#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.
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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.
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- Benefit was seen for both unvaccinated and vaccinated patients.3-5
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- 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
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