Tools for Practice


#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.
      • 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
  Context
  • 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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#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?
Read 0.25 credits available
April 17, 2023

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Author(s):

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

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: https://bit.ly/3YtN0Vg. Accessed December 21, 2022.

8. Outpatient Treatment for COVID-19 | Alberta Health Services. Available at: https://bit.ly/3RUlBJG. Accessed February 10, 2023.

9. BC Practice Tool - Drug-Drug Interactions and Contraindications. 2022. Available at: https://bit.ly/3E0DCAo. 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.