How Does Paxlovid (Nirmatrelvir/Ritonavir) Work?
Medically reviewed by Erika Prouty, PharmD
Paxlovid (nirmatrelvir/ritonavir) is a prescribed, orally administered (taken by mouth) antiviral medication used to treat symptoms of COVID-19, a viral respiratory illness caused by the SARS-CoV-2 virus.
It is a brand-name medication that combines two antiviral drugs: nirmatrelvir and ritonavir. Paxlovid is a swallowable tablet that stops the COVID-19 virus from replicating and progressing to a more severe state.
Most recently, the drug was approved by the Food and Drug Administration (FDA) to treat mild to moderate COVID-19 in adults (people 18 and older) who are at high risk for developing severe COVID-19.
Paxlovid is also approved for emergency use in specific high-risk pediatric individuals (people under the age of 18) via an Emergency Use Authorization (EUA) that was granted in December 2021. This drug can help prevent hospitalization and death related to COVID-19.
This article will focus on taking Paxlovid to treat COVID-19, how it works, potential side effects, and more.
How Does Paxlovid Work?
Paxlovid comes in a package that contains two different antiviral drugs: nirmatrelvir and ritonavir.
Nirmatrelvir works by stopping viral replication of the SARS-CoV-2 virus, a type of coronavirus. Viral replication is a crucial step in a virus's process to copy its DNA as it multiplies.
By actively preventing viral replication, nirmatrelvir stops the virus from copying its DNA, leading to death. Taking Paxlovid in the early stages of COVID-19 infection can help prevent the infection from becoming severe.
Ritonavir isn’t active against SARS-CoV-2. Instead, ritonavir works by enhancing the effectiveness of nirmatrelvir.
Ritonavir also works by acting as a booster and lengthening the time and effects of nirmatrelvir in the body. Together, ritonavir and nirmatrelvir are effective in treating COVID-19.
Paxlovid effectively reduces the risk of COVID-19-related hospitalization or death by 89%.
A study comparing Paxlovid to placebo. Within this study, 66 out of 1,046 people taking the placebo (an ineffective substance) died from COVID-19, while only 9 out of 1,039 people taking Paxlovid died from COVID.
Paxlovid Approval
Paxlovid has been available for healthcare providers to prescribe for COVID-19 since December 2021. Similar to the process used for COVID-19 vaccines, Paxlovid was initially authorized by the FDA through an EUA.
Before a drug is marketed, the FDA requires the manufacturer to submit data from several years of extensive tests and clinical studies.
However, an EUA speeding up the process during a public health emergency allows the FDA to provide urgently needed treatments more quickly.
Although EUAs do not undergo the same approval process as regular FDA reviews, drugs and vaccines must undergo safety testing before being authorized for emergency use.
On May 25, 2023, Paxlovid received full approval from the FDA to treat mild to moderate COVID-19 in high-risk adults. The EUA remains in effect for pediatric individuals.
Notably, in July 2022, the FDA authorized pharmacists to prescribe Paxlovid in some instances. By allowing pharmacists to prescribe Paxlovid, eligible patients may gain quicker access to timely treatment, which must be started within five days after symptoms begin.
Therefore, if you want to take Paxlovid, you can contact a pharmacist or healthcare provider.
When to Use Paxlovid
Paxlovid treatment should be started as soon as possible after a positive COVID-19 test or within five days of symptom onset.
Common symptoms of COVID-19 include cough, fever, chills, sore throat, shortness of breath, muscle aches, tiredness, and headache.
Paxlovid is not fully approved for pediatric individuals but remains authorized through a EUA for high-risk children who meet all of the following criteria:
Age 12 or older
Possess a body weight of at least 88 pounds
Are high risk for progression to severe COVID-19 that may result in hospitalization or death
Individuals with certain risk factors or chronic health conditions are considered to be at high risk for developing severe COVID-19.
Risk factors include:
Age 50 and older
A history of heart disease
A diagnosis of type 2 diabetes
Currently obese or overweight
Varying neurological conditions, such as Huntington's disease
A history of smoking cigarettes
Existing physical, mental, or developmental disabilities
Be aware that Paxlovid is not approved or authorized to prevent COVID-19 in people who may have been exposed to the virus. It is only meant to be used immediately after a COVID-19 diagnosis based on positive test results.
Alternative Uses of Paxlovid
Paxlovid usually is not prescribed for reasons besides COVID-19.
However, one of its ingredients, ritonavir, has been widely used in combination with other drugs to treat other viral illnesses, such as hepatitis C and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS).
Long COVID is a group of symptoms, such as fatigue, that persist for weeks to months following a COVID infection. It is also known as long-haul COVID or post-acute sequelae of SARS-CoV-2 (PASC).
Paxlovid is not approved or authorized to treat long COVID, but there is some evidence that this medication may help improve the symptoms of long COVID.
Other evidence suggests that taking Paxlovid in the acute phase of COVID-19 is associated with a reduced risk of developing long COVID.
More clinical trials are needed to determine whether Paxlovid benefits other uses, including treating or preventing long COVID.
