Drug Interactions with Paxlovid

Introduction to Paxlovid Interactions

Paxlovid (nirmatrelvir/ritonavir) can significantly increase metoprolol plasma concentrations by inhibiting CYP2D6, potentially causing bradycardia and hypotension, requiring dose reduction of metoprolol by 50% or temporary switch to a beta-blocker with less dependence on CYP metabolism during the 5-day Paxlovid treatment course, as recommended by the American College of Clinical Pharmacy 1

Paxlovid's inhibition of CYP2D6 can lead to significant increases in metoprolol exposure, similar to other CYP2D6 inhibitors like imatinib and gefitinib, which increase metoprolol AUC by 23% and 35%, respectively, in patients taking metoprolol 1

The increased metoprolol concentration can lead to excessive beta-blockade, bradycardia, hypotension, fatigue, dizziness, and heart block in patients taking metoprolol and Paxlovid, with elderly patients and those with renal impairment being more susceptible to adverse effects 1

Reduce metoprolol dose by approximately 50% during the 5-day course of Paxlovid, and monitor heart rate and blood pressure daily in patients taking metoprolol, as recommended by the American College of Clinical Pharmacy 1
Consider switching to a beta-blocker with less dependence on CYP metabolism, such as atenolol, which is primarily renally eliminated, in patients taking metoprolol and Paxlovid 1
The American Society of Health-System Pharmacists and Infectious Diseases Society of America recommend consulting pharmacists to identify and manage potential drug interactions with Paxlovid, including temporarily pausing interacting medications, adjusting doses, or selecting alternative COVID-19 treatments if interactions cannot be managed safely 2

Elderly patients require additional caution when taking Paxlovid due to reduced clearance of interacting medications, potentially necessitating dose adjustments of both Paxlovid and concomitant medications, as recommended by the American College of Clinical Pharmacy and National Institutes of Health 2, 3, 4
Patients with renal impairment require dose adjustments of both Paxlovid and concomitant medications, while those with hepatic impairment may experience altered clearance of many medications that interact with Paxlovid, as recommended by the National Institutes of Health and American Pharmacists Association 2, 4, 5
Patients with heart failure may be more sensitive to hemodynamic changes, and concomitant QT-prolonging medications may increase the risk of cardiac arrhythmias in patients taking metoprolol and Paxlovid, as recommended by the European Society of Cardiology 6

Concomitant use of Paxlovid with certain medications like rifampin, rifabutin, and rifapentine is associated with a risk of loss of virologic response due to CYP3A4 induction, as per the American Heart Association and National Institutes of Health 3, 4
Paxlovid's use with rosuvastatin is contraindicated due to a 19-fold increase in exposure, as recommended by the American Heart Association and National Institutes of Health 4, 3
Combining Paxlovid with QT-prolonging medications may increase the risk of cardiac arrhythmias, according to the European Society of Cardiology 6
Sildenafil is absolutely contraindicated with Paxlovid for patients with pulmonary arterial hypertension and requires significant dose adjustments for patients with erectile dysfunction, such as using no more than 25 mg of sildenafil in a 48-hour period, to prevent hypotension, visual changes, priapism, and other adverse effects related to sildenafil toxicity, as recommended by the American Heart Association and the American Urological Association 7
The following medications can increase sildenafil concentration:

Medication	Effect on Sildenafil Concentration
Ketoconazole	2-fold increase [8]
HIV protease inhibitors (e.g. ritonavir, saquinavir)	marked increase [8]
Cimetidine	increase [8]
Grapefruit juice	modest increase [9]
Ciprofloxacin	increase [10]
Fluconazole	considerable increase, requiring approximately 60% dose reduction [11]

Monitor heart rate, blood pressure, and symptoms daily, and consider ECG in patients with pre-existing conduction abnormalities when taking Paxlovid and metoprolol, as recommended by the American College of Clinical Pharmacy 1
Return to original metoprolol regimen after completing Paxlovid treatment, and reassess heart rate and blood pressure in patients taking metoprolol, as recommended by the American College of Clinical Pharmacy 1
Patients taking Paxlovid should be monitored for signs of drug toxicity and educated about potential interaction symptoms, as recommended by the National Institutes of Health and American Pharmacists Association 3, 4
Clinicians should carefully screen for drug interactions and implement management strategies, such as dose adjustments and increased monitoring, to safely administer Paxlovid, as recommended by the Centers for Disease Control and Prevention, American Medical Association, and National Institute of Health 3, 5, 6
Pharmacist review of Paxlovid prescriptions is essential for patient safety, and can help identify potential drug interactions, as stated by the American Pharmacists Association and National Institute of Health 4, 5
The FDA recommends monitoring for signs of toxicity with medications that have narrow therapeutic windows, and for anticoagulants like warfarin, checking INR more frequently, as per the European Society of Cardiology and American Heart Association 6, 7