Drug interactions between Crixivan and Lipitor

GENERALLY AVOID: Protease inhibitors (PIs), particularly ritonavir, may significantly increase the plasma concentrations of certain HMG-CoA reductase inhibitors. The mechanism is PI inhibition of CYP450 3A4 metabolism. In 14 healthy volunteers, ritonavir (400 mg twice a day) and saquinavir (soft gelatin capsule 400 mg twice a day) given for 14 days increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of simvastatin acid (given as simvastatin 40 mg once a day for 4 days) by over 30-fold each. The same combination increased the Cmax and AUC of atorvastatin plus atorvastatin acid (given as atorvastatin 40 mg once a day for 4 days) by 148% and 73%, respectively. In 16 study subjects, amprenavir (given as fosamprenavir 1400 mg twice a day for 2 weeks) increased Cmax and AUC of atorvastatin (10 mg once a day) by 304% and 130%, respectively. These values were increased 184% and 153%, respectively, with ritonavir-fosamprenavir (700 mg-100 mg twice a day). No significant adverse effects have been associated with the interaction. However, high levels of HMG-CoA reductase inhibitory activity in plasma is associated with an increased risk of musculoskeletal toxicity. Myopathy manifested as muscle pain and/or weakness associated with grossly elevated creatine kinase exceeding ten times the upper limit of normal has been reported occasionally. Rhabdomyolysis has also occurred rarely, which may be accompanied by acute renal failure secondary to myoglobinuria and may result in death. Neither simvastatin nor atorvastatin appeared to have any significant effect on plasma levels of the PIs based on comparison with historical controls.

MANAGEMENT: In general, lovastatin, red yeast rice (which contains lovastatin), and simvastatin should be avoided in patients treated with PIs due to the potential for severe interaction. Concomitant use of these agents is specifically contraindicated according to the product labeling for fosamprenavir, lopinavir-ritonavir, and tipranavir. Atorvastatin may be used with caution, although the dosage should start low and probably not exceed 40 mg/day (some say 20 mg/day). Fluvastatin and pravastatin are probably safer alternatives, since they are not metabolized by CYP450 3A4. All patients treated with HMG-CoA reductase inhibitors should be advised to promptly report any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed.