Contraindications for Paxlovid in Children
Paxlovid is contraindicated in children younger than 12 years of age and in those weighing less than 40 kg, as clinical trials have not included these populations and safety and efficacy data are unavailable. 1
Age and Weight Restrictions
- Children under 12 years old should not receive Paxlovid because no clinical trial data exist to establish safety or efficacy in this age group 1
- Children weighing less than 40 kg are excluded from treatment, regardless of age, due to lack of pharmacokinetic and safety data 1, 2
- European regulatory authorities have approved Paxlovid only for adolescents ≥12 years old who weigh at least 40 kg for mild-to-moderate COVID-19 in high-risk patients 3
Severe Hepatic Impairment
- Paxlovid is not recommended for children with severe hepatic impairment (Child-Pugh class C) because safety and pharmacokinetic data are lacking 1
Contraindicated Concomitant Medications
The following medications are absolutely contraindicated with Paxlovid due to ritonavir's potent CYP3A4 inhibition, which can cause life-threatening drug interactions:
Cardiovascular Drugs
- Alfuzosin, amiodarone, quinidine (risk of cardiac arrhythmias) 4
- Ranolazine (increased QT prolongation and risk of torsades de pointes) 1
- Lovastatin and simvastatin (severe rhabdomyolysis risk) 4
Sedatives and Psychotropics
Other Contraindicated Drugs
- Strong CYP3A4 inducers: carbamazepine, phenytoin, phenobarbital, rifampicin, St. John's wort, enzalutamide (these reduce nirmatrelvir exposure and compromise antiviral efficacy) 4
- Ergot derivatives, cisapride, astemizole, terfenadine 4
- Sildenafil when used for pulmonary arterial hypertension 4
Critical Drug Interaction Management in Pediatric Transplant Recipients
Special caution is required in pediatric transplant patients on tacrolimus, as ritonavir causes marked elevation of tacrolimus levels:
- A case report documented a 14-year-old kidney transplant recipient who developed supratherapeutic tacrolimus levels and acute kidney injury after starting Paxlovid 5
- Tacrolimus must be held or drastically reduced during Paxlovid treatment in pediatric transplant recipients 5
- Providers should consider alternative COVID-19 therapies (such as remdesivir) for pediatric transplant patients when possible 1
Renal Impairment Considerations
- Paxlovid is contraindicated in children with severe renal impairment (eGFR <30 mL/min) 1
- For adolescents ≥12 years with moderate renal impairment (eGFR 30-59 mL/min), dose reduction to 150 mg nirmatrelvir/100 mg ritonavir twice daily is required 1, 2
Mandatory Pre-Prescription Screening
Before prescribing Paxlovid to any eligible adolescent, systematically check all concomitant medications using the Liverpool COVID-19 Drug Interaction Tool to identify contraindications, required dose adjustments, or temporary discontinuations 1, 4. This step is explicitly recommended in multiple guidelines and represents the primary safety concern with Paxlovid use 1.
Common Pitfall to Avoid
The most critical error is failing to recognize that ritonavir's CYP3A4 inhibition persists for several days after completing the 5-day Paxlovid course, meaning drug interactions can occur even after treatment ends 1. This is particularly dangerous in pediatric patients on chronic medications with narrow therapeutic windows, such as immunosuppressants or antiepileptics.