Critical
Atorvastatin × ritonavir
HMG-CoA reductase inhibitors (statins)×HIV protease inhibitor / pharmacokinetic booster
Mechanism
Atorvastatin uses hepatic CYP3A4 for ~70% of its clearance. Ritonavir is the strongest available CYP3A4 inhibitor. Atorvastatin plasma levels rise 5- to 7-fold.
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
Cap atorvastatin at 10 mg/day. Preferable strategy: switch to pravastatin or rosuvastatin (cap rosuvastatin at 10 mg/day on ritonavir). Check creatine kinase at 4–6 weeks and on muscle symptoms.