http://www.suntimes.co.za/health/longevity/features/june/medicine.asp
Dangerous medicines
In America, doctors are said to be far more hazardous to health than gun
owners. A recent study shows that most problems arise from the promotion of
new products vital for profit. The risks are not uncovered by short-term
trials, and can take years - and many deaths worldwide - to manifest.
By Hilary Bassett
Gail Jennings, 36, sat bolt upright in the middle of the night, heart
racing. She felt acutely anxious and quite desperate, though no sound had
awakened her. "I thought I was having a heart attack", she says.
Before going to sleep, she had taken a new drug, Aminophylline, prescribed
by her doctor for the persistent bronchial cough she'd been struggling with
for three months. Luckily Gail realised it might be to blame, and her
husband made some sandwiches to dilute the drug's effect.
"I have a history of hyperthyroidism. That means I have a fast heart beat
and high metabolism three cups of coffee and I'm spinning. Next day I
asked the pharmacist, 'whatever's in this drug'? He said it was the last
thing that should have been prescribed for someone with a metabolic
disorder."
As Jennings discovered, medication can endanger your health, as you will
know if you've ever studied the leaflet that's supposed to accompany every
drug. Whether the medicine will make you worse instead of better is often
unclear, even to doctors.
It might cause serious side-effects, or interact dangerously with other
drugs or herbal treatments; it will certainly leave a chemical residue in
your body; and there may be countless variations that distinguish you from
the norm of clinical trialists which exclude the very young, the elderly
and women of child-bearing age.
Neither doctors nor pharmacists talk you through the long list of
contra-indications, though theoretically you make an informed choice about
taking it based on their advice.
New products are only thoroughly tested when they're launched;
pre-registration trials are too limited to be conclusive. Yet adverse drug
reactions (ADRs) are rarely reported by doctors, who are notoriously
reluctant to take them seriously.
According to one study, only 13 percent of GPs in the Western Cape reported
an ADR in one year, and not one medical specialist did. They may reduce the
dosage; they may inform the medical rep. But unless the reaction is unusual
and interesting, they dont report it to the monitoring body. As a result,
the dangers of new drugs remain hidden for years.
This was made clear by a study at Harvard Medical School, published in the
Journal of the American Medical Association last year. The investigators
posited that cut-throat competition among pharmaceutical companies was
causing both innovative therapies and copy-cat drugs to be rushed onto the
market prematurely.
Since 75 percent of South Africa's pharmaceutical industry is owned by
multinational corporations, eight of them American, we can be sure this
happens here too. They checked over 25 years to see how often, and how soon,
unrecognised drug reactions had been discovered after all the expensive
licensing procedures and trials had been completed.
Discovered, because there is good evidence that manufacturers were often
aware of the danger, but ignored it. "If one laboratory comes up with data
the drug company doesn't like, they continue trials elsewhere until they get
the answers they want", Dr Judith Jones, Director of Drug Experience at the
US Food and Drug Administration (FDA) is quoted as saying. Some doctors make
a mint out of drug trials a golden egg that can disappear if the wrong
results are found repeatedly. In SA, with millions of rands at stake, and
infinitely less money available for rechecking data submitted to the
Medicines Control Council, it's likely the same thing applies.
The study revealed that an alarming number of potentially fatal risks were
discovered only after people had been taking the drugs for years. Thirteen
years, for instance, in the case of an anti-histamine, terfenadine, found to
cause serious heart problems if taken concurrently with another drug. A
record 23 years, for pemoline, a central nervous system stimulant which
causes liver poisoning.
The researchers only looked at reactions so serious that they warranted a
"black box warning" in the US drugs bible, The Physician's Desk Reference.
These are warnings framed in black at the beginning of a drug description,
highlighting a problem severe enough to cause death or disablement.
Alarmingly, there is no South African equivalent of The Physician's Desk
Reference no undisputed, authoritative source of comprehensive drug data.
There is not even a comprehensive website, let alone a "black box" system.
If there were, the wealthy Constantia chemist I talked to would not be
considering spending R20 000 on American drug software. For most doctors and
pharmacists, whether they find a warning or not is hit and miss. The need
for up-to-date information is clear from the Harvard study.
Fifty-six of the 548 new chemical entities approved in America from 1975 to
1999 that's one in 10 subsequently acquired a new black box warning or
had to be withdrawn because of life-threatening potential side-effects.
Forty-five drugs (8.2 percent) acquired more than one black box warning and
16 were voluntarily withdrawn from the market.
