Major
ritonavir × Rosuvastatin
HIV protease inhibitor / pharmacokinetic booster×HMG-CoA reductase inhibitors (statins)
Mechanism
Rosuvastatin barely uses CYP3A4 but is a substrate of OATP1B1 and BCRP transporters, both inhibited by ritonavir. Rosuvastatin plasma levels rise 2- to 4-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 1–4 weeks of co-administration.
Management
On ritonavir-boosted antiretroviral therapy, cap rosuvastatin at 10 mg/day. Check creatine kinase at 4–6 weeks and on muscle symptoms.