Paxlovid Side Effects: Risks and Benefits

Introduction

Paxlovid has emerged as a significant tool in the fight against COVID-19. This oral antiviral medication, developed by Pfizer, is prescribed to adults and children (12 years and older, weighing at least 88 pounds) who have mild-to-moderate COVID-19 and are at high risk of progressing to severe illness. By taking Paxlovid early in the course of infection, many individuals can significantly reduce their chances of hospitalization and death. The medication is a combination of two active ingredients: nirmatrelvir and ritonavir. Nirmatrelvir works by inhibiting a crucial enzyme, known as 3CL protease or Mpro, that the SARS-CoV-2 virus needs to replicate. Ritonavir plays a supportive role by slowing down the body's breakdown of nirmatrelvir, allowing it to remain in the system at higher concentrations for a longer period, thereby enhancing its antiviral effect. This strategic combination underscores the sophisticated approach to combating viral infections.

While Paxlovid has demonstrated considerable effectiveness, it's essential for individuals considering or undergoing treatment to be well-informed about its potential side effects. Understanding these possibilities allows patients to make informed decisions about their health and encourages them to adhere to the prescribed treatment regimen. Although initial studies showed very promising results, more recent research indicates that the effectiveness of Paxlovid in preventing severe outcomes might vary across different populations, particularly among vaccinated older adults. This evolving understanding emphasizes the need for a nuanced approach to treatment and open communication between patients and healthcare providers. By having a clear picture of both the benefits and the potential drawbacks, individuals can better navigate their COVID-19 recovery journey.

Understanding Common Paxlovid Side Effects

While most people tolerate Paxlovid well, some may experience mild and temporary side effects.

Altered Sense of Taste ("Paxlovid Mouth")

One of the most frequently reported side effects of Paxlovid is an altered sense of taste, often described as a metallic or bitter flavor in the mouth. This phenomenon, sometimes referred to as "Paxlovid mouth," has been observed in approximately 5 to 6% of individuals who have taken the medication in clinical studies. Fortunately, this altered taste is usually temporary and typically resolves on its own once the five-day treatment course is completed. For those experiencing this bothersome side effect, several strategies may help manage it. Chewing sugar-free gum, sucking on sugar-free hard candies or mints, brushing teeth frequently, and using mouthwash can sometimes help mask the unpleasant taste. Staying well-hydrated by drinking plenty of fluids throughout the day is also generally recommended. The occurrence of this taste alteration likely stems from ritonavir, one of the components of Paxlovid, as similar taste disturbances have been noted with other medications in the protease inhibitor class. This suggests a common mechanism related to how these drugs interact with taste receptors or metabolic pathways in the body.

Diarrhea, Nausea, and Vomiting

Diarrhea is another common side effect associated with Paxlovid treatment, with studies indicating it occurs in about 3% of patients. Nausea and vomiting are also possible side effects, although they tend to be less frequent. To help manage these gastrointestinal symptoms, it is generally advised to stay well-hydrated by drinking plenty of fluids to replace any losses. Consuming bland foods that are easy to digest can also be beneficial in settling the stomach. If diarrhea persists or becomes severe, or if nausea and vomiting are unmanageable, it's important to consult with a healthcare provider for further guidance. While diarrhea is a relatively common occurrence with Paxlovid, the lower frequency of nausea and vomiting suggests that these might be less of a concern for most individuals undergoing treatment.

Headaches and Abdominal Pain

Headaches and abdominal pain have also been reported as potential side effects in individuals taking Paxlovid. Headaches associated with Paxlovid are typically mild in nature, and over-the-counter pain relievers can often provide relief if they become bothersome. While these side effects are listed as possibilities, specific data on their frequency is less prominent compared to altered taste and diarrhea. This might suggest that headaches and abdominal pain are either less commonly reported or occurred at a lower rate in clinical trials.

Temporary High Blood Pressure and General Discomfort

Temporary high blood pressure, also known as hypertension, has been observed as a less common side effect in about 1% of individuals participating in Paxlovid studies. Additionally, some people may experience a general feeling of discomfort or being unwell, often referred to as malaise. For individuals with pre-existing high blood pressure or heart conditions, it is particularly important to monitor their blood pressure closely during the Paxlovid treatment course and to discuss any concerns with their healthcare provider. The occurrence of even temporary high blood pressure underscores the importance of considering a patient's overall health status before prescribing Paxlovid.

Recognizing Serious Paxlovid Side Effects

While the common side effects of Paxlovid are generally mild and temporary, it's crucial to be aware of the possibility of more serious adverse reactions, even though they are rare.

Severe Allergic Reactions

Severe allergic reactions to Paxlovid, including anaphylaxis, are possible but occur infrequently. Recognizing the symptoms of a severe allergic reaction is vital, as immediate medical attention is necessary. These symptoms can include hives, skin rash, blisters, or peeling skin. Other signs may involve painful sores or ulcers in the mouth, nose, throat, or genital area, as well as swelling of the mouth, lips, tongue, or face. Difficulty swallowing or breathing, throat tightness, and hoarseness of voice are also indicators of a severe allergic reaction. If any of these symptoms develop, it is imperative to stop taking Paxlovid immediately and seek emergency medical help by calling 911 or going to the nearest emergency room. The rapid onset and potential severity of these reactions underscore the need for prompt recognition and action.

Liver Damage

Liver problems, also referred to as hepatotoxicity, represent another potential serious side effect of Paxlovid, although it is not commonly reported. It's important to be aware of the signs and symptoms that could indicate liver damage. These may include loss of appetite, yellowing of the skin and the whites of the eyes (jaundice), dark-colored urine, pale-colored stools, itchy skin, and pain in the stomach area (abdomen). If any of these symptoms appear, individuals should contact their healthcare provider immediately. It's also worth noting that Paxlovid is generally not recommended for patients with severe liver disease. Therefore, it is crucial for individuals with any pre-existing liver conditions to inform their healthcare provider before starting Paxlovid treatment.

Severe Skin Reactions: Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)

In rare cases, Paxlovid has been associated with severe skin reactions known as Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN). These are extremely serious conditions that can be life-threatening if not treated promptly. Symptoms of SJS and TEN can include painful red or purple skin that appears burned and may peel off. A flat red rash or blisters may also develop on the skin, as well as on the mucous membranes of the mouth, nose, and genitals. Additionally, individuals might experience red, painful, and watery eyes. If a rash develops while taking Paxlovid, especially if accompanied by these severe symptoms, the medication should be stopped immediately, and emergency medical attention should be sought. A history of clinically significant hypersensitivity reactions, including TEN or SJS, is a contraindication for using Paxlovid. These conditions are typically triggered by medications and can sometimes start with flu-like symptoms before the severe skin manifestations appear.

The Phenomenon of Paxlovid Rebound

Another aspect of Paxlovid treatment that has garnered attention is the phenomenon known as "Paxlovid rebound" or "COVID-19 rebound".

What is Paxlovid Rebound?

COVID-19 rebound is characterized by a recurrence of COVID-19 symptoms or a new positive test result occurring anywhere from 2 to 8 days after an individual initially recovers from the illness or tests negative for the virus. It's important to understand that this rebound can happen regardless of whether someone has taken Paxlovid or not. This suggests that the return of symptoms might be part of the natural course of the SARS-CoV-2 infection in some individuals.

How Often Does Rebound Occur?