Half the withdrawals occurred within two years of the drug's appearance. In
all, there was a 20 percent chance that a new drug would acquire a black box
warning or be withdrawn over 25 years. The more common side-effects, which
can also ruin a person's life, were not even considered.
What's more, the risks are escalating. "In 1997, 39 new drugs were approved
by the FDA", say the Harvard team. "Five of them (Rezulin, Posicor, Duract,
Raxar and Baycol) have already been taken off the market and an additional
two (Trovan, an antibiotic, and Orgaran, an anticoagulant) have had new box
warnings.
Thus, seven drugs approved that year (18 percent of the 39) have proved
dangerous in just four years. Based on our study, that will happen to 20
percent of drugs within 25 years. The 1997 drugs have already almost
achieved this, with 21 years to go."
Patient exposure to these new drugs is extensive, because of aggressive
marketing. Nearly 20 million Americans took at least one of the five drugs
withdrawn between 1997 and 1998. Seven drugs alone possibly contributed to 1
002 deaths, between their approval in 1993 and subsequent withdrawal.
Drug companies spend more on marketing than they do on research and
development. "We as doctors have a moral and ethical duty to understand
this", warns Dr Johan Dippenaar, a medical scheme consultant.
Pharmaceutical companies are the best marketers in the world, and doctors
are at the receiving end. They need to understand its effects. "A recent
study showed that only 30 percent of prescriptions for hypertensions were
according to the South African Hypertension Protocol", he adds. "The other
70 percent included ACE inhibitors, calcium channel blockers and other
agents, which according to evidence-based medicine, are inappropriate as
first line treatment. It seems we are listening to the medical
representative with the shortest dress rather than our academic colleagues!"
South Africans have a slight advantage in that long delays by the MCC in
registering a new drug allow some - but only about half - of these dangerous
side-effects to show up. Viagra, for instance, was held up after world
reports of 230 deaths associated with the drug. Yet this number of
fatalities - which, in a plane crash, would warrant a commission of
inquiry - only led to a change in the warning on the package insert,
relating to heart conditions.
Even when there's clear and proven danger, as with Prepulsid, a heartburn
drug withdrawn in the UK three years ago after killing hundreds because it
caused abnormal heart rhythms, the MCC can't insist the drug is withdrawn.
If, as in this case, the drug company challenges the decision, a long legal
battle ensues.
All necessary warnings have to wait for the slow wheels of the MCC to grind.
In rare cases, they insist the drug company sends a letter to warn doctors.
One hopes that, with all the medical-aid paperwork doctors have to deal
with, the letter will be filed efficiently and read when necessary.
In the meantime, the package insert, which is the only information the
public has to go by, remains unchanged until old stock is used up. Our only
safeguard, it seems, is to insist on tried and tested older drugs unless
life itself depends on it.
Cynics might say that the raison d'être of these inserts is to let medical
officers off the legal hook if anything goes wrong. Naturopath Dr Michael
Rault, asked about informed choice, laughed derisively. "Every day I see
patients suffering from drug treatment. They come to me thoroughly
disgruntled, because they're no better and getting side-effects", he says.
"I always ask, "did you read the package insert?" They rarely have. Most of
it is in High Dutch-like medicalese, difficult to understand. Often they
don't even see it: they've been dispensed 30 tablets, say, and the insert
remains with the bottle of 100".
My mind boggles at these leaflets. I tend to bow to the doctors superior
judgment since, after all, that's what I consult him/her for. I assume that
when the insert warns that "serious stomach problems including bleeding can
occur without warning" as with Cox2 non-steroidal anti-inflammatories, this
applies only to other people, or why would my doctor have prescribed them
for me?
My mistake is probably the one made by the 120 000 people who died of
adverse drug reactions in the US alone last year. In South Africa, our
paternalistic powers-that-be deem it unnecessary to tell us how many people
die this way, although the National Adverse Drug Event Monitoring Centre
(NADEMC) admit that it is a serious cause of mortality and morbidity. Up to
seven percent of hospital patients are admitted because of a drug reaction,
and up to 20 percent suffer one in hospital. Under-reporting means this is
probably the tip of the iceberg.
It seems extraordinary that in this age of information superhighways, we
cannot check the risk profile of every drug available at the touch of a
button. Money's not the problem; pharmaceutical profits are stratospheric.
While overall profits of Fortune 500 companies declined by 53 percent in
2001, those of drugmakers mushroomed by 33 percent. Pfizer alone made more
than all the home-building, apparel, railroad and publishing industries
combined.