L01CA05 - Vinflunine |
Propably not porphyrinogenic |
PNP |
Rationale
Vinflunine is a substrate of CYP3A4, but lacking capacity for induction or inhibition of CYP-enzymes. However, side effects such as nausea and vomiting may be potentially porphyrinogenic through reduction in carbohydrate intake.
Chemical description
Vinflunine is a vinca alkaloid.
Therapeutic characteristics
Vinflunine is indicated for the treatment of urotelial transitionepitelial cancer after platrinium therapy failure.
Common side effects of vinflunine that can be confused with an acute porphyria attack are nausea, vomiting, obstipation, diarrhoea and abdominal pain. Other common side effects are anorexia and infections.
Hepatic exposure
Significant
Metabolism and pharmacokinetics
Vinflunine is metabolized primarily by CYP3A4 (Ng 2011, Zhao 2007) while the only active metabolite, 4-O-deacetyl vinflunine (DVFL), is formed by multiple esterases (Campone 2011). Vinflunine and its metabolites are being excreted in faeces and in urine (Schutz 2011). The elimination half-life is 40 hours.
In vitro studies indicate absence of capacity for induction or inhibition of any of the drug metabolizing CYPs (SPC). In clinical use there are no pharmacokinetic drug interactions observed with vinflunine as perpetrator.
References
- Scientific articles
- Campone M, Isambert N, et al. A phase I study of vinflunine in combination with capecitabine in patients with metastatic breast cancer previously treated with anthracyclines and taxanes. Cancer Chemother Pharmacol. 2012 Apr;69(4):871-9. PMID 22045498. #4735
- Ng JS. Vinflunine: review of a new vinca alkaloid and its potential role in oncology. J Oncol Pharm Pract. 2011 Sep;17(3):209-24. PMID 20584744. #3037
- Schutz FA, Bellmunt J, et al. Vinflunine: drug safety evaluation of this novel synthetic vinca alkaloid. Expert Opin Drug Saf. 2011 Jul;10(4):645-53. PMID 21524237. #4736
- Zhao XP, Zhong J, et al. CYP3A4 mediated in vitro metabolism of vinflunine in human liver microsomes. Acta Pharmacol Sin. 2007 Jan;28(1):118-24. PMID 17184591. #4737
- Summary of Product Characteristics
- Norwegian medicines agency. Summary of Product Characteristics (SPC). (vinflunin). #3038
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