Paxlovid Side Effects
The most clinically significant concern with Paxlovid is not traditional adverse effects but rather potentially life-threatening drug-drug interactions caused by ritonavir, a potent CYP3A4 inhibitor, which must be systematically evaluated before prescribing using the Liverpool COVID-19 Drug Interaction Tool. 1, 2
Primary Safety Concern: Drug-Drug Interactions
The FDA includes a boxed warning specifically for significant drug interactions with Paxlovid. 2 The ritonavir component causes interactions during active treatment and potentially for several days after completion. 1
Critical Management Steps:
- Review ALL medications before prescribing to assess potential interactions with this strong CYP3A inhibitor 2
- Use the Liverpool COVID-19 Drug Interaction Tool systematically to check for specific interactions—this is explicitly recommended in guidelines 1
- Determine which concomitant medications require dose adjustment, temporary interruption, or additional monitoring 2
- Certain medications are absolutely contraindicated with Paxlovid, including drugs highly dependent on CYP3A for clearance where elevated concentrations cause serious or life-threatening reactions 2
- Statins (particularly simvastatin and lovastatin) may require temporary discontinuation during the 5-day treatment course 1
Common Adverse Effects
Dysgeusia (altered taste) and diarrhea occur more frequently with Paxlovid than placebo, but importantly, these adverse effects did not lead to increased drug discontinuation rates in clinical trials. 1 Most adverse events are mild to moderate in severity. 3
Serious Adverse Reactions
Hypersensitivity Reactions:
- Anaphylaxis, toxic epidermal necrolysis, Stevens-Johnson syndrome, and other serious hypersensitivity reactions have been reported 2
- Immediately discontinue Paxlovid and initiate appropriate supportive care if signs or symptoms of clinically significant hypersensitivity or anaphylaxis occur 2
- Paxlovid is contraindicated in patients with history of clinically significant hypersensitivity to nirmatrelvir or ritonavir 2
Hepatotoxicity:
- Hepatic transaminase elevations, clinical hepatitis, and jaundice have occurred in patients receiving ritonavir 2
- Monitor for signs of hepatotoxicity, particularly in patients with underlying liver disease 1
Special Population Considerations
Renal Impairment:
- For moderate renal impairment (eGFR 30-60 mL/min): reduce dose to 150 mg nirmatrelvir with 100 mg ritonavir twice daily for all 5 days 2
- For severe renal impairment (eGFR <30 mL/min) including hemodialysis: give 300 mg nirmatrelvir with 100 mg ritonavir once on Day 1, then 150 mg nirmatrelvir with 100 mg ritonavir once daily on Days 2-5 2
- On hemodialysis days, administer Paxlovid after dialysis 2
- Reassess renal function during treatment if clinical deterioration occurs, as COVID-19 itself can cause acute kidney injury 1
Hepatic Impairment:
- Paxlovid is not recommended in patients with severe hepatic impairment (Child-Pugh Class C) 2
- Use with caution in severe liver impairment, as clinical trials excluded these patients 1
Pregnancy:
- Paxlovid may be an option for pregnant people to reduce disease progression, though uncertainty exists regarding potential serious adverse reactions 1
- No reports of serious adverse reactions in parent or child have been documented in WHO Vigibase to date 1
Monitoring During Treatment
- Monitor for dysgeusia and diarrhea, which can be more pronounced with higher drug levels, especially in patients with renal impairment 1
- Watch for signs of drug accumulation in patients with renal dysfunction 1
- Assess for hepatotoxicity, particularly in patients with pre-existing liver disease 2