What Medications Should Not Be Mixed with Paxlovid?

October 13, 2025 •

3 min read

According to drug interaction warnings, Paxlovid can interact with over 20 classes of medications, with potential side effects ranging from serious to life-threatening. Understanding what medications should not be mixed with Paxlovid is essential for patient safety, as the drug's ritonavir component significantly alters the metabolism of many common prescriptions.

Quick Summary

Due to ritonavir's effect on drug-metabolizing enzymes, Paxlovid has numerous contraindications, especially with heart, cholesterol, and seizure medications. Safe use requires a thorough review of all current prescriptions and supplements with a healthcare provider.

Key Points

CYP3A4 Inhibition: The ritonavir in Paxlovid blocks the CYP3A4 enzyme, causing other drugs to accumulate and potentially become toxic.
High-Risk Categories: Major interaction concerns exist with statins, heart rhythm drugs, blood thinners, anticonvulsants, and immunosuppressants.
Statins and Rhabdomyolysis: Combining Paxlovid with simvastatin or lovastatin is contraindicated due to the risk of severe muscle damage.
Antiarrhythmic Dangers: Life-threatening heart rhythm problems can occur if Paxlovid is mixed with certain antiarrhythmic medications.
Ineffective Contraception: Combined hormonal contraceptives may fail while on Paxlovid, requiring a backup birth control method.
Reduced Paxlovid Efficacy: Certain anti-seizure drugs and herbal supplements like St. John's Wort can make Paxlovid less effective.

Understanding the Mechanism of Interaction

Paxlovid is a combination of nirmatrelvir and ritonavir. Nirmatrelvir is the active antiviral, while ritonavir boosts its levels by inhibiting the liver enzyme CYP3A4. This inhibition, however, affects the metabolism of many other drugs cleared by CYP3A4, potentially causing them to build up to toxic levels. Conversely, some medications induce CYP3A4, which can reduce Paxlovid's effectiveness.

Key Drug Categories to Avoid or Manage

Always inform your healthcare provider and pharmacist about all medications and supplements before taking Paxlovid. Do not stop or change any medications without consulting a doctor.

Statins (Cholesterol-Lowering Drugs)

Combining Paxlovid with certain statins can increase the risk of muscle damage (myopathy) and rhabdomyolysis. Lovastatin and simvastatin should be stopped during Paxlovid treatment. Atorvastatin and rosuvastatin may require temporary dose adjustments or interruption. Pitavastatin or pravastatin are generally safer alternatives as they are not significantly metabolized by CYP3A4.

Antiarrhythmics (Heart Rhythm Medications)

Many antiarrhythmics interact with Paxlovid, potentially causing dangerous heart rhythm abnormalities. Amiodarone, dronedarone, flecainide, propafenone, and quinidine are often contraindicated. For some, pausing may not be enough, and alternative COVID-19 treatments might be necessary.

Blood Thinners (Anticoagulants and Antiplatelets)

Paxlovid can increase the risk of bleeding by raising levels of anticoagulants. Warfarin requires close INR monitoring and possible dose changes. Direct Oral Anticoagulants (DOACs) like rivaroxaban, apixaban, and dabigatran also see increased levels; their use with Paxlovid should be carefully managed or avoided. Antiplatelets such as clopidogrel and ticagrelor also pose risks.

Anti-Seizure Medications (Anticonvulsants)

Some anticonvulsants are CYP3A4 inducers, reducing Paxlovid's efficacy and potentially leading to treatment failure. Carbamazepine, phenobarbital, phenytoin, and primidone should be avoided with Paxlovid.

Immunosuppressants

Combining Paxlovid with immunosuppressants can lead to dangerously high levels of these drugs, risking kidney damage and other serious effects. Examples include cyclosporine, tacrolimus, sirolimus, everolimus, and voclosporin, which require careful dose management or avoidance.

Hormonal Contraceptives

Paxlovid can decrease the effectiveness of combined hormonal birth control (pills, patches, rings) by affecting ethinyl estradiol levels. A backup barrier method should be used during and for one full cycle after Paxlovid treatment.

Herbal Supplements

St. John’s Wort is a strong CYP3A4 inducer and should not be used with Paxlovid as it can reduce the antiviral's effectiveness.

Comparison Table: Common Interactions


Medication Category	Examples of Interacting Drugs	Type of Interaction with Paxlovid	Potential Risk
Statins	Simvastatin, Lovastatin, Atorvastatin	Increased drug levels via CYP3A4 inhibition	Myopathy, Rhabdomyolysis
Antiarrhythmics	Amiodarone, Dronedarone, Flecainide	Increased drug levels via CYP3A4 inhibition	Life-threatening cardiac arrhythmias
Anticoagulants	Rivaroxaban, Apixaban, Warfarin	Increased drug levels via CYP3A4 inhibition and P-gp inhibition	Serious bleeding risk
Anticonvulsants	Carbamazepine, Phenobarbital, Phenytoin	Decreased Paxlovid levels via CYP3A4 induction	Reduced Paxlovid effectiveness, viral resistance
Immunosuppressants	Tacrolimus, Cyclosporine, Voclosporin	Increased drug levels via CYP3A4 inhibition	Organ toxicity (e.g., kidney damage), excessive immunosuppression
Hormonal Contraceptives	Combined oral pills, Patches, Rings	Decreased effectiveness of ethinyl estradiol	Unintended pregnancy

Conclusion

Paxlovid effectively treats COVID-19 but requires careful attention to potential drug interactions. The ritonavir component's CYP3A4 inhibition is the main cause, potentially raising levels of other drugs or reducing Paxlovid's efficacy. Significant interactions occur with statins, antiarrhythmics, blood thinners, anticonvulsants, immunosuppressants, and hormonal contraceptives. Always discuss your full medication list with a healthcare provider to ensure safety and effective treatment, which may involve temporarily pausing or adjusting doses, or considering an alternative COVID-19 therapy.

For more detailed information on interactions, the University of Liverpool COVID-19 Drug Interaction Checker is a valuable resource.

Frequently Asked Questions

Paxlovid contains a boosting agent called ritonavir, which blocks a liver enzyme known as CYP3A4. Since many common medications are broken down by this enzyme, blocking it can lead to higher, potentially toxic, drug levels in the body.

It depends on the specific medication. Statins like simvastatin and lovastatin are strictly contraindicated. Others like atorvastatin or rosuvastatin may need to be temporarily stopped or have their dosage adjusted under a doctor's supervision.

No, Paxlovid can reduce the effectiveness of combined hormonal contraceptives, such as the pill, patch, or ring. It is recommended to use an alternative or additional barrier method, like a condom, during and after treatment.

This requires careful medical management. Depending on the blood thinner, a doctor may need to temporarily pause it, adjust the dose, or switch to an alternative. Warfarin requires close monitoring. Never make changes without consulting your healthcare provider.

Yes. The herbal supplement St. John's Wort is a potent CYP3A4 inducer and is strictly contraindicated with Paxlovid because it can significantly reduce the drug's effectiveness.

You must provide a full list of all prescriptions, over-the-counter drugs, and supplements to your doctor or pharmacist. They are trained to screen for potential drug interactions and advise you on the safest course of action.

If you suspect an accidental interaction, contact your healthcare provider or seek emergency medical attention immediately. Do not wait for symptoms to develop.