In July 2019, drug and French vaccine manufacturer Sanofi signed a deal with Roche Pharmaceuticals to obtain exclusive over-the-counter (OTC) rights for Tamiflu (oseltamivir), an antiviral drug licensed for the treatment of influenza infections. Genentech, a member of the Roche Group, currently sells Tamiflu in the United States only for prescription use.1
Tamiflu is a neuraminidase inhibitor given orally and the drug is rapidly absorbed by the gastrointestinal tract and processed by the liver. In 1999, the U.S. Food and Drug Administration (FDA) gave Roche licensing approval to market Tamiflu as a treatment for type A and B influenza in adults.2 In 2000, the FDA approved use of oseltamivir for children one year and older, and Japan licensed it for adolescents and adults. In 2002, the European Medicines Agency (EMA) approved it for patients over age one. By 2012, the FDA had licensed Tamiflu’s use in infants as young as two weeks old.
Tamiflu Effectiveness Questioned
Roche sponsored 40 clinical trials on oseltamivir during the 1990s and also funded post-marketing trials. However, questions have been raised about whether the pre-licensure and post-marketing clinical trials evaluating oseltamivir were methodologically sound and of high enough quality to adequately determine effectiveness.3 4
In a 2014 report published in the British Medical Journal, researchers analyzed evidence for osteltamivir’s effectiveness and stated, “In the treatment of adults, oseltamivir reduced the time to first alleviation of symptoms by 16.7 hours.”5 They also found that use of osteltamivir in children had “no significant effect on admissions to hospital, ” adding that the drug ”does not affect asymptomatic influenza and there is no evidence that it interferes with person to person spread.“ The researchers concluded:
Given that oseltamivir is now recommended as an essential medicine for the treatment of seriously ill patients or those in higher risk groups with pandemic influenza, the issues of mode of action, lack of sizeable benefits, and toxicity are of concern. This is made worse by the record and stated intentions of governments to distribute oseltamivir to healthy people to prevent complications and interrupt transmission on the basis of a published evidence base that has been affected by reporting bias, ghost authorship, and poor methods. We believe these findings provide reason to question the stockpiling of oseltamivir, its inclusion on the WHO list of essential drugs, and its use in clinical practice as an anti-influenza drug.
Tamiflu Safety a Big Issue Too
Since 2005, there have been reports in Japan, U.K. and the U.S. that Tamiflu is associated with serious side effects, including neurological dysfunction, psychiatric symptoms and death.6 A 2015 report in Clinical Psychopharmacology and Neuroscience observed that:7
Between 1999 and 2007, a total of 480 million patients worldwide were administered oseltamivir, and psychiatric side effect surveys were conducted in Japan (n=2,772), the United States (n=190), and other countries (n=89). Psychiatric side effects were more common in infants and children aged 16 years or younger than in adults (2,218 children vs. 833 adults), and generally occurred within 48 hours of receiving oseltamivir. According to the International Classification of Diseases 10th revision (ICD-10), the major symptoms include abnormal behavior (1,160 events, 38%), delusions/perceptual disturbances (661 events, 21.7%), and delirium or delirium-like events. These side effects may lead to accidents, injuries, or suicides.
The Tamiflu package insert label lists serious skin/hypersensitivity reactions and neuropsychiatric events in the warning and precaution section and advises patients to monitor for abnormal behavior and allergic-like reactions.8 The drug’s package inserts states:
People with the flu, particularly children and adolescents, may be at an increased risk of seizures, confusion, or abnormal behavior early during their illness. These events may occur shortly after beginning TAMIFLU or may occur when flu is not treated.
U.S. Market Largest OTC Market in the World
Sanofi has not announced an exact date of availability of OTC Tamiflu. Under the agreement, Sanofi will head the clinical program and fund all studies needed to support the U.S. licensing switch of Tamiflu from prescription only to an OTC drug.1 According to Sanofi, “The U.S. market is the largest OTC market in the world, and a successful switch of Tamiflu to OTC would support our global cough and cold strategy by expanding into flu with a sustainable point of difference in the market.”1
The global over the counter drug market was valued at U.S. $300B in 2018 and is estimated to grow to $491B by 2024. A recent market forecast report by Morder Intelligence stated:9
North America currently dominates the market for over the counter drugs and is expected to continue its stronghold for a few more years. This region is expected to increase its market share in the future, owing to the leading trend among pharmaceutical companies to switch from Rx to OTC drugs. Report of the National Institute of Health has stated that 93% of adults in the United States prefer to treat their minor ailments with OTC medicines before seeking professional care, and 85% of parents in the United States prefer to treat their children’s minor ailments with an OTC medicine before seeking professional care. This is resulting in the formation of the bigger market.
The U.S Centers for Disease Control and Prevention (CDC) has conducted qualitative research into clinician knowledge, attitudes, and practices related to prescribing antiviral medications.1 The findings suggest there are many possible factors involved in clinician hesitancy to prescribe antivirals like Tamiflu, including different perceptions about how well the drugs work and lack of awareness of the CDC’s antiviral use recommendations.1
Sanofi’s executive vice president of consumer healthcare Alan Main expressed confidence in the popularity of Tamiflu after it becomes an OTC drug, He said, “Tamiflu will offer a significant public health benefit once switched by providing increased access to a safe and efficacious treatment for the prevention and treatment of flu.”10 Main added, “People would be able to either reduce their chances of getting the flu or, at the first signals, appropriately treat as early as possible during the crucial first 48 hours without having to wait for a doctor’s appointment.”3
1 Terrie Y. Tamiflu Set to Switch to OTC Status. Pharmacy Times Dec. 12, 2019.
2 Gupta YK, Meena M, Mohan P. The Tamiflu fiasco and lessons learnt. Pharmacology 2015; 47(1): 11-16.
3 Doshi P, Jefferson T, DelMar C. The Imperative to Share Clinical Study Reports: Recommendations from the Tamiflu Experience. PLoS Med Apr. 10, 2012.
4 Hsu J, Satesso N et al. Antivirals for Treatment of Influenza: A Systematic Review and Meta-analysis of Observational Studies. Ann Intern Med 2012; 156(7): 512-524.
5 Jefferson T, Jones M et al. Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. BMJ 2013; 348.
6 La Vigne. Tamiflu Again Linked to Extreme Adverse Reactions. The Vaccine Reaction Feb. 27, 2018.
7 Won Jeon S and Han C. Psychiatric Symptoms in a Patient with Influenza A (H1N1) Treated with Oseltamivir (Tamiflu): A Case Report. Clinical Psychopharmacology and Neuroscience 2015; 13: 209-11.
8 U.S. Food and Drug Administration. Tamiflu Label. Jan. 4, 2020.
9 Morder Intelligence. Over the Counter Drugs Market – Growth, Trends and Forecast (2020-2024).
10 Michael E. Sanofi signs deal for exclusive over-the-counter rights to Tamiflu. Healio July 23, 2019.