II. Indications
- FDA emergency use in 2022 for high risk outpatients age >12 years (and >40 kg) within 5 days of onset
- Emergency Use authorization in U.S. will expire at end of 2023 (and cost expected to $1400/course)
III. Contraindications
- eGFR <30 ml/min
- Severe liver disease
IV. Mechanism
- Oral Protease Inhibitor specific to SARS-COV-2 viral replication (Ritonavir slows nirmatrelvir metabolism)
V. Dosing
VI. Adverse Effects
- Dysgeusia
- Diarrhea
- Hypertension
- Myalgias
- Risk of COVID-19 rebound (recurrent symptoms within 1 week after finishing Paxlovid)
- Do not repeat Paxlovid course, but re-quarantine 5 days and mask for 10 days
VII. Drug Interactions
- Numerous Drug Interactions, esp. for Ritonavir (esp. CYP3A)
- Important interactions include Salmeterol, DOACs (esp. Rivaroxaban), Phenytoin and Clopidogrel
- Use a Drug Interaction checker
VIII. Safety
- Pregnancy
- Unknown safety, but recommended when indicated as of 2024
- Pregnancy itself is a higher risk condition, and risk increases with other comorbidities
-
Lactation
- Unknown safety, but recommended when indicated as of 2024
- Lactation may continue while using Paxlovid
- Resources
IX. Efficacy
- As of initial release in 2022
- Reduces risk of hospitalization or death at 28 days by 89% if started within first 3 days
- NNT 18 unvaccinated, high risk patients to prevent one hospitalization or death
- As of 2023, with Covid19 in Omicron phase, Paxlovid decreases hospitalizations and death (NNT 62)
- Vaccinated patients in omicron phase (with risk factors for worse prognosis)
- Paxlovid did not significantly reduce hospitalization or death
- Marginal effects would have NNT >100
- Hammond (2024) N Engl J Med 390(13): 1186-95 [PubMed]
X. Resources
- Nirmatrelvir Ritonavir (DailyMed)
XI. References
- LoVecchio (2022) Crit Dec Emerg Med 36(1): 28