Medication Interactions with Paxlovid

High-Risk Medications Requiring Action

• The American College of Cardiology recommends that patients taking rivaroxaban should switch to low molecular weight heparin during the 5-day Paxlovid course, as ritonavir increases rivaroxaban levels by approximately 2.5-fold, creating a severe bleeding risk 1, 2
• The American College of Cardiology suggests that patients taking apixaban should temporarily switch to low molecular weight heparin during Paxlovid treatment, or if continuation is necessary, reduce the apixaban dose by 25% with intensive bleeding monitoring, especially in patients over 75 years or those on concurrent antiplatelet therapy 2
• Edoxaban is considered the safest direct oral anticoagulant option with Paxlovid if switching anticoagulants is considered, as it demonstrates minimal clinically significant interactions 2
• The American Journal of Kidney Diseases recommends that patients with renal or hepatic impairment should not take colchicine during Paxlovid treatment, as ritonavir dramatically increases colchicine exposure, risking life-threatening toxicity 5
• The Journal of Hepatology advises avoiding concurrent use of carbamazepine, phenobarbital, phenytoin, and oxcarbazepine with Paxlovid, as these CYP3A inducers will decrease nirmatrelvir levels, reducing Paxlovid efficacy 6
• The American College of Cardiology recommends reducing the warfarin dose by 50% when initiating Paxlovid and monitoring INR closely, as ritonavir affects warfarin metabolism 3, 4
• The American College of Cardiology suggests reducing the digoxin dose by 30-50% and monitoring digoxin concentrations, as ritonavir inhibits P-glycoprotein 3, 4
• The Journal of the American College of Cardiology and Circulation recommend holding amiodarone during Paxlovid treatment, as ritonavir significantly increases amiodarone levels, risking QT prolongation and torsades de pointes 3, 4
• The Journal of the American College of Cardiology and Circulation advise avoiding concurrent use of flecainide and propafenone with Paxlovid, due to increased drug levels and arrhythmia risk 3, 4

Medications Safe to Continue

• The Journal of Hepatology and Clinical and Molecular Hepatology state that raltegravir, maraviroc, rilpivirine, tenofovir, emtricitabine, lamivudine, abacavir, daclatasvir, and sofosbuvir have no significant interactions with ritonavir 6, 7, 8

Critical Monitoring Parameters

• The American College of Cardiology recommends monitoring for bleeding signs, such as unusual bruising, blood in urine/stool, prolonged bleeding from cuts, severe headache, and coughing up blood, throughout the 5-day course and 2-3 days after completion of Paxlovid 2
• The Praxis Medical Insights suggests monitoring renal function, as patients with chronic kidney disease are at higher risk for drug interactions and toxicity 1