The facts about ibuprofen and COVID-19

What you should know about ibuprofen and COVID-19. Get the facts (picture of Advil tabs and GSK logo on orange background)

To Our Medical Professional Community,

At GSK Consumer Healthcare, we understand your need to have the correct information to feel confident in your treatment decisions, and to address your patients’ questions and concerns. That’s why we are sharing these updates regarding ibuprofen and COVID-19.

Ibuprofen and COVID-19

The scientific consensus is clear. OTC ibuprofen/Advil remains safe to use as directed. The current scientific literature does not show that OTC ibuprofen/Advil makes COVID-19 health outcomes worse, and the world’s leading health authorities have confirmed there is no evidence to recommend that COVID-19 patients avoid antipyretics/analgesics, like Advil (ibuprofen).

We have been constantly monitoring and evaluating research papers published in a broad range of scientific or academic journals around the world.

Recent Research Publications (March–May 2021):

  • Lancet Rheumatololgy, May 2021 – NSAID use is not associated with higher in-hospital mortality or increased severity of COVID-19. This prospective, multi-centre cohort study at 255 UK healthcare facilities included the largest number of patients admitted to hospital with COVID-19 to date (78,674) and found that those taking NSAIDs before admission had the same outcomes as those who did not. The researchers did not find any differences in mortality or disease severity, or in secondary outcomes including admission to critical care, use of ventilation, use of oxygen, or presence of acute kidney injury.8
  • Arthritis Rheumatology, May 2021 – A propensity score-matched cohort study found that “no increase in the risk of suspected or confirmed COVID-19 or mortality was observed among patients with OA in a primary care setting who were prescribed NSAIDs as compared to those who received comparator drugs”. The cohort consisted of adult patients age ≥18 years with osteoarthritis (OA), where a total of 13,202 patients were prescribed NSAIDs and compared to 12,457 patients who were prescribed the comparator drugs (paracetamol and codeine or paracetamol and dihydrocodeine). The study concluded “these results are reassuring and suggest that in the absence of acute illness, NSAIDs can be safely prescribed during the ongoing pandemic.”9
  • Annals of the Rheumatic Diseases, January 2021 – No overall increased risk of COVID-19 related death associated with current prescribed NSAID use. In two similarly designed studies, researchers studied prescribed NSAID users and non-users and “...found no evidence of a harmful effect of routinely prescribed NSAIDs on COVID-19 related death.” They separately evaluated a general population (Study 1) and population with rheumatoid arthritis or osteoarthritis (Study 2); NSAID users and non-users did not have a difference in risk for COVID-19 related deaths when adjusted for differences between them in the two study populations. The researchers concluded that “…people currently prescribed NSAIDs for their long-term conditions should continue their treatment as part of their routine care.”10
  • PLOS Medicine, September 2020 — A Danish study concluded that there was no association between NSAID use up to 30 days before testing for COVID-19 and mortality within 30 days or adverse outcomes within 14 days, including hospitalization, ICU admission and ventilation, for COVID-19 patients, and that NSAIDs do not lead to more severe coronavirus disease11.
  • American Journal of Therapeutics, July/August 2020–Researchers found no supporting evidence to discourage the use of ibuprofen although authors raised a concern regarding the safety of ibuprofen use because of its potential role in increasing ACE-2 receptor levels within the Renin–Angiotensin–Aldosterone system. However, available data from limited studies show administration of recombinant ACE2 improves lung damage caused by respiratory viruses, suggesting ibuprofen use may be beneficial in COVID-19 disease.12
  • London School of Hygiene and Tropical Medicine, August 2020 — Authors found no evidence of a harmful effect of NSAIDs on COVID-19 related deaths. Risks from COVID-19 do not need to influence decisions about therapeutic use of NSAIDs13.
  • Headache, July 2020–A study concluded that there is no specific evidence at this time against the use of NSAIDs in patients with or without COVID‐19. Authors recommend a patient should be assessed for any other chronic diseases, underlying or pre-existing illnesses or conditions (i.e., co-morbid medical conditions) that may limit the use of NSAIDs and recommend a discussion of risks and benefits with all patients prior to prescribing NSAIDs.14
  • British Pharmacological Society, July 2020 — The authors noted that epidemiological studies have suggested potential benefits for NSAID use on reducing the risk of development of severe disease in COVID-19 patients while also raising warning for ibuprofen use in COVID-19 patients15.
  • JAMA Network Open, July 2020 — Researchers found that the currently available data, including the primary endpoints in their study, do not seem to support strong recommendations against using NSAIDs in patients with viral pneumonia16.
  • Clinical Infectious Disease, July 2020 — Authors of an observational study from South Korea, suggested that the harms associated with NSAID use may outweigh their benefits for patients with COVID-19 and therefore should be used with caution. Researchers looked only at patients hospitalized with COVID-19 who were prescribed prescription-strength, not OTC NSAIDs in the 7 days before and including their inpatient hospitalization, and it is unclear if the prescribed NSAIDs were part of their COVID-19 treatment courses or for one or more underlying serious health conditions17.
  • Clinical Microbiology and Infection, June 2020 — A peer reviewed, retrospective cohort study of 403 patients with COVID-19 from Shamir Medical Centre, Israel concluded that in the studied cohort of COVID-19 patients, “ibuprofen use was not associated with worse clinical outcomes, compared with paracetamol (acetaminophen) or no antipyretic. In patients with fever, there was no difference in clinical outcomes between ibuprofen and paracetamol (acetaminophen) users”18.