Side Effects & Safety
Like all medications, Paxlovid carries the potential for adverse effects.
Read on to learn about some of the most common and severe side effects associated with Paxlovid.
Common Side Effects
The most commonly reported side effects of Paxlovid are dysgeusia (a bad taste in your mouth or changes in your sense of taste) and diarrhea.
Other side effects of Paxlovid may include:
Nausea/vomiting
Increased liver enzymes and some reports of hepatitis and jaundice (the yellowing of the skin and eyes)
Anaphylaxis, a severe allergic reaction, which may cause throat swelling, hives, swelling of the face, lips, or mouth, and trouble breathing, and requires immediate medical care
Severe Side Effects
Rarely, severe skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported with Paxlovid.
Some people may be at higher risk for Paxlovid’s side effects than others. Before starting Paxlovid, tell your healthcare provider if you have liver problems or kidney impairment.
Also, tell your provider if you have or might have human immunodeficiency virus (HIV) infection because taking Paxlovid might increase the risk of resistance to specific protease inhibitors (HIV medications).
Paxlovid isn’t safe for everyone. The drug is not recommended if:
You have a known allergy to Paxlovid, nirmatrelvir, ritonavir, or other ingredients in the medication.
You take certain medications that interact with Paxlovid. Paxlovid has numerous potential drug interactions because it is processed in the body by an enzyme called CYP34. The activity of this enzyme can be affected by many other drugs.
Paxlovid is a five-day treatment; its side effects should disappear after your last dose. The drug isn’t known to cause long-term side effects.
How to Take Paxlovid
Paxlovid treatment should begin as soon as possible after a diagnosis of COVID-19, within five days after symptoms start. You can take Paxlovid with or without food.
Each dose of Paxlovid consists of three tablets:
Two tablets of 150 milligrams (mg) of nirmatrelvir (300 mg total) and
One 100 mg ritonavir tablet
You’ll take all three tablets by mouth twice daily for five days. Paxlovid is packaged in a dose card that helps you keep track of your doses.
You may be prescribed a different dosage if you have reduced kidney function.
Paxlovid Interactions
Before taking Paxlovid, tell your prescriber about your current medications, herbs, or supplements. Certain drugs interact with Paxlovid.
Drug interactions can lead to severe side effects or may cause medications to be less effective treatments than usual.
Your body processes Paxlovid using CYP3A, an enzyme that breaks down many medications.
Taking certain medications during Paxlovid treatment can result in too much or too little Paxlovid or the other medications in your body.
Certain drugs and supplements can interact with Paxlovid, making it a less effective treatment. Examples include:
Erleada (apalutamide)
Certain seizure medications, such as Tegretol (carbamazepine), Mysoline (primidone), and Dilantin (phenytoin)
Rifadin (rifampin)
Kalydeco (ivacaftor)
Tracleer (bosentan)
Saint-John’s-wort (Hypericum perforatum)
Paxlovid can also make certain hormonal birth control medications less effective, which can increase the chance of pregnancy.
If you use a hormonal contraceptive, consider using a backup birth control method, such as condoms, during Paxlovid treatment and throughout the next menstrual cycle.
Additionally, Paxlovid can interact with certain drugs and increase their risk or severity of side effects. Examples include:
Uroxatral (alfuzosin)
Antiarrhythmic (drugs used to treat an irregular heartbeat) medications, such as Nexterone (amiodarone)
Latuda (lurasidone)
Lipitor (atorvastatin)
DHE (dihydroergotamine)
Certain migraine medications, such as Relpax (eletriptan) and Ubrelvy (ubrogepant)
This is not a complete list of drugs that interact with Paxlovid. Talk to a pharmacist or healthcare provider for more details about drug interactions with Paxlovid.
Summary
The FDA initially authorized Paxlovid under an EUA to treat COVID-19. It is now fully approved for use in high-risk adults with mild to moderate COVID-19 to help prevent progression to severe COVID-19.
Paxlovid is an antiviral medication used to treat COVID-19 and should be started within five days of symptom onset.
Each dose of Paxlovid consists of three oral tablets: two 150 mg nirmatrelvir tablets and one 100-mg ritonavir tablet.
Before taking Paxlovid, discuss your other medications with your healthcare provider.
Frequently Asked Questions
Can Paxlovid treat severe symptoms of COVID-19?
Paxlovid treats mild to moderate COVID-19 in people at high risk for progressing to severe COVID-19. Severe COVID symptoms, such as shortness of breath, can result in hospitalization and other serious complications.
Paxlovid has dramatically reduced the risk of COVID-related hospitalization and death.
Do alternative COVID-19 treatments exist?
Other FDA-approved treatment options for COVID-19 include Lagevrio (molnupiravir) and Veklury (remdesivir).
Lagevrio (molnupiravir) is an oral medication used for five days. Veklury (remdesivir) is an intravenous (IV) infusion used in hospitalized people with severe COVID-19 for up to seven days.
Additionally, hydroxychloroquine is not recommended for COVID-19.
After granting a EUA to hydroxychloroquine for COVID-19, the FDA later revoked its authorization and cautioned against its use.
