Rosuvastatin Ketoconazole

Endocrine effects Statins interfere with cholesterol synthesis and lower circulating cholesterol levels and, as such, might theoretically blunt adrenal or gonadal steroid hormone production. Small declines in total testosterone with no commensurate elevation in LH have been noted with the use of fluvastatin. Pravastatin showed inconsistent results with regard to possible effects on basal steroid hormone levels atorvastatin, lovastatin, rosuvastatin, and simvastatin did not reduce basal plasma cortisol concentration or basal plasma testosterone concentration or impair adrenal reserve. Appropriately evaluate patients who display clinical evidence of endocrine dysfunction. Exercise caution when administering HMG-CoA reductase inhibitors with drugs that affect steroid levels or activity, such as ketoconazole, spironolactone, and cimetidine. 

The catabolism of lovastatin, simvastatin, and atorvastatin proceeds chiefly through CYP3A4, whereas that of fluvastatin and rosuvastatin is mediated by CYP2C9. Pravastatin is catabolized through other pathways, including sulfation. The 3A4-dependent reductase inhibitors tend to accumulate in plasma in the presence of drugs that inhibit or compete for the 3A4 cytochrome. These include the macrolide antibiotics, cyclosporine, ketoconazole and its congeners, HIVprotease inhibitors, tacrolimus, nefazodone, fibrates, and others (see Chapter 4). Concomitant use of reductase inhibitors with amiodarone or verapamil also causes an increased risk of myopathy. 

CYP2C9 Inhibition Amiodarone, cimetidine, trimetho-primsulfamethoxazole, fluoxetine, fluvoxamine, isoniazid, itraconazole, ketoconazole, fluconazole, metro-nidasole, sulfinpyrazone, ticlopidine Fluvastatin Rosuvastatin ( ) ... 

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... 

Fluconazole modestly increases the levels of fluvastatin and rosuvastatin, but not pravastatin. Miconazoie wouid be expected to interact simiiariy. Itraconazoie causes a marked rise in the serum ieveis of atorvastatin, iovastatin, pravastatin and simvastatin, but no change in fluvastatin or rosuvastatin ieveis. Ketoconazole wouid be expected to interact simiiariy. Rhabdomyolysis has been reported in some cases. Due to the risk of myopathy, the manufacturers of voriconazoie caution, and the manufacturers of posaco-nazoie contraindicate, concurrent use with atorvastatin, iovastatin and simvastatin. 

Fluconazole 200 mg once daily for 11 days increased the AUC and maximum plasma concentration of rosuvastatin (given on day 8) by 14% and 9%, respectively, in 14 healthy subjects. The proportion of circulating active HMG-CoA reductase inhibitors was not ected by fluconazole." In similar studies by the same workers, itraconazole and ketoconazole also had no clinically significant effect on the levels of rosuvastatin. 

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