Fourth in a series
on Bactrim - Septra -Septrin side-effects
ONE WOMAN'S
FIGHT
By
Brian Deer
The
Sunday Times Magazine (London) July 9 1995
Near
the start of last year, The Sunday Times ran some
news and feature stories about the risks of a popular
drug. To tell you the truth, they were unfashionable
interventions in the chatter of modernity - stressing
the product's controversial origins and associated
injuries and deaths. And although they filled a good
bit of space, like many inquiries into
pharmaceuticals (going right back to the infamous
morning sickness treatment Thalidomide) they were
initially ignored by the rest of the press, and there
seemed nothing more to be said.
The
drug in question is an antibiotic (or, more
correctly, an "antibacterial") known most
commonly in Britain as Septrin (in the US as Bactrim,
or Septra). It is a classic, world-wide blockbuster
of a medicine, taken by one in three of the United
Kingdom's population, prescribed more than 85 million
times in England and Wales, and for the last quarter
century scribbled on pads by general practitioners
virtually as an all-purpose pill.
But
within hours of the stories hitting the streets, a
stream of calls began to pour down my phone - and has
yet to come to an end. People call me at 8.30 in the
morning to talk about Septrin. They call on Saturday
nights. Some call asking how to spell
"sulphonamide" while I drip after stepping
from the bath. Others just feel the need to call
someone - now and again to break down and cry. In
fact, since the initial publication on the subject, I
have talked to more people (including doctors,
lawyers and politicians) about Septrin, than about
the rest of my journalism combined.
The
typical caller will be a woman saying that she had
taken the pills (either for something important, like
a urinary tract infection, or something trivial and
often inappropriate, like a sore throat) and that it
had pretty much destroyed her life. She will talk
about such things as collapsing, comas, blowing up
with football-size blisters, scarring to her eyes,
multiple operations, organ failures, fatigue,
depression, suicide attempts, inexplicable allergies,
blood pressure fluctuations, pains travelling up her
spine and "exploding" in her brain, immune
malfunctions - and more.
"I've
been in bed with this since 1976," is the kind
of thing I've heard more than once.
In
the first weeks, the callers were so like each other
that it was hard to spot the joins. The phone would
ring and somebody would recount their tale, and then,
say, 40 minutes later it would ring and someone else
would say the same. It felt like being trapped on a
Mobius strip - that half-twisted, glued paper loop
you did in maths, with only one edge and just one
side. After writing about Septrin, my life became
like your finger: going round and round and round.
From
time to time, I hear other tales, most memorably
about young children. There's a four-year-old South
London boy, for instance, who was born with brain
damage and no ears after his mother was prescribed
the drug while pregnant. There is another boy in
Cardiff, who, after taking the medicine at age 18
months, is now permanently intubated and according to
his mother stops breathing several times a day.
There
are more whose parents are sick with worry about
their child's state of health or mind. There are
families where three generations used the product and
all say they suffered adverse effects.
Then
there are accounts of horrific deaths that people
phone to talk me through. An old woman in the North
of England passed away in conditions of such medical
negligence that her husband spoke of killing the
doctor. A previously fit 31-year-old rugby player in
Australia who took Bactrim (a different brand of the
same drug) dropped more or less cold in the street.
And a Sussex girl, aged 18, got her A' level results
in the hospital where a few days later she died.
"The noise the machine made became like a
continuous note," her mother recalled, when I
went to see her. "And then I knew she was
gone."
I put
many of the callers in touch with each other and as a
result of their efforts (mostly those of a group
formed in Buckinghamshire) more than 1,000 people
have since come forward with stories like those I've
heard. Probably for reasons of competitive disdain,
newspapers never much bothered to pick up my
interest, but ITV's News at Ten and BBC2's Newsnight
eventually gave the story a spin. And each time the
word "Septrin" has been raised in the
media, my phone starts jangling again.
"I
was told that I was one in a million," has been
the strongest common thread. "I thought there
was only me, until now."
If
you like bleeding heart journalism, there is grief
enough here to fill a book. But as the months have
passed a whole has emerged that is greater
than the sum of the anecdotes. Go through official
product information for almost any prescription
medicine and you will see much the same kind of
references to potential risks of adverse effects.
What then becomes clear from these calls about
Septrin is that behind all the wonder-drug hype
journalists produce, there may also be something like
a hidden epidemic of pharmaceutical casualties.
