Fact Sheet on DNA and Adverse Drug Reactions (ADR)

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Fact Sheet on DNA and Adverse Drug Reactions

 

Compiled by Genelex Corporation.

Contact Howard Coleman 425 825-2870

 

Adverse drug reactions, (ADRs), usually called side effects, and described by

the FDA as a major solvable public health problem, are long-standing and largely

neglected. These are not medical errors as they occur despite adherence to FDA

approved dosage 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 symptoms of a much greater

problem.

 

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.

(JAMA279:1200 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subsequently withdrawn from the market or given a black box warning.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)

 

Adverse drug reactions in the elderly.

 

Elderly patients have a decreased capacity to detoxify medicines they take. Drug

interactions are also an important contributor to adverse drug reactions which

makes the aging population even more vulnerable because of the large number of

drugs they are taking.

 

· 90% of all persons 65 or older take at least one medication per week,

40% use five or more, and 12% ten or more.

 

· A recent study of 30,000 Medicare out-patients showed that in a single

year there were 1,523 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)

 

· Out of 205 consecutive emergency room patients 50 or older and on 2

meds, 47% had significant risk of an adverse drug interaction and 25% were

actually suffering from one. In the general population the potential risk of

ADRs is 13% for people taking two meds and 82% for seven or more. Patients on

risky combinations are 34% more likely to be hospitalized. (reported in

Psychiatric Services http://ps.psychiatryonline.org, Drug-Drug Interactions: The

Silent Epidemic, Neil B. Sandson, Jan 2005)

 

Potential of Pharmacogenetic DNA Drug Reaction Testing to reduce ADRs and save

money.

Virtually every pathway of drug metabolism, transport and action is susceptible

to genetic variation. It is estimated that as much as 95 % of individual

variability in response to medicines is DNA based. (NEJM 348;529 & 538 2003)

Wider use of DNA drug reaction testing could 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.

 

· More than 50% of Americans have gene based variations that can be

tested for and that increase the risk of an ADR. Non genetic patient status,

such as age, physiological functioning and concomitant disease are known and can

be accounted for, leaving the genotype of the patient as a major unknown factor

in the prescribing of medicines.

 

· 59% of prescription 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 same 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 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 per year compared to patients with an

average metabolizer genotype. Virtually all antidepressants and antipsychotic

medicines are processed by enzymes with a high incidence of poor metabolizers.

Journal of Clinical Psychopharmacology 20:246 2000

 

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.

 

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 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.

 

a.. 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

b.. 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