Paxlovid Indications
Paxlovid (nirmatrelvir/ritonavir) is indicated for treatment of mild-to-moderate COVID-19 in adults at high risk for progression to severe disease, including hospitalization or death, and must be initiated within 5 days of symptom onset. 1
FDA-Approved Adult Indications
Paxlovid is FDA-approved specifically for adults with mild-to-moderate COVID-19 who are at high risk for disease progression. 1 The medication is not approved for pre-exposure or post-exposure prophylaxis for COVID-19 prevention. 1
Critical Timing Requirements
- Treatment must be initiated as soon as possible after COVID-19 diagnosis and within 5 days of symptom onset 1
- The standard dosing regimen is 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet), all three tablets taken together twice daily for 5 days 1
- Administer at approximately the same time each day, with or without food 1
Pediatric Use Considerations
While the FDA label focuses on adults, limited evidence suggests Paxlovid may be feasible in select pediatric patients aged 12 years and older weighing at least 40 kg who have high-risk features. 2 However, this remains an area requiring further study. 3
High-Risk Features in Children
According to the American Academy of Pediatrics, children with the following conditions are at increased risk for severe COVID-19 progression and may warrant antiviral treatment consideration: 4
- Congenital heart disease 4
- Chronic lung disease 4
- Neurological disorders 4
- Obesity 4
- Diabetes mellitus 4
For adolescents who meet age and weight criteria but cannot take Paxlovid due to drug interactions, remdesivir may be considered as an alternative antiviral for those 12 years and older with risk factors for severe disease. 5
Dosing Adjustments for Renal Impairment
Dose reduction is mandatory in patients with renal impairment: 1
- Moderate renal impairment (eGFR ≥30 to <60 mL/min): 150 mg nirmatrelvir with 100 mg ritonavir twice daily for 5 days 1
- Severe renal impairment (eGFR <30 mL/min) including hemodialysis: Day 1: 300 mg nirmatrelvir with 100 mg ritonavir once; Days 2-5: 150 mg nirmatrelvir with 100 mg ritonavir once daily 1
- On hemodialysis days, administer after dialysis 1
Hepatic Impairment
Paxlovid is not recommended in patients with severe hepatic impairment (Child-Pugh Class C). 1
Real-World Effectiveness Data
Recent large-scale studies demonstrate Paxlovid reduces hospitalization risk by 39% and death by 61% in real-world settings, with benefits extending to vaccinated patients and across age groups. 6 The absolute risk reduction for hospitalization was 0.9 percentage points, with particularly pronounced benefits in patients aged 65 years and older. 6
Among 699,848 adults eligible for Paxlovid during April-August 2022, prescription was associated with lower hospitalization rates overall (aHR = 0.49) and across all age groups, including those who had received ≥3 mRNA COVID-19 vaccines (aHR = 0.50). 7
Critical Contraindications and Warnings
Absolute Contraindications 1
- History of clinically significant hypersensitivity reactions to nirmatrelvir or ritonavir 1
- Co-administration with drugs highly dependent on CYP3A for clearance where elevated concentrations cause serious/life-threatening reactions 1
- Co-administration with potent CYP3A inducers that may cause loss of virologic response 1
Drug Interaction Management
Prior to prescribing Paxlovid, review ALL patient medications to assess potential drug-drug interactions with ritonavir, a strong CYP3A inhibitor. 1, 8 Ritonavir causes potent and rapid inhibition of CYP3A4, creating high potential for harm from drug-drug interactions even during the short 5-day treatment course. 8
Common problematic interactions include benzodiazepines and narcotics, which can lead to altered mental status and acute encephalopathy. 2 Management options are largely confined to preemptive or symptom-driven pausing of the comedication or counseling about additional risks. 8
Hypersensitivity and Hepatotoxicity
Anaphylaxis, serious skin reactions (including toxic epidermal necrolysis and Stevens-Johnson syndrome), and other hypersensitivity reactions have been reported. 1 If clinically significant hypersensitivity occurs, immediately discontinue Paxlovid and initiate appropriate supportive care. 1
Hepatic transaminase elevations, clinical hepatitis, and jaundice have occurred in patients receiving ritonavir. 1
Treatment Disparities
Observational data reveal concerning disparities in Paxlovid treatment, with lower prescription rates among Black and Hispanic or Latino patients and within socially vulnerable communities, despite similar eligibility. 6 Only 28.4% of eligible adults received Paxlovid prescriptions within 5 days of COVID-19 diagnosis during April-August 2022. 7