Ritonavir-boosted nirmatrelvir (marketed as Paxlovid) is a Health Canada–approved oral antiviral medication with activity against SARS-CoV-2
Treatment is indicated for adult (≥ 18 yr) outpatients with nonhypoxic COVID-19 who are at high risk of severe disease progression (e.g., advanced age, comorbidity, unvaccinated or immunosuppressed).1,2
Studies recruited primarily unvaccinated participants, predated the omicron variant and have not yet undergone peer review
According to available data, patients with 5% risk of hospital admission have an estimated number needed to treat to prevent 1 hospital admission of 24 (95% confidence interval 22–29).3,4 The most common adverse effects are dysgeusia, diarrhea, vomiting, increased blood pressure and headache.
The treatment is copackaged as nirmatrelvir (300 mg — two 150 mg tablets) with ritonavir (one 100 mg tablet); the 3 tablets are taken together twice daily for 5 days
Treatment should start as soon as possible after a confirmed diagnosis of COVID-19, ideally within 5 days of symptom onset. Although observational safety data for ritonavir in pregnancy exist, no safety data exist for nirmatrelvir. In moderate renal failure (estimated glomerular filtration rate [eGFR] 30–60 mL/min), the dose is reduced to 1 tablet of nirmatrelvir and 1 tablet of ritonavir twice daily. Nirmatrelvir-ritonavir is contraindicated with eGFR < 30 mL/min.
The ritonavir component boosts nirmatrelvir levels and is a cytochrome P450 3A4 (CYP3A4) inhibitor when taken short term, leading to important drug–drug interactions5
Particular attention should be paid to high-risk medications: antiarrhythmics (amiodarone, digoxin), oral antithrombotics (apixaban, rivaroxaban, ticagrelor), statins (atorvastatin, lovastatin, simvastatin), benzodiazepines (diazepam), opioids (methadone, fentanyl), anticonvulsants, neuropsychiatric drugs and immunosuppressants (Appendix 1, available at www.cmaj.ca/lookup/doi/10.1503/cmaj.220081/tab-related-content).
Mitigation strategies for drug–drug interactions include dose reductions, switching or temporarily holding a drug, and therapeutic drug monitoring
Strategies should be implemented during and 3–5 days after treatment.5 Some medications (Appendix 1) reduce the efficacy of nirmatrelvirritonavir and could lead to treatment failure or virologic resistance,1 and alternative treatments for COVID-19 should be considered.4 Pharmacist consultation is recommended in many instances (Appendix 1).
Footnotes
Competing interests: Emily McDonald reports receiving salary support from the Fonds de Recherche Santé–Québec, and operating funds from the Canadian Institutes of Health Research (CIHR). Dr. McDonald also holds copyright in the software MedSafer. Todd Lee reports receiving research salary support from the Fonds de Recherche Santé–Québec, and operating funds from CIHR and the Interdisciplinary Initiative in Infection and Immunity (MI4). Dr. Lee also holds copyright in the software MedSafer.
This article has been peer reviewed.
This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY-NC-ND 4.0) licence, which permits use, distribution and reproduction in any medium, provided that the original publication is properly cited, the use is noncommercial (i.e., research or educational use), and no modifications or adaptations are made. See: https://creativecommons.org/licenses/by-nc-nd/4.0/
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- Ritonavir-boosted nirmatrelvir (marketed as Paxlovid) is a Health Canada–approved oral antiviral medication with activity against SARS-CoV-2
- Studies recruited primarily unvaccinated participants, predated the omicron variant and have not yet undergone peer review
- The treatment is copackaged as nirmatrelvir (300 mg — two 150 mg tablets) with ritonavir (one 100 mg tablet); the 3 tablets are taken together twice daily for 5 days
- The ritonavir component boosts nirmatrelvir levels and is a cytochrome P450 3A4 (CYP3A4) inhibitor when taken short term, leading to important drug–drug interactions5
- Mitigation strategies for drug–drug interactions include dose reductions, switching or temporarily holding a drug, and therapeutic drug monitoring
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