The drug is contraindicated when co-administered with certain drugs, such as drugs dependent on CYP3A for removal, for which a raised concentration results in serious reactions, or those with potent CYP3A inducers, for which reduced blood concentration of the two main components may result in loss of effect against the virus and possible resistance, among others. Co-administration also affects the concentration of several drugs, sometimes requiring changing the dose or careful monitoring. Many of these drugs are widely prescribed to people at high risk from COVID-19. With the extension of the emergency authorization in August 2022, the FDA updated a checklist to help evaluate potential drug interactions and other patient factors before prescribing Paxlovid, including more than 120 drugs which are either contraindicated, should be avoided or held from use, or require dose adjustments or special monitoring.Adverse events of the co-packaged medication, regardless of causality, observed in the phase II-III EPIC-HR study included: dysgeusia (4.8–6%), diarrhea (3–3.9%), vomiting (1.3%), hypertension (1%), and myalgia (1%).There is no specific antidote for overdose with the co-packaged medication. Treatment consists of supportive measures such as monitoring of vital signs and observation of clinical status. Rebound
An additional analysis of the original EPIC-HR clinical trial data (Delta variant) showed that about 2% of both the treatment and placebo groups experienced a symptomatic rebound after the 5 day treatment, meaning they felt ill again and tested positive again (antigen test and PCR test) after testing negative. This is important, because people with rebound cannot go back to work or school.
Nirmatrelvir, the novel portion of the co-packaged medication, was first developed in the United States and was initially manufactured in small amounts in Groton, Connecticut, to support clinical trials, but the Freiburg facility in Germany was responsible for figuring out how to mass-produce the co-packaged medication on an industrial scale. Pfizer selected another factory in Ascoli Piceno, Italy, to assist the Freiburg factory with packaging tablets into blister packs. History
The primary data supporting the US Food and Drug Administration (FDA) emergency use authorization for nirmatrelvir/ritonavir are from EPIC-HR, a randomized, double-blind, placebo-controlled clinical trial studying nirmatrelvir/ritonavir for the treatment of non-hospitalized symptomatic adults with a laboratory confirmed diagnosis of SARS-CoV-2 infection. Participants were adults 18 years of age and older with a prespecified risk factor for progression to severe disease or were 60 years and older regardless of prespecified chronic medical conditions. All participants had not received a COVID-19 vaccine and had not been previously infected with COVID-19. The main outcome measured in the trial was the proportion of people who were hospitalized due to COVID-19 or died due to any cause during 28 days of follow-up. 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.