Adverse Drug Reactions
Adverse drug reactions, (ADRs) usually called side effects,
are a long-standing and largely neglected major medical problem.
These are not medical errors and occur within the FDA approved
dosage and labeling recommendations. The recently reported problems
with antidepressant induced teen suicides, the recalls of Vioxx
and Baycol and the upgrading of Accutane monitoring by the FDA
are the tip of the iceberg.
Incidence of Adverse Drug Reactions
ADRs are the fourth to sixth greatest killer in US with more
than 100,000 deaths per year; and 2.2 million serious adverse
reactions per year according to a 1998 Journal of the American
Medical Association report. (JAMA 279:1200 1998) This study is
a meta analysis of 39 research reports published from 1966 to
1996.
21.3% of the 548 most recently FDA approved medications were
subsequently withdrawn from the market or given a black box warning.
JAMA 287:2215 2002
The GAO reports that 51% of new drugs have serious, undetected
adverse effects at the time of approval.
Of the best selling prescription drugs, 148 can cause depression,
133 hallucinations or psychoses, 105 constipation, 76 dementia,
27 insomnia and 36 parkinsonism. "Worst Pills Best Pills:
A Consumers Guide to Avoiding Drug-Induced Death or Illness," third
edition, 1999.
Financial Consequences
$1.77 billion in added health care costs per year. J Am Pharm
Assoc 41:192 2001 HMOs spend more treating ADRs than on drugs.
ADRs are the cost leader for malpractice payouts. Up to one-third
of drug prescriptions are not needed and therefore wasted. Potential
of Pharmacogenetic DNA Drug Reaction Testing to reduce ADRs and
save money.
More than 50% of Americans have gene based variations that can
be tested for and that increase the risk of an ADR.
The wide use of DNA drug reaction testing has the potential
to save tens of thousands of lives, prevent hundreds of thousands
of serious events that initiate or extend hospital stays, and
save hundreds of millions of dollars in health care costs.
Fifty-nine
percent of drugs most commonly cited in ADR studies are processed
by enzymes with genes known to have poor metabolizer variants.
This is compared to 7% of a random selection of the top selling
drugs. (JAMA 286:2270 2001).
Currently available tests help predict a patient's response
to many prescription, OTC (over-the-counter) and herbal medicines
including those used to treat depression, anxiety, seizures
and
psychoses; blood pressure, anticoagulation and other heart
medicines; anti-diabetic agents, and many pain relievers.
Many known drug drug interactions are based on a knowledge
of the drug metabolizing systems that have a high level of
genetic
variation. When those variations are present in individuals
taking more than one drug the chance of having an adverse
drug reaction
is greatly increased.
Hospitalized psychiatric patients who are poor metabolizers
cost $4,000 - $6,000 more in medical care compared to patients
with
an average metabolizer genotype. All antidepressants and
antipsychotic medicines are processed by enzymes with a high
incidence of
poor metabolizers. Journal of Clinical Psycopharmacology
20:246 2000
Some examples of studies pointing out the results of adverse
drug reactions.
41,000 hospitalizations per year for NSAID induced ulcers. Health
Affairs 1990
16,000 car crashes per year from anti-psychotics. American Journal
Epidemiology 1992
32,000 hip fractures per year leading to 1,500 deaths. NEJM 1987:A.J.Epi
1991
Drug induced Parkinson's has developed in 63,000 CMAJ 1982
Why adverse drug reactions are a growing problem.
The 1992 Prescription Drug User Fee Act requiring drug companies
to pay "user fees" to fund the FDA in order to accelerate
the drug approval process. None of the $825 million in user fees
collected from 1993 to 2001 can be used for drug safety or post
marketing surveys.
Percent of new drugs first introduced in the US.
1980 - 3% 1998 - 60%
Drug Approval Time
1993 - 27 months 2001 - 14 months
Percent of Drugs Recalled
1993 - 1996 - 1.56% 1997 - 2001 - 5.35%
According to the FDA Vioxx may have contributed to almost 28,000
heart attacks in the US between 1999 and 2003.
Adverse drug reactions in the elderly.
Elderly patients have a decreased capacity to detoxify drugs
they are taking. Drug drug interactions are also an important
contributor to adverse drug reactions which makes the aging population
vulnerable because of the large number of drugs they are taking.
90% of all persons 65 or older are taking at least one medication
per week, 40% use five or more and 12% ten or more.
A recent one year study of 30,000 Medicare out-patients showed
that in a single year there were 1523 identified adverse drug
events, 421 of which were preventable. 578 of these events were
serious, life threatening or fatal. The most serious events were
also the most preventable. JAMA 289:1107 2003
Adverse drug reactions in children and adolescents.
Few drugs are tested in children prior to release. Many are
used off label in pediatric populations. For example, only Prozac
(fluoxetine) has been approved for use in children, yet many
others are prescribed off label.
The FDA recently released an analysis of previous studies showing
that suicidality doubled in children taking antidepressants compared
to placebo resulting in a black box warning being added to antidepressant's
required labeling. NEJM 351:16 2004
While the rate of adverse drug reactions in children is lower
than in adults, children with severe medical conditions are the
most affected. Drug Safety 27:819 2004
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