Atorvastatin × Ritonavir

Atorvastatin is broken down in the liver by CYP3A4, and ritonavir inhibits this enzyme. In studies of ritonavir-containing regimens, atorvastatin area under the curve (AUC) rose 2.5- to 9.4-fold depending on the partner protease inhibitor: 5.9-fold with lopinavir/ritonavir and 9.4-fold with tipranavir/ritonavir. Higher atorvastatin levels raise the risk of muscle damage.

Muscle pain, cramps or weakness, sometimes with fever and malaise, dark urine, raised creatine kinase in the blood. Severe cases progress to rhabdomyolysis with kidney injury.

Avoid the combination where possible and consider non-interacting alternatives (atorvastatin label). If atorvastatin is still needed, start with a lower dose, use a lower maximum dose and monitor the patient (atorvastatin label). The European Medicines Agency (EMA) advises the lowest possible atorvastatin dose and, if a statin is needed, pravastatin or fluvastatin (ritonavir label, EMA). The dose cap depends on the other drug in the regimen. The US Food and Drug Administration (FDA) does not recommend atorvastatin with tipranavir plus ritonavir and limits it to 20 mg a day with ritonavir-boosted darunavir, saquinavir or fosamprenavir (atorvastatin FDA label). Ask the patient to report muscle pain, cramps or weakness right away. If these occur, check creatine kinase and stop atorvastatin if it is more than 5 times the upper limit of normal (atorvastatin label).