Drug Interaction Report

ADJUST DOSE: Coadministration with darunavir/ritonavir may increase the plasma concentrations of pravastatin. The mechanism of interaction has not been described. In 14 study subjects, administration of pravastatin (40 mg single dose) in combination with darunavir/ritonavir (600 mg/100 mg twice a day) increased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of pravastatin by 63% and 81%, respectively, compared to administration without darunavir/ritonavir. Pravastatin AUC increased by up to 5-fold in some patients.

MANAGEMENT: Because high levels of HMG-CoA reductase inhibitory activity in plasma is associated with an increased risk of musculoskeletal toxicity including severe myopathy and rhabdomyolysis, pravastatin should be initiated at the lowest possible dosage when prescribed with darunavir/ritonavir. The dosage may be increased gradually based on clinical response. 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.

ADJUST DOSING INTERVAL: Food enhances the absorption and oral bioavailability of darunavir administered in combination with low-dose ritonavir. The mechanism is unknown. When administered with food, the peak plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of darunavir were approximately 30% higher than when administered in the fasting state. Darunavir exposure was similar for the range of meals studied. The total caloric content of the various meals evaluated ranged from 240 Kcal (12 grams fat) to 928 Kcal (56 grams fat).

MANAGEMENT: To ensure maximal oral absorption, darunavir coadministered with ritonavir should be taken with food. The type of food is not important.

MONITOR: Concomitant use of statin medication with substantial quantities of alcohol may increase the risk of hepatic injury. Transient increases in serum transaminases have been reported with statin use and while these increases generally resolve or improve with continued therapy or a brief interruption in therapy, there have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins. Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury. Active liver disease or unexplained transaminase elevations are contraindications to statin use.

MANAGEMENT: Patients should be counseled to avoid substantial quantities of alcohol in combination with statin medications and clinicians should be aware of the increased risk for hepatotoxicity in these patients.