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#338 Ritonavir-boosted nirmatrelvir (Paxlovid®): And you thought we were done with COVID!

Is ritonavir-boosted nirmatrelvir (Paxlovid®) a safe and effective oral therapy for the treatment of COVID-19?

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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  • 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.
      • 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
  • 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

erica buck April 17, 2023

very useful info

Donald HIckman April 17, 2023

Very useful knowledge in advising the infected patients at risk to avoid hospitalization and death.

Gilbert Bretecher May 9, 2023

Paxlovid effective in non vaccinated patients

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  • Tony Nickonchuk BScPharm
  • Michael R Kolber BSc MD CCFP MSc

1. Hammond J, Leister-Tebbe H, Gardner A, et al. N Engl J Med. 2022; 386(15):1397-1408.

2. Arbel R, Wolff Sagy Y, Hoshen M, et al. N Engl J Med. 2022; 387(9):790-798

3. Schwartz KL, Wang J, Tadrous M, et al. CMAJ. 2023; 195(6):220-226.

4. Dryden-Peterson S, Kim A, Kim AY, et al. Ann Intern Med. 2023; doi:10.7326/M22-2141

5. Aggarwal NR, Molina KC, Beaty LE, et al. Lancet Infect Dis. 2023; doi:10.1016/S1473-3099(23)00011-7.

6. Nyberg T, Ferguson NM, Nash SG, et al. Lancet. 2022; 399(10332):1303-1312.

7. BC Practice Tool – COVID Treatment Assessment Guide for Clinicians. 2022. Available at: Accessed December 21, 2022.

8. Outpatient Treatment for COVID-19 | Alberta Health Services. Available at: Accessed February 10, 2023.

9. BC Practice Tool - Drug-Drug Interactions and Contraindications. 2022. Available at: Accessed December 21, 2022.

10. Malden DE, Hong V, Lewin BJ, et al. MMWR Morb Mortal Wkly Rep. 2022; 71(25):830-833.

Authors do not have any conflicts of interest to declare.

Les auteurs n’ont aucun conflit d’intérêts à déclarer.