Pfizer received an emergency use authorization (EUA) for Paxlovid, an oral pill for the treatment of mild to moderate COVID-19 in certain adult and pediatric populations.
Editors Note: The information provided in this month’s New Drug Review column is based on the FDA’s emergency use authorization (EUA).
Per the EUA,1 “Paxlovid has not been approved, but has been authorized for emergency use by FDA under an EUA, for the treatment of mild to moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death; and the emergency use of Paxlovid is only authorized for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of drugs and biological products during the COVID- 19 pandemic under Section 564(b)(1) of the Act, 21 U.S.C. § 360bbb- 3(b)(1), unless the declaration is terminated or authorization revoked sooner.”
On December 22, 2021, the FDA issued an EUA for nirmatrelvir copackaged with ritonavir (Paxlovid; Pfizer).2 Paxlovid is the first oral pill indicated for the treatment of mild to moderate COVID-19 for certain adult and pediatric patients 12 years and older, weighing at least 40 kg, who have a positive SARS-CoV-2 viral test, whose symptoms have been present for at least 5 days, and who are at high risk for progression to severe disease, including hospitalization or death.
Paxlovid is not indicated for treatment in those requiring hospitalization for severe disease, as exposure prophylaxis, or for those with symptoms that have been present for more than 5 days.3,4
The Paxlovid EUA came from a planned interim analysis of the EPIC-HR Trial (NCT04960202), a phase 2/3 randomized, double-blind, placebo-controlled trial.2 At randomization, the trial enrolled 2246 nonhospitalized, symptomatic (< 5 days) adult patients 60 years or older with at least 1 risk factor for progression to severe disease. Patients with a history of COVID-19 infection or evidence of vaccination against the virus were not included.
The primary efficacy end point was the proportion of patients with COVID-19–related hospitalization or death from any cause through day 28. In a modified intention-to-treat analysis (n = 2085) of patients whose symptom onset was within 5 days and who were not expected to receive monoclonal antibody therapy, 8 patients in the Paxlovid group (n = 1039; 0.8%) and 66 patients (n = 1046; 6.3%) in the placebo group were hospitalized or died.2 This represented an 88% decreased risk of hospitalization or death in those treated with Paxlovid vs placebo (–5.62 reduction relative to placebo; 95% CI –7.21 to –4.03). This is an interim analysis; effectiveness continues to
Initial safety data also come from the EPIC-HR Trial. Notable adverse effects in the Paxlovid group vs placebo included dysgeusia, diarrhea, hypertension, and myalgia.2 As stated in the EUA, rates of reactions observed may not reflect the rates observed in clinical practice and may become more apparent with widespread use. Health care providers and/or facilities are required to track all serious medication errors and adverse events that are considered related to the drug and must report them to both the FDA and Pfizer.
Paxlovid is supplied as two 150-mg tablets of nirmatrelvir copackaged with one 100-mg tablet of ritonavir. The current dosing recommendation is 300 mg/100 mg every 12 hours for 5 days. A dose adjustment to 1 tablet of nirmatrelvir (150 mg) plus ritonavir (100 mg) is recommended in moderate renal impairment (eGFR 30-60 mL/min). Pharmacokinetic or safety data are not available for severe renal or hepatic impairment and pregnancy; therefore, use is not recommended in these populations.2
Paxlovid (ritonavir component) inhibits cytochrome P450 3A4 metabolism pathways, and many potentially significant drug interactions may exist. Contraindications to use are any clinically significant hypersensitivity reactions to active drug components of Paxlovid.
The Paxlovid Fact Sheet for Healthcare Providers provides an extensive and comprehensive list of potential drug interactions.2 Given the significant potential for many drug interactions, pharmacists should review all concomitant medications and monitor for any adverse events that may be associated.
Cassandra R. Doyno, PharmD, BCPS, BCCCP, is an assistant clinical professor at the University of Connecticut School of Pharmacy in Storrs.