Paxlovid Has More Drug Interactions Than Almost Any Other Common Medication — Here's What You Need to Know

Paxlovid 150 Mg /100 Mg Dose Pack is one of the most effective treatments for COVID-19, but it comes with a long list of drug interactions that can be serious — even life-threatening. If your doctor is considering prescribing Paxlovid, or if you've already received a prescription, understanding these interactions is essential for your safety.

This guide breaks down which medications interact with Paxlovid, why these interactions happen, and exactly what you should tell your doctor before starting treatment.

How Drug Interactions With Paxlovid Work

Paxlovid contains two active ingredients: Nirmatrelvir (the antiviral) and Ritonavir (the booster). The drug interactions come almost entirely from the Ritonavir component.

Ritonavir is a powerful inhibitor of an enzyme in your liver called CYP3A. This enzyme is responsible for breaking down a huge number of medications. When Ritonavir blocks CYP3A, those other medications aren't broken down normally — their levels build up in your blood, sometimes to dangerous concentrations.

Ritonavir can also affect other enzymes and transport proteins, but CYP3A inhibition is the primary concern.

The flip side is also true: medications that strongly activate (induce) CYP3A can speed up the breakdown of Nirmatrelvir, reducing Paxlovid's effectiveness to the point where it may not work against COVID-19.

Medications That Have Major Interactions With Paxlovid

The following medications are contraindicated with Paxlovid — meaning they absolutely should not be taken together. In some cases, your doctor may pause or switch these medications during your 5-day Paxlovid course.

Cholesterol Medications (Statins)

• Lovastatin (Mevacor) — Must stop. Taking Lovastatin with Paxlovid can cause rhabdomyolysis, a dangerous breakdown of muscle tissue that can lead to kidney failure.
• Simvastatin (Zocor) — Must stop. Same risk of rhabdomyolysis as Lovastatin.

Heart Rhythm Medications

• Amiodarone (Cordarone, Pacerone) — Risk of serious cardiac arrhythmias. Amiodarone has an extremely long half-life, making this interaction particularly complex.
• Flecainide (Tambocor) — Risk of cardiac arrhythmias.
• Propafenone (Rythmol) — Risk of cardiac arrhythmias.

Ergot Alkaloids

• Ergotamine (Ergomar) — Risk of ergot toxicity, which can cause severe blood vessel constriction.
• Dihydroergotamine (D.H.E. 45, Migranal) — Same risk of ergot toxicity.

Sedatives and Sleep Medications

• Oral Midazolam (Versed) — Risk of excessive sedation and respiratory depression.
• Triazolam (Halcion) — Same risk of excessive sedation.

Psychiatric Medications

• Pimozide (Orap) — Risk of QT prolongation and dangerous heart rhythms.
• Lurasidone (Latuda) — Risk of serious adverse effects from elevated drug levels.

Other Contraindicated Medications

• Colchicine (in patients with kidney or liver impairment) — Risk of life-threatening toxicity. Since the 150 Mg /100 Mg Dose Pack is specifically for patients with kidney impairment, this interaction is especially relevant.
• Ranolazine (Ranexa) — Risk of serious adverse effects.
• Sildenafil (Revatio) for pulmonary arterial hypertension — Contraindicated. Note: Sildenafil for erectile dysfunction (Viagra) requires dose adjustment but is not absolutely contraindicated.

Medications That Reduce Paxlovid's Effectiveness

These drugs are potent CYP3A inducers that speed up Nirmatrelvir's breakdown, potentially making Paxlovid ineffective:

• Rifampin (Rifadin) — Used for tuberculosis
• Carbamazepine (Tegretol) — Used for seizures and nerve pain
• Phenytoin (Dilantin) — Used for seizures
• Phenobarbital — Used for seizures
• St. John's Wort — An herbal supplement (discussed below)

Medications That Have Moderate Interactions With Paxlovid

These medications may require dose adjustments, temporary pausing, or closer monitoring during your 5-day Paxlovid course:

