Vinblastine

Indications

Vinblastine is used for: Histiocytic lymphoma, Hodgkin's disease, Kaposi's sarcoma, Letterer-Siwe disease, Lymphocytic lymphoma, Mycosis fungoides, Testicular cancer

Adult Dose

Intravenous Cancers Testicular CA, Squamous cell CA of head & neck, Hodgkin's Dz, Kaposi's sarcoma; histiocytic lymphoma, mycosis fungoides, & Letterer-Siwe disease (histiocytosis X) General Dosing Ranges 3.7-18 mg/sq.meter/day IV q7-10d 1st dose 3.7 mg/sq.meter/day IV Incr by 1.85 mg/sq.meter qweek until WBC equal 3000/cu.mm NMT 18.5 mg/sq.meter Hepatic impairment Decrease dose by half if bilirubin >3 mg/dL [>51 umol/L]

Child Dose

Intravenous Cancers Testicular CA, Squamous cell carcinoma CA of head & neck, Hodgkin's Dz, Kaposi's sarcoma; histiocytic lymphoma, mycosis fungoides, & Letterer-Siwe disease (histiocytosis X) General dosing ranges 2.5- 12.5 mg/sq meter IV q7-10d 1st dose 2.5 mg/sq.meter IV Incr by 1.25 mg/sq.meter qWeek until WBC = 3000/cu.mm No more than 12.5 mg/sq.meter

Renal Dose

Administration

IV Preparation IV push 1 mg/mL (dose/syringe); max syringe size for IVP is a 30 mL syringe & syringe should be <75% full Powder: reconstitute w/ 10 mL NS or bacteriostatic NS to obtain 1 mg/mL soln Continuous infusion: 250-1000 mL D5W or NS (dose)

Contra Indications

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.

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. Lactation: not known if excreted in breast milk, do not nurse

Pregnancy-Lactation

Pregnancy Category: D Lactation: not known if excreted in breast milk, do not nurse

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.

Side Effects

Side effects of Vinblastine : 1-10% Anemia, Leukopenia, Myelosuppression, Alopecia Frequency Not Defined Peripheral neuropathy, Hypertension, Bronchospasm, Nausea, Vomiting, Anorexia, Diarrhea, Constipation, Paralytic ileus, Jaw pain, Aspermia, Amenorrhea

Mode of Action

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.