Interaction between
Atorvastatin
and
Fosamprenavir
Major
Metabolism
Basic Information
| ID | DDInter133 and DDInter777 |
| Interaction | Protease inhibitors (PIs), particularly ritonavir, may significantly increase the plasma concentrations of atorvastatin. The mechanism is PI inhibition of CYP450 3A4 metabolism. |
| Management | The benefits of using atorvastatin in combination with protease inhibitors should be carefully weighed against the potentially increased risk of myopathy including rhabdomyolysis. A lower dosage of atorvastatin should be considered if concomitant use is required. Atorvastatin labeling recommends that the dosage not exceed 20 mg/day when used in combination with fosamprenavir or with dual protease inhibitor therapy consisting of ritonavir plus darunavir, saquinavir, or fosamprenavir. Use of atorvastatin with the fixed combination of atazanavir-cobicistat is not recommended. The dosage should not exceed 40 mg/day when used with nelfinavir. Fluvastatin, pitavastatin, and pravastatin may be safer alternatives, since they are not metabolized by CYP450 3A4. All patients receiving statin therapy should be advised to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by fever, malaise and/or dark colored urine. 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 Fosamprenavir |
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.