Vinca alkaloids extravasation

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

Vinca alkaloids are potential vesicants (76-78) and accidental drug extravasation can cause severe soft tissue ulceration. The initial symptoms include marked pain, erythema, and local swelling for several hours up to a day later effects include blisters and severe painful skin ulcers, several days and 3 weeks after extravasation respectively. The lesions usually heal very slowly and sometimes require surgical intervention. Because vinca alkaloid extravasation can have severe effects, the use of antidotes is highly recommended when extravasation is suspected. In addition, venous irritation can be worsened if the vinca alkaloid is infused over at least 20-30 minutes rather than 6-10 minutes. 

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). 

Vinca alkaloids Vinorelbine Myelosuppression Fatigue, nausea, vomiting, ulceration necrosis with extravasation... 

If extravasation occurs, the infusion should be stopped immediately, with aspiration of fluid from the site, needle, and tubing as much as possible. The affected limb or area should be elevated (if possible). The site should be documented photographically as well as the time, date, site, patient complaints, and estimated volume of extravasated drug.36 Both hot and cold packs have been used to manage extravasations, but use of the proper therapy for certain agents is critical. For example, warm compresses have been shown to worsen doxorubicin extravasations, whereas cold packs may exacerbate vinca alkaloid... 

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. 

Vinblastine -vinca alkaloid inhibits tubulin polymerization G2 phase specific -bone marrow suppression -vesicant if extravasated -nausea and vomiting -constipation (often secondary to neuropathy induced ileus) -neuropathy (jaw pain, peripheral neuropathy, autonomic neuropathy) -SIADH -tumor pain... 

The most important adverse effects of vinca alkaloids include nervous system disorders, hematological effects, and gastrointestinal discomfort. Respiratory and cardiovascular adverse effects have to be particularly considered during combination chemotherapy. All the vinca alkaloids are tissue irritants, and extravasation without any adequate supportive management can result in severe local ulceration (1,2,5,8,20). 

Bertelli G, Dini D, Forno GB, Gozza A, SUvestro S, Venturini M, Rosso R, Pronzato P. Hyalnronidase as an antidote to extravasation of vinca alkaloids clinical resnlts. J Cancer Res Clin Oncol 1994 120(8) 505-6. 

All vinca alkaloids are considered vesicants, and extravasations should be avoided. Ail vinca alkaloids may be fatal if given intrathecally. 

Mitomycin is administered IV in the treatment of disseminated adenocarcinoma of the stomach or pancreas, and it has been used intravesically in superficial bladder cancer. Biotransformation pathways are saturable, and approximately 10% of an administered dose is eliminated unchanged via the kidneys. Myelosuppression is the major use-limiting side effect of this drug, which is slow to manifest but quite prolonged in duration. Severe skin necrosis can occur on extravasation, and potentially fatal pulmonary toxicities have been noted as well. Mitomycin can induce hemolytic uremia accompanied by irreversible renal dysfunction and thrombocytopenia, and the drug should not be administered to patients with serum creatinine levels greater than 1.7 mg/dL. Severe bronchospasm also has been noted in patients treated with vinca alkaloids who also are receiving (or who have previously received) mitomycin. 

All vinca alkaloids are severe vesicants that can induce necrosis, cellulitis, and/or thrombophlebitis. Proper needle placement before administration should be assured to eliminate the risk of extravasation. Unlike the tissue damage caused by the vesicant action of nitrogen mustards and antibiotic antineoplastics, cold exacerbates tissue destruction. If extravasation occurs, apply heat for 1 hour fours time a day for 3 to 5 days, coupled with local hyaluronidase injections. Vinca alkaloids are all Category D teratogens and are fatal if administered by the intrathecal route. 

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