Nefazodone metabolic pathways

The risk of myopathy appears to be increased by high levels of HMG-CoA reductase inhibitory activity in plasma. Lovastatin is metabolized by the CYP isoform 3A4. Certain drugs, that share this metabolic pathway can raise the plasma levels of lovastatin and may increase the risk of myopathy. These include cyclosporine, itraconazole, ketoconazole and other antifungal azoles, the macrolide antibiotics erythromycin and clarithromycin, HIV protease inhibitors, the antidepressant nefazodone, or large quantities of grapefruit juice (greater than 1 quart daily)... 

SCHEME 8 Metabolic pathways of the antidepressant nefazodone in humans. 

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. 

Nefazodone competes for hepatic oxidative pathways that metabolize most benzodiazepines, as well as zolpidem, zopiclone, and buspirone (SEDA-22, 39) (SEDA-22, 41). 

Omeprazole, like cimetidine, can impair benzodiazepine metabolism and lead to adverse effects (SEDA-18, 43). Other drugs, including antibiotics (erythromycin, chloramphenicol, isoniazid), antifungal drugs (ketoconazole, itraconazole, and analogues), some SSRIs (fluoxetine, paroxetine), other antidepressants (nefazodone), protease inhibitors (saquinavir), opioids (fentanyl), calcium channel blockers (diltiazem, verapamil), and disulfiram also compete for hepatic oxidative pathways that metabolize most benzodiazepines, as well as zolpidem, zopiclone, and buspirone (SEDA-22,39) (SEDA-22,41). 

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