Should Repatha (evolocumab) be held when starting Paxlovid (nirmatrelvir/ritonavir) for COVID-19 treatment?

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Last updated: October 4, 2025View editorial policy

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Should Repatha be Held When Starting Paxlovid?

Yes, Repatha (evolocumab) should be temporarily held during the 5-day course of Paxlovid (nirmatrelvir/ritonavir) treatment due to potential drug-drug interactions with ritonavir.

Mechanism of Interaction

  • Paxlovid contains ritonavir, a potent inhibitor of cytochrome P450 3A4 (CYP3A4), which can significantly affect the metabolism of many medications, including cardiovascular drugs 1, 2
  • Ritonavir is included in Paxlovid specifically to boost nirmatrelvir levels by inhibiting its metabolism, but this also affects other medications metabolized through similar pathways 1
  • Even though Paxlovid is only a 5-day course, the inhibition of CYP3A4 is rapid and potent, creating a high potential for drug-drug interactions 1

Management Approach for Repatha

  • Repatha (evolocumab) is a PCSK9 inhibitor administered every 2 weeks or monthly, making it feasible to temporarily pause without significant impact on long-term lipid management 2
  • The short 5-day course of Paxlovid means that Repatha can be safely held during this period and resumed after completion of COVID-19 treatment 1
  • Missing a single dose of Repatha during the Paxlovid treatment period poses minimal risk to cardiovascular outcomes compared to the potential risks of drug interactions 2, 3

Balancing COVID-19 Treatment Benefits vs. Risks

  • Paxlovid has demonstrated significant effectiveness in reducing hospitalization by 39% and death by 61% in real-world data, making it an important treatment option for COVID-19 patients 4
  • The benefit of Paxlovid in preventing progression to severe COVID-19 outweighs the temporary interruption of lipid-lowering therapy 4, 5
  • Proper management of potential drug-drug interactions must balance the benefit of nirmatrelvir/ritonavir to prevent severe disease with the risk of adverse events 2

Practical Recommendations

  • If Repatha is due during the 5-day Paxlovid course, delay the Repatha injection until after completing the full course of Paxlovid 1, 3
  • If Repatha was recently administered, it's still safe to start Paxlovid as needed, since the interaction concern is primarily about concurrent administration 2
  • Resume regular Repatha dosing schedule after completing the 5-day course of Paxlovid 1
  • No dosage adjustment is needed for Repatha after resuming - simply continue with the regular dosing schedule 3

Important Considerations

  • This recommendation applies specifically to the short 5-day course of Paxlovid used for COVID-19 treatment 1
  • The temporary holding of Repatha is a precautionary measure to minimize potential drug interactions 2
  • Document the temporary interruption of Repatha in the patient's medical record and ensure they understand when to resume their regular schedule 3

Professional Medical Disclaimer

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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