First in a series on
Bactrim - Septra -Septrin side-effects
TOP-SELLING
DRUG MAY HAVE KILLED
HUNDREDS IN BRITAIN
The
Sunday Times (London) February 27 1994
By
Brian Deer
Scientific evidence which has accumulated over
more than 20 years suggests that hundreds of people
may have died after taking a controversial drug
marketed throughout the world by Britain's Wellcome
Foundation and the Swiss-based pharmaceutical company
Hoffman-La Roche.
The
drug, marketed in Britain under the brand names
Septrin and Bactrim, has been one of the most
commercially successful drugs ever. Since 1969 it has
been prescribed for many complaints, especially
urinary tract infections and bronchitis. Annual
world-wide sales may have reached 100m courses, worth
more than $5 billion.
But
research - largely ignored by the medical profession
- shows that one of the product's ingredients was
unnecessary for it to be effective in most cases. It
is this element which is held responsible for the
most serious side-effects, such as fatal blood
reactions.
Deaths
linked to this ingredient, a sulphur-based compound,
reported to the Committee on the Safety of Medicines
in England, have so far reached 113. But the
committee's research shows this may underestimate the
real number by up to 10 times. With the British
pharmaceutical market less than a tenth of the global
market for the drug, related deaths could have run
into the thousands.
In
the late 1970s nearly 4m courses a year were
prescribed by English family doctors. This has since
halved - but Septrin has retained a strong position
elsewhere. It is now the top-selling drug in India
and sales are rising sharply in Russia.
Though
the drug continues to be widely prescribed,
especially in developing countries, some specialists
are alarmed by the growing evidence of side-effects.
"I think it's one of the biggest scandals of all
time," said Richard Lacey, professor of medical
microbiology at Leeds University. "In all the
hospitals where I've been a consultant, we've banned
it."
The
Sunday Times consulted seven specialists about
Septrin, all professors, who agreed that the drug is
useful for treating less common conditions. But none
recommended it for the main uses for which it has
been promoted.
Problems
have stemmed from the fact that the drug is composed
of two rival antibacterials put together in an
unusual deal in the 1960s between Wellcome and
Hoffman-La Roche. The Wellcome drug, called
trimethoprim, is relatively safe and effective, while
sulphamethoxazole, from Roche, poses significant
risks and is largely redundant.
Sebastian
Amyes, professor of medical microbiology at Edinburgh
University, condemned the general use of Septrin and
Bactrim. "One has to examine the moral argument,
the ethical argument, of administering a drug known
to provoke serious side-effects - some leading to
death - when it doesn't have an active role," he
said.
Roche,
manufacturer of the Bactrim brand, said the product
was continually reviewed by authorities and that the
company had not promoted it for years. "Serious
and occasionally fatal reactions have been associated
with the product," it said, "but these are
rare."
Disclosures
about Septrin come at an awkward time for Wellcome,
which is facing doubts about its Aids drug AZT. The
company was also forced to pay £2.75m last year
after a ruling in the Irish courts that its whooping
cough vaccine caused brain damage. Wellcome said
millions had benefited from Septrin, that it was
better for treating drug-resistant strains of
bacteria, and disputed the claim that associated
deaths were unnecessarily high. Neither Septrin nor
Bactrim has been compulsorily withdrawn from any
market world-wide.
The
drug sprang from the success of a Nobel prize-winning
Wellcome scientist, Dr George Hitchings, who patented
trimethoprim in 1957. From the outset it was clear
that it could be a powerful rival to the traditional
penicillin antibiotics and to older sulphur-based
compounds, or sulphonamides.
Roche
was the biggest sulphonamide manufacturer and saw the
implications of a newer and safer alternative.
Wellcome was still a small pharmaceutical house with
little industrial muscle. Rather than launch
trimethoprim, executives realised that the best way
to proceed was to go into partnership with Roche. So
the two drugs were combined in a large, multipurpose
pill.
Commercially,
the advantages were clear. Together they could
effectively promote to doctors the idea of switching
from penicillins to the new combination product. But
soon after the combined pill was marketed, evidence
began to accumulate that there was rarely any
justification in taking two antibacterials rather
than one.
A
paper in the British Medical Journal in 1972 reported
an identical cure rate with Hitchings's compound as
there was with the combination. Moreover, it noted,
"trimethoprim alone was remarkable in causing
fewer than half the side-effects." Many more
reports followed over the next decade.
But
despite these reports, which were not challenged,
Wellcome, in particular, stepped-up its promotion.
From 1981, for instance, it had a full-colour
advertisement for Septrin in every issue of the
journal World Medicine for a year.
Dr
Joe Collier, editor of the Drug and Therapeutics
Bulletin, believes this heavy promotion explains why
the product is still widely prescribed. "The
drug companies have enormous power to produce their
advertisements, which they can hammer on home, bang,
bang," he said.
Copyright,
Brian Deer. All rights reserved. No portion of this
article on Bactrim, Septrin, Septra, Sulfatrim,
Cotrim, co-trimoxazole, Septran may be copied,
retransmitted, reposted, duplicated or otherwise used
without the express written approval of the author.
Responses, information and other feedback are
appreciated - via Brian Deer's homepage.
