Roche, the Swiss pharmaceutical group hit on Wednesday by sharp restrictions imposed by Japanese regulators on the use of its anti-flu medicine Tamiflu, stressed the absence of any proven link between the drug and a small number of reported severe neuro-psychiatric side-effects.
David Reddy, franchise leader at Roche, said that among the 45m people worldwide who have taken Tamiflu since its launch at the start of the decade, 128 deaths from all causes had been reported, including eight associated with neuro-psychiatric behaviour, and none had been shown to be caused by the drug. From a total of 10,000 “adverse events”, 1,200 were classified as neuro-psychiatric.
His comments came after the Japanese health ministry told Chugai, Roche’s local subsidiary, to warn doctors not to prescribe Tamiflu to flu patients aged 10-20 years old, except those at “high risk.” The move followed an official investigation launched last month after two 14-year-olds who had taken the drug fell to their deaths from apartment blocks, in separate incidents.
The fresh restrictions in Japan highlight the broader difficulties in understanding cause and effect in treatment using medicine, and the challenge for regulators in balancing their risks against benefits.
It has extra international resonance because Tamiflu, an antiviral drug that has had limited success as a treatment for seasonal flu, has become a blockbuster for Roche over the past two years as governments worldwide stockpile it for potential treatment and prophylactic use in the event of a flu pandemic.
US, European and Japanese regulators have all stressed that they have identified no causal link between neuro-psychiatric events and Tamiflu. This was reiterated on Wednesday by Roche, helping lift its shares in spite of the potential hit to sales for the drug, which generated SFr2.6bn ($2.1bn) last year.
However, the US Food and Drug Administration last November required a change to the label issued with the medicine, warning that those with flu were at an “increased risk of self-injury . . . and should be closely monitored for signs of unusual behaviour.”
European regulators last month recommended a modification to stress that there had been “reports” of such side-effects. The Japanese continue to emphasise the lack of a causal link, although the country’s doctors and public opinion tend to be less tolerant of side-effects from medicine than their counterparts in the US.
Tatsuo Kurokawa, a counsellor at the Japanese health ministry’s secretariat, said: “While we are not positive about the causal relations between Tamiflu and the falls, we think that a separate measure from a different perspective is necessary.”
Rokuro Hama, chairman of Japan Institute of Pharmacovigilance, a non-profit organisation that has long raised concerns about the drug, welcomed the decision for highlighting problems.
But he described the ministry’s response as “half-baked” in continuing to advocate its use in children younger than 10. “I think it’s completely wrong,” he said, adding that Tamiflu produced “sudden” side-effects in young children.
Eduard Holdener, Roche’s head of global pharmaceutical development, stressed that Japan had a high suicide rate, and that flu itself was often associated with neuro-psychiatric symptoms. He added that Tamiflu had saved many lives,