7 Common Paxlovid Interactions You Should Know About (Plus Other Medications to Avoid)

If you have mild-to-moderate COVID-19, you may be eligible to receive a prescription for Paxlovid (nirmatrelvir / ritonavir). It’s an oral antiviral medication that helps lessen the risk of hospitalization or death from COVID, and it’s become more widely available in the U.S. over time.

While availability has improved, safety precautions have remained a priority. A healthcare professional should do a couple of routine checks to make sure Paxlovid is safe for you to take.

Among these, they’ll likely ask you about medications and supplements you take at home. Screening for interactions is one of Paxlovid’s recommended prescribing steps and can help you avoid unwanted side effects.

7 common Paxlovid drug interactions to know about

Paxlovid is made up of two antiviral medications, nirmatrelvir and ritonavir. They’re both necessary parts of treatment. But ritonavir appears to be responsible for the bulk of Paxlovid’s interactions.

Paxlovid gets in the way of certain enzymes (proteins) that are responsible for breaking down medications. This makes the medications stay in your body for longer, which can worsen side effects. Similarly, some medications may make Paxlovid less effective.

Before you head to the pharmacy to get Paxlovid, make sure to bring along an updated list of medications you take. This should include prescription and over-the-counter medications, supplements, and vitamins. This will help your care team prevent and manage any potential interactions.

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This isn’t an exhaustive list, but here are some common Paxlovid interactions to be aware of.

1. Statins

Statins are common medications that treat high cholesterol. Atorvastatin (Lipitor), a type of statin, has even been described as the most commonly prescribed medication in the U.S.

While statins are popular at pharmacies, they’re not so agreeable when it comes to interacting with other medications. Paxlovid is no exception to this. Paxlovid can block an enzyme responsible for breaking down statins, causing them to linger in your body. This can worsen the risk of statin side effects, such as muscle pain. In rare cases, rhabdomyolysis (intense muscle breakdown) is also possible.

If you take atorvastatin, you should avoid taking it while you’re taking Paxlovid. You can start it up again shortly after you finish Paxlovid. Rosuvastatin (Crestor) may interact too, but potentially to a lesser extent.

If you take simvastatin (Zocor, FloLipid) or lovastatin (Altoprev), there’s a stricter recommendation. You should stop taking them 12 hours before your first dose of Paxlovid. After this, you should keep avoiding them until 5 days have passed since your last dose of Paxlovid.

2. Heart and blood pressure medications

Dozens of heart and blood pressure medications are available in the U.S. Some of the most widely used ones are angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and beta blockers. Thankfully, these don’t interact with Paxlovid. But many other ones do.

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Heart medications

Digoxin (Lanoxin) is a medication that treats heart failure and an abnormal heart rate. You don’t need to avoid combining digoxin and Paxlovid, but know that digoxin levels can go up if you take them together. This in turn increases the risk of digoxin side effects.

Due to a high risk of serious heart changes or other side effects, it’s recommended to avoid Paxlovid with these medications:

• Amiodarone (Pacerone)

• Dofetilide (Tikosyn)

• Dronedarone (Multaq)

• Eplerenone (Inspra)

• Flecainide

• Ivabradine (Corlanor)

• Propafenone

• Quinidine

• Ranolazine (Ranexa)

Blood thinners

If you take a blood thinner or antiplatelet medication for blood clots, there are a few more interactions to keep in mind.

If you take these medications, a healthcare professional may be hesitant to prescribe Paxlovid:

• Warfarin (Coumadin, Jantoven)

• Rivaroxaban (Xarelto)

• Apixaban (Eliquis)

• Dabigatran (Pradaxa)

• Clopidogrel (Plavix)

• Ticagrelor (Brilinta)

• Vorapaxar (Zontivity)

Blood pressure medications

Certain blood pressure medications should also be avoided, such as aliskiren (Tekturna).

Other ones can be taken with Paxlovid, but you may be told to use a lower dose. This mostly applies to calcium channel blockers:

• Amlodipine (Norvasc)

• Diltiazem (Cardizem)

• Felodipine

• Nicardipine

• Nifedipine (Procardia)

• Verapamil

3. Certain mental health medications

A few medications for anxiety and depression are known to interact with Paxlovid.

Bupropion (Wellbutrin XL, Wellbutrin SR), bupropion / dextromethorphan (Auvelity), and trazodone are three antidepressants to keep in mind. Paxlovid can make bupropion levels go down, potentially making it less effective. But, in reality, this interaction may not be too worrisome because you'll only take Paxlovid for a few days. It has the opposite effect on trazodone. It can elevate trazodone levels, worsening side effects like dizziness and low blood pressure.

Antipsychotics also fall into this category. Paxlovid can raise the levels of quetiapine (Seroquel) and clozapine (Clozaril) in your body, making side effects more likely to happen. A healthcare professional may want you to take a lower quetiapine or clozapine dose while you’re taking Paxlovid.

Paxlovid can also cause serious reactions with lurasidone (Latuda), and pimozide. You should avoid combining Paxlovid with these medications.

