Vinblastine

Indications
 Intravenous
Hodgkin's disease, Mycosis fungoides, Testicular cancer, Lymphocytic lymphoma, Histiocytic lymphoma, Kaposi's sarcoma, Letterer-Siwe disease
Adult: Initially, 3.7 mg/m2, increase dose wkly based on WBC counts in increments of about 1.8 mg/m2 until leukocyte count decreases to about 3000/mm3, or max wkly dose of 18.5 mg/m2 reached. 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/m2 per wk. Do not admin next dose, even though 7 days have lapsed unless the leukocyte count has returned to at least 4000/mm3.
Child: Initial 2.5 mg/m2 of BSA, increased dose at wkly intervals in increments of about 1.25 mg/m2 until leukocyte count decreases to about 3000/ mm3, or max wkly dose of 12.5 mg/m2 reached. 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.
Hepatic impairment: Serum bilirubin >3 mg/100ml: Reduce dose by 50%.

Special Populations: Hepatic impairment: Serum bilirubin: 1.5-3 mg/dL or AST 60-80 units: 50% of normal dose; 3-5 mg/dL: 25% of dose; >5 mg/dL or AST >180 units: Omit dose.

Incompatibility: Incompatible with furosemide.
Contraindications
 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.
Warnings / Precautions
 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.
Adverse Reactions
 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.
Overdose Reactions
 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.
Drug Interactions
 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.
Potentially Fatal: Increased toxicity of vinblastine with erythromycin. Increased neurotoxicity and myelotoxicity with azole antifungals e.g. itraconazole and posaconazole. Increased risk of severe neutropenia with ritonavir. Increased risk of acute pulmonary toxicity with mitomycin. Increased toxicity when ganciclovir is given with, immediately before or after vinblastine.
See Below for More vinblastine Drug Interactions
Mechanism of Actions
 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.
Absorption: Not absorbed reliably from GI tract.
Distribution: Protein binding: Extensive. Concentrated in blood platelets. Does not cross blood-brain barrier significantly.
Metabolism: Metabolised by CYP3A, to active metabolite desacetylvinblastine.
Excretion: Excreted in urine and via bile into faeces (some as unchanged drug). Terminal half life: 25 hr.
Storage Conditions
 Intravenous: Store at 2-8°C.
ATC Classification
 L01CA01 - vinblastine ; Belongs to the class of plant alkaloids and other natural products, vinca alkaloids and analogues. Used in the treatment of cancer.
Storage
 Intravenous: Store at 2-8°C.
Available As
  • Vinblastine 10 mg

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