Nisoldipine Ketoconazole

The effects of ketoconazole 200 mg on the pharmacokinetics of nisoldipine 5 mg have been investigated in a randomized, cross-over trial (34). Pretreatment with and concomitant administration of ketoconazole resulted in 24-fold and 11-fold increases in the AUC and C ax of nisoldipine, respectively. The ketoconazole-induced increase in plasma concentrations of the metabolite M9 was of similar magnitude. Thus, ketoconazole and other potent inhibitors of CYP3A should not be used concomitantly with nisoldipine. 

Clinically important, potentially hazardous interactions with amiloride, aminoglycosides, amphotericin B, ampicillin, anisindione, anticoagulants, armodafinil, atorvastatin, azathioprine, azithromycin, bacampicillin, basiliximab, bezafibrate, bosentan, bupropion, carbenicillin, caspofungin, cholestyramine, clarithromycin, cloxacillin, co-trimoxazole, corticosteroids, cyclophosphamide, daclizumab, danazol, dicloxacillin, dicumarol, digoxin, diltiazem, disulfiram, echinacea, erythromycin, ethotoin, etoposide, ezetimibe, flunisolide, fluoxymesterone, fluvastatin, foscarnet, fosphenytoin, gemfibrozil, hemophilus B vaccine, HMG-CoA reductase inhibitors, imatinib, imipenem/cilastatin, influenza vaccines, ketoconazole, lanreotide, lopinavir, lovastatin, mephenytoin, methicillin, methoxsalen, methylphenidate, methylprednisolone, methyltestosterone, mezlocillin, mizolastine, mycophenolate, nafcillin, nisoldipine, NSAIDs, orlistat, oxacillin, penicillins, phellodendron, phenytoin, pravastatin, prednisolone, prednisone, pristinamycin, ranolazine, red rice yeast, rifabutin, rifampin, rifapentine, ritonavir, rosuvastatin, simvastatin, sirolimus, spironolactone, St John s wort, sulfacetamide, sulfadiazine, sulfamethoxazole, sulfisoxazole, sulfonamides, tacrolimus, telithromycin, tenoxicam, testosterone, ticarcillin, tolvaptan, trabectedin, triamterene, troleandomycin, ursodeoxycholic acid, vaccines, vecuronium, warfarin, zofenopril... 

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... 

Itraconazole can markedly raise the serum levels of felodipine, which Increases Its adverse effects, In particular ankle and leg oedema. A few case reports suggest that isradipine and nifedipine can interact similarly with itraconazole, and that fluconazole can also interact with nifedipine. Ketoconazole can markedly raise the plasma levels of lercanidipine and nisoldipine. Caution is warranted with all calcium-channel blockers when azole antifungals, particularly itraconazole and ketoconazole, are used. 

A study in 7 healthy subjects found that ketoconazole 200 mg daily for 5 days increased the AU( and peak plasma levels of a single 5-mg dose of nisoldipine by 24-fold and 11-fold, respectively. The levels of nisoldipine metabolite were similarly increased. ... 

The interaction between felodipine and itraconazole would appear to be established and elinieally important. It also seems that isradipine, lercanidipine, nifedipine and nisoldipine ean interaet similarly with fluconazole, itraconazole or ketoconazole and, because they are metabolised by CYP3A4, it is likely that other calcium-channel blockers will behave in the same way. If itraconazole, ketoconazole, or fluconazole is given to a patient on established treatment with any calcium-channel blocker be alert for the need to lower the dosage of the calcium-channel blocker. However, some manufaeturers (e.g. felodipine, lercanidipine ) actually contraindicate concurrent use of itraconazole or ketoconazole, and others (e.g. nisoldipine ) additionally contraindicate fluconazole. In the US the guidance differs slightly and only caution is considered necessary with felodipine. The manufacturers of nimodipine predict that fluconazole, itraconazole and ketoconazole will substantially raise nimodipine levels. They say that concurrent use should be avoided, but, if this is not possible then the patient s blood pressure should be carefully monitored."... 

HeinigR, AdelmannHG, Ahr G. The effect of ketoconazole on the pharmacokinetics, phar-macocfynamics and safety of nisoldipine. EurJ CUn Pharmacol (1999) 55, 57-60. 

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