Monograph
L01CE01 - Topotecan |
Propably not porphyrinogenic |
PNP |
Rationale
Topotecan is shown not to have capacity for CYP-inhibition. Topotecan did not exert a significant effect on the PXR-mediated induction of CYP3A4. Insignificant metabolic load. Side effects such as nausea, anorexia and vomiting may be potentially porphyrinogenic through reduction in caloric intake.
Chemical description
Topotecan is a semisynthetic derivative of the alkaloid camptothecin. It is a polycyclic compound with quinolinic structure.
Therapeutic characteristics
Topotecan is an antineoplastic agent used in the treatment of ovarial cancer, in lung cancer, and together with cisplatin in cervical cancer. It is administered as an intravenous infusion or orally. Common adverse reactions of topotecan that can be confused with an acute porphyric attack are nausea, vomiting, diarrhoea, obstipation, and abdominal pain. Side effects such as nausea, anorexia and vomiting may be potentially porphyrinogenic through reduction in caloric intake.
Hepatic exposure
Insignificant.
Metabolism and pharmacokinetics
Topotecan is metabolized to a minor extent in the liver to N-desmethyl topotecan. About 75% of a dose of topotecan is excreted, mostly unchanged, in urine (55%) and feces (20%) within 9 days. Topotecan does not inhibit CYP3A4 or 2C9 in vitro. Topotecan did not exert a significant effect on the PXR-mediated induction of CYP3A4 (Harmsen, 2009). Topotecan was found to down-regulate PXR whilst having no impact on CAR expression (Haslam, 2008).
References
| # | Citation details | PMID |
|---|---|---|
| * | Scientific articles | |
| 1. | Nuclear receptor mediated induction of cytochrome P450 3A4 by anticancer drugs: a key role for the pregnane X receptor.
Harmsen S, Meijerman I, et al. Cancer Chemother Pharmacol. 2009;64(1):35-43. |
18839173 |
| 2. | Induction of P-glycoprotein expression and function in human intestinal epithelial cells (T84).
Haslam IS, Jones K, et al. Biochem Pharmacol. 2008;76(7):850-61. Epub 2008 Jul 23. |
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| * | Drug reference publications | |
| 3. | McEvoy GK, editor. Topotecan. The AHFS Drug Information 2008. Bethesda, MD: American Society of Health-System Pharmacists; 2009. Electronic version (08.06.10).
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| 4. | Sweetman SC, editor. Martindale: The complete drug reference. Topotecan. Pharmaceutical Press 2009.
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| * | Government bodies | |
| 5. | European Public Assessment Report, Hycamtin (Scientific discussion).European Medicines Agency (EMEA) 2005.
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| * | Summary of Product Characteristics | |
| 6. | Norwegian medicines agency. Summary of Product Characteristics (SPC). Hycamtin.
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