L01CA01 - Vinblastine |
Propably not porphyrinogenic |
PNP |
Rationale
Substrate of CYP 3A4. Evidence speaks against capacity for significant irreversible CYP-inhibition. No observations of CYP-induction. However side effects such as anorexia, nausea and vomiting may be potentially porphyrinogenic through reduction in caloric intake.
Chemical description
Vinblastine is a naturally occurring vinca alkaloid. Vinblastine sulfate is the freely watersoluble and highly hygroscopic sulphate salt of a dimeric alkaloid isolated from Cantharanthus roseus.
Therapeutic characteristics
Vinblastine sulfate is an antimicrotubule antineoplastic agent used in the treatment of Hodgkins disease and other lymphomas, for some inoperable malignant neoplasms including those of the breast, bladder, and kidney, and in non-small cell lung cancer, choriocarcinoma, and Kaposis sarcoma. It is usually given with other antineoplastics, and is administered intervenously, not more often than once a week. Common adverse reactions of vinblastine that can be confused with an acute porphyric attack are nausea, vomiting, abdominal pain, and obstipation. Peripheral neuropathy, paraesthesia, loss of deep tendon refelexes are less common. Side effects such as anorexia, nausea and vomiting may be potentially porphyrinogenic through reduction in caloric intake.
Metabolism and pharmakokinetics
Vinblastine is metabolised in the liver by CYP 3A4 to desacetylvinblastine, which is excreted mainly via bile. Administered as watersoluble sulphate salt with low PXR affinity. Listed as substrate and inhibitor of CYP3A4 by Rendic (2002), Zhou (2007) and Baumhakel (2001), however the concentrations of vinblastine required for a 50 % inhibition of vinblastine is 10 times higher those occuring during treatment (Baumhakel, 2001)(Fischer, 1998). No observations of interference with CYP-metabolism of other drugs.
Published experience
Reports of uneventful use: Arbus (1981) reported uneventful use of vinblastine to treat testicular cancer in a male AIP-patient.
References
- Scientific articles
- Arbus, M.H. Relationship between Porphyria and the use of Antineoplastics. Am J of Hosp Pharm 1981; 38:631. #1951
- Baumhakel, M., Kasel, D. Screening for inhibitory effects of CYP 3A4 in human liver microsomes. Int J Clin Pharmacol and Ther 2001; 39(12):517-28. #1952
- Fischer, V., Rodriguez-Gascon, A. et al. The multidrug resistance modulator valspodar (PSC 833) is metabolized by human cytochrome P450 3A. Implications for drug-drug interactions and pharmacological activity of the main metabolite. Drug Metab Dispos 1998; 26(8):802-11. #1953
- Rendic, S. Summery of information on human CYP enzymes: human P450 metabolism. Drug metabolism reviews 2002; 34(1&2), 83-448. #1025
- Zhou, S.F., Xue, C.C., et al. Clinicallay important drug interactions potentially involving mechanism-based inhibition of cytochrome P450 3A4 and the role of therapeutic drug monitoring. Ther Drug Monit 2007; 29(6):687:710. #1957
- Drug reference publications
- McEvoy GK, editor. Vinblastine Sulfate. The AHFS Drug Information 2008. Bethesda, MD: American Society of Health-System Pharmacists; 2009. Electronic version (22.01.10). #1954
- Sweetman SC, editor. Martindale: The complete drug reference. Vinblastine Sulfate. Pharmaceutical Press 2009. #1956
- Summary of Product Characteristics
- Norwegian medicines agency. Summary of Product Characteristics (SPC). Velbe. #1955
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