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.

Irinotecan is a semisynthetic derivative of the alkaloid camptothecin.

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.

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.

Uneventful use reported in 1 patient with acute porphyria.