*****
Of
all those who called me, one of the people who sticks
in my mind is a lady from East London called Kate
Reid. She phoned shortly after my first piece
appeared - and straight away won my heart. "You
know what I did," she chuckled, in an accent I
later discovered was polished in a Stepney children's
home. "I rang round all the papers, and I asked
for the medicine correspondent, and told them they
were bastards."
She
hated journalists, particularly those she had been
writing to since 1987. Her own experience with
Septrin was by no means the worst, but the problems
she complained of after taking it aroused little more
than PR sympathy. The now-axed comedy-and-caring
programme, That's Life, for instance, wrote to her
that the medical problems from which she suffered
were "self-limiting" and "not
life-threatening". The Sun's agony aunt
suggested she see a counsellor to "release the
anger", adding: "I am enclosing my own
leaflet on nervous stress."
But
Kate's anger was what grabbed me, even though she
wasn't suffering nearly as badly as some. After
taking Septrin for two days in August 1986, she spent
six weeks in intensive care, needed two operations
and four skin grafts, and now suffers from permanent
fatigue, scarred eyes and bouts of depression.
But
though others have fared worse (and, to be balanced,
many much better) her response to misfortune has been
so tenacious that she is top of an alternative
league. More than anybody, she has shouted down every
avenue and alley for a remedy or route to redress.
More than anybody, her experience since being injured
exposes how the epidemics remain concealed.
At
the time she took the drug, she had just moved into a
flat above a butcher's shop in Barking, Essex. She
remembers acquiring the knack of sleeping through the
sound of meat-chopping at dawn. She was then 30,
divorced six years, and with a small mortgage that
made the flat the first place she felt was truly her
home. "It was somewhere I could start again, you
know?" she told me one afternoon, while we sat
on the floor and rooted through her case papers.
"It was like the first time I was in
control."
Things
were also looking up on the relationship front. Since
her marriage ended, she had worked as a telex
operator for a Japanese bank and lived for nothing
more keenly than package holidays at Mediterranean
resorts. With a gang of girlfriends, she had visited
Lloret de Mar eight times and Corfu once; drinking
and dancing at all-night clubs and slapping down
randy boys.
The
August she took Septrin, she was leaving for the
Greek island of Spetsai on her first holiday with a
man. He was a broad-shouldered Underground guard
called Kelvin, who she met while buying a kebab. On
the Saturday morning before they were to due to go,
she visited her local surgery complaining of thrush
in her mouth (probably linked to an eating disorder).
She was seen by a locum, who prescribed Septrin
(known generically as co-trimoxazole). It was an
eccentric decision, since thrush is a fungus, which
is not treated by antibacterials. But Kate took the
medicine and within hours of the first tablet began
to get seriously ill.
At
first, she lost energy, collapsing into lethargy, and
by next morning her eyes were stinging. These proved
to be early signs of a blistering and sometimes fatal
allergic reaction called Stevens-Johnson Syndrome. In
the last year of phone calls, I've heard of this a
lot. It's association with Septrin is not disputed. A
doctor was summoned to visit Kate at home, but once
again, the treatment was wrong. Instead of spotting
that she was suffering a reaction (and was at risk of
coma), he prescribed an optical ointment, chatted her
up, she says, and then continued on his weekend
round.
"I
was really lucky after that, though," she told
me of how she came to be hospitalised next day.
"Kelvin woke up about five o'clock on the Monday
morning and he found I wasn't in bed. I'd gone into
the bathroom, and I'd laid down on the floor. I felt
like I was burning up and it was cool on the floor.
And he came in and found me there. Saved my life, he
did."
She
was well cared-for during her weeks in hospital, but
when she was sufficiently well to go home she found
herself clobbered again. Inquiries revealed that her
GP records for the incident were virtually
non-existent (If I had a fiver for every person who
has told me about their incomplete medical
records...) obscuring the use of an antibacterial in
an attempt to treat oral thrush. And, though she was
quite sick, when she complained to the local doctors
committee, the response was like the bite of a
cornered ferret: she was struck off her doctor's
list.
"It
may help you to understand the position," the
committee secretary wrote, "if I explain that,
just as you have the right to change your doctor
without having to give any reason, so a doctor has a
similar right to have a patient removed from his
list." Don't blink too hard, or assume it's
unusual. During the last year, tales from the surgery
have got so bizarre they are usually best
passed-over. Victims have variously said that their
GPs insisted that Septrin had no side-effects.
