Laird Harrison

January 14, 2014

SAN FRANCISCO — Clinicians can safely prescribe off-label medications in intensive care units (ICUs), a new study suggests.

"Using a medication off-label does not put a patient at greater risk of adverse drug reactions," said Pamela Smithburger, PharmD, assistant professor of pharmacy and therapeutics at the University of Pittsburgh.

Dr. Smithburger presented the findings here at the Society of Critical Care Medicine 43rd Critical Care Congress.

Clinicians in the United States often prescribe medications for purposes other than those approved by the US Food and Drug Administration (FDA). The practice has raised concerns because off-label uses frequently have not undergone careful scrutiny.

Intensive care patients can be at particular risk for adverse reactions because of the complexity of their conditions and medication regimens, explained Dr. Smithburger. In fact, more patients in the ICU than in other hospital units experience life-threatening adverse events (26% vs 11%), she explained.

To see whether off-label prescriptions are harming patients, Dr. Smithburger and her team reviewed all medications being taken by adults admitted to ICUs at 2 academic medical centers on admittance and every 24 hours afterward for a period of 3 months. They classified the uses as either approved by the FDA or unapproved.

All adverse drug reactions were recorded and evaluated using 3 separate adverse drug reaction causality instruments — the Kramer algorithm (JAMA. 1979;242:623-632), the Naranjo criteria (Clin Pharmacol Ther. 1981;30:239-245), and the Jones algorithm (J Rheumatol Suppl. 1988;17:14-19).

Researchers then categorized the severity of the adverse reactions using the Common Terminology Criteria for Adverse Events. Grade 3 to 5 events were considered severe or life threatening. They also assigned a MEDMARX classification of harm or no harm.

Of the 13,580 medications prescribed over 950 patient days, 5639 (41.5%) were used off label. Of the off-label prescriptions, the researchers categorized 132 as not indicated for the patient population, 4662 as not indicated for the condition, 662 as not indicated for the dose, and 180 as not indicated for the route of administration.

Of the 107 adverse drug reactions identified, "you could confidently say that the majority of them were due to 1 particular drug," rather than interactions of multiple drugs, Dr. Smithburger noted.

Adverse Reactions

The patients suffered adverse reactions at a rate of 0.67% for FDA-approved uses and 0.73% for off-label uses; the difference was not statistically significant (P = .38).

I think, as the study researchers said very astutely, there should be a lot more study and evaluation.

There was also no significant difference in adverse reactions classified as severe or life threatening between FDA-approved and off-label uses (17 vs 19; P = 1.0). And there was no significant difference in adverse reactions with a MEDMARX classification of harm between FDA-approved and off-label uses (31 vs 28; P = .26).

Opioids and sedatives accounted for 25% of these adverse reactions.

The adverse events ranged widely, from delirium, hypotension, and tachycardia to diarrhea, rash, and nausea.

Session moderator Joshua Roberts, PharmD, senior clinical pharmacist at the University of California, Davis, who was not involved in the study, told Medscape Medical News that he agrees with the study conclusions.

"I think it validates what everyone does on a day-to-day basis," he said.

But, he added, further research is needed. "I think, as the study researchers said very astutely, there should be a lot more study and evaluation," said Dr. Roberts. In particular, he would like to know whether findings would be similar in a study conducted in a small community setting.

This study was supported by an award from the American Society of Health-System Pharmacists. Dr. Smithburger and Dr. Roberts have disclosed no relevant financial interests.

Society of Critical Care Medicine (SCCM) 43rd Critical Care Congress: Abstract 898. Presented January 11, 2014.


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