The new Food and Drug Administration drug package insert: implications for patient safety and clinical care.

Watson KT, Barash PG.
Department of Anesthesiology, Yale University School of Medicine, New Haven, Connecticut 06520-8051, USA.

The United States Food and Drug Administration (FDA) is the scientific, regulatory, and public health agency that regulates many products, including food products, drugs, medical devices, radiation emitting devices, and cosmetics for the federal government of the United States. The FDA’s mission is to assure that consumer products made and sold in the United States are safe, effective, and pure. The purpose of the package insert (also known as prescription drug product insert or professional labeling) is to provide detailed drug information compiled and distributed by the drug manufacturer, after FDA review and approval.

In 2006, the standard format for the package insert was changed in an attempt to make it more user-friendly and a more efficient resource tool for practitioners.

According to the Institute of Medicine, in-hospital adverse drug reactions occur at a rate of 400,000 per year and incur $3.5 billion of extra hospital expense. It is expected that the new package insert format will enhance rapid access to important pharmacologic information and improve patient safety by decreasing medication errors.

Eleven percent, including Remicade (infliximab), used to treat Crohn’s disease and rheumatoid arthritis, and Avastin (bevacizumab), used to treat cancer, have been issued a “black box” warning.

The findings, from Dutch scientists, are published in the Oct. 22/29 issue of the Journal of the American Medical Association.

“This suggests the need for more in-depth investigation before approval and highlights the importance of vigilance in post-marketing surveillance for adverse effects,” Dr. Phil B. Fontanarosa, the journal’s executive deputy editor, said during a a Tuesday teleconference on the themed issue.

“[Adverse effects] generally occurred in general disorders, like serious allergic reaction or cardiac arrest, administration site problems, infections and infestations,” said Fontanarosa. “A lot of these drugs act on the immune system, so infections are common complications of these products.”

“We’ve always known that because biologics were going to modulate the immune system, there would be this risk,” said Lisa Saubermann, associate director of clinical pharmacy services at the University of Rochester Medical Center.

The first biologic treatment, recombinant insulin, was approved in the United States in 1982. Since then, more than 250 biologics have flooded the pharmaceutical market, representing roughly one-quarter of all new drugs approved by U.S. and European Union authorities.

Although all drugs carry risks, biologics are in a special class, because they are derived from biological sources, including antibodies, enzymes and hormones.

Enbrel (etanercept), for instance, is a tumor necrosis factor, a protein made by the body’s immune system. The drug, used to treat various forms of arthritis as well as psoriasis, was also the recipient of a black box warning (for infections and central nervous system disorders).

The authors of this paper, from Utrecht University, reviewed 174 biologics approved in the United States and/or the European Union between January 1995 and June 2007.

Between January 1995 and June 2008, 82 safety-related regulatory actions were issued for 41 of the medications, or almost 24 percent of the total.

Of these 82 actions, 63 were advisory letters to health-care professionals in the United States and Europe, and 19 were black box warnings. None of the drugs were withdrawn from the market.