They have told me that they were prescribed the drug
even after reacting badly to it in the past. And most
commonly they say that their suspicions about the
drug were brushed aside in "I'm the doctor"
style. Nobody has said they thought their mishap was
notified to the government's watchdog: the Committee
on the Safety of Medicines (which maintains its own
list of 137 deaths and 6,000 notified injuries that
may be linked to Septrin).
*****
Kate's
next move was to try to turn up the heat. She put her
case in the hands of solicitors.
"Com-pen-sation", of course, is the
universal war cry of the aggrieved these days, from
police officers who have witnessed calamities, to
people who are wrongly nicked. So she thought that
she had better get screaming too - less for personal
gain than to warn others. With newspapers endlessly
running DRUG VICTIMS TO SUE-type headlines, she
assumed this was a way of alerting the public, and
supposed others had got somewhere this way.
But
she was quickly to discover that the legal process
offered little to achieve her goals. Although product
documents contain more than 100 lines of warnings
about the potential risks of Septrin, when it comes
to any one particular injured person, medicines and
their prescribers are always reckoned blameless
unless cause and effect can be proved. No
number of similar complaints, like those of the
thousand who have come forward after my stories, can
be accumulated to make the case.
For
Kate to succeed in suing the doctors, she would have
to prove that they had acted unreasonably -
a hopeless task without detailed notes. If she
targeted the drug's manufacturer, she would not only
have to prove that its product caused
the injury (and wasn't just co-incidental to it), but
also that the firm was reckless or negligent
in bringing the stuff to market. And apart from a few
media-driven "admit nothing" settlements,
like the deal to resolve the Thalidomide catastrophe,
this cause and effect plus culpability hurdle has
never been cleared in Britain.
Kate,
nevertheless, trudged down both paths, determined to
make what progress she could. First a firm of lawyers
ordered medical reports for an action against the
doctors, who shouldn't have prescribed the drug for
thrush, and should have recognised the adverse
effects. But legal aid was withdrawn because she
couldn't stand it up. She couldn't prove the
doctors were at fault. Then, last year, another
solicitor got her hopes up with a plan to go after
the manufacturer. "I'll try anything," Kate
told me. "I've just got to keep trying."
Solicitors
just keep trying as well: it is essential for the
system to work. In the last big side-effects case
(over tranquillisers), lawyers and their medical
experts grossed an astonishing £30m from the legal
aid fund in an action that was abandoned as hopeless.
Thousands of alleged victims, meanwhile, got zilch
(less years of wasted effort and stress). Over
Septrin, some solicitors are placing advertisements
for customers in local newspapers, while others have
instigated what they call an "action group"
in a bid to channels clients to themselves.
These
firms argue that the drug was poorly tested. But
while probing this claim would be lucrative for
lawyers, it's a blind alley for plaintiffs like Kate.
If anything, when Septrin was launched (in 1969), its
ingredients had been rather over-researched, compared
with some medicines - and the side-effects were
forecast from the start. Its formulation was
considered so uncontroversial that the inventor,
George Hitchings (who won a Nobel Prize), told me
that he had finalised the product's specific
formulation during a train ride from Zurich to Basle.
His
confidence sprang from the fact that Septrin is not
just an antibacterial, but rather two
mixed together. And the one which probably has the
worst side-effects profile - a compound called
sulphamethoxazole (in the US: sulfamethoxazole) - had
not only been around for donkey's years, but was
among the massively prescribed sulphonamide class of
bug-busters that dated back to the 1930s. They were
actually an offshoot of chemical colorants whose
therapeutic properties were accidentally discovered
from their effect on dye-workers' skin complaints.
The
other component - called trimethoprim - is safer than
its partner, according to published research,
although its pedigree goes back to mustard gas. It
kills bacteria at least 10,000 times more effectively
than it does human cells, so, the theory has it that
if you don't use too much of it you shouldn't suffer
any adverse effects.
Both
compounds operate by blocking the sythesis of folic
acid, at different stages, and it was assumed by the
developers that combining them together would yield
some synergistic benefit. But in almost every
situation in which Septrin is used (mostly urinary
tract infections, bronchitis and other common
complaints) little-publicised research shows that
this is not the case: trimethoprim alone would do the
job. Using both together to zap a bug is like
stabbing a person with a knife who somebody has
already shot to death.
