Nefazodone Lovastatin

Acetaminophen, bosentan, diclofenac, isoniazid, lovastatin, methyldopa, niacin, nefazodone, phenytoin, propylthiouracil, rifampin, trazodone, valproic acid, and venlafaxine... 

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)... 

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. 

A4/3A5 Midazolam, buspirone, felodipine, lovastatin, eletriptan, sildenafil, simvastatin, triazolam Atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin Rifampin, carbamazepine... 

CYP3A4 Inhibition Amiodarone, clarithromycin, erythromycin, cimetidine, cyclosporine, fluoxetine fluvoxamine, itraconazole, ketoconazole, nefazodone, verapamil, diltiazem HIV antivirals delaviridine, indanavire, nelfmavire, ritonavire, sequinavire Atorvastatin Lovastatin Simvastatin ... 

Via CYP450 3A4 inhibition, netazodone could theoretically Increase concentrations of certain cholesterol lowering HMG CoA reductase inhibitors, especially simvastatin, atorvastatin, and lovastatin, but not pravastatin orfluvastatin, which would increase the risk of rhabdomyolysis thus, coadministration of nefazodone with certain HMG CoA reductase inhibitors should proceed with caution... 

Drugs that participate in major CYP3A4 interactions with macrohdes are listed in Table 4. Other drugs that may be affected include alprazolam (138), the water-soluble artemisinin analogue artehnic acid (139), gallopamil (140), lovastatin (141), nefazodone (142), and risperidone... 

Clinically important, potentially hazardous interactions with barbiturates, carbamazepine, clarithromycin, cyclosporine, CYP3A inhibitors, digoxin, grapefruit juice, itraconazole, ketoconazole, lovastatin, nefazodone, nelfinavir, p-gp inhibitors, phenytoin, rifabutin, rifampin, rifapentin, ritonavir, saquinavir, St John s wort, telithromycin... 

Nefazodone has been implicated in cases of muscle toxicity and rhabdomyolysis in patients taking simvastatin, lovastatin, and possibly pravastatin. 

In a review of the FDA spontaneous reports of statin-associated rhabdomyolysis eovering the period November 1997 to March 2000, nefazodone was potentially implieated in 2 cases of rhabdomyolysis involving lovastatin. ... 

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