When used as directed, ibuprofen can be used safely and effectively to relieve pain and reduce fever associated with COVID-19 based on general medical consensus.

For more information refer to the websites for these public health authorities. These organizations are not officially affiliated with Advil and use of their logos does not imply endorsement.

Health Canada

There is no scientific evidence that establishes a link between ibuprofen, or other non-steroidal anti-inflammatory drugs (NSAIDs), and the worsening of COVID-19 symptoms.” The Government of Canada is monitoring the situation closely, including reviewing new information and reports as they become available, and will take the appropriate action to help protect the health and safety of Canadians.19 When choosing a fever or pain relief medication for COVID-19, patients and healthcare professionals should consider all available treatment options, including acetaminophen and NSAIDs.19,20

World Health Organization (WHO)

"Based on currently available information,WHO does not recommend against the use of ibuprofen. We are also consulting with physicians treating COVID-19 patients and are not aware of reports of any negative effects of ibuprofen, beyond the usual known side effects that limit its use in certain populations. WHO is not aware of published clinical or population-based data on this topic" 21

National Institute of Allergy and Infectious Diseases (NIH)

The NIH COVID-19 Treatment Guidelines recommend the following for the use of NSAIDs in patients with COVID-1922:

  • Persons with COVID-19 who are taking NSAIDs for a co-morbid condition should continue therapy as previously directed by their physician (AIII).
  • The Panel recommends that there be no difference in the use of antipyretic strategies (e.g. with acetaminophen or NSAIDS) between patients with or without COVID-19 (AIII).
Canadian Pharmacists Association

“There is insufficient evidence that NSAIDs negatively impact morbidity or mortality of COVID-19. Health Canada continues to recommend both ibuprofen and acetaminophen for treatment of fever due to COVID-19.”23

Canadian Paediatric Society

Guidance for COVID-19 in Children published on Mar 25, 2020 recommends that current data and best practice both support the use of either acetaminophen or ibuprofen for COVID-19 symptoms relief.24

The acute management of COVID-19 in paediatrics (spring 2021 update) outlines that “fever can be managed by administering either acetaminophen or ibuprofen. Early concerns about ibuprofen use increasing risk for COVID-19 morbidity and mortality are not supported by evidence.”25

A legacy of evidence-based safety26

Ibuprofen is a well-established medicine that when used as labeled is considered safe for fever reduction and providing pain relief.

  • It has been used by millions of consumers across 40 countries for more than 3 decades
  • It has been extensively studied and is strictly regulated to ensure its use complies with local healthcare authority requirements
  • It has been used extensively to relieve some of the symptoms of influenza (pain and fever)

Moving forward in these times

Consistent with the current recommendations of the major public health organizations, GSK Healthcare recommends that you speak directly with your patients regarding their individual treatment needs.

In addition, based on the general medical consensus from health agencies and global public health authorities, we hope that you continue to feel confident about using antipyretics/analgesics, like Advil (ibuprofen) appropriately to reduce pain and fever to provide comfort and care for your patients with COVID-19.

We will continue to monitor the published data and provide you with updates as they are made available. As always, we remain committed to providing balanced information about our medicines, maintaining transparency about our work, operating with integrity, and always putting the interests of patients first.