But
some firms make knives and others make guns - and
pharmaceuticals is an industry (mostly a branch of
fine petrochemicals) with products it needs to sell.
The two components belonged to different companies:
one of which was a giant, Hoffman-La Roche, with vast
production and marketing set-ups, while the other,
the smaller Wellcome organisation, which had the
patent on the new and better drug. So they pooled
their strengths in Septrin (Bactrim, Septra,
co-trimoxazole) and ran a massive campaign to
persuade doctors to prescribe it. The ageing
sulphonamides got a fresh lease of life. The new drug
saw the light of day. Both firms made a lot of money:
more than $5bn in world-wide sales.
But
there was one important snag: the side effects of the
combined product were bound to be more severe than
one or the other alone. A circular issued by the
Committee on the Safety of Medicines in the year
before Kate was injured showed that the number of
deaths (at least those they knew of) associated with
the combined tablet was nearly eight times greater
per million prescriptions than those linked to the
antibiotic, ampicillin.
Kate
was outraged when she learnt all this. And also, at
times, depressed. Back in 1986 she, like others who
told me their stories, thought that she was merely
one in a million. Emotionally it felt like being
injured in a car accident: just one of those unlucky
things. But now she wondered if the driver was sober,
and if the car was fitted with brakes. If anything,
learning the facts made her feel worse than before.
"How is it they can do this?" she asks me
today. "Why? It doesn't make sense."
In
her anger for answers, she opened another front:
putting her questions in the hands of politicians.
Over the past year, scores of Septrin casualties have
contacted members of parliament - a few of which have
written to ministers or expressed their personal
concern. But most have been satisfied get local
newspaper publicity of the "MP DEMANDS
INQUIRY" sort. Kate, however, was determined to
create hell and nagged her constituency's Labour
incumbent, Margaret Hodge, into calling a brief
parliamentary debate.
On
March 22, a dozen Septrin casualties trooped with her
to the Commons, chattering excitedly about the
progress they felt that the political process might
make. "I thought that now we were going to get
some answers," she says. "I mean, this is
where the government and everybody is, and I thought:
'If they can't explain it, then who could?"'
Only six MPs came for the brief discussion in the
chamber, but Kate and her supporters clapped wildly
in the gallery when her representative got up to
speak.
But
then politics failed her just as comprehensively as
she had been failed by medicine and the law. Her MP
could not really be said to be on top of the issue,
and on the government benches, drowning in a sea of
empty green leather, a junior health minister, Tom
Sackville, promptly announced that officials had
denied any knowledge of a problem. The "pattern
of adverse reactions" was the same with all
antibiotics, he read out. A one-ingredient tablet
would need "much larger doses".
Trimethoprim alone "leads to greater
resistance" among bacteria. "What we have
to be clear about," he said, "is whether
co-trimoxazole has a higher level of risk than
antibiotics generally. The evidence that has been
given to me is that this is not the case."
*****
Looking
back at those words, printed in the parliamentary
minutes, Hansard, I feel like James Stewart up the
bell tower in Vertigo.What Sackville had parroted to
MPs was not only contradicted his own department's
statistics, but by basic reference books on the
shelves of every doctor, decades of published
research and product documents published by drug
companies where every comma is scrupulously checked.
That the two drugs together were more dangerous than
only one of Septrin's ingredients was a simple,
unarguable, fact.
While
the minister dissembled in the Commons, moreover,
doctors had abandoned the cause. The former chairman
of the Committee on the Safety of Medicines, Sir
William Asscher, told Newsnight that the drug's use
should be sharply curtailed. Dr John Griffin, a
former health department official and the past head
of the Association of the British Pharmaceutical
Industry, declared that it probably wouldn't get a
license today. And although at its peak in the 1980s
Septrin had been prescribed an average of four times
a day by every general practitioner in Britain,
Central Television was forced to cancel a studio
debate because none would come on camera to say why.
But
it's not that the minister was talking garbage that
caused my sense of unease. (As it happens, other
Septrin victims had already been dismissed by the
health secretary, Virginia Bottomley, who wrote to
another backbencher last October that "direct
comparisons between these medicines cannot be
made.") What was so weird about the Commons
event was that it proved that the system was not
capable of coherence in the face of Kate's one-woman
campaign. It was like an error message appearing on a
computer screen, revealing some malfunction within.
