Statins Ketoconazole

Specific concomitant medications or consumptions (check specific statin package insert for warnings) fibrates (especially gemfibrozil, but other fibrates too), nicotinic acid (rarely), cyclosporine, azole antifungals such as itraconazole and ketoconazole, macrolide antibiotics such as erythromycin and clarithromycin, protease inhibitors used to treat Acquired Immune Deficiency Syndrome, nefazodone (antidepressant), verapamil, amiodarone, large quantities of grapefruit juice (usually more than 1 quart per day), and alcohol abuse (independently predisposes to myopathy)... 

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. 

Clinically important, potentially hazardous interactions with alcohol, CNS depressants, erythromycin, grapefruit juice, ketoconazole, statins... 

CYP3A4 Alfentanil Alprazolam Astern izole Carbamazepine Cisapride Cyclosporine Diltiazem Erythromycin Felodipine Fluconazole Itraconazole Ketoconazole Lidocaine Lova statin Midazolam Nifedipine Quinidine Simvastatin Tacrolimus Terfenadine Verapamil... 

Ajmaline, ajamlicine, flecainide, fluoxetine, isoniazid, ketoconazole, lobeline, nefazodone, paroxetine, (7 )-propaphenooe, quinidine, ritonavir, "statins," yohimbine, venlafaxine... 

The evidence suggests that all the azole antifungals can raise ciclosporin levels to a greater or lesser degree. Ketoconazole may cause five- to tenfold rises, while itraconazole, fluconazole and voriconazole may cause two- to threefold rises. A case report suggests that intravenous miconazole interacts similarly and in theory, miconazole oral gel may also interact. Posaconazole may also modestly raise ciclosporin levels. Rhabdomyolysis has been reported with the combination of ciclosporin and itraconazole, but four of these cases were complicated by the presence of statins. 

The LDL-C should be kept well below 90 mg/dL, actually closer to 50 mg/dl, utilizing a low cholesterol, low animal fat diet, exercise, and a powerful statin (97). Statins have pleiotropic effects plaque stabilization, vasodilatation, anti-inflammatory, antithromotic, antiproliferative, and antioxidant (98). Most statins are metabolized via the CYP 3A4 pathway. Hence, drugs which also use the CYP 3A4 metabolic pathway, like ketoconazole, nefazodone, cyclosporine, nifedipine, felodipine. 

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