Paxlovid (Nirmatrelvir/Ritonavir) Treatment Regimen for COVID-19
The standard treatment regimen for Paxlovid is 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet), taken together twice daily for 5 days, with treatment initiated within 5 days of symptom onset in high-risk patients with mild-to-moderate COVID-19. 1, 2
Indications and Effectiveness
Paxlovid is indicated for:
- Adults with mild-to-moderate COVID-19 who are at high risk for progression to severe disease 3, 1
- Patients aged ≥12 years weighing ≥40 kg 2
- Treatment must be started within 5 days of symptom onset 1, 2
Paxlovid has demonstrated significant clinical benefits:
- 86% reduction in hospitalization risk and 100% reduction in mortality compared to placebo in high-risk outpatients 1
- 39% reduction in hospitalization risk and 61% reduction in death according to real-world data 4
- Less than 1% of patients treated with Paxlovid require hospitalization or emergency department visits after treatment 5
Dosing Guidelines
Standard Dosing
- 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet)
- Taken together twice daily for 5 days
- Can be taken with or without food 2
- Should be administered at approximately the same time each day 2
Renal Dose Adjustments 1, 2
| Renal Function | Dosing Regimen |
|---|---|
| Normal renal function | 300 mg nirmatrelvir with 100 mg ritonavir twice daily for 5 days |
| Moderate impairment (eGFR ≥30 to <60 mL/min) | 150 mg nirmatrelvir with 100 mg ritonavir twice daily for 5 days |
| Severe impairment (eGFR <30 mL/min) | Day 1: 300 mg nirmatrelvir with 100 mg ritonavir once; Days 2-5: 150 mg nirmatrelvir with 100 mg ritonavir once daily |
Note: For patients on hemodialysis, Paxlovid should be administered after hemodialysis 2
Contraindications and Drug Interactions
Paxlovid is contraindicated in:
- Patients with hypersensitivity to nirmatrelvir or ritonavir 2
- Patients taking medications highly dependent on CYP3A for clearance where elevated concentrations could lead to serious reactions 2
- Patients taking potent CYP3A inducers where reduced nirmatrelvir/ritonavir concentrations may reduce effectiveness 2
Important Drug Interaction Considerations
- Ritonavir is a strong CYP3A inhibitor that can significantly increase serum levels of many medications 1, 6
- Prior to prescribing, all patient medications must be reviewed to assess potential drug-drug interactions 1, 6
- Options for managing drug interactions include:
- Temporarily pausing the interacting medication during the 5-day Paxlovid course
- Dose adjustment of the interacting medication
- Close monitoring for adverse effects 6
Adverse Effects
Most common adverse effects:
Special Populations
- Hepatic Impairment: Not recommended in patients with severe hepatic impairment (Child-Pugh Class C) 2
- Pregnancy: Paxlovid represents an option for pregnant people with COVID-19 1
- Breastfeeding: Not contraindicated during Paxlovid treatment 1
Clinical Pearls and Pitfalls
Timing is critical: Treatment must begin within 5 days of symptom onset to be effective 3, 1
Drug interaction screening: Always screen for potential drug interactions before prescribing, as ritonavir is a potent CYP3A inhibitor 2, 6
Rebound symptoms: Some patients may experience recurrence of COVID-19 symptoms or positive test results 2-8 days after recovery, but severe illness after Paxlovid treatment is rare 5
Inappropriate antibiotic use: Antibiotics are not indicated following Paxlovid treatment unless there is clear evidence of a secondary bacterial infection 1
Alternative treatments: Consider molnupiravir or remdesivir when Paxlovid is contraindicated due to drug interactions 1
By following these guidelines, Paxlovid can be effectively used to reduce the risk of hospitalization and death in high-risk patients with COVID-19.