E-DRUG: Halcion (2)
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As I am the person who wrote the assessment report that led to
the withdrawal of Halcion and other triazolam products in Norway,
I would like to make some comments.
Protocol 321 was a clinical trial in prison inmates (this is now,
I believe, considered a non-ethical practice, but this was before
the Helsinki declaration). The doses were way above those
recommended in Norway - and I suppose, elsewhere - at the time of
withdrawal. UK made a suspension from the market (I'm not sure
whether the drug is formally withdrawn in UK or whether the
suspension has been prolonged indefinitely). They CSM based the
suspension on the fact that Upjohn had withheld safety
information so that the approval was based on a fraudulent
scientific basis. Since the documentation was no longer valid,
the approval was suspended.
In Norway, a complete reassessment of the clinical documentation
was done. In several of the files, there was documentation
showing that aggressiveness and anxiety were quite common - up to
15% as far as I can remember - even with doses of 0.25 mg. It is
a very long time since 1.0 milligram was an approved dose.
So, Britain made a legal suspension. Norway made a medical one.
And in Norway the drug was actually withdrawn physically from the
market. Now it is prescribed on individual license in perhaps 0.1
percent of the original sales. At its height, Halcion had a 50
percent share of the entire hypnotic market.
There are some non-clinical studies - quoted in Trends Pharmacol
Sci (Phillis JW, O'Regan MH. Benzodiazepine interaction with
adenosine systems explains some anomalies in GABA hypothesis.
Trends Pharmacol Sci 1988; 9: 153-4)
that show triazolam to be not just another benzodiazepine, but
with additional effects as well. I have never been able to lay
hands on the actual paper.
We have made it very well without triazolam.
Gaut Gadeholt
Norway
Email: gaut@online.no
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