Thank you and stay safe.

Please consult the Product Monograph available upon request (1-888-275-9938) or on the Health Canada website for information to assist in benefit-risk assessment. Always direct the patient to read the label. Terms of Market Authorization is also available upon request through (1-888-275-9938).

FAQs about managing the side effects of the COVID-19 vaccine

  • Are antipyretics/analgesics, like Advil, recommended to help treat symptoms (eg, aches and pain or fever) post COVID-19 vaccination?

    Yes, antipyretics/analgesics, like Advil, are indicated to treat symptoms of pain and fever as they occur.27 This is consistent with the clinical study approach used by Pfizer-BioNTech and Moderna for treating symptoms as they occur with their approved vaccines.3,4

    The appropriate use of ibuprofen is recommended by public health authorities, such as the CDC and NHS, to help relieve mild pain and fever symptoms that may be experienced following vaccination.1,2 These same health authorities, and societies, along with NACI (National Advisory Committee on Immunization)7 do not recommend the prophylactic use of antipyretics/analgesics right before or at the time of COVID-19 vaccination, but their use is not a contraindication to vaccination.

    Patients should carefully read and follow the post-vaccination information or instructions provided to them at the time of vaccination, including any recommendations about the use of ibuprofen to relieve pain and fever symptoms that some people might experience following a COVID-19 vaccine. If there are any questions, a doctor or pharmacist should be consulted for further advice.

  • Can antipyretics/analgesics, like ibuprofen, suppress the immune response to the COVID-19 vaccine?

    Published clinical studies assessing vaccine immunogenicity and the impact of antipyretic/analgesic use are limited and vary depending on the vaccines evaluated and the study population (ie., adult or paediatric). Although some studies have observed no significant difference and other studies have shown a diminished immune response to vaccines in the setting of NSAID or acetaminophen use, the data are inconsistent and vary among different vaccines, serotypes, antipyretic agent, and timing of administration (prophylactically or for treating symptoms).

    The appropriate use of antipyretics/analgesics, like ibuprofen, is recommended by public health authorities to help relieve symptoms that may be experienced following vaccination.1,2 This is consistent with the fact that in the late-stage COVID-19 vaccine studies, participants were allowed to use antipyretics/analgesics to treat symptoms.3-6

    Patients should carefully read and follow the post-vaccination information or instructions provided to them at the time of vaccination, including any recommendations about the use of ibuprofen to relieve pain and fever symptoms that some people might experience following a COVID-19 vaccine. If there are any questions, a doctor or pharmacist should be consulted for further advice.

  • Can ibuprofen be taken prophylactically against potential side effects of the COVID-19 vaccine?

    Advil is indicated to relieve symptoms of pain and fever as they occur.27 It is not indicated for prophylactic use to prevent symptoms.

    Patients already taking ibuprofen to manage pain or fever symptoms should consult their healthcare professional ahead of any planned vaccination. At this time, there is no clinical evidence with the COVID-19 vaccines that suggests against using ibuprofen right before or after a COVID-19 vaccination. Ibuprofen is a well-established treatment recommended by healthcare organizations globally, like the CDC and NHS, for fever reduction and to relieve possible pain or discomfort from a COVID-19 vaccination.1,2

  • Does ibuprofen affect COVID-19 vaccine immunogenicity?

    In general, published clinical studies assessing vaccine immunogenicity and the impact of antipyretic/analgesic use are limited and vary with regard to the vaccines evaluated and the study population (ie., adult or paediatric). Although some studies have observed no significant difference and other studies have shown a diminished immune response to vaccines in the setting of NSAID or acetaminophen use, the data are inconsistent and vary among different vaccines, serotypes, antipyretic agent, and timing of administration (prophylactically or for treating symptoms). 

    The impact of an antipyretic/analgesic, such as Advil, on COVID-19 vaccine immunogenicity is not expected to differ from the impact that an antipyretic/analgesic has on the immunogenicity of non–COVID-19 vaccines. The use of antipyretics and pain medications, like ibuprofen, to treat symptoms associated with vaccine administration or ongoing medical conditions was permitted in the Pfizer-BioNTech and Moderna COVID-19 vaccine protocols (as well as the AstraZeneca and Janssen COVID-19 vaccine protocols).3-6

    In these studies, some participants experienced local pain, fever, and other systemic adverse events and used such medications to treat these post-vaccination symptoms. Both Pfizer-BioNTech and Moderna vaccine studies showed remarkably high efficacy (around 95%) and immunogenicity similar to, if not better than, the immunogenicity experienced by patients who had a natural COVID-19 infection, thus implying that the use of antipyretics/analgesics likely did not blunt the immune response.28,29 However, specific immunogenicity data on the cohort of subjects who took an antipyretic/analgesic are not available.

