What are the Possible Side Effects of Paxlovid?

Introduction to Side Effects of Paxlovid

Paxlovid is a promising medication for coronavirus disease 2019 (COVID-19) treatment. (1) The latest data from the Centers for Disease Control and Prevention says that COVID-19 took over 1.1 million Americans’ lives till January 2023. (2) Paxlovid reduces the risk of progression to severe COVID-19 by 89% compared to placebo, “without evident safety concerns”, a recent study shows. (3)

This medication, a combination of nirmatrelvir and ritonavir, has limited safety data due to obtaining authorization for emergency use before completing the studies. Changed sense of taste, diarrhea, muscle pain, or hypertension are side effects reported more frequently.

Yet, some side effects, such as severe allergic reactions, are not frequent; however, they might be life-threatening and require emergency care. (1)

Keep reading this article to find out more about the allergic reactions that this effective medication may cause. In addition, you can learn about the known side effects reported in studies and real-life data and when you should call your doctor.

Paxlovid side effects known so far

If you are positive for COVID-19 and at high risk for disease progression or hospitalization, then you are eligible for Paxlovid treatment. Your doctor may prescribe Paxlovid and give you the Fact sheet for patients, parents, and caregivers. (4)

Read the Fact sheet carefully as for any other prescription drug. Paxlovid may cause the following side effects with a frequency reported in clinical studies: (1)

altered sense of taste (6%);
diarrhea (3%);
high blood pressure (1%);
muscle aches (1%).

In the post-authorization period, Paxlovid users reported abdominal pain, nausea, hypersensitive reactions, anaphylaxis, and malaise (a feeling of discomfort, illness, or lack of well-being). (1,4)

Allergic reaction to Paxlovid

Some people may be allergic to any Paxlovid active substances or the other components; if you are one, you shouldn’t use Paxlovid. The symptoms of allergic reaction that can appear soon after taking the first dose are: (4)

hives;
trouble swallowing or breathing;
swelling of the mouth, lips, tongue, or face;
throat tightness;
hoarseness;
skin rash.

If you notice any of these symptoms, stop taking the drug and call your doctor immediately. (1,4)

All side effects of Paxlovid are not yet known. Paxlovid has a narrow indication for use; therefore, a small number of patients have been treated and reported side effects. If you take Paxlovid, inform your doctor of any adverse reaction you experience that bothers you and doesn’t go away. (4)

You can report adverse reactions to FDA MedWatch at www.fda.gov/medwatch or call 1-800-FDA-1088, or you can report it to the manufacturer, Pfizer Inc. It will help health authorities to evaluate all serious and unexpected side effects and their frequency. (4)

Paxlovid: Warning and precautions

Paxlovid may cause some serious side effects, as described in the Fact Sheet for Patients, Parents, and Caregivers. Patients with previous liver disease who have hepatitis or enzyme abnormalities should use it with caution due to potential hepatotoxicity. (4)

You should also be aware of the following potential life-threatening situations:

Drug interaction – Paxlovid interacts with some medications metabolized by CYP3A in the human body. (1) CYP3A is cytochrome P450, a protein present in the liver and gastrointestinal tract that plays an essential role in drug metabolism. (5-6)

Paxlovid inhibits CYP3A, so if given with medication whose clearance depends on CYP3A, it may result in increased concentrations of that medication and its side effects. If the medication inhibits or induces CYP3A, it will affect Paxlovid concentrations in the body. (1)

Such drug interaction may lead to a lost therapeutic effect of Paxlovid and virus resistance, adverse reactions due to higher Paxlovid concentration, and severe, life-threatening, or even fatal adverse reactions (1). Tell your doctor all the medications you already take to avoid any interaction and complications.

Medications that, given together with Paxlovid, may cause serious or life-threatening side effects or affect Paxlovid efficacy are listed in the Fact sheet. If you use amiodarone, carbamazepine, eplerenone, lovastatin, phenytoin, propafenone, sildenafil, simvastatin, triazolam, and some of the medications specified in the Fact sheet, then you should not take Paxlovid. Read all the details in the Fact sheet. (4)

Anaphylaxis – a severe allergic and life-threatening reaction has been reported by some patients using Paxlovid. (1,4) A rapid or weak pulse, skin rash, nausea, and vomiting are some signs and symptoms of an anaphylactic reaction that require emergency care. (7)

