Limit Prescribing Opioids, Benzos Together, FDA Warns


August 31, 2016

To reduce the risk for overdose deaths, clinicians should not prescribe opioid pain medicines together with benzodiazepines to patients unless there are no adequate alternative treatments available, the US Food and Drug Administration (FDA) announced today.

Both classes of drugs are central nervous system (CNS) depressants, which can trigger respiratory depression, coma, and death, especially when they are combined.

The FDA is spelling out this and other precautions in class-wide boxed warnings on the labels of opioid painkillers such as oxycodone, prescription cough medicines containing opioids, benzodiazepines, which include alprazolam (Xanax, Pharmacia and Upjohn), and other CNS depressants. All told, boxed warnings will be required for 389 products.

Warnings about the risks of prescribing opioids together with benzodiazepines are nothing new. They have long been featured on the labels of these drugs, but not in a so-called black box. Putting them inside one is the equivalent of the FDA raising its voice about the problem.

"When a boxed warning goes out, it alerts all kinds of people who might have missed the message," said FDA Commissioner Robert Califf, MD, in a news conference today.

The decision to essentially classify the combination of opioids and benzodiazepine as a last-resort therapy is the FDA's latest measure to battle the nation's epidemic of prescription opioid abuse. An agency review found that the rate of emergency department visits related to the nonmedical use of opioids and benzodiazepines in combination tripled from 2004 to 2011, going from 11 visits per 100,000 population to 34.2 visits. In this same time span, the rate of deaths related to overdoses on this mix of drugs tripled as well.

This rising death toll coincided with a 41% increase in the number of patients who were prescribed both an opioid painkiller and a benzodiazepine between 2002 and 2014, according to the FDA.

The agency advises clinicians that if they have no choice but to prescribe the opioid analgesics and benzodiazepines together, they should limit the dosage and duration of each drug to the minimum needed to effectively treat the patient. Clinicians should warn patients about the risks for slowed or labored breathing. They also should avoid prescribing opioid cough medicines for patients taking benzodiazepines and other CNS depressants, including alcohol.

A Victory for State and City Public Health Officials

Today's FDA decision represents a victory for public health officials from 17 states and territories and 13 cities who petitioned the agency in February to require a boxed warning on concomitant use of opioids and benzodiazepines. Dr Califf credited them during the news conference with "valuable input."

Baltimore City Health Commissioner Leana Wen, MD, one of the leaders of the petition drive, appeared with Dr Califf in the news conference. Dr Wen, an emergency medicine physician, said current clinical practice in prescribing the drugs in question is rooted more in tradition than scientific research.

"There is no scientific reason why in medical training I was taught to prescribe benzodiazepines and opioids together," said Dr Wen. "Like many other things, clinicians do what we do because it's routine care."

She recalled a common drug cocktail for car-accident victims. "To treat their back spasms, we give them a benzodiazepine, and to treat their pain, we give them an opioid," Dr Wen said. "And if a patient required (just) an opioid, we might ask if they are on another opioid, but we might not always ask if they are on a benzodiazepine, and vice versa."

More information on today's FDA announcement is available on the agency's website.

Follow Robert Lowes on Twitter @LowesRobert


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