Acute Porphyria Drug Database

Monograph

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 pharmacokinetics
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

# Citation details PMID
*Scientific articles
1. 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.
2. Rendic, S. Summery of information on human CYP enzymes: human P450 metabolism. Drug metabolism reviews 2002; 34(1&2), 83-448.
3. Samuels, B., Bezwoda, W.R., et al. Chemotherapy in porphyria. South African Medical Journal 1984;65:924-6.
4. 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.
*Drug reference publications
5. McEvoy GK, editor. Vincristine Sulphate. The AHFS Drug Information 2008. Bethesda, MD: American Society of Health-System Pharmacists; 2009. Electronic version 21.01.10.
6. Sweetman SC, editor. Martindale: The complete drug reference. Vincristine Sulphate. Pharmaceutical Press 2009.
*Drug interaction databases
7. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). ://medicine.iupui.edu/clinpharm/ddis/table.asp. Accessed 21.01.10.
Flockhart DA.
*Summary of Product Characteristics
8. Norwegian medicines agency. Summary of Product Characteristics (SPC). Vincristine HOSPIRA.

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Tradenames and packages
From some sources, we get a list of packages (United Kingdom, Ireland, Estonia). Other sources contain more or less "clean" versions of the trade name (Denmark, Finland, Iceland, Lithuania, Norway). What you see here is the raw data we get from each country, so there will appear to be duplicates. The bold names are the searchable terms. The gray names that follow are all mapped to the bolded term.
Note: The cleaning is done automatically by a proprietary algorithm, and it may produce errors. We strive to improve it continuously.
Netherlands
Vincristinesulfaat · Vincristinesulfaat Eureco-Pharma 1 mg/ml, oplossing voor injectie · Vincristinesulfaat Teva 1 mg/ml, oplossing voor injectie
Belgium
Vincrisin · Vincrisin 1 mg/ml sol. inj. i.v. flac.
United Kingdom
Oncovin · Oncovin 1mg/1ml solution for injection vials · Vincristine · Vincristine 1mg/1ml solution for injection vials · Vincristine 1mg/50ml in Sodium chloride 0.9% infusion bags · Vincristine 2mg/2ml solution for injection vials · Vincristine 2mg/50ml in Sodium chloride 0.9% infusion bags · Vincristine 5mg/50ml in Sodium chloride 0.9% infusion bags · Vincristine 5mg/5ml solution for injection vials
Denmark
Cellcristin · Oncovin
Norway
Vincristine Pfizer
Poland
Vincristine Teva
Luxembourg
VINCRISIN
Finland
Oncovin
Latvia
Vincristine · Vincristine Teva
Serbia
Vincristine · Vincristine Pfizer
 
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