: (Maximum daily dose) Day one: 1000 mg/m² (2000 mg) Day two: 1000 mg/m² (2000 mg) Day three: 500 mg/m² (1000 mg) 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 the extravasation. Reduce dose by 50% for patients with creatinine clearance <40 mL/min.
Epirubicin	Vesicant	Cold	Dexrazoxane	Dexrazoxane once daily for 3 consecutive days. The first infusion should be initiated as soon as possible and within the first six hours after extravasation. Recommended dose: (Maximum daily dose) Day one: 1000 mg/m² (2000 mg) Day two: 1000 mg/m² (2000 mg) Day three: 500 mg/m² (1000 mg) 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 the extravasation. Reduce dose by 50% for patients with creatinine clearance <40 mL/min.
Etoposide	Irritant	Heat - Apply 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 5-10 subcutaneous injections of 0.1-0.2 mL in a pinwheel fashion using a 25 gauge needle, changing needles between each injection, into affected area up to 250 units or until symptoms resolve.
Fluorouracil	Irritant	Cold	None	None
Idarubicin	Vesicant	Cold	Dexrazoxane	Dexrazoxane once daily for 3 consecutive days. The first infusion should be initiated as soon as possible and within the first six hours after extravasation. Recommended dose: (Maximum daily dose) Day one: 1000 mg/m² (2000 mg) Day two: 1000 mg/m² (2000 mg) Day three: 500 mg/m² (1000 mg) 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 the extravasation. Reduce dose by 50% for patients with creatinine clearance <40 mL/min.
Ifosfamide	Irritant	Cold - 60 minutes every 8 hours for 3 days.	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	Irritant	Cold	None	None
Liposomal cytarabine	Irritant	Cold	None	None
Liposomal daunorubicin	Irritant	Cold	None	None
Liposomal doxorubicin	Irritant	Cold	None	None
Liposomal vincristine	Irritant	Cold	None	None
Mechlorethamine	Vesicant	Cold	Sodium Thiosulfate	Mix 4 mL of 10% sodium thiosulfate with 6 mL sterile water (yields 10mL 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.
Melphalan	Irritant	Cold	None	None
Mitomycin C	Vesicant	Cold	Sodium Thiosulfate	Mix 4 mL of 10% sodium thiosulfate with 6 mL sterile water (yields 10mL of 1/6 molar sodium thiosulfate). Inject 5 mL subcutaneously using a 25 gauge needle, changing needles between each injection, into afftected area in a pinwheel fashion.
Mitoxantrone	Irritant	Cold - Apply cold packs for 15-20 minutes 4 times per day for 1-2 days.	None	None
Oxaliplatin	Vesicant	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 10mL of 1/6 molar sodium thiosulfate). Inject 5 mL subcutaneously using a 25 gauge needle, changing needles between each injection, into afftected area in a pinwheel fashion.
Paclitaxel	Irritant	Cold - Apply ice to the area for 15-20 minutes each hour for 4 hours. Caution: excessive cold can cause tissue damage.	Hyaluronidase	Inject a total of 1 mL (200 units) divided into 5-10 subcutaneous injections of 0.1-0.2 mL in a pinwheel fashion using a 25 gauge needle, changing needles between each injection, into affected area up to 250 units or until symptoms resolve.
Paclitaxel, nanoparticle albumin-bound	Irritant	Cold	None	None
Plicamycin	Irritant	Cold	None	None
Teniposide	Irritant	Cold	Hyaluronidase	Inject a total of 1 mL (200 units) divided into 5-10 subcutaneous injections of 0.1-0.2 mL in a pinwheel fashion using a 25 gauge needle, changing needles between each injection, into affected area up to 250 units or until symptoms resolve.
Thiotepa	Irritant	Cold	None	None
Topotecan	Irritant	Cold	None	None
Vinblastine	Vesicant	Heat	Hyaluronidase	Inject a total of 1 mL (200 units) divided into 5-10 subcutaneous injections of 0.1-0.2 mL in a pinwheel fashion using a 25 gauge needle, changing needles between each injection, into affected area up to 250 units or until symptoms resolve.
Vincristine	Vesicant	Heat	Hyaluronidase	Inject a total of 1 mL (200 units) divided into 5-10 subcutaneous injections of 0.1-0.2 mL in a pinwheel fashion using a 25 gauge needle, changing needles between each injection, into affected area up to 250 units or until symptoms resolve.
Vinorelbine	Vesicant	Heat	Hyaluronidase	Inject a total of 1 mL (200 units) divided into 5-10 subcutaneous injections of 0.1-0.2 mL in a pinwheel fashion using a 25 gauge needle, changing needles between each injection, into affected area up to 250 units or until symptoms resolve.

Reference

Chemotherapy extravasation injury (UpToDate)