Nirmatrelvir/ritonavir, sold under the brand name Paxlovid, is a co-packaged medication used as a treatment for COVID-19. It contains the antiviral medications nirmatrelvir and ritonavir and was developed by Pfizer. Nirmatrelvir inhibits SARS-CoV-2 main protease, while ritonavir is a strong CYP3A inhibitor, slowing down nirmatrelvir metabolism and therefore boosting its effect. It is taken by mouth. In unvaccinated high-risk people with COVID-19, nirmatrelvir/ritonavir can reduce the risk of hospitalization or death by 88% if taken within five days of symptom onset. People who take nirmatrelvir/ritonavir also test negative for COVID-19 about two and a half days earlier than people who do not. Side effects of nirmatrelvir/ritonavir include changes in sense of taste (dysgeusia), diarrhea, high blood pressure (hypertension), and muscle pain (myalgia). In December 2021, the United States Food and Drug Administration (FDA) granted nirmatrelvir/ritonavir emergency use authorization (EUA) to treat COVID-19. It was approved in the United Kingdom later that month, and in the European Union and Canada in January 2022. In May 2023, it was approved in the US to treat mild-to-moderate COVID-19 in adults who are at high risk for progression to severe COVID-19, including hospitalization or death, relative to the general population. The FDA considers the combination to be a first-in-class medication. In 2023, it was the 159th most commonly prescribed medication in the United States, with more than 3 million prescriptions.
Medical uses In the United States, nirmatrelvir/ritonavir is indicated for the treatment of mild-to-moderate COVID-19 in adults who are at high risk for progression to severe COVID-19, including hospitalization or death. This includes people above 50, people with diabetes, cancer, coronary artery disease, chronic lung diseases, pregnancy, or on immunosuppressant drugs. The co-packaged medication is not authorized or suggested for the pre-exposure or post-exposure prophylaxis of COVID-19. In the European Union, the co-packaged medication is indicated for the treatment of COVID-19 in adults who do not require supplemental oxygen and who are at increased risk for progressing to severe COVID-19. If administered within five days of symptom onset in confirmed COVID-19 infections, the efficacy of the co-packaged medication against hospitalization or death in unvaccinated high-risk adults, as of 2022, was about 88% (95% CI, 75–94%).
Pregnancy The suggestion of the use of co-packaged medication during pregnancy in people who can become pregnant and are not using contraception, and for people who are breastfeeding, needs further study. Given the risk of morbidity, hospitalization and mortality associated with severe COVID-19 disease in females and fetuses, nirmatrelvir/ritonavir can provide an important option to reduce the risks associated with acute COVID-19 infection in at-risk and unvaccinated patients after careful consideration of the benefits and risks for each patient. There is limited human data on the use of nirmatrelvir during pregnancy related to the risk of congenital disabilities, spontaneous abortions (i.e., miscarriage), or adverse outcomes. As of February 2026, data on the transfer of nirmatrelvir/ritonavir from breastfeeding parents to infants are limited. Nonetheless, Dai and colleagues reported in a 2024 article in Clinical Pharmacology & Therapeutics that the relative infant dose of drug conferred by breast milk was minimal and "well under the standard 10% safety threshold", supporting the use of the medication during pregnancy and breastfeeding. A temporary reduction in body weight was observed in the offspring of nursing rats. Other observational studies have also demonstrated the safety of ritonavir during pregnancy.
Contraindications The medication is contraindicated in those with hypersensitivity to either of the two main components, and in those with severely reduced kidney or liver function. Co-administration with certain drugs may have serious, sometimes fatal, effects.
Side effects Nirmatrelvir/ritonavir has a high potential for potentially serious drug interactions due to strong CYP3A inhibition by ritonavir. The US FDA label, the FDA fact sheet, and the FDA EUA contain a boxed warning about the CYP3A inhibition. Adverse events of the co-packaged medication, regardless of causality, observed in the phase II-III EPIC-HR study included dysgeusia (6% vs. < 1% for placebo), diarrhea (3% vs. 2% for placebo), hypertension (1% vs. < 1% for placebo), and myalgia (1% vs. < 1% for placebo). In clinical trials, 2% of people discontinued treatment due to side effects with nirmatrelvir/ritonavir while 4% in the placebo group did so. Nirmatrelvir/ritonavir is under investigation, so its side effects have yet to be fully evaluated and may not be completely known. Other side effects of nirmatrelvir/ritonavir may include hypersensitivity reactions, liver toxicity, and development of HIV drug resistance in people with uncontrolled or undiagnosed HIV infection. Hypersensitivity reactions (allergic reactions) may manifest as skin rash, hives, difficulty swallowing, difficulty breathing, angioedema, and/or anaphylaxis. Liver toxicity may manifest as elevated transaminases and clinical hepatitis, including symptoms like appetite loss, jaundice (yellowing of the skin and whites of eyes), dark-colored urine, pale-colored stools, itchy skin, and abdominal pain.
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