Irinotecan Carbamazepine

IRINOTECAN 1. ANTIBIOTICS-rifampicin 2. ANTICANCER AND IMMUNOMODULATING DRUGS - dexamethasone 3. ANTIDEPRESSANTS -St John s wort 4. ANTI EPILEPTICS -carbamazepine, phenobarbital, phenytoin 1 plasma concentrations of irinotecan and risk of 1 therapeutic efficacy. The effects may last for 3 weeks after discontinuation of CYP-inducer therapy Due to induction of CYP3A4-mediated metabolism of irinotecan Avoid concomitant use when ever possible if not, t dose of irinotecan by 50%... 

Aminopentane-carboxyUc acid (APC) is a second major metabolite of irinotecan it is formed by oxidation of the terminal piperidine ring, catalysed by CYP3A4. APC itself is not hydrolysed to SN-38 and is only a weak inhibitor of topoisomerase I (44-48). However, potent CYP3A4 inducers (for example St John s wort, carbamazepine, and phe-njdoin) or inhibitors (for example itraconazole) alter irinotecan pharmacokinetics (49-54). Other identified metabolites include NPC (7-ethyl-10-(4-amino-l-piperidono)-carbonyloxycamptothecin), 5-hydroxyirinotecan, and RPR112526 (a decarboxylated product of the acid form of the irinotecan lactone). 

Clinically important, potentially hazardous interactions with alprazolam, astemizole, carbamazepine, cisapride, clarithromycin, dexamethasone, diltiazem, docetaxel, ifosfamide, imatinib, irinotecan, itraconazole, ketoconazole, methylprednisolone, midazolam, nefazodone, oral contraceptives, paroxetine, phenytoin, pimozide, rifampin, ritonavir, terfenadine, tolbutamide, trabectedin, troleandomycin, vinblastine, vincristine, warfarin... 

Avoid co-administration of carbamazepine with azoles (consider using fluconazole), epierenone, irinotecan (if not able to avoid, t dose of irinotecan by 50%) or tamoxifen. Avoid co-administration of telithromycin for up to... 

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