Drug interactions with atorvastatin
Pro Research Analysisby 
Searched over 200M research papers
Consensus Meter
Drug Interactions with Atorvastatin
Introduction to Atorvastatin and Its Metabolism
Atorvastatin is a widely prescribed statin used to lower cholesterol levels and reduce the risk of cardiovascular disease. It is metabolized primarily by the cytochrome P450 (CYP) 3A4 enzyme and undergoes extensive first-pass metabolism in the liver, producing several active metabolites, including 2-hydroxy-atorvastatin acid and atorvastatin lactone . Understanding the drug-drug interactions (DDIs) involving atorvastatin is crucial for optimizing its therapeutic efficacy and minimizing adverse effects.
Atorvastatin and Cytochrome P450 Inhibitors
Interaction with Cyclosporin A (CsA)
In renal transplant recipients treated with cyclosporin A (CsA), atorvastatin has been shown to increase CsA blood trough levels in some patients. This interaction necessitates careful monitoring and potential dose adjustments of CsA to avoid toxicity. The increase in CsA levels is attributed to the inhibition of CYP3A4 by atorvastatin, which reduces the metabolism of CsA.
Interaction with Antiviral Protease Inhibitors
Atorvastatin's interaction with antiviral protease inhibitors, particularly those used in HIV treatment, is significant. Protease inhibitors like ritonavir and cobicistat are potent CYP3A4 inhibitors, leading to increased atorvastatin plasma concentrations and a higher risk of adverse effects such as myopathy and rhabdomyolysis . Therefore, when coadministered with these inhibitors, the atorvastatin dose should be reduced, and patients should be closely monitored for signs of toxicity.
Interaction with Other CYP3A4 Inhibitors
Other CYP3A4 inhibitors, such as itraconazole, clarithromycin, and verapamil, also significantly increase atorvastatin exposure. For instance, clarithromycin can increase the area under the concentration-time curve (AUC) of atorvastatin by more than fourfold, necessitating dose adjustments and careful monitoring.
Atorvastatin and Organic Anion Transporting Polypeptides (OATP) Inhibitors
Atorvastatin is also a substrate for OATP1B1/1B3, which facilitates its hepatic uptake. Inhibitors of these transporters, such as cyclosporine and rifampin, can significantly increase atorvastatin plasma levels, leading to a higher risk of adverse effects . This interaction underscores the importance of dose adjustments and monitoring when atorvastatin is coadministered with OATP inhibitors.
Atorvastatin and Other Lipid-Lowering Agents
Fenofibrate
Studies have shown that the coadministration of atorvastatin with fenofibrate does not result in significant pharmacokinetic interactions. This combination is considered safe and effective for patients requiring intensive lipid-lowering therapy.
Ezetimibe
Similarly, the combination of atorvastatin with ezetimibe has been shown to have no relevant pharmacokinetic interactions. This combination is effective in significantly reducing LDL-C levels without altering the pharmacokinetic profiles of either drug.
Omega-3 Fatty Acids
The interaction between atorvastatin and omega-3 fatty acids has been evaluated, revealing a pharmacokinetic interaction that affects the plasma levels of both atorvastatin and its metabolites. This interaction suggests that dose adjustments may be necessary when these agents are coadministered.
Conclusion
Atorvastatin is a highly effective statin with a complex pharmacokinetic profile influenced by various drug-drug interactions. The most significant interactions occur with CYP3A4 and OATP inhibitors, which can increase atorvastatin plasma levels and the risk of adverse effects. Clinicians should be aware of these interactions and adjust doses accordingly to ensure patient safety and therapeutic efficacy.
Sources and full results
Most relevant research papers on this topic