Vinblastine Sulfate
Vinblastine is M phase specific. It binds to microtubular proteins and arrests mitosis at the metaphase by disrupting mitotic spindle formation. It blocks glutamic acid utilization, thus inhibiting purine synthesis, the citric acid cycle, and the formation of urea. It may also interfere with nucleic acid and protein synthesis.
Adult (Intravenous): Initially, 3.7 mg/m2, increase dose wkly based on WBC counts in increments of about 1.8 mg/m2until leukocyte count decreases to about 3000/mm3, or max wkly dose of 18.5 mg/m2reached. Do not increase dose if leukocyte count is reduced to approximately 3000 cells/mm3; administer the max dose that does not cause leucopenia for maintenance. Do not increase subsequent doses if onolytic activity occurs before leucopenic effect. Usual dose: 5.5-7.4 mg/m2per wk. Do not admin next dose, even though 7 days have lapsed unless the leukocyte count has returned to at least 4000/mm3.Child (Intravenous): Initial 2.5 mg/m2of BSA, increased dose at wkly intervals in increments of about 1.25 mg/m2until leukocyte count decreases to about 3000/ mm3, or max wkly dose of 12.5 mg/m2reached. Do not increase dose once leukocyte count reaches approximately 3000 cells/mm3, instead, a dose of 1 increment smaller to be admin at wkly intervals for maintenance i.e. patient receives the max dose that does not cause leucopenia. If onolytic activity is encountered before leucopenic effect, then there is no need to increase subsequent doses. Do not admin next dose, even though 7 days have lapsed unless the leukocyte count has returned to at least 4000/mm3. Duration of maintenance therapy depends on disease state and the antineoplastic agent combination.
Possible increase in vinblastine levels with aprepitant. Reduced vinblastine metabolism with miconazole. Variable interactions with phenytoin, monitor serum phenytoin levels. Reduced immune response with vaccines. Additive myelotoxicity with zidovudine. Concurrent admin of vinblastine with CYP3A inhibitors may cause an earlier onset and/or an increased severity of side effects.
Severe bone marrow suppression; presence of bacterial infection; maglignant cell infiltration of bone marrow; Inj into extremity with poor circulation; porphyria; granulocytopenia. Elderly with cachexia or extreme skin ulcerations. Pregnancy; lactation. Intrathecal use may result in death.
Alopecia, constipation, malaise, stomatitis, dose-limiting bone marrow suppression (e.g. granulocytopenia, thrombocytopenia, anaemia), hypertension, central and peripheral neurotoxicity, 8th cranial nerve damage resulting in vestibular and auditory toxicity, ischaemic cardiac toxicity, breathlessness, bone, tumour or jaw pain. Nausea, vomiting, GI bleed, syndrome of inappropriate antidiuretic hormone. Necrosis, cellulitis if extravasation occurs.
Category D: There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
Hepatic impairment; neurotoxicity; ischemic heart disease; preexisting pulmonary dysfunction; extravasation may cause tissue damage and pain. Discontinue immediately if extravasation occurs, with local Inj of hyaluronidase and local heat application to decrease discomfort and risk of cellulitis; remaining Inj to be injected into another vein. Routine prophylaxis against constipation recommended especially in high doses. Nadir in leukocyte count occur 4-10 days after vinblastine admin; recovery observed 7-14 days after treatment.
Symptoms: Severe bone marrow suppression and extensions of its usual side effects.Management: Treatment is supportive. Restrict fluid and use of loop diuretics to counteract the effects of syndrome of inappropriate secretion of antidiuretic hormone. Monitor the patient's CV system and daily blood counts for transfusion requirement.
Cytotoxic Chemotherapy
Store at 2-8° C.
Hepatic Impairment:Serum bilirubin >3 mg/100ml: Reduce dose by 50%.
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