What are the side effects of Paxlovid (nirmatrelvir/ritonavir)?

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Last updated: April 22, 2025View editorial policy

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From the Guidelines

Paxlovid can cause several side effects, but the most recent and highest quality study from 2024 1 suggests that the benefits of Paxlovid in reducing the risk of severe COVID-19 typically outweigh these potential side effects for high-risk patients. The most common side effects of Paxlovid include:

  • Metallic or bitter taste in the mouth (dysgeusia)
  • Diarrhea
  • Increased blood pressure
  • Muscle aches
  • Nausea
  • Abdominal pain Most of these side effects are mild to moderate and typically resolve when treatment ends. Paxlovid can also interact with many medications because ritonavir, one of its components, inhibits liver enzymes that metabolize other drugs, as reported in a study from 2024 1. This can lead to increased levels of certain medications in the body, potentially causing serious adverse effects. Before starting Paxlovid, patients should inform their healthcare provider about all medications they're taking, including over-the-counter drugs and supplements. Patients with kidney or liver disease may need dose adjustments, as suggested by a study from 2022 1. If severe side effects occur, such as signs of allergic reaction or severe diarrhea, medical attention should be sought immediately. It is essential to weigh the benefits and risks of Paxlovid, considering the individual patient's condition and medical history, as emphasized in the study from 2024 1. The study from 2024 1 provides the most recent and highest quality evidence, and its findings should be prioritized when making treatment decisions. In general, the side effects of Paxlovid are manageable, and the medication can be an effective treatment option for high-risk patients with COVID-19, as supported by the study from 2024 1.

From the FDA Drug Label

PAXLOVID may cause serious side effects, including: • Allergic reactions, including severe allergic reactions (anaphylaxis) have happened during treatment with PAXLOVID • Liver problems The most common side effects of PAXLOVID include: • altered sense of taste • diarrhea Other possible side effects include: • headache • vomiting • abdominal pain • nausea • high blood pressure • feeling generally unwell

The possible side effects of PAXLOVID include:

  • Serious side effects: allergic reactions and liver problems
  • Common side effects: altered sense of taste and diarrhea
  • Other possible side effects: headache, vomiting, abdominal pain, nausea, high blood pressure, and feeling generally unwell 2

From the Research

Side Effects of Paxlovid

  • The side effects of Paxlovid (nirmatrelvir/ritonavir) include dysgeusia and diarrhea, as reported in a study published in 2022 3.
  • Treatment-related adverse events such as dysgeusia and diarrhea were more common in the Paxlovid group compared to the placebo group (RR 2.06,95% CI 1.44 to 2.95; 1 study, 2224 participants; moderate-certainty evidence) 3.
  • Serious adverse events were less common in the Paxlovid group compared to the placebo group (RR 0.24,95% CI 0.15 to 0.41; 1 study, 2224 participants; low-certainty evidence) 3.
  • Treatment-emergent adverse events were similar in the Paxlovid group and the placebo group (RR 0.95% CI 0.82 to 1.10; 1 study, 2224 participants; moderate-certainty evidence) 3.
  • Discontinuation of study drug due to adverse events was less common in the Paxlovid group compared to the placebo group (RR 0.49,95% CI 0.30 to 0.80; 1 study, 2224 participants; moderate-certainty evidence) 3.

Drug Interactions

  • Nirmatrelvir-ritonavir has a high risk of drug interactions, particularly with medications that are highly dependent on CYP3A4 for clearance 4, 3.
  • Ritonavir, a component of Paxlovid, inhibits the metabolizing enzyme cytochrome P450 3A, which can increase the levels of other medications that are metabolized by this enzyme 5.

Safety and Efficacy

  • Paxlovid has been shown to be effective in reducing the risk of hospitalization and death in patients with mild to moderate COVID-19 who are at high risk of progression to severe disease 6, 3.
  • The safety and efficacy of Paxlovid in certain populations, such as hospitalized patients with COVID-19 and those with certain comorbidities, are still being studied and are not yet well established 3.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Nirmatrelvir combined with ritonavir for preventing and treating COVID-19.

The Cochrane database of systematic reviews, 2022

Research

Molnupiravir and Nirmatrelvir-Ritonavir: Oral Coronavirus Disease 2019 Antiviral Drugs.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2023

Research

Paxlovid (Nirmatrelvir/Ritonavir): A new approach to Covid-19 therapy?

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2023

Research

Paxlovid for the treatment of COVID-19: a systematic review and meta-analysis.

Journal of infection in developing countries, 2024

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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