Irinotecan Phenytoin

Aprepitant may be affected by paroxetine, CYP2C9 substrates (eg, phenytoin, tolbutamide, warfarin), CYP3A4 substrates (eg, alprazolam, cisapride, dexamethasone, docetaxel, etoposide, ifosfamide, imatinib, irinotecan, methylprednisolone, midazolam, paclitaxel, pimozide, triazolam, vinblastine, vincristine, vinorelbine), and oral contraceptives. 

Murry DJ, Cherrick I, Salama V, et al. Influence of phenytoin on the disposition of irinotecan a case report. J Pediatr Hematol Oncol 2002 24(2) 130—133. 

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%... 

Mathijssen RH, Sparreboom A, Dumez H, van Oosterom AT, de Bruijn EA. Altered irinotecan metabolism in a patient receiving phenytoin. Anticancer Drugs 2002 13(2) 139-40. 

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... 

The information is limited but serves to emphasise the need for caution and monitoring if irinotecan is given with phenytoin, which may reduce the availability of its active metabolite. Note that phenytoin has also been shown to increase the clearance of a related topoisomerase inhibitor, topo-teean (see Topoteean + Phenytoin , p.667)and 9-aminocamptothecin(see 9-Aminocamptotheein + Antiepileptics , p.610). 

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