Adverse Drug Reactions

The World Health Organization defines an adverse drug reaction (ADR) as any noxious, unintentional, and undesired effect of a drug, which occurs at doses used in humans for prophylaxis, diagnosis, or therapy. Numerous organizations have their own definition.

Any drug may cause an adverse drug reaction. Undoubtedly, all drugs produce an ADR in someone who has used them.

Three to five percent (3-5%) of hospital admissions are caused by ADRs.  

The incidence of serious and fatal adverse reactions in hospital patients has been reported between 0.32% and 6.7%.

Adverse drug reactions may be separated into two groups, Type A and Type B.

Type A reactions: 

are expected exaggerations of the drugs known effect. These are usually dose dependent and predictable and account for the majority of ADRs. Characteristics Type A reactions include: higher than normal dose administered, impaired metabolism or excretion, or very sensitive individuals. These reactions are often found in the FDA approved product labeling. 

 

Type B reactions:

are idiosyncratic and usually unrelated to the drug's known pharmacology. Normally they are not related to the dose, are unpredictable, uncommon, and usually more serious than Type A.   Examples are carcinogen and teratogens. These reactions are more commonly reported after a drug has been on the market for a number of years.

 Type A reactions include medication errors. Therefore, there  may be some difficultly in deciding the correct reporting procedure. If the reaction is caused by a prescribing, administering or monitoring error, a medication error has occurred and medication error report should be completed.  If the patient develops an ADR when the prescribing, administering and monitoring are appropriately carried out, an adverse drug reaction report form should be completed. 

The FDA compiles information on adverse drug events.  If a medicine causes a serious adverse event due to a either medication error or ADR the FDA  should be notified.  If a medication is commonly associated with medication errors the FDA should be notified. This feedback is essential so that the package labeling can be updated and the risk benefit ratio of the drug may be better understood.   

In order for drugs to obtain FDA approval they must be proven safe and effective. The 1962 amendment to the Federal Food, Drug, and Cosmetic Act requires manufacturers to report adverse drug events detected in postmarketing settings to the FDA.  The Food and Drug Modernization act of 1997 states that substantial evidence of drug effectiveness may consist of data from one adequate and well-controlled clinical investigation plus confirmatory evidence.

Most drugs are studied in less than 4,000 patients before FDA approval. Drug reactions that occur in less than 1 in 1000 patients are difficult to detect. Premarketing trials generally excluded special populations such as children, elderly, and women of child bearing age.  Most drug withdrawn from the market for serious side effects, are withdrawn within 1-2 years of FDA approval, as experience is gained in a larger population outside of the narrow confines of clinical trials.

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