Critical
ritonavir × Simvastatin
HIV protease inhibitor / pharmacokinetic booster×HMG-CoA reductase inhibitors (statins)
Mechanism
Simvastatin is cleared via hepatic CYP3A4. Ritonavir is the strongest available CYP3A4 inhibitor. Simvastatin plasma levels rise 30-fold or more. The FDA lists the combination as an absolute contraindication.
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Severe cases progress to rhabdomyolysis with acute kidney injury. Symptoms appear within 1–2 weeks of co-prescription.
Management
The combination is not prescribed. For HIV patients on ritonavir-boosted therapy who need a statin, use low-dose pravastatin or rosuvastatin. Cap rosuvastatin at 10 mg/day with ritonavir.
Check the full regimen, not just this pair
Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.