  • What do the Centers for Disease Control and Prevention (CDC) and the National Health Service (NHS) say about using ibuprofen to help treat pain or fever as a result of the COVID-19 vaccine?

    The CDC and NHS recommend appropriate use of antipyretics/analgesics to help relieve pain and fever symptoms that may be experienced following COVID-19 vaccination.1,2 They do not recommend the prophylactic use of oral analgesics or antipyretics (eg, ibuprofen or acetaminophen) right before or at the time of COVID-19 vaccination, but their use is not a contraindication to vaccination.

    CDC: “If you have pain or discomfort, talk to your doctor about taking over-the-counter medicine, such as ibuprofen, aspirin, antihistamines, or acetaminophen, for any pain and discomfort you may experience after getting vaccinated. You can take these medications to relieve post-vaccination side effects if you have no other medical reasons that prevent you from taking these medications normally.”1

    NHS: “You can take painkillers, such as paracetamol [acetaminophen], if you need to.”2

    Patients should carefully read and follow the post-vaccination information or instructions provided to them at the time of vaccination, including any recommendations about the use of ibuprofen to relieve pain and fever symptoms that some people might experience following a COVID-19 vaccine. If there are any questions, a doctor or pharmacist should be consulted for further advice.

FAQs about managing symptoms of COVID-19

  • Has GSK’s statement regarding the use of ibuprofen/Advil in patients with suspected COVID-19 changed?

    No, ibuprofen/Advil is considered safe and can effectively relieve pain and reduce fever in COVID-19 patients when used as directed based on general medical consensus from health agencies and global public health authorities19-25.

    • It has been used by millions of consumers across 40 countries for more than 3 decades26
    • It has been extensively studied and is strictly regulated to ensure its use complies with local healthcare authority requirements26
    • It has been extensively used to relieve some of the symptoms of influenza (pain and fever)26
  • Where did the concern about ibuprofen use in patients with COVID-19 originate from?

    Controversy has arisen regarding use of ibuprofen and other non-steroidal anti-inflammatory drugs (NSAIDs) in treating symptoms of COVID-19 infections following the publication of a commentary article (Fang et al 2020) in The Lancet Respiratory Medicine30. This controversy further amplified after a subsequent tweet from France’s Health Minister suggested that anti-inflammatory drugs like ibuprofen or cortisone may be a factor in worsening COVID-19 infections.

    The commentary from Fang et al discussed the data from three retrospective medical records reviews from China, covering almost 1,300 patients gravely ill with Covid-19. The authors observed that significant numbers of those patients had high blood pressure and diabetes, from 12 percent to 30 percent depending on the study. Although data on concomitant treatments were not available, they hypothesized that higher rates of expression of ACE2 receptors might be raising the risk of coronavirus infection. The ACE2 receptors are expressed on alveolar cells (among other tissues) and act as the main entry point/portal for the SARS-CoV-2 virus (COVID-19), as well as for the whole family of severe acute respiratory syndrome (SARS) viruses31. COVID-19 seems to have a particular affinity for ACE2 receptor expressed by humans31. Therefore, Fang et al speculate that use of ACE2 blockers and similar drugs may exacerbate the degree of COVID-19 infections and increase the risk of mortality. In addition, Fang et al have placed ibuprofen in the same category of drugs, however without any clinical or preclinical supporting evidence provided.

    This speculation regarding the use of nonsteroidal anti-inflammatory drugs (NSAIDs)—specifically ibuprofen—worsening COVID-19 symptoms, is without conclusive clinical evidence, and has caused considerable confusion and controversy within the medical community.

  • What hypotheses were suggested by the authors of the commentary article in The Lancet Respiratory Medicine?

