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vincristine; 22-oxovincaleukoblastine; leurocristine (Oncovin, Vincasar PFS)

C46-H56-N4-O10. Tradename: Oncovin. Indications: - lymphoma (Hodgkin's disease & non-Hodgkin's lymphoma) - metastatic breast cancer - multiple myeloma - neuroblastoma - Wilm's tumor - induction therapy in acute lymphocytic leukemia (ALL) - Kaposi's sarcoma - rhabdomyosarcoma - Ewing sarcoma [7] - small cell carcinoma - ovarian cancer - anaplastic astrocytoma - glioblastoma multiforme - chronic lymphocytic leukemia [7] Contraindications: - intrathecal administration Dosage: 1) do NOT give intrathecally 2) IV: 0.5-1.4 mg/m2 every 1-4 weeks a) 0.5 mg/m2/day continuous infusion for 4 days b) max dose 2 mg 3) SC (Kaposi's sarcoma): 0.1-0.2 mg/mL in 2% lidocaine intralesional injection Injection: 1 mg/mL (1 mL, 2 mL). Pharmacokinetics: 1) widely distributed 2) metabolized in the liver by cyt P450 3A4 3) eliminated in the urine & feces 4) elimination 1/2life is 10-150 hours Adverse effects: 1) common (> 10%) - alopecia (20-70%) 2) less common (1-10%) - rash, weight loss, orthostatic hypotension, phlebitis, neurotoxicity, numbness, weakness, motor difficulties, seizures, CNS depression, cranial nerve palsies, paralytic ileus, jaw pain, leg pain, myalgias, cramping, hyperuricemia 3) uncommon (< 1%) - stomatitis 4) other a) extravasation: vesicant; tissue irritation & necrosis can occur with extravasation b) myelosuppression - occasional mild leukopenia & thrombocytopenia - onset 7 days - nadir 10 days - recovery 21 days c) gastrointestinal - constipation, paralytic ileus*, oral ulceration, nausea/vomiting, diarrhea, bloating, abdominal cramps, anorexia, metallic taste d) neurologic# - depression, confusion, insomnia, paralytic ileus*, cranial nerve palsies, headaches, jaw pain, optic atrophy, seizures [6] e) peripheral neuropathy - frequently dose-limiting toxicity - most frequent in patients > 40 years of age - loss of deep tendon reflexes in lower extremities - numbness, paresthesias, pain in stocking glove pattern f) urinary retention g) SIADH h) ototoxicity i) photophobia j) fever k) hypertension l) hypotension * paralytic ileus secondary to neurotoxicity # intrathecal administration of vincristine uniformly causes death Toxicology: 1) treatment is supportive 2) no known antidotes Drug interactions: 1) aminoglycosides: increased risk of ototoxicity given within 3-5 days 2) zalcitabine: in combination increases neurotoxicity 3) asparaginase may decrease vincristine clearance 4) mytomycin C in combination may result in acute pulmonary reactions 5) any drug that inhibits cyt P450 3A4 may increase levels of vincristine 6) any drug that induces cyt P450 3A4 may diminish levels of vincristine Test interactions: increase in serum K+. Mechanism of action: 1) vinka alkaloid 2) inhibits microtubule formation in the mitotic spindle arresting cell division Mechanism of drug resistance: -> alteration of tubulin

Related

cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4) intravenous (IV) extravasation microtubule tubulin

General

antimitotic agent; mitotic inhibitor (antineoplastic agent) vinca alkaloid

Properties

SIZE: MW = 824.94 G/M MISC-INFO: elimination route LIVER pregnancy-category D 1/2life 10-150 HOURS

References

  1. Merck tenth ed. (1983)
  2. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  3. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  4. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 529, 533
  5. Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: 220233 (subscription needed) http://www.prescribersletter.com
  6. Medications Can Cause Seizures Prescriber's Letter 10(3):16 2003 Detail-Document#: 190320 (subscription needed) http://www.prescribersletter.com
  7. Deprecated Reference

Component-of

cyclophosphamide/dexamethasone/doxorubicin/vincristine; cyclophosphamide/vincristine/adriamycin/dexamethasone (CVAD) cyclophosphamide/doxorubicin (Adriamycin)/vincristine (VAC) cyclophosphamide/doxorubicin/vincristine (Oncocin)/prednisone (CHOP) cyclophosphamide/vincristine (Oncocin)/prednisone (CVP, COP) cyclophosphamide/vincristine (Oncovin)/prednisone/procarbazine (C-MOPP) lomustine/procarbazine/vincristine (PCV) nitrogen mustard/vincristine (Oncovin)/prednisone/ procarbazine (MOPP) rituximab/cyclophosphamide/doxorubicin/vincristine (Oncocin)/dexamethasone (R-CVAD) rituximab/cyclophosphamide/doxorubicin/vincristine (Oncocin)/prednisone (R-CHOP) rituximab/cyclophosphamide/vincristine (Oncocin)/prednisone (R-CVP)

Databases & Figures

PUBCHEM correlations Therapeutic Inducers of Apoptosis