Nirmatrelvir Ritonavir

Aka: Nirmatrelvir Ritonavir, Paxlovid

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II. 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)

III. Contraindications

  1. eGFR <30 ml/min
  2. Severe liver disease

IV. Mechanism

  1. Oral Protease Inhibitor specific to SARS-COV-2 viral replication (Ritonavir slows nirmatrelvir metabolism)

V. Efficacy

  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

VI. 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

VII. 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

VIII. 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

IX. Resources

  1. Nirmatrelvir Ritonavir (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7bdddfba-bd31-44cb-ba9e-23a4e17a4691

X. References

  1. LoVecchio (2022) Crit Dec Emerg Med 36(1): 28

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