    The commentary article by Fang et al published in The Lancet Respiratory Medicine on March 11, 2020 hypothesized that patients with cardiac diseases, hypertension, or diabetes, who are treated with drugs that increase ACE 2 expression, are at higher risk for severe COVID-19 infection and should be monitored for these types of ACE2-increasing medications, such as ACE inhibitors or Angiotensin Receptor Blockers (ARBs) 30.
     
    In addition, the article suggests that an aspect that should be investigated is the genetic predisposition for an increased risk of SARS-CoV-2 infection, which may be due to ACE2 receptor polymorphisms that have been linked to diabetes mellitus, stroke, and hypertension, as well as in specific ethnic populations. The authors emphasize that the sensitivity of an individual might result from a combination of both therapy and ACE2 receptor polymorphisms.
     
    In this commentary, the authors state that ACE2 can also be increased by thiazolidinediones (glitazones) and ibuprofen, however, they have not provided any clinical or preclinical supporting evidence. Contrary to several media discussions, the authors have not hypothesized a link between the use of ibuprofen and worsening COVID-19 infection in the article.
     
    It is important to note that commentary articles, unlike scientific publications, are not peer-reviewed and are opinion pieces. They serve the purpose of hypothesis generation rather than validation.
  • What is Health Canada’s position on the use of ibuprofen in patients with COVID-19?

    There is no scientific evidence that establishes a link between ibuprofen, or other non-steroidal anti-inflammatory drugs (NSAIDs), and the worsening of COVID-19 symptoms." The Government of Canada is monitoring the situation closely, including reviewing new information and reports as they become available, and will take the appropriate action to help protect the health and safety of Canadians.19 When choosing a fever or pain relief medication for COVID-19, patients and healthcare professionals should consider all available treatment options, including acetaminophen and NSAIDs.19,20

  • What is the World Health Organization’s (WHO) position on the use of ibuprofen in patients with COVID-19?

    “Based on currently available information, WHO does not recommend against the use of ibuprofen. We are also consulting with physicians treating COVID-19 patients and are not aware of reports of any negative effects of ibuprofen, beyond the usual known side effects that limit its use in certain populations. WHO is not aware of published clinical or population-based data on this topic.”21

  • What is the National Institutes of Health’s (NIH) position on the use of ibuprofen in patients with COVID-19?

    The NIH COVID-19 Treatment Guidelines recommend the following for the use of NSAIDs in patients with COVID-1922:

    • Persons with COVID-19 who are taking NSAIDs for a co-morbid condition should continue therapy as previously directed by their physician (AIII).
    • The Panel recommends that there be no difference in the use of antipyretic strategies (e.g. with acetaminophen or NSAIDS) between patients with or without COVID-19 (AIII).
  • What is the position of specific Canadian Health Professional Societies on the use of ibuprofen in patients with COVID-19?

    Canadian Pharmacists Association: “There is insufficient evidence that NSAIDs negatively impact morbidity or mortality of COVID-19.  Health Canada continues to recommend both ibuprofen and acetaminophen for treatment of fever due to COVID-19.”23

    Canadian Paediatric Society: Guidance for COVID-19 in Children published on Mar 25, 2020 recommends that current data and best practice both support the use of either acetaminophen or ibuprofen for COVID-19 symptoms relief.24

    The acute management of COVID-19 in paediatrics (spring 2021 update) outlines that “fever can be managed by administering either acetaminophen or ibuprofen. Early concerns about ibuprofen use increasing risk for COVID-19 morbidity and mortality are not supported by evidence.”25

  • What is GSK doing to ensure that the latest information about Advil’s safety is being provided?

    As we continue to closely monitor COVID-19 and ibuprofen use (the active ingredient in Advil), we will remain transparent in our communications, and committed to the health and safety of our customers.

    Consistent with the current recommendations of the major public health organizations, GSK Healthcare recommends that you speak directly with your patients regarding their individual treatment needs.

    With the growing consensus within public health authorities, we hope that you continue to feel confident about using Advil (ibuprofen) appropriately as a fever and pain reducer to provide comfort and care for your patients with COVID-19.

  • Where can I find more information about the safety of ibuprofen?

    Please call 1-888-275-9938 for more information about Advil and its established safety profile.

  • What resources are available for me to provide to my patients who want more information about ibuprofen use in COVID-19?

    You and your patients can visit https://www.advil.ca/coronavirus/faqs for important resources about COVID-19 and ibuprofen use. Please also continue to visit GSK Health Partner for future updates.