Paxlovid Drug Interactions

Paxlovid is a combination antiviral medication that contains nirmatrelvir (a protease inhibitor) and ritonavir (originally used to treat HIV infections).

Paxlovid is a treatment for the respiratory virus COVID-19. The U.S. Food and Drug Administration (FDA) has approved it for adults with mild to moderate COVID-19 who risk developing severe illness.

Though Paxlovid is very effective, its use is limited by various drug interactions, including some with common heart and seizure medications.

Here's what you need to know about Paxlovid's safety, including its side effects and drug interactions.

What Drugs Should You Not Take With Paxlovid?

The ritonavir in Paxlovid blocks some critical pathways that metabolize (break down) drugs. Specifically, Paxlovid blocks both the liver enzyme cytochrome P450 3A4 and p-glycoprotein. This results in increased levels of medications metabolized by these pathways in the body and a higher risk of side effects.

According to the National Institutes of Health, you should not take Paxlovid with any of the following prescription medications:

• Seizure medications, including Tegretol (carbamazepine), Sezaby (phenobarbital), and Dilantin (phenytoin)
• Heart medications, including Pacerone (amiodarone), Plavix (clopidogrel), Norpace (disopyramide), flecainide, propafenone, Tekturna (aliskiren), Aspruzyo Sprinkle (ranolazine), and Brilinta (ticagrelor)
• Cholesterol medications, including Lipitor (atorvastatin), Altoprev (lovastatin), and Zocor (simvastatin)
• Antibiotics, including rifampin and erythromycin
• Psychiatric medications, including Clozaril (clozapine), Nayzilam (midazolam), Halcion (triazolam), Latuda (lurasidone), and pimozide
• Pulmonary hypertension medications, including Revatio (sildenafil) and Adcirca (tadalafil)
• Prostate medications, including Uroxatral (alfuzosin) and Rapaflo (silodosin)
• Migraine medications, including Relpax (eletriptan), Nurtec (rimegepant), and Ubrelvy (ubrogepant)
• Immunosuppressants for organ transplants, including Rapamune (sirolimus) and Prograf (tacrolimus)
• Certain chemotherapy medications for cancer
• Gout medication colchicine (if you also have kidney or liver problems)
• Ergot derivatives, including Ergomar (ergotamine)
• Breathing medications, including Serevent (salmeterol)

In some situations, these medicines may be held when you take Paxlovid and for about three days after you've finished it. If you can't safely stop taking certain medicines (even temporarily), you should take another medicine for COVID-19.

Keep in mind that in addition to the drugs listed above, you will need to reduce your doses of many other medicines if you take them with Paxlovid. This is to prevent dangerous or even fatal side effects. Some examples of medications that may require lower doses while you're on Paxlovid include the following:

• Anxiety medications, including Xanax (alprazolam), Klonopin (clonazepam), and Valium (diazepam)
• Opioid pain medications, including Fentora (fentanyl), Hysingla ER (hydrocodone), and Oxycontin (oxycodone)
• Diabetes medications, including Onglyza (saxagliptin)
• Heart medications, including Norvasc (amlodipine), Lanoxin (digoxin), Tiazac (diltiazem), Procardia (nifedipine), and Verelan (verapamil)

Paxlovid also interacts with some over-the-counter (OTC) medicines and herbal supplements. Most notably, it would be best if you didn't take it with St. John's wort, a supplement commonly used for depression.

Other supplements may interact with Paxlovid, but further clinical trials are necessary to know this definitively. Some potential herbal interactions include the following:

• Sweet wormwood (Artemisia annua)
• Turmeric (Curcuma longa)
• Licorice (Glycyrrhizae radix et rhizoma)
• Devil's claw (Harpagophytum procumbens)
• Cat's claw (Uncaria tomentosa)
• Bitter leaf (Vernonia amygdalina)
  

Make sure you follow any directions your healthcare provider gives you so you can minimize drug interactions and any side effects of therapy.

What Are the Worst Side Effects of Paxlovid?

Paxlovid may cause mild side effects such as the following:

• Metallic taste
• Diarrhea
• Vomiting
• Headache

It may also cause serious side effects. These can include the following:

• Hepatitis, a liver infection
• Jaundice, yellowing of the skin or eyes
• Anaphylaxis, a life-threatening allergic reaction
• Hypersensitivity reactions, such as skin rashes or hives
• Resistance to HIV medications

If you experience any of the following while taking Paxlovid, stop taking the medicine and contact your healthcare provider or emergency services:

• Rash
• Difficulty breathing or swallowing
• Swelling of any part of the face or mouth

What Should You Not Eat With Paxlovid?

Paxlovid can be taken with or without food. There aren't any specific foods or drinks to avoid while you're taking Paxlovid.

How to Use Paxlovid

Start Paxlovid as soon as possible and within five days after COVID-19 symptoms start.

It's only approved for adults, and you shouldn't take it if you have severe kidney or liver problems.

There's not enough information to know if Paxlovid is safe during pregnancy or breastfeeding,

The medicine comes in a dose pack and is taken twice daily, with or without food.

Most people will take 300 milligrams (mg) of nirmatrelvir (as two tablets) plus 100 mg ritonavir (one tablet) twice a day for five days.

People with kidney problems that aren't severe should take an adjusted dose with a lower amount of nirmatrelvir. The dose pack for people with kidney problems contains 150 mg nirmatrelvir plus 100 mg ritonavir twice daily for five days.

What Are Some Alternatives to Paxlovid?

Despite Paxlovid's many drug interactions, it's the preferred treatment for adults with COVID-19 who are not hospitalized.

Paxlovid is more accessible than other treatments and is available at most pharmacies. And it's taken by mouth, whereas some other options have to be injected into a vein (IV).

Other medications approved by the FDA to treat COVID-19 include:

• Veklury (remdesivir): a medicine injected into a vein (IV) authorized for adults and children over 28 days old, either in or out of the hospital. It works by stopping the COVID-19 virus from making more of the virus.
• Olumiant (baricitinib): an oral tablet approved for adults in the hospital who need supplemental oxygen or ventilator support
• Actemra (tocilizumab): an IV monoclonal antibody approved for adults in the hospital who are taking corticosteroids and need supplemental oxygen or ventilator support

Two additional therapies may be taken under FDA Emergency Use Authorizations, though they're not fully approved by the FDA:

• Lagevrio (molnupiravir): an oral tablet taken twice a day for five days, not to be taken during pregnancy, breastfeeding, or in children
• COVID-19 convalescent plasma (CCP): blood from people who have recovered from COVID-19 infections and may provide antibodies to the virus for people who have impaired immune function

Unless Paxlovid and remdesivir are unavailable or ruled out for other reasons, these aren't recommended.

Your healthcare provider will help you determine which medicines may be best for you. This choice will depend on factors like:

• Your age
• Other health conditions
• Whether or not you are in the hospital
• Whether or not you need oxygen

Summary

Paxlovid is a combination antiviral medication that is recommended for adults with COVID-19 who are not hospitalized but have risk factors for severe illness.

Be aware, though, that Paxlovid is associated with many drug interactions. It can increase the levels of some medicines in the body and cause dangerous side effects, including death.

Be sure to discuss your medication regimen with your healthcare provider and pharmacist to ensure Paxlovid is compatible with your medicines. You can also check for drug interactions with Paxlovid using the online Liverpool COVID-19 Interaction database.