Phenytoin with voriconazole

Coadministration with phenytoin Phenytoin may be coadministered with voriconazole if the IV maintenance dosage of voriconazole is increased to 5 mg/kg every 12 hours. 

Phenytoin [P] Decreased metabolism of phenytoin with fluconazole and probably voriconazole. 

Coadministration with rifampin, rifabutin, or ritonavir is contraindicated because of accelerated voriconazole metabolism. Efavirenz and perhaps other normucleoside reverse transcriptase inhibitors (NNRTIs) significantly increase voriconazole metabolism and slow the metabolism of the NNRTI. When given with phenytoin, the voriconazole dose should be doubled. Drugs that significantly accumulate in patients receiving voriconazole include cyclosporine,... 

Significant drug interactions include cyclosporins (increased cyclosporine levels), phenytoin, rifampin, and rifabutin (decreased voriconazole levels). Because of its low toxicity profile, this drug may gain importance in the chronic treatment of infections with invasive dimorphic fungi and resistant Candida spp. 

ITRACONAZOLE, KETOCONAZOLE, MICONAZOLE, POSACONAZOLE, VORICONAZOLE CARBAMAZEPINE, PHENYTOIN L plasma concentrations of itraconazole and of its active metabolite, ketoconazole, posaconazole and voriconazole, with risk of therapeutic failure, t phenytoin levels, but clinical significance uncertain. Carbamazepine plasma concentrations are also t These azoles are highly lipophilic, and clearance is heavily dependent upon metabolism by CYP isoenzymes. Phenytoin and carbamazepine are powerful inducers of CYP3A4 and other CYP isoenzymes (CYP2C18/19, CYP1A2) the result is veiy low or undetectable plasma levels. Phenytoin extensively 1AUC of itraconazole by more than 90%. Inhibition of P-gp T bioavailability of carbamazepine Avoid co-administration of posaconazole or voriconazole with carbamazepine. Watch for inadequate therapeutic effects and t dose of itraconazole. Higher doses of itraconazole may not overcome this interaction. Consider the use of less lipophilic fluconazole, which is less dependent on CYP metabolism. Necessaiy to monitor phenytoin and carbamazepine levels... 

Clinically important, potentially hazardous interactions with atazanavir, carbamazepine, clarithromycin, itraconazole, ketoconazole, nefazodone, nelfinavir, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, ritonavir, saquinavir, St John s wort, troleandomycin, voriconazole, warfarin... 

Clinically important, potentially hazardous interactions with alfentanil, alfuzosin, alprazolam, amiodarone, amprenavir, aprepitant, astemizole, atazanavir, bepridil, buprenorphine, bupropion, carbamazepine, chlordiazepoxide, ciclesonide, clozapine, conivaptan, cyclosporine, cyproterone, dasatinib, diazepam, dihydroergotamine, ergot alkaloids, estazolam, eszopidone, etravirine, ezetimibe, fentanyl, fesoterodine, flecainide, flurazepam, fluticasone, halazepam, ivabradine, ixabepilone, ketoconazole, lapatinib, levothyroxine, meperidine, meptazinol, methysergide, midazolam, nifedipine, nilotinib, oral contraceptives, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quazepam, quinidine, ranolazine, rifabutin, rifampin, rifapentine, rimonabant, rivaroxaban, saquinavir, sildenafil, silodosin, simvastatin, solifenacin, St John s wort, tadalafil, temsirolimus, trabectedin, triazolam, vardenafil, voriconazole, zolpidem... 

Note also that carbamazepine may reduce the levels of azole antifungals a marked reduction in itraconazole levels has been reported, and some manufacturers of itraconazole consequently say that concurrent use of potent enzyme inducers such as carbamazepine is not recommended. Based on the interaction with phenytoin , (p.552), which results in reduced posaconazole levels, the manufacturer of posaconazole suggests that concurrent use of posaconazole and carbamazepine should be avoided, unless the benefits outweigh the risks. If both drugs are given it would seem sensible to consider increasing the posaconazole dose, and increase monitoring of carbamazepine levels. Based on the interaction with phenytoin , (p.552), the manufacturers of voriconazole also contraindicate the concurrent use of carbamazepine and voriconazole. " ... 

Based on the evidence with phenytoin , (p.552), the manufacturer of voriconazole predicts that phenobarbital will reduce voriconazole levels, and... 

The oral dose of voriconazole does not have to be adjusted in patients who have renal impairment. However, intravenous administration of voriconazole should be avoided in these patients as the carrier vehicle sulfobu-tyl ether P-cyclodextrin sodium can accumulate in these patients. Dosage adjustment is required in patients who have chronic hepatic impairment. As voriconazole is a substrate for a number of cytochrome P450 enzymes, a number of clinically important dmg interactions occur with dmgs including ciclospotin, tacrolimus, phenytoin, warfarin, HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors. 

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