Nirmatrelvir
What is Nirmatrelvir?
Nirmatrelvir is an antiviral medication developed by Pfizer that acts as an orally active 3C-like protease inhibitor (1). It is part of a nirmatrelvir/ritonavir combination used to treat COVID-19 and sold under the brand name Paxlovid (1)(5). Nirmatrelvir was developed by modification of the earlier clinical candidate lufotrelvir, which is also a covalent protease inhibitor but its active element is a phosphate prodrug of a hydroxyketone (1). Lufotrelvir needs to be administered intravenously limiting its use to a hospital setting. Stepwise modification of the tripeptide peptidomimetic led to nirmatrelvir, which is suitable for oral administration (1).
Dosage
The recommended dosage for nirmatrelvir is 300 mg with ritonavir 100 mg orally twice daily for 5 days (1). Treatment should be initiated as soon as possible and within 5 days of symptom onset (1). Nirmatrelvir is currently only available from Emergency Use Authorization (EUA) supplies, so its use must be consistent with the terms and conditions of the EUA (1).
Side Effects
As nirmatrelvir/ritonavir is an investigational drug, there is limited clinical data about its potential adverse effects (2). However, data from the EPIC-HR trial suggests that it is generally well-tolerated by patients with COVID-19 (2). The most common adverse effects include dysgeusia, diarrhea, hypertension, and myalgia (2). Other potential side effects might include headache, nausea, vomiting, general ill feeling, abdominal pain, altered taste, and muscle aches (3). If you experience any serious side effects, such as an allergic reaction, seek medical attention immediately (3).
Interactions
Nirmatrelvir/ritonavir has significant drug-drug interactions due to the ritonavir component (2)(5). As a potent CYP3A inhibitor, ritonavir can increase the plasma concentrations of concomitant medications whose metabolism depends on CYP3A, increasing the risks of serious and life-threatening toxicities (2)(5)(6). In addition, ritonavir use is associated with hepatotoxicity, with reports of hepatitis, jaundice, and elevated transaminases (2). Patients taking nirmatrelvir/ritonavir, with or without other medications, should be monitored for drug-related toxicities (2).
Time of Day and With or Without Food
Nirmatrelvir and ritonavir can be taken with or without food (1)(5). The tablets should be swallowed whole and not chewed, broken, or crushed (6). The first dose of nirmatrelvir/ritonavir should be taken as soon as possible and within 5 days of symptom onset (1).
Human Studies
Nirmatrelvir is an antiviral medication developed by Pfizer that acts as an orally active 3C-like protease inhibitor (1). It is part of a nirmatrelvir/ritonavir combination used to treat COVID-19 and sold under the brand name Paxlovid (1)(5). The safety and efficacy of nirmatrelvir/ritonavir have been evaluated in clinical trials, and the results have shown that it can reduce the risk of hospitalization or death in high-risk patients with mild-to-moderate COVID-19 (1)(5).
To summarize, Nirmatrelvir is an antiviral medication developed by Pfizer that acts as an orally active 3C-like protease inhibitor. The recommended dosage is 300 mg with ritonavir 100 mg orally twice daily for 5 days. Nirmatrelvir can be taken with or without food. As an investigational drug, there is limited clinical data about its potential adverse effects, but it is generally well-tolerated by patients with COVID-19. Nirmatrelvir/ritonavir has significant drug-drug interactions due to the ritonavir component, and patients taking nirmatrelvir/ritonavir, with or without other medications, should be monitored for drug-related toxicities. The first dose of nirmatrelvir/ritonavir should be taken as soon as possible and within 5 days of symptom onset. The safety and efficacy of nirmatrelvir/ritonavir have been evaluated in clinical trials, and the results have shown that it can reduce the risk of hospitalization or death in high