L01CA02 - Vincristine |
Propably not porphyrinogenic |
PNP |
Rationale
No data supporting capacity for CYP-induction. Found to be weak CYP-inhibitor in in-vitro studies, but the concentration needed to inhibit is much higher than reached during therapy. Relatively low hepatic exposure. Side effects such as nausea and vomiting may be potentially porphyrinogenic through reduction in caloric intake.
Chemical description
Vincristine sulfate is the sulfate of an alkaloid, 22-oxovincaleukoblastine, obtained from Catharanthus roseus (Vinca rosea) (Apocynaceae). Very hygroscopic, freely soluble in water.
Therapeutic characteristics
Vincristine is an antineoplastic agent that may act similarly to vinblastine. It is used in combination chemotherapy in the treatment of leukaemia, malignant lymphoma, lungcancer. Administered as intravenous injection or infusion. Adverse reactions of vincristine that can be confused with an acute porphyric attack are abdominal pain, obstipation and paralytic ileus, peripheral neuropathy, hyponatremia, constipation, nausea, vomiting and diarrhoea. Side effects such as nausea and vomiting may be potentially porphyrinogenic through reduction in caloric intake.
Metabolism and pharmakokinetics
How vincristine is metabolised has not been clearly determined, but CYP 3A4 probably takes part in its metabolism. Listed as substrate and inhibitor of CYP 3A4 by Rendic (2002) and Zhou (2007). Found to be a weak inhibitor of CYP 3A4 by Baumhakel et al (2001). However, the concentration needed to inhibit is much higher than those reached during therapy. Not listed as CYP-inducer or inhibitor by Flockhart (2007). No clear observations of interference with CYP-metabolism of other drugs. Eighty percent of the dose is recovered in faeces, 10 percent in urine.
Preclinical data
Published experience
Reports of uneventful use: Samuels (1984) reported uneventful use of vincristine in two female PV-patients.
IPNet drug reports
No.
References
- Scientific articles
- Baumhakel, M. Kasel, D. et al. Screening for inhibitory effects of antineoplastic agents on CYP3A4 in human liver microsomes.International Journal of Clinical Pharmacology and Therapeutics 2001; 39:517-28. #1958
- Rendic, S. Summery of information on human CYP enzymes: human P450 metabolism. Drug metabolism reviews 2002; 34(1&2), 83-448. #1025
- Samuels, B., Bezwoda, W.R., et al. Chemotherapy in porphyria. South African Medical Journal 1984;65:924-6. #1962
- Zhou, S.f., Xue, C.C., et al. Clinically 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. #1964
- Drug reference publications
- McEvoy GK, editor. Vincristine Sulphate. The AHFS Drug Information 2008. Bethesda, MD: American Society of Health-System Pharmacists; 2009. Electronic version 21.01.10. #1960
- Sweetman SC, editor. Martindale: The complete drug reference. Vincristine Sulphate. Pharmaceutical Press 2009. #1963
- Drug interaction databases
- Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). ://medicine.iupui.edu/clinpharm/ddis/table.asp. Accessed 21.01.10. #1959
- Summary of Product Characteristics
- Norwegian medicines agency. Summary of Product Characteristics (SPC). Vincristine HOSPIRA. #1961
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