Paxlovid Contraindications | Effective, But Is It for Everyone

Paxlovid Contraindications Introduction

Reflections on COVID-19 uncertainty are still strong, even today. The medicine was not prepared for this unpredictable virus from the very first start, neither to cure nor to prevent it. It took about two years to have Paxlovid available, a medical treatment for COVID-19, but not for all patients.

Paxlovid, a two-component medication treatment, was authorized only to those with mild to moderate disease at the start of symptoms development and risk for progression, hospitalization, or death. (1)

Another limitation of Paxlovid use is for those allergic to any components, including active ingredients (nirmatrelvir and ritonavir). Moreover, Paxlovid interacts with certain medications; with some, it is contraindicated. (1)

This article explains how Paxlovid interacts with certain medications, what the effects are, and the reasons for contraindications. Keep reading to find out what drugs cannot be used at the same time as Paxlovid.

Paxlovid Contraindications – Who shouldn’t use Paxlovid

Paxlovid was authorized in December 2021 for emergency use before its approval. Critical patients who need to go to the hospital cannot benefit from Paxlovid therapy. It is not authorized to use for prevention before or after exposure to the virus. (1)

Paxlovid usage is contraindicated under the following conditions:

Paxlovid Contraindications

Paxlovid Contraindications – You may have allergic to its components

1. Don’t use Paxlovid if you are allergic to its components

Hypersensitive reactions are possible for all medications, so for Paxlovid. Paxlovid contains nirmatrelvir and ritonavir, and you can be allergic to them.

In addition to active substances, tablets contain inactive ingredients such as colloidal silicon dioxide, sodium stearyl fumarate, hydroxypropyl methylcellulose, polyethylene glycol, titanium dioxide, and many more. You could be allergic to some of them, too. (1)

Stevens-Johnson syndrome (SJS) and Toxic epidermal necrolysis (TEN) are severe allergic reactions that can be life-threatening. Ritonavir, one of the Paxlovid components, is associated with Stevens-Jonsons syndrome, a rare side effect that affects the skin. (1-3)

It begins with flu-like symptoms and continues with a painful skin rash and blisters. The skin dies, sheds, and needs several days for healing. If the rash affects more than 30% of the skin, it is about TEN. (1-2)

These skin wounds are painful and are an open door for infection. In addition, SJS can lead to dehydration, dry eye or light sensitivity, or lack of oxygen because the lungs can be affected too. (2) Call your doctor immediately if you develop SJS symptoms.

Tell your doctor if you have a history of clinically significant hypersensitivity reactions to medication you used before. Based on that, your doctor might know if Paxlovid is contraindicated.

2. Don’t use Paxlovid with drugs which higher concentration, due to CYP3A inhibition, are life-threatening

Paxlovid interacts differently with various medications, and the outcome of this interaction may increase the risk of side effects of those medications or reduce Paxlovid activity.

CYP3A is a protein, cytochrome P450, present in different body parts, including the liver and gastrointestinal tract. Its role is to metabolize drugs so the body can eliminate the end products. (4-5)

Ritonavir, one of the active compounds in Paxlovid, is a CYP3A inhibitor. If the clearance of a particular medication depends on CYP3A, with its inhibition, the drug concentrations will increase and its possible side effects. If the side effects are life-threatening, Paxlovid is contraindicated for use with such medications. (1)

Alfuzosin, amiodarone, silodosin, simvastatin, sildenafil, and triazolam are medications that should not be used at the same time as Paxlovid. The full list of contraindicated medications is available in the Medication guide (1).

3. Don’t use Paxlovid with drugs that are CYP3A inducers; Paxlovid loses its therapeutic effect

Certain medications can induce CYP3A activity. Its induced activity can result in a reduction of nirmatrelvir or ritonavir plasma concentrations. When concentrations are lower, the therapeutic effect can be lost. The virus will not respond to a low level of the medication and may develop resistance. (1)

The effect of the medications that induce CYP3A last for some time, so Paxlovid cannot be initiated in this context. Apalutamide, carbamazepine, phenobarbital, primidone, phenytoin, lumacaftor/ivacaftor, rifampin, and herbal products hypericum perforatum are CYP3A inducers. (1)

The complete list of contraindicated medications is a consistent part of the Paxlovid Medication Guide. However, tell your doctor the medicines you use before you begin Paxlovid therapy. No matter how Paxlovid is needed for COVID-19 treatment, in such cases, Paxlovid may not be effective or would initiate side effects.

