What you should know 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. As your trusted partner in the healthcare and well-being of your patients, we are committed to supporting you.

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 OTC ibuprofen.

Health Canada1, Canadian Paediatric Society2, Canadian Pharmacists Association3, NIH4 and The National Institute for Health and Care Excellence (NICE) in the UK5, continue to acknowledge the lack of scientific evidence connecting NSAIDs, including ibuprofen, with worsening COVID-19.

On May 27, 2020, the World Health Organization listed ibuprofen as an essential medicine in their guidelines for treating pain and fever associated with COVID-19.6

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–September 2020):

  • 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 disease7.
  • 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 NSAIDs8.
  • 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 patients9.
  • 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 pneumonia10.
  • 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 conditions11.
  • 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”12.

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.1 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.1,13

World Health Organization (WHO)

The WHO guidance on Clinical management of COVID-19 published on 27 May 2020 recommends antipyretics (including NSAIDs) for the symptomatic relief of fever and pain in patients with mild COVID-19. Furthermore, ibuprofen is listed as an essential medicine for the prevention and relief of pain related to COVID-19.6

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-194:

  • 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.”3

Canadian Paediatric Society

“While there may be reasons to be cautious with NSAID therapy in older adults, there is no evidence that parents and clinicians caring for children over 6 months of age with suspected COVID-19 should avoid the use of ibuprofen for fever control.”2

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.14

A legacy of evidence-based safety15

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 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 (1-855-367-7349) 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 (1-855-367-7349).

Frequently Asked Questions

  • 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 authorities1-6.

    • It has been used by millions of consumers across 40 countries for more than 3 decades15
    • It has been extensively studied and is strictly regulated to ensure its use complies with local healthcare authority requirements15
    • It has been extensively used to relieve some of the symptoms of influenza (pain and fever)15
  • 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 Medicine16. 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) viruses17. COVID-19 seems to have a particular affinity for ACE2 receptor expressed by humans17. 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) 16.
     
    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.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.1,13

  • 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.”18

    A rapid systematic review was carried out by the WHO on 20 March 2020 with the aim to assess the effects of prior and current use of NSAIDs in patients with acute viral respiratory infections on acute severe adverse events, acute health care utilization, as well as on quality of life and long-term survival. The review included studies conducted in humans of any age with viral respiratory infections exposed to systemic NSAIDs of any kind. All studies on COVID-19, the Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS) were included irrespective of their sample size. The review concluded that at present there is no evidence of severe adverse events, acute health care utilization, long-term survival, or quality of life in patients with COVID-19, as result of the use of NSAIDs. A Scientific Brief was published on 19 April 2020 detailing the Methods, Results, and Limitations of the systematic review.19

    The WHO guidance on Clinical management of COVID-19 published on 27 May 2020 recommends antipyretics (including NSAIDs) for the symptomatic relief of fever and pain in patients with mild COVID-19. Furthermore, ibuprofen is listed as an essential medicine for the prevention and relief of pain related to COVID-19.6

  • 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-194:

    • 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.”3

    Canadian Paediatric Society: “While there may be reasons to be cautious with NSAID therapy in older adults, there is no evidence that parents and clinicians caring for children over 6 months of age with suspected COVID-19 should avoid the use of ibuprofen for fever control.”2

    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.14

  • 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 1-855-367-7349 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.