Voriconazole Alfentanil

OPIOIDS ANTIFUNGALS 1, Ketoconazole T effect of buprenorphine 2. Fluconazole and itraconazole T the effect of alfentanil 3. Fluconazole and possibly voriconazole T effect of methadone this is a recognized pharmacokinetic effect but of uncertain clinical significance 1. Ketoconazole 1 the CYP3A4-mediated metabolism of buprenorphine 2.1 clearance of alfentanil 3.1 hepatic metabolism 1. The dose of buprenorphine needs to be 1 (by up to 50%) 2. i dose of alfentanil 3. Watch for T effects of methadone... 

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... 

Some patients may experience prolonged and increased alfentanil effects if they are given fluconazole or voriconazole. In vitro data surest itraconazole and ketoconazole may interact similarly. Intravenous fentanyl does not appear to interact with itraconazole in healthy subjects, but one case of possible opioid toxicity from transdermal fentanyl has been reported. 

A randomised, crossover study in 12 healthy subjects found that oral voriconazole (400 mg twice daily on the first day and 200 mg twice daily on the second day) caused an approximately fivefold increase in the mean AUC of alfentanil 20 micrograms/kg, given intravenously one hour after the last dose of the antifungal. The mean plasma clearance of alfentanil was decreased by 85% and its elimination half-life was prolonged from 1.5 to 6.6 hours. Nausea occurred in 5 subjects and vomiting in 4 subjects. ... 

The interaction of alfentanil with fluconazole and voriconazole appears to be established and clinically important. In vitro data indicate that ketoco-nazole and itraconazole may interact in a similar wayAlfentanil should be given with care to those who have recently received these drugs, and it may be necessary to use a lower alfentanil dose. Be alert for evidence of prolonged alfentanil effeets and respiratory depression. 

Saari TI, Laine K, Leino K, Valtonen M, Neuvonen PJ, Olkkola KT. Voriconazole, but not terbinafine, markedly reduces alfentanil clearance and prolongs its half-life. Clin Pharmacol Ther 2006) 80, 502-8. 

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