When influenza strikes, when should we use oseltamivir?

For the public who plan to choose oseltamivir to fight influenza, it is necessary to understand three pieces of information: oseltamivir is only an auxiliary medication; only a part of patients are suitable for using this antiviral drug; its effect is not as magical as everyone initially knew, and it also has side effects.

Written by | Wang Chenguang

Based on previous experience in Europe and the United States, the first flu season after the COVID-19 lockdown is lifted will see an outbreak of respiratory infectious diseases. This has been verified in various parts of China, with flu-related visits and hospitalizations already higher than normal, and this winter is likely to be one of the worst flu seasons in the past decade. The reason is obvious, and that is the cancellation of the strict social isolation policy during the COVID-19 pandemic (see "Why are respiratory diseases so rampant this year?" for details).

At this time, Oseltamivir, which is regarded by many as a "magic drug" against influenza, has once again come into the spotlight. Contrary to what many people think, Oseltamivir is not recommended for everyone who has influenza.

Oseltamivir, also known as Tamiflu, is an antiviral drug that can be used to treat or prevent influenza. It has long been approved for use in adults, pregnant women, and children over two weeks old. But six years ago, in June 2017, the World Health Organization (WHO) downgraded the status of oseltamivir from a core drug for influenza treatment to an auxiliary drug. What happened?

Oseltamivir was approved by the U.S. Food and Drug Administration (FDA) in 1999. In 2002, based on two randomized clinical trials, the European Medicines Agency (EMA) used it to treat uncomplicated influenza patients within 48 hours of symptom onset. The China Food and Drug Administration also approved oseltamivir to enter the Chinese market in 2006. In 2010, oseltamivir was added to the WHO Essential Medicines List.

The 2009-2010 flu season became the season of oseltamivir's success. Based on the prediction that avian influenza and H1N1 influenza might break out in 2009, governments around the world stockpiled large quantities of oseltamivir. As of 2010, oseltamivir's global sales had exceeded $18 billion, half of which came from government stockpiles.

However, more and more evidence does not support that oseltamivir can reduce influenza complications, hospitalization rates or mortality. Based on the consideration of the evidence, in June 2017, WHO downgraded oseltamivir and removed it from the list of core drugs to an auxiliary drug.

In fact, the doubts about oseltamivir have never stopped. As early as 2014, a commentary article in the British Medical Journal pointed out the "multi-system failure" of oseltamivir in treating influenza, pointing directly to the European Medicines Agency, the US Centers for Disease Control and Prevention, and the World Health Organization's decision to recommend the use of oseltamivir based on flawed evidence, including selective publication of evidence and ignoring the limitations of observational data.

An analysis of the unpublished trial data, obtained at the request of the British Medical Journal, found that oseltamivir relieved symptoms for less than 20 hours on average and showed no evidence that it reduced the incidence of pneumonia complications, hospitalizations or complications requiring antibiotic intervention.

A subsequent study led by Professor Jefferson of the Oxford University Center for Evidence-Based Medicine analyzed more unpublished research data and confirmed the above findings, and found further evidence that the drug harms health. Like any drug, oseltamivir has potential side effects, the most common of which are nausea, vomiting and headache, which may aggravate existing conditions or worsen dehydration. Other side effects, such as severe allergic reactions, confusion, abnormal behavior, seizures and life-threatening rashes may also occur, but are rare.

In the face of scientific evidence, WHO's decision to downgrade the drug's status was a responsible move towards the public, even though a lot of unnecessary losses had already been caused.

Who should use oseltamivir? The CDC and the Infectious Diseases Society of America recommend that patients who are at higher risk for complications of influenza (such as pneumonia) use oseltamivir. These high-risk patients include: patients who have been hospitalized after infection (due to more severe symptoms); pregnant women; obese patients; children under five years old; people over 65 years old; patients with chronic heart, neurological or respiratory diseases (such as asthma or stroke); patients with immunosuppressive diseases such as HIV; organ transplant recipients; and people with diabetes and/or sickle cell disease.

If you belong to any of the above categories and test positive for influenza virus, taking oseltamivir early may be beneficial; if you have close contact with influenza patients, you can also consider taking this drug to prevent influenza infection. The vast majority of ordinary patients do not need antiviral drug treatment, and the abuse of "magic drugs" reflects people's excessive panic about influenza.

So, apart from the high-risk groups mentioned above, what should ordinary people do after being infected with the influenza virus?

Influenza is a self-limiting disease, and most people recover from it on their own. The immune system of healthy people will respond and eventually eliminate the flu virus, so most people recover from it on their own. People with mild symptoms are advised to take the following measures: stay home to avoid infecting others, get plenty of rest, drink plenty of water and electrolyte drinks (especially if you have a fever), and take antipyretics if you have a high fever.

The best response to flu season is to prevent infection, and vaccination is the best way to prevent the flu. Flu vaccines have been used for more than 60 years and have been proven to be safe and effective. Vaccination does not ensure that everyone will not be infected, but even if infected, the vaccine can reduce symptoms and severe disease. The effect of vaccination will weaken over time, so it is recommended to get vaccinated every year to prevent the flu.

References and links

[1] Jefferson T, Jones M, Doshi P, Spencer EA, Onakpoya I, Heneghan CJ. Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. BMJ. 2014 Apr 9;348:g2545.

[2] Hanula R, Bortolussi-Courval É, Mendel A, Ward BJ, Lee TC, McDonald EG. Evaluation of Oseltamivir Used to Prevent Hospitalization in Outpatients With Influenza: A Systematic Review and Meta-analysis. JAMA Intern Med. 2023 Jun 12:e230699.

[3] https://cdn.who.int/media/docs/default-source/essential-medicines/2021-eml-expert-committee/applications-for-deletion-of-medicines-formulations/

The author of this article is a PhD in biology. He has served as a researcher at the Sidney Kimmel Cancer Center of Thomas Jefferson University, an associate professor in the Department of Cancer Biology, a researcher at the Institute of Radiation Medicine, Chinese Academy of Medical Sciences/director of the Radiation Damage Protection and Drug Research Laboratory, and a professor/doctoral supervisor at Peking Union Medical College. He is currently engaged in the research and development of anti-tumor drugs.

This article is supported by the Science Popularization China Starry Sky Project

Produced by: China Association for Science and Technology Department of Science Popularization

Producer: China Science and Technology Press Co., Ltd., Beijing Zhongke Xinghe Culture Media Co., Ltd.

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