Anthracyclines extravasation

Hyaluronidase is the antidote of choice for vinca alkaloid and high-concentration epipodophyllotoxin extravasations. Hyaluronidase breaks down hyaluronic acid, which functions as tissue cement. This promotes absorption of the extravasated drug away from the local site. Hyaluronidase also may be used for paclitaxel extravasations, but there are conflicting reports regarding its efficacy.39 Hyaluronidase should not be used with anthracycline extravasations because enhancement of local spread may occur. 

Dimethyl sulfoxide has also been investigated as a potential therapeutic agent in conditions such as scleroderma, interstitial cystitis, rheumatoid arthritis, and acute musculoskeletal injuries, and as an analgesic. It has also been recommended for the treatment of anthracycline extravasation and has been investigated as a potential cryoprotectant. ... 

Anthracyclines Doxorubicin, epirubicin Myelosuppression, cardiomyopathy Alopecia, nausea, vomiting, stomatitis, ulceration necrosis with extravasation, red-colored urine, radiation-recall effect... 

Anthracycline, mechlorethamine, and vinca alkaloid extravasations typically cause immediate pain. 

Anthracyclines Cold packs DMSO 50-99% Alternative Dexrazoxane Apply 1-2 mL to area of skin twice the size of lesion every 6-8 hours for 7-14 days 1000 mg/m2 IV within 5 hours of extravasation followed by 1000 mg/m2 on day 2,500 mg/m2 day 3 Allow to air dry. Do not cover Promising new agent expensive, may not be reimbursed by payors. 

Dimethylsulfoxide (DMSO) is the antidote of choice for anthracycline and mitomycin C extravasations. It readily penetrates tissues and increases diffusion in the tissue area. In addition, DMSO is a free-radical scavenger that functions to block this principal mechanism of anthracycline- and mitomycin C-mediated tissue injury. DMSO generally is well tolerated but may cause some mild burning and redness. Dexrazoxane is a free-radical scavenger typically used for cardio-protection from anthracyclines. Promising results have been seen with large-volume extravasations and in a mouse model.38... 

Anthracyclines—monitor cumulative dose for possible cardiac toxicity vesicant-avoid extravasation... 

Daunorubicin -anthracycline antitumor antibiotic DNA intercalating agent -bone marrow suppression -nausea and vomiting—mild to moderate -mucocutaneous effects (mucositis, stomatitis, diarrhea) -vesicant if extravasated —cardiotoxicity (550 mg/M2) -Liposomal daunorubicin there is significantly less bone marrow suppression, nausea and vomiting, stomatitis, and cardiotoxicity... 

Jensen JN, Lock-Andersen J, Langer SW, Mejer J. Dexrazoxane—a promising antidote in the treatment of accidental extravasation of anthracyclines. Scand J Plast Reconstr Surg Hand Surg 2003 37(3) 174—5. 

Bos AM, van der Graaf WT, WUlemse PH. A new conservative approach to extravasation of anthracyclines with dimethylsulfoxide and dexrazoxane. Acta Oncol 2001 40(4) 541-2. 

Among several antidotes for the treatment of vinca alkaloid extravasation, hyaluronidase is the most effective (79). Seven patients with extravasation of vincristine, vinblastine, or vinorelbine received hyaluronidase 250 units diluted in 6 ml of 0.9% saline, through the indwelling needle or, when the needle had been already removed, as six subcutaneous injections around the extravasation site. None developed skin necrosis. Local mild skin warming in order to produce local vasodilatation may have an additional beneficial effect, but should be avoided when simultaneous extravasation of a vinca alkaloid and an anthra-cycline is suspected, because local warming can worsen the anthracycline-associated local reaction, whereas local cooling, which is generally beneficial in anthracycline-related extravasation alone, can worsen skin necrosis due to vinca alkaloids (76). 

Trade names Cardioxane (Novartis) Totect Zinecard (Pfizer) Indications Protective agent against cardiomyopathy, anthracycline-induced extravasation Category Cardioprotective agent Half-life 2-4 hours... 

Myelosuppression mucositis worse with continuous infusion moderately emetogenic may cause acute and delayed (by 24 8 hours) emesis vesicant severe extravasation injury cardiotoxicity (similar to other anthracyclines) may be less cardiotoxic than doxorubicin controversy about equ ivalent doses cardiac toxicity associated with cumulative doses >900 mg/m Myelosuppression moderately emetogenic may be worse with oral and high-dose regimens alopecia mucositis hypotension infusion rate-related etoposide phosphate can be given IV push without hypotension risk hypersensitivity reactions especially common in children... 

The recommended dosage for idarubicin (Idamycin) is 12 mg/m daily for 3 days by intravenous injection in combination with cytarabine. Slow injection with care over 10 to 15 minutes is recommended to avoid extravasation, as with other anthracyclines. 

Daunorubicin, doxorubicin, epirubicin, and idarubicin usually are administered intravenously. Careful infusion over 10-15 minutes is recommended to prevent extravasation, since severe local vesicant action may result. The drugs are cleared by a complex pattern of hepatic metabolism and biliary excretion. The plasma disappearance curve for doxorubicin is multipha-sic, with elimination half-lives of 3 hours and - SO hours. All anthracyclines are converted to an active alcohol intermediate that plays a variable role in their therapeutic activity. Idarubicin has a tj of 15 hours, and its active metabolite, idarubicinol, has a tj of - 40 hours. There is rapid upt e of the drugs in the heart, kidneys, lungs, liver, and spleen. They do not cross the blood-brain barrier. Daunorubicin and doxorubicin are eliminated by metabolic conversion to a variety of aglycones and other inactive products. Idarubicin is primarily metabolized to idarubicinol, which accumulates in plasma and likely contributes significantly to its activity. Clearance is delayed in the presence of hepatic dysfunction, and at least a 50% initial reduction in dose should be considered in patients with elevated serum bilirubin levels. 

In addition, the risk of ulceration and necrosis on extravasation, as well as of nonmarrow-related toxicities such as nausea, vomiting, mucositis, and alopecia, is significantly less than observed with true anthracyclines. There is a significant risk of bone marrow suppression, however. The risk of myelosuppression increases with dose, but it can be observed even when low doses are used. 

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