What Should Be Avoided with Paxlovid?: A Guide to Drug, Food, and Supplement Interactions

October 12, 2025 •

3 min read

Paxlovid, a highly effective oral antiviral treatment for COVID-19, has a complex drug interaction profile due to its ritonavir component, which acts as a powerful enzyme inhibitor. Understanding what should be avoided with Paxlovid is crucial for preventing severe or fatal adverse events during the treatment course.

Quick Summary

Paxlovid contains ritonavir, a strong enzyme inhibitor that interacts with many medications. Before starting treatment, consult a healthcare provider about all current prescriptions, supplements, and health conditions, as dose adjustments or temporary cessation of certain drugs, including some statins, heart medications, and herbal supplements, may be necessary to avoid serious complications.

Key Points

Consult a professional: Always inform your healthcare provider or pharmacist of all medications and supplements you take before starting Paxlovid.
Avoid grapefruit and St. John's Wort: These can seriously alter Paxlovid's effectiveness or increase side effects.
Temporary holds are common: Some regular medications, like certain statins (lovastatin, simvastatin) and blood thinners, may need to be temporarily stopped or adjusted under medical supervision.
Beware of heart medication interactions: Specific antiarrhythmic drugs are strictly contraindicated with Paxlovid due to the risk of life-threatening cardiac events.
Use backup birth control: Paxlovid can reduce the effectiveness of hormonal contraceptives, so an alternative method is recommended.
Not for everyone: Paxlovid may not be recommended for individuals with severe kidney or liver disease.
No DIY changes: Never stop or change the dosage of any prescribed medication on your own; always seek a doctor's advice.

Understanding the Mechanism Behind Paxlovid Interactions

Paxlovid consists of two medications: nirmatrelvir, the antiviral component that directly targets the SARS-CoV-2 virus, and ritonavir. Ritonavir's role is to 'boost' the level of nirmatrelvir in the body by inhibiting a key liver enzyme system known as cytochrome P450 3A (CYP3A). This allows nirmatrelvir to remain at a therapeutic concentration for longer. However, because the CYP3A enzyme also metabolizes a vast number of other drugs, ritonavir's effect can dangerously increase the blood levels of those medications, leading to a risk of severe or life-threatening side effects. Conversely, some medications can induce the CYP3A enzyme, which can lower the effectiveness of Paxlovid.

Medications to Avoid (Contraindicated)

For certain medications, the risk of a severe or life-threatening interaction is so high that they are absolutely contraindicated with Paxlovid. These include drugs whose elevated concentrations can cause serious cardiac arrhythmias, bleeding, or other severe adverse effects. In such cases, a healthcare provider will either prescribe an alternative COVID-19 treatment or manage the patient's existing medication regimen carefully.

Specific contraindicated medications include certain antiarrhythmics, antianginals, and cardiovascular agents like amiodarone, dronedarone, flecainide, propafenone, quinidine, ranolazine, ivabradine, and eplerenone. Anticonvulsants such as carbamazepine, phenobarbital, phenytoin, and primidone should also not be taken with Paxlovid. Certain migraine medications like eletriptan, ubrogepant, ergotamine, and dihydroergotamine are contraindicated. Specific blood thinners (rivaroxaban) and antiplatelets (ticagrelor) should be avoided. Other contraindicated drugs include certain statins (lovastatin, simvastatin), antipsychotics (lurasidone, pimozide), alfuzosin, and sildenafil when used for pulmonary arterial hypertension.

Medications Requiring Dose Adjustments or Monitoring

Many medications can still be taken with Paxlovid but require careful monitoring and potential dose adjustments by a healthcare provider. Always consult your doctor before making any changes.

Some statins (Atorvastatin, Rosuvastatin) may require temporary discontinuation or dose reduction. Close monitoring of INR is crucial for warfarin users, and dose reduction or temporary holds may be needed for dabigatran and apixaban. Calcium channel blockers like amlodipine, diltiazem, nifedipine, and verapamil require careful monitoring. Immunosuppressants such as cyclosporine, tacrolimus, and sirolimus need monitoring. Blood levels of certain opioids, including fentanyl, oxycodone, and hydrocodone, may increase.

Herbal Supplements, Foods, and Other Substances to Avoid

Certain supplements and foods can interact with Paxlovid and should be avoided. St. John's Wort should not be taken during or near treatment as it can significantly reduce Paxlovid's effectiveness. Avoid grapefruit and its juice entirely. Limiting or avoiding alcohol during treatment is recommended. Paxlovid can reduce the effectiveness of some hormonal birth control; use a backup non-hormonal method.

Medication Interaction Management: Avoidance vs. Adjustment


Drug Class	Example Drugs	Action with Paxlovid	Reason for Action
HMG-CoA Reductase Inhibitors (Statins)	Simvastatin, Lovastatin	Avoid (Contraindicated)	Can cause muscle pain and breakdown (rhabdomyolysis) due to increased blood levels.
HMG-CoA Reductase Inhibitors (Statins)	Atorvastatin, Rosuvastatin	Adjust/Monitor	Requires dose adjustment or temporary hold to manage elevated drug levels.
Antiarrhythmics	Amiodarone, Dronedarone	Avoid (Contraindicated)	Can lead to severe, life-threatening cardiac arrhythmias.
Anticoagulants	Warfarin	Adjust/Monitor	Requires close monitoring of INR to avoid bleeding risks due to fluctuating blood levels.
Calcium Channel Blockers	Amlodipine, Verapamil	Adjust/Monitor	Requires careful monitoring and possible dose reduction to prevent dangerously low blood pressure.
Ergot Derivatives	Ergotamine, Dihydroergotamine	Avoid (Contraindicated)	Risk of acute ergot toxicity, causing severe vasoconstriction and ischemia.
Herbal Supplements	St. John's Wort	Avoid (Contraindicated)	Significantly reduces the effectiveness of Paxlovid, leading to potential treatment failure.

Conclusion

A thorough discussion with your healthcare provider or pharmacist is essential before starting Paxlovid due to the extensive potential for drug interactions. Inform them of all medications and supplements. Your doctor will evaluate the benefits and risks. For additional detailed guidance on drug interactions, the official Pfizer prescribing information provides comprehensive tables and management recommendations. {Link: Pfizer https://paxlovid.pfizerpro.com/drug-interactions}

Frequently Asked Questions

Lovastatin and simvastatin are contraindicated with Paxlovid due to the risk of dangerously high drug levels, which can lead to muscle damage. Your doctor may temporarily stop these medications.

While there is no direct interaction between Paxlovid and alcohol, it is recommended to limit or avoid alcohol consumption. Alcohol can weaken the immune system and worsen side effects.

Paxlovid may affect the efficacy of certain hormonal contraceptives. To prevent unintended pregnancy, it is recommended to use an alternative barrier method, such as condoms, during treatment and until your next menstrual cycle.

Yes, you should avoid grapefruit and grapefruit juice. Grapefruit can inhibit the same liver enzymes as ritonavir, potentially increasing Paxlovid's side effects. It's best to avoid it completely while on treatment.

No, St. John's Wort should be avoided completely. It is a strong enzyme inducer that can significantly decrease the effectiveness of Paxlovid and lead to treatment failure.

Paxlovid can increase the effects of blood thinners like warfarin, apixaban, and rivaroxaban, raising the risk of bleeding. Close monitoring or dose adjustment may be required for some, while others are contraindicated.

Individuals with severe kidney or liver disease are generally advised against taking Paxlovid, as the drug levels can become too high and cause increased side effects. A healthcare provider will assess if a dose adjustment is possible for moderate renal impairment.