#338 Ritonavir-boosted nirmatrelvir (Paxlovid®): And you thought we were done with COVID!
CLINICAL QUESTION
Is ritonavir-boosted nirmatrelvir (Paxlovid®) a safe and effective oral therapy for the treatment of COVID-19?
BOTTOM LINE
In unvaccinated patients at risk of severe outcomes, oral ritonavir-boosted nirmatrelvir (Paxlovid®) reduces the risk of hospitalization due to COVID-19 from 6.2% to 0.8% and all-cause mortality from 1.2% to 0%. Real-world evidence suggests effectiveness in Omicron-infected. Adverse events include taste disturbances and potentially serious drug interactions exist.
Reading Tools for Practice Article can earn you MainPro+ Credits
Join NowAlready a CFPCLearn Member? Log in
EVIDENCE
- Outcomes statistically significant unless noted.
- Manufacturer funded, randomized, placebo-controlled trial of 2246 unvaccinated COVID-19 outpatients [median age 46, ≥1 risk factor like BMI ≥25 (81%), smoking (39%) or hypertension (33%)]. Randomized to 5-day course of ritonavir-boosted nirmatrelvir or placebo within 5 days of symptom onset. Patients enrolled prior to Omicron dominance.1 Outcomes at 28 days:
- COVID-19 hospitalization: 8/1039 (0.8%) versus 65/1046 (6.2%) placebo; number needed to treat (NNT)=19.
- All-cause death: 0/1039 (0%) versus 12/1046 (1.2%; placebo); NNT=88.
- Stopping due to adverse event: No difference (<1%).
- Taste disturbances: ~6% versus 0.3% (placebo).
- Real-world evidence finds higher rates of taste disturbances (~60%) and gastrointestinal upset (10-30%).2
- Cohort studies:
- Israel: 109,254 COVID-positive patients aged 40 years or older at high risk of severe outcomes during Omicron wave.2 COVID-19 related hospitalization:
- Aged 65+: 75% relative risk reduction.
- From 59 to 15 cases per 100,000 person-years. Relative risk reductions did not change based on previous infection or vaccination status.
- Aged 40-64: No statistically significant difference.
- Aged 65+: 75% relative risk reduction.
- Similar (>50% relative risk reduction in hospitalization or death,3, 4 or hospitalization alone5) found in other North American cohort studies (Ontario & Colorado) of adults >17 years old performed during Omicron wave.
-
- Benefit was seen for both unvaccinated and vaccinated patients.3-5
-
- Israel: 109,254 COVID-positive patients aged 40 years or older at high risk of severe outcomes during Omicron wave.2 COVID-19 related hospitalization:
- COVID-19 hospitalizations significantly lower, ~50%, with Omicron versus Delta.6
- Prescribing recommendations vary by jurisdictions: British Columbia,7 Alberta.8
- Generally, jurisdictions direct eligibility toward those with higher age and more comorbidities, fewer vaccine doses, and immunocompromised patients.
- Drug interactions with medications common: Drug interactions resource.9
- Renal dosing adjustment required.
- Post-Paxlovid® “rebound” possible:
- Revert to testing positive, mild symptoms return, but <1% return to hospital within 15 days of treatment.10
Latest Tools for Practice
#363 Making a difference in indifference? Medications for apathy in dementia
In patients with dementia, how safe and effective are stimulants, antidepressants, and antipsychotics for treating apathy?
#362 Facing the Evidence in Acne, Part I: Oral contraceptives and spironolactone in females
How effective are combined oral contraceptives (COC) and spironolactone for treating acne of at least mild-moderate severity in females?
#361 Preventing RSV Infections in Infants
How safe and effective are monoclonal antibodies to prevent respiratory syncytial virus (RSV) infections in infants?
very useful info
Very useful knowledge in advising the infected patients at risk to avoid hospitalization and death.
Paxlovid effective in non vaccinated patients