Drug Interactions with Paxlovid (Nirmatrelvir/Ritonavir)
Paxlovid has numerous significant drug interactions due to ritonavir's strong inhibition of CYP3A4, CYP2D6, P-gp, and OATP1B1, which can result in potentially severe, life-threatening, or fatal events when co-administered with certain medications. 1
Contraindicated Medications (Do Not Co-administer)
Cardiovascular Medications
Antiarrhythmics:
- Amiodarone, dronedarone, flecainide, propafenone, quinidine 1
- Risk: Potentially fatal cardiac arrhythmias
Antianginals:
- Ranolazine 1
- Risk: Serious/life-threatening reactions
Alpha-1 Adrenoreceptor Antagonists:
- Alfuzosin 1
- Risk: Severe hypotension
Anticancer Drugs
- Apalutamide, enzalutamide 1
- Risk: Loss of virologic response to Paxlovid
Anticonvulsants
- Carbamazepine, phenobarbital, phenytoin, primidone 2
- Risk: Loss of virologic response to Paxlovid due to CYP3A4 induction
Other Contraindicated Medications
- St. John's wort 1
- Rifampin, rifabutin, rifapentine 3
- Sildenafil (when used for pulmonary arterial hypertension) 4
Medications Requiring Dose Adjustments or Close Monitoring
Anticoagulants
- Warfarin: Closely monitor INR 1
- Rivaroxaban: Avoid concomitant use due to increased bleeding risk 1
- Dabigatran: Reduce dose or avoid based on indication and renal function 1
- Apixaban: Dose adjustment required; refer to apixaban label 1
Anticancer Drugs
- Avoid: Encorafenib, ivosidenib, neratinib, venetoclax, ibrutinib 1
- Monitor: Abemaciclib, ceritinib, dasatinib, nilotinib, vinblastine, vincristine 1
- Risk: Significant hematologic or gastrointestinal side effects
Antiseizure Medications
- Monitor: Cannabidiol, clobazam, clonazepam, diazepam, ethosuximide, everolimus, felbamate, lacosamide, midazolam, oxcarbazepine, perampanel, stiripentol, tiagabine, zonisamide 2
- Risk: Increased plasma concentrations and potential toxicity
Immunosuppressants
- Tacrolimus 5
- Risk: Increased toxicity
Calcium Channel Blockers
- Nifedipine, manidipine, verapamil 5
- Risk: Increased exposure and potential toxicity
Statins
- Atorvastatin 5
- Risk: Increased exposure and myopathy
- Rosuvastatin: Contraindicated due to 19-fold increase in exposure 3
Antipsychotics
- Clozapine, quetiapine 5
- Risk: Increased exposure and potential toxicity
Clinical Management Algorithm
Before prescribing Paxlovid:
- Complete medication reconciliation
- Check for absolute contraindications
- Assess for potential interactions requiring dose adjustments
If contraindicated medications are present:
- Consider alternative COVID-19 treatments
- Do NOT attempt to co-administer with contraindicated medications
If medications requiring dose adjustment are present:
- Adjust doses according to specific medication guidelines
- Implement increased monitoring during Paxlovid treatment
- Consider temporary discontinuation of interacting medication if clinically appropriate
For all patients on Paxlovid:
- Monitor for signs of drug toxicity
- Educate patients about potential interaction symptoms
- Resume normal medication dosing after completing the 5-day Paxlovid course
Important Clinical Considerations
- The interaction potential persists throughout the entire 5-day course of Paxlovid treatment 4
- Approximately 87% of patients prescribed Paxlovid require interventions to prevent drug-related problems 6
- Pharmacist review of Paxlovid prescriptions is essential for patient safety 6
- Herbal medicines can also interact with Paxlovid through CYP3A and P-glycoprotein mechanisms 7
Special Population Considerations
- Renal impairment: Requires dose adjustments of both Paxlovid and concomitant medications 6
- Elderly patients: May have reduced clearance of interacting medications, requiring additional caution
By carefully screening for drug interactions and implementing appropriate management strategies, clinicians can safely administer Paxlovid to eligible patients while minimizing the risk of adverse events.