Å®ÉúСÊÓƵ

One of the world’s largest drug comanies ignored warnings from its British
division and sold a sedative in the US in 1986 that it knew had already
proved fatal, says a consumer watchdog.

The Health Research Group (HRG), based in Washington DC, last week petitioned
the US government to investigate the company, Hoffman-La Roche. The company
denies wrongdoing and accuses the HRG of making statements that are ‘false
and misleading, and medically unjustified’.

In Britain, in January 1983, Roche marketed midazolam, a replacement
for its own drug Valium. Called Hypnovel, it was designed for general anaesthesia
and for inducing ‘twilight sleep’, a wakeful state for procedures such as
oral surgery and endoscopy. Things quickly went wrong, says Sidney Wolfe,
a doctor and director of the HRG.

According to documents, from the drug company and its law firm, acquired
by the HRG, scientists at Roche’s British division soon heard complaints
from doctors. Hypnovel was too concentrated, they said, and was difficult
to ‘titrate’, or properly measure into a syringe. In November 1983, a memo
from Roche’s British marketing department noted cases of ‘excess sedation’.
Another memo from Roche UK to Roche US, dated 17 October 1984, said the
drug had caused ‘oversedation, prolonged apnoea (cessation of breathing)
and death’.

Roche US British division introduced a dilute version in 1985. They
continued to warn their counterparts at Roche US of the drug’s potency and
associated deaths. Roche US was then trying to gain approval from the Food
and Drug Administration for midazolam at the original high concentration,
to be marketed in the US. This time it was called Versed.

According to Roche documents, the parent company in Basel preferred
the higher concentration despite the misgivings of its US arm. This was
partly because ampoules of the drug at that concentration were more like
the injectable Valium that doctors were used to. Valium’s patent was about
to expire and cheaper generic versions would soon flood the market. Roche
wanted doctors to buy Versed instead.

Roche US won approval for the concentrated version of midazolam in December
1985 and put it on the shelves in April 1986. In May, doctors complained
to Roche that the concentration was too strong. But Roche waited seven months
to submit an application to the FDA to market a lower concentration, one-fifth
as strong. It was granted and the lower dosage was on the market by July
1987.

By then, a number of deaths had been reported in the US says Wolfe.

Roche called for an analysis of its own documents on the case. According
to that analysis, carried out by Roche’s lawyers, and obtained by the HRG,
‘one interpretation possible from these documents is that Roche (US) disregarded
its own concerns for safety of the drug in favour of the marketing and political
pressure from Roche Basel’.

Last week, Roche officials said they had notified the FDA of the deaths
but were not required by law to report concerns from Britain about oversedation.
Nancy Mattison, a spokeswoman for the drug company, acknowledged that Roche
US did disagree with Roche’s head office in Basel on the proper concentration.
But supervised trials of concentrated Versed in the US showed no problems.
So the company decided to market the higher concentration even though ‘it
contradicted what the British were seeing in the field’, said Mattison.
She also noted that some of the deaths were from misuse of the drug, including
two cases of suspected suicides by health care workers.