L01CA04 - Vinorelbine |
Propably not porphyrinogenic |
PNP |
Rationale
No observations pointing to interference with CYP-metabolism of other drugs. Not listed as CYP-inducer. Found to be weak CYP-inhibitor in in-vitro studies, but the concentration needed to inhibit is much higher than reached during therapy. However, side effects such as anorexia, nausea and vomiting may be potentially porphyrinogenic through reduction in caloric intake.
Chemical description
Vinorelbine is a semisynthetic derivative of vinblastine, structuturally modified in the catharantine part of the molecule. Administered as tartrate salt, hygroscopic and freely soluble in water.
Therapeutic characteristics
Vinorelbine is used in the treatment of advanced breast cancer and non-small cell lung cancers, and has been tried in other malignancies including lymphomas and tumours of ovary and prostate. It can be administered by intravenous injection or orally. Common adverse reactions of vinorelbine that can be confused with an acute porphyric attack are nausea, vomiting, diarrhoea or obstipation, neuromotor disturbances, peripherel neuropathy or peripheral numbness and loss of deep tendon refelexes. Side effects such as anorexia, nausea and vomiting may be potentially porphyrinogenic through reduction in caloric intake.
Metabolism and pharmakokinetics
Metabolism of vinorelbine is mediated by CYP3A4. The main active metabolite is 4-O-deacetyl vinorelbine. Metabolites mainly excreted via bile. Kajita (2000) found that vinorelbine is a substrate and an inhibitor of CYP 3A4 in-vitro, however the plasmakoncentrations of vinorelbine needed for inhibition are much higher than those reached during therapy. Listed as an inhibitor of CYP 2D6 and as a substrate and a weak inhibitor of CYP 3A4 by Rendic (2002) and Zhou (2007). Metabolites excreted mainly via bile. No observations of interferences with CYP-metabolism of other drugs. Not listed as CYP-inducer.
Published experience
Reports of uneventful use: Kristiansen (2006) reported uneventful use of vinorelbine in the treatment of breast cancer in a 42 year old female AIP-patient.
IPNet drug reports
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References
- Scientific articles
- Kajita, J., Kuwabara, T. et al. CYP 3A4 is mainly responsible for the metabolism of a new vinca alcaloid, vinorelbine, in human liver microsomes. Drug metabolism and Disposition 2000; 28:1121-7. #1967
- Kristensen, C., Langkjer, S.T. Treatment and treatment considerations in a patient with advanced breast cancer and aucte intermittant porphyria. Acta Oncologica 2006; 45:337-9. #1968
- 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. Vinorelbine Tartrate. The AHFS Drug Information 2008. Bethesda, MD: American Society of Health-System Pharmacists; 2009. Electronic version (21.01.10). #1969
- Sweetman SC, editor. Martindale: The complete drug reference. Vinorelbine Tartrate. Pharmaceutical Press 2009. #1971
- Summary of Product Characteristics
- Norwegian medicines agency. Summary of Product Characteristics (SPC). NAVELBINE. #1970
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