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Adverse Drug Events

Prescription pill bottles and pink pills

There are more than 1,400 unique drugs available for human use, and along with their many benefits come risks. An adverse drug event (ADE) is an injury caused by a medication. The Office of Disease Prevention and Health Promotions estimates that ADEs result in 125,000 hospitalizations and 3.5 million office visits per year. One mechanism for reducing ADEs is the FDA’s approval of drugs.

The FDA approves drugs for specific uses based upon rigorous studies. However, clinicians are not limited to prescribing for those specific uses and may prescribe medications “off-label.” Drugs may be used for other conditions that have not been approved by the FDA. An example is gabapentin which is FDA approved to treat seizures and pain from shingles. It is commonly used off-label to treat pain due to pinched nerves in the back. Some off-label uses have been well studied, but the manufacturer has not received FDA approval for that use, while some off-label uses are not as well studied.


“The FDA approves drugs for specific uses based upon rigorous studies. However, clinicians are not limited to prescribing for those specific uses and may prescribe medications “off-label.” Drugs may be used for other conditions that have not been approved by the FDA. ”


A study done in Canada evaluated on- and off-label drug use and the risk of ADEs. 46,000 patient charts in Quebec were reviewed for visits between 2005 and 2009. Canada is conducive to this type of study because electronic records there require documentation of indication for a prescription, reason for dose change or discontinuation and nature of adverse event if it occurred. Off-label use was further classified into prescriptions with or without strong evidence for off-label use, as shown in Table 1.

Table 1. Drugs used by label status and evidence

Over 150,000 medications were prescribed in the study — 88% were on-label use while 12% were off-label. The off-label prescriptions had good evidence for use 19% of the time. Table 2 shows discontinuation rates for adverse events based on label status. The study found a significant increase in adverse events for off-label vs on-label prescribing (19.7 vs 12.5 adverse drug events/10,000 patient-months.) Sixty percent of the prescriptions that were stopped did not have good evidence for off-label use. Women had more events than men (14.3 vs 11.7) and there was a five-fold increase in adverse events in people taking eight or more drugs compared to one or two drugs. Medications approved after 1995 were more likely to involve adverse reactions compared with older medications.

Table 1. Drugs used by label status and evidence

Proponents of limiting off-label prescribing view this study as strongly supporting prescribing limits to only FDA-approved indications. Others look at the same data and say that FDA approval is hindering proper prescribing as it is very difficult to get new indications for old drugs and that with good evidence, drugs can be used for more than current FDA indications.

Before long, all electronic prescriptions will be required to have the diagnosis associated with the prescription, allowing easier categorization of on-label or off-label use. While this may decrease off-label use, patients may find that they cannot get a medication that they have successfully used previously to treat a condition.

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