Nirmatrelvir/ritonavir, sold under the brand name Paxlovid, is a co-packaged medication used as a treatment for COVID19. It contains the antiviral medications nirmatrelvir and ritonavir and was developed by Pfizer. Both are protease inhibitors: nirmatrelvir inhibits SARS-CoV-2 main protease, while ritonavir inhibits HIV-1 protease, and is additionally a strong CYP3A inhibitor.
Side effects of nirmatrelvir/ritonavir include changes in sense of taste (dysgeusia), diarrhea, high blood pressure (hypertension), and muscle pain (myalgia).
In December 2021, nirmatrelvir/ritonavir was granted emergency use authorization by the United States Food and Drug Administration (FDA) for the treatment of COVID19. It was approved in the United Kingdom later that month, and in the European Union and Canada in January 2022. In May 2023, it got full FDA approval for high-risk adults, while children 12-18 were still covered under the EUA.
Medical uses
In the United States, nirmatrelvir/ritonavir is indicated for the treatment of mild-to-moderate COVID19 in adults who are at high risk for progression to severe COVID19, including hospitalization or death. It is not authorized for the pre-exposure or post-exposure prevention of COVID19.
In the European Union, the co-packaged medication is indicated for the treatment of COVID19 in adults who do not require supplemental oxygen and who are at increased risk for progressing to severe COVID19.
If administered within five days of symptom onset, the efficacy of the co-packaged medication against hospitalization or death in unvaccinated high-risk adults is about .
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.
Pregnancy
The co-packaged medication is not recommended during pregnancy, in women who can become pregnant and who are not using contraception, and for women who are breastfeeding. These recommendations are because laboratory studies in animals suggest that high doses of the co-packaged medication may affect the growth of the fetus.
There are no human data on the use of nirmatrelvir during pregnancy related to the risk of birth defects, spontaneous abortions (miscarriage), or adverse outcomes. There are also no human data on the presence of nirmatrelvir in human milk, its effects on milk production or the infant. In pregnant rabbits, a reduction in fetal body weight was observed with systemic exposure ten times higher than the authorized human dose of the co-packaged medication. A temporary reduction in body weight was observed in the offspring of nursing rats.
Side effects
Nirmatrelvir/ritonavir has a high potential for potentially serious drug interactions due to strong CYP3A inhibition by ritonavir.
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 still 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.