Eplerenone Fluconazole

Clinically important, potentially hazardous interactions with alfentanil, aminophylline, amisulpride, amoxicillin, ampicillin, anticonvulsants, astemizole, atorvastatin, benzodiazepines, bromocriptine, buprenorphine, bupropion, carbamazepine, cilostazol, ciprofloxacin, cisapride, clindamycin, colchicine, cyclosporine, dasatinib, digoxin, dihydroergotamine, diltiazem, disopyramide, enoxacin, eplerenone, ergotamine, eszopiclone, everolimus, fluconazole, fluoxetine, fluvastatin, gatifloxacin, HMG-CoA reductase inhibitors, imatinib, itraconazole, ketoconazole, lomefloxacin, lorazepam, lovastatin, methadone, methylprednisolone, methysergide, midazolam, mizolastine, moxifloxacin, nitrazepam, norfloxacin, ofloxacin, paroxetine, pimozide, pravastatin, quinolones, ranolazine, repaglinide, rupatadine, sertraline, sildenafil, simvastatin, sparfloxacin, sulpiride, tacrolimus, terfenadine, triazolam, troleandomycin, vardenafil, verapamil, vinblastine, warfarin, zaleplon, zolpidem, zuclopenthixol... 

In the UK, the manufacturers recommend that the dose of eplerenone should not exceed 25 mg daily in patients taking mild to moderate CYP3A4 inhibitors such as amiodarone, diltiazem, erythromycin, fluconazole, saquinavir and verapamil. In the US, the manufacturer recommends that the starting dose for hypertension should be reduced to 25 mg daily for patients taking these drugs. This seems a sensible precaution. However, note that in many cases erythromycin appears to be a more potent inhibitor of CYP3A4 than clarithromycin (and certainly the other moderate CYP3A4 inhibitors listed above), and so extra caution is probably warranted with this combination. 

Both nifedipine and eplerenone are metabolized by CYP3A4, which is inhibited by voriconazole. Other azoles, such as fluconazole, reportedly also interact with nifedipine, but such an interaction has not been demonstrated with eplerenone. 

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