State, City Health Officials Seek Boxed Warning for Opioids and Benzos

Alicia Ault

February 24, 2016

Health officials from 17 states and territories and 13 cities are asking the US Food and Drug Administration (FDA) to give opioids and benzodiazepines a new black box warning, saying that concurrent use is helping to fuel the overdose crisis.

In a Citizen's Petition delivered to the FDA on February 22, the commissioners proposed that both classes carry the warning that "Concurrent use with [benzodiazepines/opioids] reduces the margin of safety for respiratory depression and contributes to the risk of fatal overdose, particularly in the setting of misuse."

Nicole Alexander-Scott, MD, director of the Rhode Island Department of Health, Providence, said in a statement that existing warnings on concurrent use "are inconsistent, infrequent, and insufficient."

The health officials, along with a handful of academic researchers, chose to file a Citizen's Petition — which can be submitted by any member of the public to seek a review of FDA policy — because it is an expeditious way to inform the agency of new data, Baltimore Health Commissioner Leanna Wen, MD, told Medscape Medical News.

Relatively new epidemiologic data indicate that in 2010, 33% of overdoses were due to concurrent use of opioids and benzodiazepines — an increase from about 17% in 2006, according to the petition. Treatment admissions for co-occurring addiction to benzodiazepines and opioids increased 570% from 2000 to 2010, while admissions due to all other substance use disorders decreased by almost 10%, said the petition.

The officials said that in 2012, prescribers wrote 82.5 opioid prescriptions per 100 people and 37.6 benzodiazepine prescriptions per 100 people in the United States.

Physicians are routinely coprescribing both medications for certain ailments, in particular chronic pain, said Dr Wen. But that practice "is not evidence-based," she said.

A warning could change practice because "doctors notice black box warnings," Dr Wen said, adding that prescriptions for droperidol, for instance, declined after the FDA issued a boxed warning in 2001 about the risk for sudden cardiac death in psychiatric patients, even with very small doses.

Adding a warning to benzodiazepines and opioids can also "give additional credibility and credence to medical organizations that are designing their guidelines" on opioid use, Dr Wen told Medscape Medical News.

The petition urges medication guides for patients to specifically warn about the risks of combined opioid and benzodiazepine use. Patients and the general public are being encouraged to sign a second petition in support of the Citizen's Petition.

The FDA said it had not yet received the health officials' petition. But an agency spokesperson said the FDA "appreciates the diligent work of the state and city public health leaders in raising concerns related to the use of benzodiazepines in combination with opioids."

The agency "will continue to monitor the combined use of these products and take necessary actions to ensure prescribers and the public are informed of the risks involved with the use of these medications," spokesperson Sarah Peddicord told Medscape Medical News.

By law, the FDA has 180 days to respond to a petition.


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