Solifenacin Ketoconazole

Ketoconazole It is recommended not to exceed a 5 mg daily dose of solifenacin when administered with therapeutic doses of ketoconazole or other potent CYP3A4 inhibitors. 

ANTIMUSCARINICS ANTIFUNGALS -ITRACONAZOLE, KETOCONAZOLE 1. i ketoconazole levels. 2. t darifenacin, solifenacin and tolterodine levels 1. 1 absorption 2. Inhibited metabolism 1. Watch for poor response to keto-conazole 2. Avoid co-administration of itraconazole, ketoconazole and these antimuscarinics. The US manufacturer of darifenacin recommends that its dose should not exceed 7.5 mg/day... 

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 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... 

Clinically important, potentially hazardous interactions with alprazolam, astemizole, clindamycin, darunavir, dasatinib, dihydroergotamine, eplerenone, ergot derivatives, fentanyl, garlic, ixabepilone, ketoconazole, lapatinib, methysergide, midazolam, phenytoin, pimozide, rifampin, ritonavir, sildenafil, solifenacin, St John s wort, temsirolimus, tolvaptan... 

Ketoconazole markedly Increases solifenacin levels, and the solif-enacln dose should be limited If ketoconazole or other potent Inhibitors of CYP3A4 are used. 

In a crossover study in healthy subjects, ketoconazole 200 mg daily for 20 days increased the AUC of a single 10-mg dose of solifenacin given on day 7 twofold. Moreover, the manufacturer notes that a higher dose of ketoconazole 400 mg daily increased the AUC threefold. ... 

Solifenacin is principally metabolised by the cytochrome P450 isoenzyme CYP3A4, of which ketoconazole is a known, potent inhibitor. 

Although the clinical relevance of this interaction has not been assessed, the manufacturers recommend that the daily dose of solifenacin succinate is limited to 5 mg if it is given with ketoconazole or other potent inhibitors of CYP3A4. The UK manufacturer specifically names itraconazole, nelfinavir and ritonavir. In addition, in patients with severe renal impairment or moderate hepatic impairment, the combined use of solifenacin and potent CYP3A4 inhibitors is contraindicated. For a list of clinically significant CYP3A4 inhibitors, see Table 1.4 , (p.6). 

Swart PJ, Krauwinkel WJJ, Smulders RA, Smith NN. Fhannacokmetic effect of ketoconazole on solifenacin in healthy volunteers. Basic Clin Pharmacol Toxicol (200 99,33-6. 

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