What are the potential interactions between Paxlovid (nirmatrelvir/ritonavir) and atorvastatin (Lipitor)?

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Last updated: June 13, 2025View editorial policy

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From the Research

Atorvastatin (Lipitor) should be temporarily discontinued during the 5-day course of Paxlovid (nirmatrelvir/ritonavir) treatment due to significant drug interactions. The ritonavir component of Paxlovid strongly inhibits CYP3A4, an enzyme responsible for metabolizing atorvastatin, which can lead to dangerously high statin levels in the bloodstream, as noted in studies discussing drug interactions with nirmatrelvir-ritonavir 1. This interaction increases the risk of serious side effects like rhabdomyolysis, a condition where muscle breaks down and can cause kidney damage. Patients should stop taking atorvastatin when starting Paxlovid and can safely resume their statin 1-2 days after completing the full 5-day Paxlovid course. This temporary discontinuation of atorvastatin for 7-8 days is unlikely to significantly impact long-term cholesterol management or cardiovascular risk. If a patient is at extremely high cardiovascular risk, their healthcare provider might consider temporarily substituting atorvastatin with pravastatin or rosuvastatin at a reduced dose, as these statins are less affected by this interaction, although specific guidance on this is not provided in the most recent studies such as 2 and 3. Patients should always inform their healthcare provider about all medications they're taking before starting Paxlovid, to ensure safe management of potential drug interactions. Given the potential for underutilization of nirmatrelvir/ritonavir in eligible COVID-19 patients as highlighted in 3, it's crucial that healthcare providers are aware of the necessary precautions, including managing drug interactions, to maximize the benefits of Paxlovid while minimizing risks. The most recent and highest quality study directly addressing the use of nirmatrelvir/ritonavir is 2, which, although focused on long COVID, underscores the importance of careful patient selection and management of potential interactions. However, for the specific interaction between Paxlovid and atorvastatin, the guidance provided is based on the understanding of ritonavir's effect on CYP3A4 and the potential for increased risk of adverse effects with atorvastatin, as would be considered in clinical practice based on principles outlined in studies like 4 and 5.

References

Research

Underutilization of nirmatrelvir/ritonavir in eligible COVID-19 patients.

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology, 2025

Research

Nirmatrelvir plus ritonavir in COVID-19: a profile of its use.

Drugs & therapy perspectives : for rational drug selection and use, 2023

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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