How to Use Paxlovid

Paxlovid treatment should begin after COVID-19 is diagnosed, within five days after symptoms occur. This combination treatment contains 20 pink tablets of 150 mg of nirmatrelvir and ten white tablets of 100 mg of ritonavir for five days of treatment. (1)

Take 2 pink and 1 white tablet at the same time, twice a day. Don’t miss the dose and complete the 5-days treatment even if you start feeling better. In case you miss the dose, take it once you realize it. If the time is 3-4 hours or closer to the next dose, wait until the time comes. (1)

Possible Side Effects and Warnings

At the end of 2021, during the COVID-19 pandemic, FDA authorized Paxlovid for emergency use, although not fully investigated. However, not all regular trials have been performed by the authorization day. Therefore, this medication may be associated with some side effects not identified so far.

Until authorization, the following side effects have been reported in a frequency >1%:

  • Altered sense of taste (6%);
  • Diarrhea (3%);
  • High blood pressure (1%);
  • Muscle aches (1%). (1, 6)

Rarely patients taking Paxlovid may feel generally unwell or experience abdominal pain or nausea. During the practice, patients also reported hypersensitive reactions, nausea, abdominal pain, and discomfort or lack of well-being. (1, 6)

Some of the reported side effects, such as severe allergic reactions like anaphylaxis, can be life-threatening, requiring immediate emergency care. Some symptoms of anaphylaxis reactions are skin rash, nausea, vomiting, and weak or rapid pulse. (1, 6, 7)

If you have previous liver disease, there is a risk of hepatotoxicity. Tell your doctor if you experience yellowing of the skin or the whites of the eyes, loss of appetite, itchy skin, pale-colored stools, dark-colored urine, pain in the stomach, or symptoms of liver problems. (1)

Paxlovid interacts with certain medications and increases the concentration of the concomitant drug, resulting in higher dosing than needed and possible side effects. Other medicines that induce CYP3A may reduce the Paxlovid therapeutic effect. (1)

Read carefully the list of medications that interact with Paxlovid in the Medication Guide and tell your doctor if you use any of those medications.

See Also: Side Effects of Paxlovid

Final Thoughts

Paxlovid is authorized for use at an early stage of the disease when the virus is not yet present in the body in a high amount. Nirmatrelvir disables the COVID virus from entering the human cell and replicating there by enzyme inhibition. In addition, ritonavir inhibits CYP3A, which makes nirmatrelvir stay longer and play its role.

The effect of ritonavir on CYP3A can have the same effect on other medications used at the same time. Because of their severe side effects, they should not be used simultaneously. Moreover, medicines that induce CYP3A have a negative effect on Paxlovid efficacy. Find the complete list of drugs in the Medication Guide and inform your doctor if you use other medications.

Don’t underestimate previous allergic reactions to a drug that you used. You might be allergic to an ingredient that is present in Paxlovid or allergic to Paxlovid active ingredients.

Report adverse reactions that you experience to FDA MedWatch at or call 1-800-FDA-1088. It will help authorities to evaluate the safety profile and inform future patients about what to care.

See Also:

Acetaminophen Side Effects

Bupropion Side Effects

Trazodone Side Effects

Atorvastatin Side Effects

Metformin Side Effects

Prednisolone Side Effects

Side Effects of Paxlovid

1. FDA Food and Drug Administration, Fact Sheet for Healthcare Providers, Emergency use authorization for Paxlovid, 2023 Feb,

2. Mayo Clinic, Stevens-Johnson syndrome, 2023 Jan,

3. FDA, NORVIR (ritonavir) Prescribing information, 2017 Jun,

4. G.R. Wilkinson, Cytochrome P4503A (CYP3A) metabolism: prediction of in vivo activity in humans, J Pharmacokinet Biopharm. 1996 Oct;24(5):475-90.

5. A.M. McDonnell and C.H. Dang, Basic Review of the Cytochrome P450 System, J Adv Pract Oncol. 2013 Jul-Aug; 4(4): 263–268.

6. FDA Food and Drug Administration, Fact Sheet for Patients, Parents, and Caregivers, Emergency use authorization for Paxlovid, 2023 Feb,

7. Mayo Clinic, Anaphylaxis, 2021 Oct,

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