Global Insight Perspective | |
Significance | Following a number of changes to the drug’s labelling in recent months, regulatory authorities worldwide continue to insist that there is no proven link between the use of oseltamivir and suicidal behaviour in children and teenagers. |
Implications | Due to the drug’s high profile as a potential treatment for avian influenza (bird 'flu) and its very widespread use in Japan, the reports have inevitably prompted interventions by regulators and politicians. |
Outlook | There is currently no evidence of a link between oseltamivir and sudden-onset psychiatric conditions, but some medical evidence suggests that extreme cases of influenza may cause this. Without definitive evidence of a causal link between Tamiflu and suicidal behaviour, sales of the product should remain robust. |
Regulators in Asia, the United States and Europe have reiterated their confidence in the safety of the anti-influenza medicine Tamiflu (oseltamivir), but Japan’s Ministry of Health, Labour and Welfare (MHLW) has announced plans to review all cases of ”abnormal behaviour” among older children and teenagers that had been prescribed the drug from 2006 onwards.
The MHLW notes that 22 reports of abnormal behaviour linked to the drug have been received since 2004, of which four related to deaths; as with many other widely prescribed drugs, reports of other adverse reactions—principally minor gastro-intestinal complications—run to many hundreds per year.
The ministry’s intervention was most likely inspired by public concerns, rather than medical evidence. The catalyst appears to have been the non-fatal fall from a building by a 12-year-old patient in the early hours of 20 March—an event that was quickly linked to recent reports of an association between suicidal behaviours and the use of the drug. Doctors were swiftly advised to cease prescribing the drug to teenagers.
Labelling Changes Already in Place
As the reports imply, such claims of a link are not new, and are already reflected in recent changes to labelling for the drug in most major pharmaceutical markets. In November 2006, the U.S. Food and Drug Administration (FDA) ordered labelling to be altered to make mention of reported “delirium” associated with the use of Tamiflu, and in mid-February the European Medicines Agency (EMEA) authorised a similar change to product literature. Late last week, the agency also pledged to monitor the situation, presumably in light of the Japanese health ministry’s actions. Significantly, however, the European Union (EU)’s Committee for Medicinal Products for Human Use (CHMP) remains convinced that the drug’s benefits outweigh any known risks; the United Kingdom’s Medicines and Healthcare Products Regulatory Agency (MHRA) has followed suit.
All eyes, therefore, are on Japan. The country should be a good test-bed for a review, given that it has historically been the largest geographical market for Tamiflu; during the severe 2004/05 flu season in Japan, it is estimated that six million people took the drug. AFX News reports that the country accounts for 60% of the global market for Tamiflu. For its part, Roche stated in a release dated June 2006 that some 42 million people have taken the drug since its commercial launch in the United States in 1999.
Simply put, it would therefore be surprising if a few members of this very large patient population had not engaged in abnormal behaviour during this time. Perhaps more significantly, the U.S. FDA’s guidance suggests that severe forms of influenza—rather than the treatments associated with it—are more likely culprits for the reported psychological disturbances. Although there are known associations between some antiviral drugs and neurological side-effects, no such link has ever been proven with oseltamivir.
Evidence May Not Convince
Yet, at least in Japan, public confidence in another review of the evidence could prove problematic; indeed, reports in the media have been sceptical. There are even claims that the conclusions of a recent large-scale study by Yokohama University, which found no evidence of a link, owed much to the fact that the institution is a beneficiary of donations from Chugai, the Japanese affiliate of Roche. In terms of domestic politics, support from Japan’s beleaguered prime minister, Shinzo Abe, for a thorough review may owe much to a desire to seize the initiative.
Almost needless to say, there are also geopolitical issues at stake. The World Health Organization (WHO) has insisted that there will be no changes to the stockpiling of the drug against a possible pandemic of avian influenza; oseltamivir is widely seen as a potential treatment in the event of mass transmission.
Outlook and Implications
For the time being, a wait-and-see approach makes sense, especially since the public needs to be properly engaged in the monitoring process this time. From a safety point of view, most bases are already covered in terms of consumer information. However, given the scale of the concerns and the stakes involved, Roche’s claim to be “mystified” by reports of a causal link between Tamiflu and abnormal behaviour look a little disingenuous.
That aside, there is currently no reason to take anything less than an upbeat view of the drug’s future prospects. Roche confidently predicts sales of up to 1.2 billion Swiss francs (US$985 million) for the drug this year; given Tamiflu’s status as a household name and its perceived applications in pandemic flu, the product’s onward march seems unlikely to stumble.
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