The reported rates of COVID-19 rebound have varied across different studies. Initial data from Pfizer, the manufacturer of Paxlovid, suggested an occurrence rate of 1 to 2%. However, more recent data has indicated higher rates, ranging from 10 to 16% in some analyses. A study conducted by researchers at Mass General Brigham found that approximately 20% of individuals who took Paxlovid experienced a rebound, compared to only about 2% of those who did not take the medication. In contrast, another study reported rebound rates of 3.53% at 7 days and 5.40% at 30 days after Paxlovid treatment. Experts at Johns Hopkins University have also cited a figure of around 1 in 5 people experiencing rebound with Paxlovid. It's worth noting that some instances of rebound might be asymptomatic, meaning individuals may test positive again without experiencing a return of symptoms, which could lead to an underestimation of the actual occurrence rate. The variability in these figures highlights the ongoing research and the complexity of understanding this phenomenon. The observation in the Mass General Brigham study of a potentially higher rebound rate in Paxlovid users compared to non-users is a notable finding, though the researchers acknowledge that their study was observational and not a randomized controlled trial.

Managing Paxlovid Rebound

For individuals who experience a COVID-19 rebound after taking Paxlovid, the Centers for Disease Control and Prevention (CDC) provides specific guidance. It is recommended to follow isolation protocols again, which typically involve re-isolating for at least 5 full days until fever has resolved for 24 hours without the use of fever-reducing medication and symptoms are improving. Additionally, the CDC advises wearing a mask for a total of 10 days after the rebound symptoms first appeared. Currently, there is no evidence to suggest that additional treatment with Paxlovid or other COVID-19 therapies is needed for rebound cases. However, if symptoms persist or worsen during the rebound, it is advisable to contact a healthcare provider for further evaluation.

Paxlovid Rebound vs. Initial COVID-19 Symptoms

Generally, the symptoms experienced during a COVID-19 rebound are mild and tend to resolve within a few days. These symptoms are often similar to those experienced during the initial COVID-19 infection, but they are frequently reported as being less severe. Common rebound symptoms can include cough, fatigue, headache, sore throat, runny nose, muscle aches, and fever. Importantly, studies have not shown an increased risk of hospitalization or death in individuals who experience COVID-19 rebound after taking Paxlovid. This information can be reassuring for those who might be concerned about a return of symptoms.

Conclusion

Paxlovid remains a highly effective medication for reducing the risk of severe outcomes from COVID-19, particularly for individuals who are at high risk. While it offers significant protection against hospitalization and death, it is associated with potential side effects, ranging from common and manageable issues like altered taste and diarrhea to rare but serious reactions such as severe allergic reactions, liver damage, and severe skin conditions. The phenomenon of COVID-19 rebound is also a possibility, but it is typically mild and resolves without the need for additional treatment.

The decision to take Paxlovid should always be made in consultation with a healthcare provider. They can assess an individual's risk factors, medical history, and current medications to determine if Paxlovid is the right treatment option. It is especially crucial to inform your doctor about all other medications you are taking, including over-the-counter drugs and supplements, as Paxlovid, particularly the ritonavir component, can interact with many common medications, potentially leading to serious adverse events. This is because ritonavir is a strong inhibitor of an enzyme called CYP3A, which is involved in the metabolism of many drugs. A thorough review of potential drug interactions by a healthcare professional is therefore paramount for ensuring patient safety. Ultimately, by understanding both the benefits and the potential side effects of Paxlovid, and by working closely with their healthcare team, individuals can make well-informed decisions about their treatment and recovery from COVID-19.

