Drugs That Interact With Atorvastatin

Drug Interactions with Atorvastatin

Introduction to Atorvastatin and Its Metabolism

Atorvastatin, a widely prescribed statin, is primarily used to lower cholesterol levels and prevent cardiovascular diseases. It is metabolized in the liver by the cytochrome P450 (CYP) 3A4 enzyme and is also a substrate for the organic anion transporter polypeptide (OATP) 1B1, which facilitates its uptake into hepatocytes .

Interactions with Antiviral Protease Inhibitors

Atorvastatin's metabolism through CYP3A4 makes it susceptible to interactions with drugs that inhibit or induce this enzyme. HIV protease inhibitors (PIs) such as ritonavir and cobicistat, which are potent CYP3A4 inhibitors, can significantly increase atorvastatin concentrations, leading to a higher risk of adverse effects like myopathy and rhabdomyolysis . Similarly, hepatitis C virus (HCV) PIs like boceprevir and telaprevir also inhibit CYP3A4, necessitating careful monitoring and dose adjustments when coadministered with atorvastatin.

Interaction with Dronedarone

Dronedarone, an antiarrhythmic agent, interacts with atorvastatin through CYP3A4. Both atorvastatin and its lactone form inhibit the binding and metabolism of dronedarone, with atorvastatin lactone showing a higher affinity for CYP3A4. This interaction can alter the pharmacokinetics of both drugs, necessitating careful management when used together.

Impact of Antiretrovirals in HIV Patients

In people living with HIV, the coadministration of boosted antiretrovirals (ARVs) significantly affects atorvastatin pharmacokinetics. Boosted ARVs, which include CYP3A4 inhibitors, can decrease atorvastatin clearance by 58% and reduce the formation of its major metabolite, ortho-OH-atorvastatin, by 88%. This interaction can lead to a 180% increase in atorvastatin exposure, highlighting the need for dose adjustments and regular monitoring in this population.

Non-Interacting Combinations

Studies have shown that atorvastatin does not exhibit significant pharmacokinetic interactions with fenofibrate or ezetimibe. When coadministered with fenofibrate, atorvastatin's pharmacokinetic parameters remain largely unchanged, suggesting no relevant clinical interaction. Similarly, the combination of atorvastatin with ezetimibe does not significantly alter the pharmacokinetics of either drug, making it a safe and effective combination for lowering LDL cholesterol levels.

Interaction with Omega-3 Fatty Acids

The coadministration of atorvastatin with omega-3 fatty acids has shown a pharmacokinetic interaction. Omega-3 fatty acids can alter the pharmacokinetics of atorvastatin and its metabolite, 2-OH-atorvastatin, indicating the need for careful consideration when these agents are used together.

Herb-Drug Interactions

Piperine, a component of black pepper and a potent CYP3A4 inhibitor, can significantly increase the plasma concentration of atorvastatin when coadministered. This interaction underscores the importance of considering herbal supplements and their potential to affect drug metabolism.

Conclusion

Atorvastatin is subject to numerous drug-drug interactions primarily due to its metabolism by CYP3A4 and its role as a substrate for OATP1B1. Interactions with antiviral protease inhibitors, dronedarone, and certain herbal supplements can significantly alter its pharmacokinetics, necessitating dose adjustments and careful monitoring. Conversely, combinations with fenofibrate and ezetimibe do not show significant interactions, making them safe options for combined therapy. Understanding these interactions is crucial for optimizing atorvastatin therapy and minimizing adverse effects.

Summary

Not a yes or no question

Drug Interactions with Atorvastatin

Introduction to Atorvastatin and Its Metabolism

Interactions with Antiviral Protease Inhibitors

Interaction with Dronedarone

Impact of Antiretrovirals in HIV Patients

Non-Interacting Combinations

Interaction with Omega-3 Fatty Acids

Herb-Drug Interactions

Conclusion

Sources and full results

Drug–Drug Interactions Between HMG-CoA Reductase Inhibitors (Statins) and Antiviral Protease Inhibitors

Drug-Drug Interactions between Atorvastatin and Dronedarone Mediated by Monomeric CYP3A4.

Influence of Drug–Drug Interactions on the Pharmacokinetics of Atorvastatin and Its Major Active Metabolite ortho-OH-Atorvastatin in Aging People Living with HIV

Absence of a significant pharmacokinetic interaction between atorvastatin and fenofibrate: a randomized, crossover, study of a fixed-dose formulation in healthy Mexican subjects

Physiologically based pharmacokinetic modeling of disposition and drug-drug interactions for atorvastatin and its metabolites.

Pharmacokinetic non-interaction analysis in a fixed-dose formulation in combination of atorvastatin and ezetimibe

Pharmacokinetic Interaction between Atorvastatin and Omega-3 Fatty Acid in Healthy Volunteers

Pharmacokinetics and Pharmacodynamic Herb-Drug Interaction of Piperine with Atorvastatin in Rats.

Optical Isomers of Atorvastatin, Rosuvastatin and Fluvastatin Enantiospecifically Activate Pregnane X Receptor PXR and Induce CYP2A6, CYP2B6 and CYP3A4 in Human Hepatocytes

Cholesterol-lowering drugs the simvastatin and atorvastatin change the protease activity of pepsin: An experimental and computational study.

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