Indications
Nirmatrelvir with Ritonavir is under an EUA for treating mild-to-moderate coronavirus disease 2019 (COVID-19) in adults and paediatric patients (12 years of age and older weighing at least 40 kg). Nirmatrelvir is a SARS-CoV-2 main protease inhibitor (Mpro, also called 3CLpro or nsp5 protease). Ritonavir is an HIV-1 protease inhibitor and a CYP3A inhibitor. The patient must have a positive result on direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral testing, and must be at high risk for progression to severe COVID-19, including hospitalization or death. This combination is not authorized for starting treatment in patients who need hospitalization because of severe or critical COVID-19, for pre-exposure or post-exposure prophylaxis to prevent COVID-19, or for use longer than 5 consecutive days.
⚠️ Always consult a registered physician before taking any medicine.
Pharmacology
Nirmatrelvir is a peptidomimetic inhibitor of the SARS-CoV-2 main protease (Mpro), which is also called 3C-like protease (3CLpro) or nsp5 protease. When Mpro is blocked, the virus can't process its polyprotein precursors, and so it can't replicate. In a biochemical assay, Nirmatrelvir inhibited the activity of recombinant SARS-CoV-2 Mpro with a ki value of 3.1 nM and an IC50 value of 19.2 nM. X-ray crystallography showed that Nirmatrelvir binds directly to the active site of SARS-CoV-2 Mpro.
Ritonavir is an HIV-1 protease inhibitor, but it is not active against SARS-CoV-2 Mpro. Its job here is different. Ritonavir inhibits the CYP3A-mediated metabolism of Nirmatrelvir, and this raises the plasma concentrations of Nirmatrelvir.
Pregnancy & Breastfeeding
We have no human data on Nirmatrelvir use in pregnancy, so its risk of major birth defects, miscarriage, or other harmful outcomes for the mother or baby can't be judged. For Ritonavir, published observational studies in pregnant women have not found a higher risk of major birth defects. The published studies are not enough to say whether Ritonavir carries a risk of miscarriage. Untreated COVID-19 in pregnancy also carries risks for both the mother and the baby.
Nothing is known about whether Nirmatrelvir passes into human or animal milk, what it does to a breastfed infant, or whether it affects milk production. A mother should weigh the developmental and health benefits of breastfeeding against her own clinical need for Nirmatrelvir and Ritonavir. She should also weigh the possible side effects of these medicines on the infant, and the effects of the illness itself if it goes untreated. Women who are breastfeeding and have COVID-19 should follow clinical guidelines on feeding practices so the infant isn't exposed to COVID-19.
⚠️ Talk to your doctor before taking any medicine during pregnancy or while breastfeeding.
Dosage Reference
⚠️ Reference ranges from official sources only. Consult your doctor for personalized dosing.