Pharm

Nirmatrelvir Ritonavir

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Nirmatrelvir Ritonavir, Paxlovid

  • See Also
  1. Covid19
  2. Molnupiravir
  • Indications
  1. FDA emergency use in 2022 for high risk outpatients age >12 years (and >40 kg) within 5 days of onset
  2. Emergency Use authorization in U.S. will expire at end of 2023 (and cost expected to $1400/course)
  • Contraindications
  1. eGFR <30 ml/min
  2. Severe liver disease
  • Mechanism
  1. Oral Protease Inhibitor specific to SARS-COV-2 viral replication (Ritonavir slows nirmatrelvir metabolism)
  • Dosing
  1. Distributed in Blister pack (pharmacist adjusts based on eGFR)
  2. eGFR>=60 ml/min
    1. Take Nirmatrelvir 300 (2 tabs) AND Ritonavir 100 mg twice daily for 5 days
  3. eGFR 30 to 59
    1. Take Nirmatrelvir 150 (1 tab) AND Ritonavir 100 mg twice daily for 5 days
  • Adverse Effects
  1. Dysgeusia
  2. Diarrhea
  3. Hypertension
  4. Myalgias
  5. Risk of COVID-19 rebound (recurrent symptoms within 1 week after finishing Paxlovid)
    1. Do not repeat Paxlovid course, but re-quarantine 5 days and mask for 10 days
  • Drug Interactions
  1. Numerous Drug Interactions, esp. for Ritonavir (esp. CYP3A)
  2. Important interactions include Salmeterol, DOACs (esp. Rivaroxaban), Phenytoin and Clopidogrel
  3. Use a Drug Interaction checker
  • Safety
  1. Pregnancy
    1. Unknown safety, but recommended when indicated as of 2024
    2. Pregnancy itself is a higher risk condition, and risk increases with other comorbidities
  2. Lactation
    1. Unknown safety, but recommended when indicated as of 2024
    2. Lactation may continue while using Paxlovid
  3. Resources
    1. Pregnancy, Lactation, and COVID-19 Therapeutics (NIH)
      1. https://www.covid19treatmentguidelines.nih.gov/special-populations/pregnancy/pregnancy-lactation-and-covid-19-therapeutics/
  • Efficacy
  1. As of initial release in 2022
    1. Reduces risk of hospitalization or death at 28 days by 89% if started within first 3 days
    2. NNT 18 unvaccinated, high risk patients to prevent one hospitalization or death
  2. As of 2023, with Covid19 in Omicron phase, Paxlovid decreases hospitalizations and death (NNT 62)
    1. Schwartz (2023) CMAJ 195(6): e220-6 [PubMed]
  3. Vaccinated patients in omicron phase (with risk factors for worse prognosis)
    1. Paxlovid did not significantly reduce hospitalization or death
    2. Marginal effects would have NNT >100
    3. Hammond (2024) N Engl J Med 390(13): 1186-95 [PubMed]
  • Resources
  1. Nirmatrelvir Ritonavir (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7bdddfba-bd31-44cb-ba9e-23a4e17a4691
  • References
  1. LoVecchio (2022) Crit Dec Emerg Med 36(1): 28