L01CE02 - Irinotecan |
Propably not porphyrinogenic |
PNP |
Rationale
Mechanism-based inhibitor of CYP3A4, but of insufficient potency for porphyrinogenic action. Interactions with CYP-metabolism of other drugs in clinical use are not reported. However, side effects such as nausea and vomiting may be potentially porphyrinogenic through reduction in caloric intake.
Chemical description
Irinotecan is a semisynthetic derivative of the alkaloid camptothecin.
Therapeutic characteristics
Irinotecan is an antineoplastic agent used alone or in combination with fluorouracil-based chemotherapy, in the treatment of colorectal cancer. It is administered as an intravenous infusion. Common adverse reactions of irinotecan that can be confused with an acute porphyric attack are nausea, vomiting, abdominal cramps and severe, delayed diarrhoea. Side effects such as nausea and vomiting may be potentially porphyrinogenic through reduction in caloric intake.
Metabolism and pharmacokinetics
Irinotecan is partly metabolised by CYP3A isoenzymes. About 50 per cent of the parent compound is excreted in unchanged form. About 12 per cent of the dose is hydrolyzed in body tissues by carboxyesterase to the active metabolite SN-38, or subjected to piperadine ring opening effected by CYP 3A4. Irinotecan, as well as the metabolite SN-38, are listed as a mechanism based inhibitor of CYP3A4, however the apparent activation rates are low (irinotecan: maximum activation rate k-max= 0.06/min; apparent inactivation constant Ki= 24 uM; SN-38: k-max 0.10/min and Ki = 26 uM, plasmaconcentration of irinotecan in humans approx 5µM)(Zhou, 2007). Interactions with CYP-metabolism of other drugs not reported, indicating a relatively low inhibitory capacity in clinical use.
IPNet drug reports
Uneventful use reported in 1 patient with acute porphyria.
References
- Scientific articles
- 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. #1027
- Drug reference publications
- McEvoy GK, editor. Irinotecan Hydrochloride. The AHFS Drug Information 2008. Bethesda, MD: American Society of Health-System Pharmacists; 2009. (Electronic version 09.06.10.) #2103
- Sweetman SC, editor. Martindale: The complete drug reference. Irinotecan Hydrochloride. Pharmaceutical Press 2009. #2105
- Summary of Product Characteristics
- Norwegian medicines agency. Summary of Product Characteristics (SPC). Campto. #2104
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