Vesicant & irritant chemotherapy

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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.

The following information is a compilation from the various resources listed below.[1][2][3][4][5]

Drug Vesicant or Irritant Apply Heat or Cold Additional treatment/antidote
Ado-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 (Treanda) Vesicant Cold - for 6 to 12 hours None known
Bleomycin (Blenoxane) Irritant 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 (BiCNU) 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 <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 Cold - 15 to 20 minutes at a time for at least four times per day for 24 hours None known
Cyclophosphamide (Cytoxan) Irritant 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 <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 <40 mL/min.

Doxorubicin liposomal (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 <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.
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 <40 mL/min.

Ifosfamide (Ifex) Irritant 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 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 4 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 8 mg PO BID 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
Streptozocin (Zanosar) Vesicant 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 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.

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

  1. Chemotherapy extravasation injury (UpToDate)
  2. Beth Israel Deaconess Medical Center. Administration and Extravasation Management of Vesicant Chemotherapy Agents. 11/2010 revision.
  3. 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.
  4. ONS (Oncology Nursing Society) chemotherapy extravasation FAQs
  5. Wengström 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 PubMed
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