vincristine; 22-oxovincaleukoblastine; leurocristine (Oncovin, Vincasar PFS)
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Introduction
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
Dosage
- do NOT give intrathecally
- IV: 0.5-1.4 mg/m2 every 1-4 weeks
- 0.5 mg/m2/day continuous infusion for 4 days
- max dose 2 mg
- SC (Kaposi's sarcoma): 0.1-0.2 mg/mL in 2% lidocaine intralesional injection
Injection: 1 mg/mL (1 mL, 2 mL).
Pharmacokinetics
- widely distributed
- metabolized in the liver by cyt P450 3A4
- eliminated in the urine & feces
- elimination 1/2life is 10-150 hours
elimination via liver
1/2life = 10-150 hours
Adverse effects
- common (> 10%)
- alopecia (20-70%)
- less common (1-10%)
- uncommon (< 1%)
- other
- extravasation: vesicant; tissue irritation & necrosis can occur with extravasation
- myelosuppression
- occasional mild leukopenia & thrombocytopenia
- onset 7 days
- nadir 10 days
- recovery 21 days
- gastrointestinal
- neurologic#
- 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
- urinary retention
- SIADH
- ototoxicity
- photophobia
- fever
- hypertension
- hypotension
* paralytic ileus secondary to neurotoxicity
# intrathecal administration of vincristine uniformly causes death Toxicology:
- treatment is supportive
- no known antidotes
Drug interactions
- aminoglycosides: increased risk of ototoxicity given within 3-5 days
- zalcitabine: in combination increases neurotoxicity
- asparaginase may decrease vincristine clearance
- mytomycin C in combination may result in acute pulmonary reactions
- any drug that inhibits cyt P450 3A4 may increase levels of vincristine
- any drug that induces cyt P450 3A4 may diminish levels of vincristine
Test interactions
increase in serum K+
Mechanism of action
- vinka alkaloid
- inhibits microtubule formation in the mitotic spindle arresting cell division Mechanism of drug resistance:
- alteration of tubulin
More general terms
Additional terms
- cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)
- intravenous (IV) extravasation
- microtubule
- tubulin
Component of
- cyclophosphamide/dexamethasone/doxorubicin/vincristine; cyclophosphamide/vincristine/adriamycin/dexamethasone (CVAD)
- rituximab/cyclophosphamide/vincristine (Oncocin)/prednisone (R-CVP)
- rituximab/cyclophosphamide/doxorubicin/vincristine (Oncocin)/dexamethasone (R-CVAD)
- rituximab/cyclophosphamide/doxorubicin/vincristine (Oncocin)/prednisone (R-CHOP)
- cyclophosphamide/doxorubicin (Adriamycin)/vincristine (VAC)
- cyclophosphamide/doxorubicin/vincristine (Oncocin)/prednisone (CHOP)
- nitrogen mustard/vincristine (Oncovin)/prednisone/ procarbazine (MOPP)
- cyclophosphamide/vincristine (Oncovin)/prednisone/procarbazine (C-MOPP)
- cyclophosphamide/vincristine (Oncocin)/prednisone (CVP, COP)
- lomustine/procarbazine/vincristine (PCV)
References
- ↑ Merck tenth ed. (1983)
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 529, 533
- ↑ Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220233&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 6.0 6.1 Medications Can Cause Seizures Prescriber's Letter 10(3):16 2003 Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=190320&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 7.0 7.1 7.2 Deprecated Reference