Interaction between
Atorvastatin
and
Darunavir
Major
Metabolism
Basic Information
| ID | DDInter133 and DDInter482 |
| Interaction | Coadministration with darunavir/ritonavir may significantly increase the plasma concentrations of atorvastatin. The mechanism is inhibition of the CYP450 3A4-mediated metabolism of atorvastatin by darunavir/ritonavir. High levels of statin or HMG-CoA reductase inhibitory activity in plasma is associated with an increased risk of musculoskeletal toxicity. Myopathy manifested as muscle pain and/or weakness associated with grossly elevated creatine kinase exceeding ten times the upper limit of normal has been reported occasionally. Rhabdomyolysis has also occurred rarely, which may be accompanied by acute renal failure secondary to myoglobinuria and may result in death. |
| Management | Atorvastatin should be initiated at the lowest possible dosage when prescribed with darunavir/ritonavir. The dosage may be increased gradually based on clinical response and tolerance, but should not exceed 20 mg/day. Fluvastatin and rosuvastatin may be safer alternatives in patients treated with protease inhibitors, since they are not metabolized by CYP450 3A4. 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. |
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| Alternative for Atorvastatin |
C10B
C10A |
| Alternative for Darunavir |
J05A
|
Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.