Works cited

1. How Does Paxlovid Work - Consensus Academic Search Engine, accessed April 1, 2025, https://consensus.app/questions/how-does-paxlovid-work/
2. Why More People Should be Prescribed Paxlovid for COVID | Johns Hopkins, accessed April 1, 2025, https://publichealth.jhu.edu/2024/why-more-people-should-be-prescribed-paxlovid-for-covid
3. Paxlovid side effects: 8 key things to know - Drugs.com, accessed April 1, 2025, https://www.drugs.com/medical-answers/paxlovid-side-effects-8-key-things-3573430/
4. Effect of nirmatrelvir/ritonavir (Paxlovid) on hospitalization among adults with COVID-19: An electronic health record-based target trial emulation from N3C - PubMed, accessed April 1, 2025, https://pubmed.ncbi.nlm.nih.gov/39823513/
5. 13 Things To Know About Paxlovid, the Latest COVID-19 Pill > News > Yale Medicine, accessed April 1, 2025, https://www.yalemedicine.org/news/13-things-to-know-paxlovid-covid-19
6. About | PAXLOVID™ (nirmatrelvir tablets; ritonavir tablets), accessed April 1, 2025, https://www.paxlovidhcp.com/about
7. Understanding the science behind PAXLOVID | NextGen Global Brand site, accessed April 1, 2025, https://www.paxlovid.my/mechanism-of-action
8. Paxlovid: Mechanism of Action, Synthesis, and In Silico Study - PMC, accessed April 1, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC9283023/
9. Mechanism Of Action|PAXLOVID™ nirmatrelvir tablets; ritonavir tablets, accessed April 1, 2025, https://paxlovid.pfizerpro.com/about-paxlovid/mechanism-of-action
10. Paxlovid: Impact on death, hospitalization rates in older vaccinated adults weaker than thought - UCLA Newsroom, accessed April 1, 2025, https://newsroom.ucla.edu/stories/paxlovids-impact-on-hospitalization-and-death-in-covid-vaccinated-older-adults-far-weaker-than-previously-thought
11. Paxlovid's impact on hospitalization and death in COVID-vaccinated older adults far weaker than previously thought - Internal Medicine | UCLA Health, accessed April 1, 2025, https://www.uclahealth.org/news/release/paxlovids-impact-hospitalization-and-death-covid-vaccinated
12. Insights from Investigator Evaluating Paxlovid's Effectiveness in Vaccinated Older Adults, accessed April 1, 2025, https://www.contagionlive.com/view/insights-from-investigator-evaluating-paxlovid-s-effectiveness-in-vaccinated-older-adults
13. Paxlovid for COVID-19: Uses, Side Effects, Interactions Dose - Drugs.com, accessed April 1, 2025, https://www.drugs.com/paxlovid.html
14. www.fda.gov, accessed April 1, 2025, https://www.fda.gov/media/155051/download#:~:text=The%20most%20common%20side%20effects,sense%20of%20taste%20and%20diarrhea.&text=These%20are%20not%20all%20of,your%20healthcare%20provider%20or%20pharmacist.
15. Safety & Side Effects|PAXLOVID™ (nirmatrelvir tablets, accessed April 1, 2025, https://www.paxlovid.com/side-effects
16. Paxlovid (nirmatrelvir and ritonavir): Uses, Side Effects, Interactions, Pictures, Warnings & Dosing - WebMD, accessed April 1, 2025, https://www.webmd.com/drugs/2/drug-183241/paxlovid-oral/details
17. 5 Paxlovid Side Effects You Should Know About - GoodRx, accessed April 1, 2025, https://www.goodrx.com/paxlovid/known-side-effects
18. What are the possible side effects of PAXLOVID? - Pfizer, accessed April 1, 2025, https://labeling.pfizer.com/ShowLabeling.aspx?id=19599&Section=PPI
19. Safety | PAXLOVID™ (nirmatrelvir tablets; ritonavir tablets), accessed April 1, 2025, https://www.paxlovidhcp.com/safety
20. Safety | PAXLOVID™ (nirmatrelvir tablets; ritonavir tablets), accessed April 1, 2025, https://paxlovid.pfizerpro.com/safety
21. Understanding PAXLOVID: An oral treatment authorized for COVID-19, accessed April 1, 2025, https://na.eventscloud.com/ereg/newreg.php?eventid=673371&language=eng
