Paxlovid Dosing and Medication Interactions
The standard dosage of Paxlovid is 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) taken together orally twice daily for 5 days, with dose adjustments required for renal impairment due to ritonavir's significant drug interaction profile as a strong CYP3A inhibitor. 1
Standard Dosing Regimen
- Paxlovid consists of nirmatrelvir tablets co-packaged with ritonavir tablets, which must be taken together 1
- Standard dosage: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) taken together orally twice daily for 5 days 1
- Should be initiated as soon as possible after COVID-19 diagnosis and within 5 days of symptom onset 1
- Can be taken with or without food 1
- Should be administered at approximately the same time each day 1
Dose Adjustments for Special Populations
- Moderate renal impairment (eGFR ≥30 to <60 mL/min): 150 mg nirmatrelvir (one tablet) with 100 mg ritonavir (one tablet) twice daily for 5 days 1
- Severe renal impairment (eGFR <30 mL/min):
- Day 1: 300 mg nirmatrelvir (two tablets) with 100 mg ritonavir (one tablet) once
- Days 2-5: 150 mg nirmatrelvir (one tablet) with 100 mg ritonavir (one tablet) once daily 1
- For hemodialysis patients, the dose should be administered after hemodialysis 1
- Not recommended in patients with severe hepatic impairment (Child-Pugh Class C) 1
Common Drug Interactions
Ritonavir is a strong CYP3A inhibitor and perpetrator of many drug-drug interactions, warranting serious consideration before prescribing Paxlovid 2.
High-Risk Drug Interactions (Contraindicated)
- Antiarrhythmics: Amiodarone, flecainide, propafenone 2, 3
- Anticoagulants: Rivaroxaban 2, 3
- Statins: Lovastatin, simvastatin 2, 3
- Sedatives/hypnotics: Midazolam, triazolam 2
- Antipsychotics: Clozapine, quetiapine, pimozide 2, 3
- Ergot derivatives: Dihydroergotamine, ergotamine, ergonovine, methylergonovine 2
- Other: Alfuzosin, ranolazine, sildenafil (for pulmonary hypertension), St. John's Wort 2, 3
Drug Interactions Requiring Dose Adjustments
- Immunosuppressants: Tacrolimus, cyclosporine (reduce tacrolimus dose significantly or temporarily discontinue; reduce cyclosporine to 20% of initial dose) 4
- Calcium channel blockers: Nifedipine, verapamil, amlodipine, manidipine (dose reduction needed) 3
- Anticoagulants: Warfarin (close monitoring of INR required) 3
- Statins: Atorvastatin (dose reduction or temporary discontinuation) 3
- Antiseizure medications: Carbamazepine, phenobarbital, phenytoin (may reduce nirmatrelvir levels) 5, 6
Mechanism of Drug Interactions
- Ritonavir is a potent inhibitor of CYP3A4, CYP2D6, and P-glycoprotein (P-gp) transporters 5
- Nirmatrelvir is a substrate of CYP3A and P-gp 5
- Ritonavir increases nirmatrelvir concentrations by inhibiting its metabolism through CYP3A 4, 5
- These interactions can lead to increased plasma concentrations of concomitant medications metabolized by CYP3A, potentially resulting in serious adverse effects 1, 3
Clinical Considerations and Pitfalls
- Always check for drug interactions before prescribing Paxlovid using resources like the Liverpool COVID-19 Drug Interaction Tool 2
- Monitor patients closely for adverse effects when Paxlovid is co-administered with medications that cannot be temporarily discontinued 3
- Duration of interaction risk extends beyond the 5-day treatment period due to ritonavir's effects on metabolism and clearance 2
- Common adverse effects of Paxlovid include dysgeusia (altered taste), diarrhea, and potential hepatotoxicity 1, 2
- Rebound symptoms may occur after completing the 5-day course, but this does not typically require additional treatment 7