PROVIDENCE – In a citizen’s petition, public health officials from across the country are asking the U.S. Food and Drug Administration to take action and get explicit in their warnings about the dangers of mixing prescriptions for anti anxiety drugs and pain drugs, making it clear the risks from combined use can result in fatal overdoses.

The dramatic action comes at a time when communities across the nation are struggling to develop strategies to contain the epidemic of drug overdoses that plague the nation.

Led by Dr. Nicole Alexander Scott, director of the R.I. Department of Health and Dr. Leana Wen, commissioner of public health in Baltimore, some 30 public health officials from around the nation are scheduled to submit a petition today to the FDA, asking the agency to place a “black box warning” on such prescriptions.

In addition to Rhode Island, the state petitioners include Alaska, Arizona, Arkansas, Connecticut, Delaware, Maine, Maryland, Massachusetts, Minnesota, Montana, Pennsylvania, South Carolina, Vermont, West Virginia and the U.S. territories of Guam and the Northern Marianas.

In addition to Baltimore, the city petitioners Boston, Chicago, Dallas, Denver, Detroit, Houston, Long Beach, Minneapolis, New York City, Philadelphia, Sacramento and San Francisco.

More cities and states are expected to sign onto the petition in the coming days. A companion petition from citizens is also being launched.

Traci Green, Ph.D., one of the authors of the Rhode Island strategic plan on addiction and overdose prevention, called the petition effort an important exercise of citizens’ rights.

“I think what’s really amazing,” she told ConvergenceRI, “is that, as citizens, we have this right, if we’re worried about the safety of a product, to petition the FDA. We have that kind of power as a people in America.”

The FDA, Green continued, “is compelled to respond, to look at the data, and then [act to] help stop some of the deaths.”

The black box language

The proposed language for the black box warnings is as follows:

For all opioid medications, it reads: WARNING: Concurrent use with benzodiazepines reduces the margin of safety for respiratory depression and contributes to the risk of fatal overdose, particularly in the setting of misuse.

For benzodiazepine medications, it reads: WARNING: Concurrent use with opioids reduces the margin of safety for respiratory depression and contributes to the risk of fatal overdose, particularly in the setting of misuse.

Redefining the problem

In a draft of the petition to be sent to the FDA, data from the R.I. