Warfarin Aprepitant

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. 

APREPITANT ANTICOAGULANTS - ORAL Possible 1INR when aprepitant is added to warfarin Aprepitant t CYP2C9-mediated metabolism of warfarin Monitor INR carefully for 2 weeks after completing each course of 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... 

Clinically important, potentially hazardous interactions with amiodarone, amprenavir, anisindione, antacids, anticoagulants, aprepitant, atazanavir, atovaquone, beclomethasone, buprenorphine, corticosteroids, cortisone, cyclosporine, cyproterone, dabigatran, dapsone, darunavir, delavirdine, dexamethasone, dicumarol, digoxin, eszopiclone, flunisolide, fosamprenavir, gadoxetate, gestrinone, halothane, imatinib, isoniazid, itraconazole, ketoconazole, lapatinib, lorcainide, methylprednisolone, midazolam, nelfinavir, nifedipine, oral contraceptives, phenylbutazone, prednisone, protease inhibitors, pyrazinamide, ramelteon, ritonavir, saquinavir, solifenacin, sunitinib, tacrolimus, telithromycin, temsirolimus, tipranavir, tolvaptan, trabectedin, triamcinolone, triazolam, voriconazole, warfarin, zaleplon... 

Clinically important, potentially hazardous interactions with aprepitant, astemizole, carbamazepine, colchicine, cyclosporine, dihydroergotamine, ergot alkaloids, ergotamine, erythromycin, fluoxetine, fluvoxamine, methylprednisolone, methysergide, oral contraceptives, paroxetine, pimozide, prednisolone, rifampicin, sertraline, solifenacin, terfenadine, warfarin... 

After absorption, aprepitant is bound extensively to plasma proteins (>95%) it is extensively metabolized, primarily by hepatic CYP3A4, and is excreted in the stool its t is 9—13 hours. Aprepitant has the potential to interact with other substrates of CYP3A4, requiring adjustment of other drugs, including dexamethasone, methylprednisolone (whose dose may need to be reduced by 50%), and warfarin. Aprepitant is contraindicated in patients on cisapride (see above) or pimozide, in whom life-threatening ventricular tachyarrthmias has been reported. 

Aprepitant modestly reduces warfarin levels and slightly decreases the INR in healthy subjects. It is expected to interact similarly with acenocoumarol. 

In a double-blind study, healthy subjeets were stabilised on warfarin and then given either aprepitant (125 mg on day one, then 80 mg daily on days 2 and 3) or placebo. On day 3, there was no change in warfarin levels. However, by day 8 (5 days after stopping aprepitant) there was a 34% decrease in trough 5-warfarin levels, and a 14% decrease in INR in the aprepitant group. ... 

Aprepitant is an inducer of the cytochrome P450 isoenzyme CYP2C9, by which 5-warfarin is metabolised. The manufacturer recommends that, in patients taking warfarin, the INR should be monitored closely for 2 weeks, particularly at 7 to 10 days, after each 3-day course of aprepitant, and this seems a prudent precaution. They similarly recommend caution with acenocoumarol, which is also metabolised by CYP2C9.3... 

Depr M, Van Hecken A, Oeyen M, De Lepeleire I, Laethem T, Rothenberg P, Petty KJ, Ma-jumdar A, Crumley T, Panebianco D, Bergman A, de Hoon JN. Effect of aprepitant on the pharmacokinetics and pharmacodynamics of warfarin. EurJ Clin Pharmacol (2005) 61, 341-6,... 

Warfarin decrease in plasma levels of warfarin are seen due to the induction of the metabolic enzyme CYP2C9 by concomitant administration of aprepitant... 

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