Benzodiazepines 4- Aprepitant

Clinically important, potentially hazardous interactions with alprazolam, aprepitant, astemizole, atorvastatin, benzodiazepines, carbamazepine, chlordiazepoxide, cilostazol, clonazepam, clorazepate, colchicine, conivaptan, cyclosporine, dabigatran, dasatinib, diazepam, digoxin, dihydroergotamine, disopyramide, ergot alkaloids, fesoterodine, fluoxetine, flurazepam, fluvastatin, HMG-CoA reductase inhibitors, imatinib, ixabepilone, lapatinib, lopinavir, lorazepam, lovastatin, methylprednisolone, methysergide, midazolam, nilotinib, oxazepam, paroxetine, pimozide, pravastatin, prednisone, quazepam, repaglinide, rimonabant, rivaroxaban, sertraline, silodosin, simvastatin, solifenacin, temazepam, temsirolimus, tolvaptan, trabectedin, triazolam, warfarin, zidovudine... 

Clinically important, potentially hazardous interactions with amlodipine, anisindione, anticoagulants, aprepitant, atorvastatin, barbiturates, benzodiazepines, butabarbital, carbamazepine, chlordiazepoxide, clarithromycin, clonazepam, dorazepate, corticosteroids, cyclosporine, dexamethasone, diazepam, dicumarol, erythromycin, ethotoin, felodipine, flurazepam, fluvastatin, fosphenytoin, isradipine, itraconazole, ketoconazole, lorazepam, lovastatin, mephenytoin, mephobarbital, midazolam, nicardipine, nifedipine, nimodipine, nisoldipine, oxazepam, pentobarbital, phenobarbital, pimozide, pravastatin, primidone, quazepam, rifampin, secobarbital, simvastatin, St John s wort, temazepam, warfarin... 

Based on the way midazolam interaets with similarly potent inhibitors of CYP3A4, aprepitant may be expeeted to increased the drowsiness and length of sedation and amnesia in patients given midazolam. Consider re-dueing the midazolam dose in patients given aprepitant and monitor the outeome of eoneurrent use earefully. The manufaeturer notes that the potential effeets of inereased levels of other benzodiazepines metabolised via CYP3A4, sueh as alprazolam and triazolam, should be eonsidered if... 

In the first few days of use, aprepitant 125/80 mg markedly increased levels of midazolam, a probe drug subsfrafe for fhe cyfoehrome P450 isoenzyme CYP3A4. Then, within 2 weeks, a reduction in levels was seen, see Benzodiazepines + Aprepitant , p.721. This effect was not seen with the 40/25 mg dose regimen. Aprepitant is therefore both a dose-dependent inhibitor and an inducer of CYraA4. 

Benzodiazepines midazolam is also metabolized by the isoenzyme CYP3 A4, which when inhibited by high-dose aprepitant will lead to an increase in plasma levels for any given dose. 

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