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FDA requires new warnings on danger of combining opioids, benzodiazepines

The Food and Drug Administration will require that opioid painkillers, such as OxyContin, include tough new labels warning of the dangers of combining them with benzodiazepines. (Toby Talbot/AP)

The Food and Drug Administration, alarmed that increasing numbers of Americans are combining opioid painkillers and benzodiazepines, said Wednesday that it will require tough new warnings on the product labels that spell out the serious dangers of mixing the drugs.

The agency said it will require “boxed warnings” — its strongest category — on 389 separate products and will mandate the warning on opioid-containing cough medications. The new language will list the hazards of using the medications in tandem, which include extreme sleepiness, respiratory depression, coma and even death.

The agency noted that the misuse of opioids, powerful pain medications such as prescription oxycodone, hydrocodone and morphine, has “increased significantly” in the United States over the past two decades. Benzodiazepines are used to treat anxiety, insomnia and seizure disorders. Both classes of drugs depress the central nervous system and together can raise the risk of adverse outcomes.

FDA officials said the number of patients prescribed both an opioid and a benzodiazepine increased by 41 percent — about 2.5 million people — between 2002 and 2014.

From 2004 to 2011, the rate of emergency-department visits involving the non-medical use of both drug classes increased significantly and overdose deaths nearly tripled, the FDA said.

In a call with reporters, FDA Commissioner Robert Califf implored doctors “to heed these new warnings” and to carefully evaluate, on a patient-by-patient basis, whether the benefits of using opioids and benzodiazepines together outweigh the serious risks involved.

Current labels on the drugs warn of potentially dangerous interactions. But FDA officials said the tougher warnings, sometimes called “black box warnings,” are designed to catch the attention of physicians and patients and to underscore the seriousness of the threat.

The combination of opioid pain pills and anti-anxiety medications is leading to premature death.

Califf said the FDA move was partly in response to pleas from state and local health officials dealing most immediately with the damage caused by the national opioid epidemic. In February, several state and local officials petitioned the FDA for action, saying that “a strong black box warning will provide a clear general message to improve care and save lives.”

Baltimore City Health Commissioner Leana Wen, who was a leader of the petition effort and participated in Wednesday’s FDA call with reporters, said the tougher warnings are needed because it’s “routine practice” for physicians to prescribe the two types of drugs together. For example, someone who has been in a car accident might be prescribed opioids for pain and benzodiazepines, which include such drugs as Xanax and Valium, for back spasms.

She said that nearly one in three unintentional overdose deaths from prescription opioids also involve benzodiazepines.

Douglas Throckmorton, deputy director of the FDA’s Center for Drug Evaluation and Research, said that the agency will require manufacturers to update their medication guides, which are given out by pharmacists when consumers get prescriptions filled.

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The Centers for Disease Control and Prevention warned doctors in the spring against prescribing opioids with benzodiazepines, except for patients battling diseases such as cancer. But the CDC has no power to mandate changes.

Califf said the boxed warnings are part of the agency’s Opioids Action Plan, which is designed to try to reverse the prescription opioid epidemic. Earlier this year, the FDA required new warnings about the risk of addiction, abuse, overdose and death for short-acting opioid medications. The agency has been criticized by some for failing to move earlier and more aggressively to counter the epidemic.

Read more:

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