4. Anti-seizure medications

Anti-seizure medications, also called antiepileptic medications, have a different relationship with Paxlovid. Many of them make Paxlovid less effective. This can lead to an undertreated infection and possible medication resistance.

Avoid combining Paxlovid with these medications:

• Carbamazepine (Tegretol)

• Phenobarbital

• Phenytoin (Dilantin, Phenytek)

• Primidone (Mysoline)

5. Certain migraine medications

Over the years, many medications and medical devices have been approved and cleared to treat or prevent migraines. They work in unique ways to tackle migraine symptoms, but some of them can interact dangerously with Paxlovid.

One example is eletriptan (Relpax). When taken with Paxlovid, it can cause severe heart or brain-related side effects. Because of this, you should separate Paxlovid and eletriptan doses by at least 3 days (72 hours). Other triptans appear safe to take with Paxlovid.

Ubrogepant (Ubrelvy), rimegepant (Nurtec ODT), and ergot derivatives, including dihydroergotamine, ergotamine, and methylergonovine, are also important to be aware of. You should avoid taking Paxlovid with these migraine medications due to side effects.

6. Hormonal birth control

The world of birth control (contraception) is diverse. Birth control pills, intrauterine devices (IUDs), arm implants, and other options are available for you to choose from.

If you take an oral birth control pill, you may want to check the label and see if it contains ethinyl estradiol. It’s a type of estrogen that’s found in most generic and name-brand birth control pills, including Sprintec, Apri, Junel, and others. It’s also found in vaginal rings and birth control patches.

You can take Paxlovid if you’re taking ethinyl estradiol. But it’s a good idea to use a backup method of contraception, like condoms, while you’re taking it. You may also want to use backup contraception until you get your first period after your last Paxlovid dose. In theory, Paxlovid can diminish ethinyl estradiol’s effectiveness, raising the risk for unintended pregnancies. But since Paxlovid is used for just 5 days at a time, this effect may not be significant.

7. Erectile dysfunction medications

PDE-5 inhibitors are popular medications for erectile dysfunction. They’re used as needed to prior to sexual intercourse. Unfortunately, you may want to keep these medications in the medicine cabinet if you come home with a prescription for Paxlovid.

Avanafil (Stendra) is one of these medications. Paxlovid can raise the amount of avanafil in your body, but we don’t know by how much. Out of caution, avoid this combination.

Sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra) are also PDE-5 inhibitors. They’re more common than avanafil. Combining them with Paxlovid may be OK, but you should ask your prescriber about lowering your dose. Paxlovid can raise the levels of these medications too.

Sildenafil (Revatio) and tadalafil (Adcirca, Alyq, Tadliq) can also treat a condition called pulmonary arterial hypertension (PAH). If you're taking sildenafil or tadalafil for PAH, it's recommended to avoid Paxlovid.

Other Paxlovid drug interactions you should avoid

Due to how often they’re prescribed, the medications above are some of the most common interactions you may come across. But you should also avoid taking Paxlovid — or at least consider a medication dose adjustment — with these medications:

• Alfuzosin (Uroxatral)

• Apalutamide (Erleada)

• Bosentan (Tracleer)

• Colchicine (Colcrys)

• Cyclosporine (Sandimmune)

• Encorafenib (Braftovi)

• Enzalutamide (Xtandi)

• Erythromycin (Ery-Tab)

• Everolimus (Afinitor)

• Finerenone (Kerendia)

• Flibanserin (Addyi)

• Glecaprevir / pibrentasvir (Mavyret)

• Lomitapide (Juxtapid)

• Lumacaftor / ivacaftor (Orkambi)

• Midazolam

• Naloxegol (Movantik)

• Opioids like fentanyl

• Rifampin

• Riociguat (Adempas)

• Salmeterol-containing inhalers, such as Wixela Inhub

• Silodosin (Rapaflo)

• Sirolimus (Rapamune)

• St. John’s wort

• Suvorexant (Belsomra)

• Tacrolimus (Prograf)

• Tamsulosin (Flomax)

• Tofacitinib (Xeljanz)

• Tolvaptan (Samsca)

• Triazolam (Halcion)

• Upadacitinib (Rinvoq)

• Voclosporin (Lupkynis)

• Voriconazole (Vfend)

• Zolpidem (Ambien)

• Many cancer medications

Can you take OTC cold and flu medicines like NyQuil with Paxlovid?

Yes. In general, it’s OK to take over-the-counter (OTC) cold and flu medicines with Paxlovid. OTC cold and flu medicines usually contain one or more of these ingredients:

• Dextromethorphan, a cough suppressant

• Guaifenesin, an expectorant

• An antihistamine like doxylamine or diphenhydramine

• A pain reliever like acetaminophen or ibuprofen

• A decongestant like pseudoephedrine or phenylephrine

Of these, a minor interaction may only affect some people taking dextromethorphan. It’s available as a standalone medication (Delsym) and in combination products like NyQuil, Mucinex DM, and Theraflu.

If you take Paxlovid and dextromethorphan at the same time, there’s a chance you may experience slightly more dextromethorphan side effects. You don’t need to avoid the combination, but it’s a good idea to let your prescriber know if you experience any new or worsening side effects.

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Written by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

Reviewed by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

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