22. Side effects of Paxlovid - NHS, accessed April 1, 2025, https://www.nhs.uk/medicines/paxlovid/side-effects-of-paxlovid/
23. Safety & Side Effects|PAXLOVID™ (nirmatrelvir tablets, accessed April 1, 2025, https://www.paxlovidinformation.com/side-effects
24. FAQs | PAXLOVID™ (nirmatrelvir tablets; ritonavir tablets) For Patients, accessed April 1, 2025, https://www.paxlovid.com/faq
25. paxlovid.pfizerpro.com, accessed April 1, 2025, https://paxlovid.pfizerpro.com/safety#:~:text=Contraindications,other%20components%20of%20the%20product.
26. Stevens Johnson Syndrome / Toxic Epidermal Necrolysis. SJS/TEN - DermNet, accessed April 1, 2025, https://dermnetnz.org/topics/stevens-johnson-syndrome-toxic-epidermal-necrolysis
27. Stevens-Johnson syndrome - NHS, accessed April 1, 2025, https://www.nhs.uk/conditions/stevens-johnson-syndrome/
28. Efficacy and safety of Paxlovid for COVID-19:a meta-analysis - PMC - PubMed Central, accessed April 1, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC9523907/
29. Types of COVID-19 Treatment - CDC, accessed April 1, 2025, https://www.cdc.gov/covid/treatment/index.html
30. Is Paxlovid Rebound Real? What to Do If COVID-19 Symptoms Return After Taking Medication - GoodRx, accessed April 1, 2025, https://www.goodrx.com/conditions/covid-19/paxlovid-rebound
31. What to Know About COVID Rebound | Johns Hopkins | Bloomberg School of Public Health, accessed April 1, 2025, https://publichealth.jhu.edu/2024/what-to-know-about-covid-rebound
32. COVID-19 rebound after Paxlovid treatment - CDC stacks, accessed April 1, 2025, https://stacks.cdc.gov/view/cdc/117609
33. Can you take Paxlovid twice if COVID rebounds? - Drugs.com, accessed April 1, 2025, https://www.drugs.com/medical-answers/you-paxlovid-covid-rebounds-3569972/
34. COVID-19 Rebound After Paxlovid Treatment | Medication Safety Resources, accessed April 1, 2025, https://www.ihs.gov/nptc/pharmacovigilance/medication-safety-resources/covid-19-rebound-after-paxlovid-treatment/
35. COVID-19 Response and Recovery Unit Therapeutics - Oregon.gov, accessed April 1, 2025, https://www.oregon.gov/oha/covid19/Documents/Paxlovid-Rebound.pdf
36. New Report from the CDC Addresses COVID-19 Rebound - AHCA/NCAL, accessed April 1, 2025, https://www.ahcancal.org/News-and-Communications/Blog/Pages/New-Report-from-the-CDC-Addresses-COVID-19-Rebound.aspx
37. One in Five Patients Experience Rebound COVID After Taking Paxlovid, New Study Finds, accessed April 1, 2025, https://www.massgeneralbrigham.org/en/about/newsroom/press-releases/study-finds-1-in-5-patients-experience-rebound-covid-after-taking-paxlovid
38. One in Five Experience Rebound COVID After Antiviral Drug, New Study Shows, accessed April 1, 2025, https://hms.harvard.edu/news/one-five-experience-rebound-covid-after-antiviral-drug-new-study-shows
39. COVID-19 rebound after Paxlovid and Molnupiravir during January-June 2022 - PMC, accessed April 1, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC9258292/
40. COVID-19 Rebound: Understanding the Symptoms - Ada Health, accessed April 1, 2025, https://ada.com/covid/covid-19-rebound-symptoms/
41. What Is Paxlovid Rebound? 9 Things to Know > News > Yale Medicine, accessed April 1, 2025, https://www.yalemedicine.org/news/what-is-paxlovid-rebound-covid-rebound
42. Understanding COVID-19 Rebound After Paxlovid - Santos Research Center Corp., accessed April 1, 2025, https://www.santosresearch.com/covid-19-rebound-after-paxlovid/
43. How To Take PAXLOVID™ (nirmatrelvir tablets, accessed April 1, 2025, https://www.paxlovid.com/how-to-take
44. warning: significant drug interactions with paxlovid - Pfizer, accessed April 1, 2025, https://labeling.pfizer.com/ShowLabeling.aspx?id=19599