To
me, that's what this story is all about: a warning of
things unseen. Lurking behind the minister's
statements is a system which has kept side-effects
off the public agenda, but allows hidden suffering to
continue. And while doctors, lawyers, politicians,
and even journalists, dip into such matters from time
to time - giving the reassuring impression that
remedies are at hand - they often become invaluable
players in obscuring how things have gone wrong.
To
understand what has happened, you could return to the
1960s and the uproar caused by Thalidomide. In those
days, the pharmaceutical industry was wholly
unregulated, with no medicine licensing, or
standard-setting: a complete commercial free-for-all.
But the political heat from hundreds of babies being
born with terrible handicaps after their mothers took
the product, led to the first-ever controls. In 1971,
these came into effect in a Medicines Act, which
sought to guard against the most spectacular
calamities, but in effect did a trade-off on the
rest.
Firms
had to show that their medicines had some benefit and
did not carry intolerable risks. A scheme was
launched to allow GPs to report side-effects to a
central register. And a review was begun through
which nearly forty thousand marketed medicines were
whittled down to 5,300. But these arrangements were
to be controlled by the industry itself, and although
watchdogs were set up - including the Committee on
the Safety of Medicines - their memberships were
packed with drug firm executives, contract
researchers, and shareholders. Typically, at a
meeting with 20 people present, only three or four
are not payrolled in some way.
There's
no better proof than the calls I get on Septrin that
this arrangement has a life of its own. Experts
(often the government's own) have shown that
medicines can easily be compared with others for
their usefulness and withdrawn if they fail.
Monitoring would cost a few hundred thousand pounds a
year to watch over product safety. Compensation
schemes could provide financial help for those who
are casualties of adverse events. But these would all
tease out the true risks. And the system, it seems,
can't handle that.
*****
Whether
the post-Thalidomide accommodation is as resilient as
it appears, however, is a question that Kate is still
testing. She says she is far from finished with her
battle, and each defeat makes her more furious.
"The thing is there's lots of people coming
forward and they have all been told that they are one
in a million, and that isolates them," she says.
"Do you think I'm going to stop? No.
Because somebody has got to be made accountable for
what's happened - to my life and to other people's
lives."
She
doesn't talk a lot about her own situation - partly I
think, because she finds it hard to discuss with a
man some aspects of her problems. She sometimes
mentions a desire to adopt children - revealing, in
passing, that her internal injuries have left her
unable to give birth. She did once tell me about
Kelvin walking out, yelling at her in a rage,
"You can't do anything for me any more".
But then she changed the subject to her crusade.
Her
next plan is to get victims to band together for a
campaign of direct action. After being let down by
doctors, lawyers and politicians, she reckons that
the only course left for her is to bring the Septrin
battle "to the streets". During the House
of Commons debate, she and some of the others who
turned up to listen vowed to target those who ought
to help but don't. Top of their list is the London
headquarters of the British Medical Association,
where they have plans to trespass until a doctor is
produced to explain how they can improve their
health.
"I
mean there are so many answers that people want that
nobody will give them," she says. "Suppose
we go down the BMA and say we ain't leaving till we
see a doctor? What are they going to do? They've got
to listen."
In
the year that I have listened, the casualties of
Septrin have more and more talked in such terms. Kate
has even thought through the consequences of such an
action, when the staff at the citadel of medicine
pick up the phone to call the police to clear them
out. "What are they gonna nick you for?"
she laughs. "The people who are going to nick
you have probably got a wife and children, and he'll
probably go home and tell his wife: 'Don't take
Septrin'."
As
for me, I won't trespass. I'm a watcher, not a doer.
Like doctors, lawyers and politicians, our role is to
do a job, but not get involved. Maybe I will just
hang around here and wait for the phone calls. A
sense of action without taking risks. The calls are
calming down now (with a flurry yesterday when Kate
appeared on Good Morning with Anne and Nick). And to
be honest, I dread the thought that the
call-after-call sessions will soon start up again.
Copyright,
Brian Deer. All rights reserved. No portion of this
article on Septrin, Bactrim, Septra, Sulfatrim,
Cotrim, cotrimoxazole, Septran may be copied,
retransmitted, reposted, duplicated or otherwise used
without the express written approval of the author.
Responses, information and other feedback are
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