[21] Side effects of nirmatrelvir/ritonavir include changes in sense of taste (dysgeusia), diarrhea, high blood pressure (hypertension), and muscle pain (myalgia).

[10] In December 2021, the United States Food and Drug Administration (FDA) granted nirmatrelvir/ritonavir emergency use authorization (EUA) to treat COVID‑19.

[15][24][25] 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.

[27][28] 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.

[12][14][30] 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.

[15] 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%).

[31] There is limited human data on the use of nirmatrelvir during pregnancy related to the risk of birth defects, spontaneous abortions (miscarriage), or adverse outcomes.

[29] A 2025 recent report indicates that Paxlovid may benefit certain long COVID patients, though it remains unclear which individuals are most likely to respond.

[41] The findings highlight the ongoing uncertainty surrounding effective treatments for long COVID, nearly five years into the pandemic.

[43][44] In June 2022, a US case report of ten people with rebound COVID‑19 had found viral load during relapse was comparable to levels during an initial infection, and high enough to cause secondary transmission.

As of June 2022, Pfizer studied the phenomenon in a new trial it called EPIC-SR (standard risk) while the omicron variant was circulating.

[47] The engineering of a nirmatrelvir-resistant chimera of vesicular stomatitis virus (VSV) under laboratory conditions was published without formal peer review in July 2022.

[51] Nirmatrelvir/ritonavir significantly reduced the proportion of people with COVID‑19-related hospitalization or death from any cause by 88% compared to placebo among participants treated within five days of symptom onset and who did not receive COVID‑19 therapeutic monoclonal antibody treatment.

[14] In December 2021, nirmatrelvir/ritonavir was granted emergency use authorization by the United States Food and Drug Administration (FDA) for the treatment of COVID‑19.

[13] In December 2021, the United Kingdom's Medicines and Healthcare products Regulatory Agency (MHRA) approved the use of nirmatrelvir combined with ritonavir for adults with mild to moderate infection and at high risk of their illness worsening.

[53][55] Likewise, findings were not statistically significant for reducing hospitalization rates in a subgroup of vaccinated adults with at least one risk factor for severe COVID‑19 (treatment: 3/361 [0.8%]; placebo: 7/360 [1.9%]; 57% reduction – RR 0.43, 95% CI 0.11–1.64).

[53][55] However, the trial did find a statistically significant 62% decrease in COVID‑19-related medical visits, similar to the 67% reduction from the EPIC-HR study of high-risk individuals.

[53][55] In May 2023, nirmatrelvir/ritonavir received FDA approval 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.

[7][24][59][60][61] In February 2022, China approved the medication for the treatment of adults who have mild to moderate COVID‑19 and are at a high risk of progressing to a severe condition.

[63] The Japanese Ministry of Health, Labour and Welfare approved the use of the co-packaged medication for treating adults in February 2022.

[8][9][67] In November 2021, Pfizer submitted an application to the US Food and Drug Administration (FDA) for emergency use authorization for the co-packaged medication.

[13][18][58][73] Pfizer selected its largest oral tablet factory in Freiburg as the launch facility for manufacturing the co-packaged medication.

As of August 2022 the treatment guidelines German family doctors follow had not been updated since February 2022 and recommended nirmatrelvir/ritonavir only in unvaccinated risk patients, i.e., only a few people.

[71] In July 2022, the FDA allowed state-licensed pharmacists to prescribe it to people with COVID‑19 at high risk of progressing to severe disease.

[29] Reasons are suspected to be concerns about "rebound, unfamiliarity with the treatment and cost" as well as "confusion around who's at high risk for severe disease".

[29] Paxlovid treatment was free through the end of 2024, for Medicare and Medicaid beneficiaries and insured persons covering out-of-pocket costs.

[29][80] Paxlovid continues to be free for some Medicare and Medicaid beneficiaries through the end of 2025, via the US Government Patient Assistance Program.