Drug-drug interactions between HMG-CoA reductase inhibitors (statins) and antiviral protease inhibitors.
Article Details
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Chauvin B, Drouot S, Barrail-Tran A, Taburet AM
Drug-drug interactions between HMG-CoA reductase inhibitors (statins) and antiviral protease inhibitors.
Clin Pharmacokinet. 2013 Oct;52(10):815-31. doi: 10.1007/s40262-013-0075-4.
- PubMed ID
- 23703578 [ View in PubMed]
- Abstract
The HMG-CoA reductase inhibitors are a class of drugs also known as statins. These drugs are effective and widely prescribed for the treatment of hypercholesterolemia and prevention of cardiovascular morbidity and mortality. Seven statins are currently available: atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin. Although these drugs are generally well tolerated, skeletal muscle abnormalities from myalgia to severe lethal rhabdomyolysis can occur. Factors that increase statin concentrations such as drug-drug interactions can increase the risk of these adverse events. Drug-drug interactions are dependent on statins' pharmacokinetic profile: simvastatin, lovastatin and atorvastatin are metabolized through cytochrome P450 (CYP) 3A, while the metabolism of the other statins is independent of this CYP. All statins are substrate of organic anion transporter polypeptide 1B1, an uptake transporter expressed in hepatocyte membrane that may also explain some drug-drug interactions. Many HIV-infected patients have dyslipidemia and comorbidities that may require statin treatment. HIV-protease inhibitors (HIV PIs) are part of recommended antiretroviral treatment in combination with two reverse transcriptase inhibitors. All HIV PIs except nelfinavir are coadministered with a low dose of ritonavir, a potent CYP3A inhibitor to improve their pharmacokinetic properties. Cobicistat is a new potent CYP3A inhibitor that is combined with elvitegravir and will be combined with HIV-PIs in the future. The HCV-PIs boceprevir and telaprevir are both, to different extents, inhibitors of CYP3A. This review summarizes the pharmacokinetic properties of statins and PIs with emphasis on their metabolic pathways explaining clinically important drug-drug interactions. Simvastatin and lovastatin metabolized through CYP3A have the highest potency for drug-drug interaction with potent CYP3A inhibitors such as ritonavir- or cobicistat-boosted HIV-PI or the hepatitis C virus (HCV) PI, telaprevir or boceprevir, and therefore their coadministration is contraindicated. Atorvastatin is also a CYP3A substrate, but less potent drug-drug interactions have been reported with CYP3A inhibitors. Non-CYP3A-dependent statin concentrations are also affected although to a lesser extent when coadministered with HIV or HCV PIs, mainly through interaction with OATP1B1, and treatment should start with the lowest available statin dose. Effectiveness and occurrence of adverse effects should be monitored at regular time intervals.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Atorvastatin Aryl hydrocarbon receptor Protein Humans UnknownAgonistDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareAtorvastatinCobicistat The serum concentration of Atorvastatin can be increased when it is combined with Cobicistat. AtorvastatinSimeprevir The serum concentration of Atorvastatin can be increased when it is combined with Simeprevir. AtorvastatinTelaprevir The serum concentration of Atorvastatin can be increased when it is combined with Telaprevir. LovastatinFluconazole The metabolism of Lovastatin can be decreased when combined with Fluconazole. LovastatinSimeprevir The serum concentration of Lovastatin can be increased when it is combined with Simeprevir.