Stevens-Johnson syndrome (SJS) – cases have been reported when using ritonavir (one of the active substances of Paxlovid). (1,8) SJS is a rare side effect of some medications where the skin is affected. In the beginning, the patient can experience flu-like symptoms (fever, a sore mouth and throat, fatigue, and burning eyes), and after, a painful skin rash follows. The rash spreads, blisters are formed, and the damaged skin dies. Toxic Epidermal Necrolysis (TEN) is a more severe form of SJS where over 30% of the skin is affected. (9)

SJS complications include dehydration, permanent skin damage, blood infections, dry eye or light sensitivity, or lack of oxygen in the blood due to lung involvement. For these reasons, call your doctor immediately if you experience the symptoms described above. (9)

Hepatotoxicity – yellowing of the skin or the whites of the eyes, dark-colored urine, pale-colored stools, loss of appetite, itchy skin, or pain in the stomach are signs and symptoms when liver problems occur. Tell your healthcare provider right away if you have any of these signs. (1)

Resistance to HIV Medicines – in those who have untreated HIV infection (undiagnosed or uncontrolled infection), Paxlovid may lead some HIV medicines to lose efficacy. (1)

When can Paxlovid be used?

Paxlovid is a medication available for over a year and is used to treat mild-to-moderate COVID-19 in adults and children older than 12 years who have at least 40 kg. The doctor can prescribe Paxlovid only to a patient with positive SARS-CoV-2 viral test results and who has a high risk of the disease progressing to severe COVID-19, including hospitalization or death. (1,4)

Paxlovid is a combination of two drugs:

Nirmatrelvir – SARS-CoV-2 main protease inhibitor, and
Ritonavir – HIV-1 protease inhibitor and CYP3A inhibitor. (1)

Nirmatrelvir inhibits the enzyme necessary for COVID virus replication to grow and spread in the body. In the early stage of the disease, thanks to nirmatrelvir, the COVID virus is disabled to enter and infect cells, so the infection is stopped. (1)

Ritonavir is a medication previously used for the treatment of HIV infection. The role of ritonavir in COVID infection is to inhibit CYP3A that mediates nirmatrelvir metabolism. In that way, nirmatrelvir is available for longer and can fight the COVID infection more than on its own. (1)

In 2021, the U.S. Food and Drug Administration authorized Paxlovid to be used in the COVID-19 emergency and protect public health from the life-threatening disease. (1,10)

Following how Paxlovid works, Paxlovid cannot be used to prevent COVID-19 before or after the individual has been exposed to it. Paxlovid is not approved for use in those who have severe COVID-19 or are critical and need hospitalization. (1,4)

Those who have severe renal or hepatic impairment cannot take Paxlovid. (1,4)

How you should take Paxlovid?

Paxlovid pack contains 20 pink tablets of 150 mg nirmatrelvir and 10 white tablets of 100 mg ritonavir. The therapy should be initiated after diagnosis of COVID-19 and within five days of the occurrence of the symptoms. (1)

Take two nirmatrelvir tablets and one ritonavir tablet at the same time, in the morning and the evening. Use Paxlovid for five days in a row and complete the course. Don’t stop taking Paxlovid earlier than completing the five days’ therapy, even if you feel better. (1)

If you miss the dose, take it as soon as possible, and don’t double the dose to make up for the missed one. If you are late for more than eight hours, wait until the time for the other dose comes. (1)

Final thoughts Side Effects of Paxlovid

In the urgency of the COVID-19 pandemic and saving lives, FDA authorized emergency usage of the investigation medication, Paxlovid. The controlled trial results have shown Paxlovid as highly effective in the risk reduction of disease progression and hospitalization when given in the first five days of symptomatic patients.

The side effects known so far are described in the Fact sheet of the drug. While some can be mild and don’t bother, allergic reactions, drug interactions, or liver problems can be severe and life-threatening, requiring medical care. Call your doctor when described signs appear.

Not all severe and unexpected side effects are known so far. Therefore, it is important to recognize any of the described side effects or changes that appear and report them to the doctor, FDA, and manufacturer.

Take Paxlovid following your doctor’s instructions and stay home according to the latest recommendations. Take the time needed to feel better and get cured.

References:

FDA Food and Drug Administration, Fact Sheet for Healthcare Providers, 2022 Sep, https://www.fda.gov/media/155050/download
CDC Centers for Disease Control and Prevention, COVID Data Tracker, 2023 Jan, https://covid.cdc.gov/covid-data-tracker/#datatracker-home
J. Hammond, Ph.D., H. Leister-Tebbe, B.S.N., A. Gardner, M.P.H., et al., Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19, N Engl J Med 2022 Apr; 386:1397-1408

https://www.nejm.org/doi/full/10.1056/NEJMoa2118542