• Atorvastatin (Lipitor) — Temporarily hold or reduce dose during treatment. Unlike Lovastatin and Simvastatin, Atorvastatin can sometimes be managed with dose adjustment.
• Rosuvastatin (Crestor) — Use the lowest dose possible during Paxlovid treatment.
• Amlodipine (Norvasc), Felodipine, Nifedipine (Procardia) — Blood pressure-lowering calcium channel blockers. Monitor blood pressure closely, as levels may increase.
• Warfarin (Coumadin) — Monitor INR closely. Ritonavir can affect Warfarin levels unpredictably.
• Methadone — May require dose monitoring.
• Quetiapine (Seroquel) — Reduce dose during Paxlovid treatment.
• Fluticasone (Flonase, Flovent) — Inhaled corticosteroid. Prolonged use with Ritonavir can lead to Cushing syndrome, though this is less concerning for a 5-day course.
• Rivaroxaban (Xarelto) — Increased bleeding risk. Dose adjustment needed.
• Apixaban (Eliquis) — Increased bleeding risk. Dose adjustment needed.
• Tacrolimus (Prograf), Cyclosporine (Neoral, Sandimmune), Sirolimus (Rapamune) — Immunosuppressants used in transplant patients. Requires close monitoring and dose adjustment to avoid nephrotoxicity.
• Certain hormonal contraceptives — Ethinyl Estradiol levels may decrease, potentially reducing effectiveness. Use backup contraception during treatment.

Supplements and Over-the-Counter Products to Watch

St. John's Wort

This is the most important supplement interaction. St. John's Wort is contraindicated with Paxlovid. It strongly induces CYP3A, which can reduce Nirmatrelvir levels so much that Paxlovid may not work. Stop taking St. John's Wort before starting Paxlovid.

Other Supplements

While most common vitamins and minerals don't have significant interactions, always tell your doctor about all supplements you take. Some herbal products may have mild effects on liver enzymes.

Over-the-Counter Medications

• Acetaminophen (Tylenol) — Generally safe with Paxlovid.
• Ibuprofen (Advil, Motrin) — Generally safe, but check with your doctor if you have kidney impairment (which is likely if you're on the 150 Mg /100 Mg Dose Pack).
• Antihistamines — Most are safe, but check specific products with your pharmacist.

Food and Drink Interactions

Paxlovid can be taken with or without food — there are no major food interactions. Grapefruit may theoretically increase Nirmatrelvir levels (since grapefruit also inhibits CYP3A), but this is not a major clinical concern for a short 5-day course.

There are no specific alcohol restrictions listed, but drinking alcohol while fighting COVID-19 and taking medication is generally not recommended.

What to Tell Your Doctor Before Starting Paxlovid

Before your doctor prescribes Paxlovid, make sure they know about:

1. Every prescription medication you take — Bring a complete list, including the name, dose, and how often you take each one.
2. All over-the-counter medications — Including pain relievers, cold medicines, and sleep aids.
3. All supplements and herbal products — Especially St. John's Wort.
4. Your kidney function — This determines whether you need the standard dose or the 150 Mg /100 Mg Dose Pack.
5. Your liver health — Paxlovid is not recommended for severe liver impairment.
6. Your HIV status — Ritonavir is also used in HIV treatment, and taking Paxlovid in uncontrolled HIV infection could potentially lead to drug resistance.
7. If you are pregnant, breastfeeding, or planning to become pregnant — Limited data is available.

Your doctor or pharmacist can review your complete medication list and determine whether any drugs need to be paused, adjusted, or switched during your 5-day Paxlovid course.

Final Thoughts

Paxlovid's drug interactions are the most important safety consideration with this medication. The Ritonavir component interacts with a wide range of prescription drugs, and some of these interactions can be life-threatening. However, with proper medical oversight, many patients can safely take Paxlovid even if they're on other medications — it just requires careful planning.

Never start or stop any medication without talking to your doctor. If you've been prescribed Paxlovid and need help finding it, visit Medfinder to check pharmacy availability near you. For more information about this medication, see our guides on Paxlovid side effects and what Paxlovid is and how to take it.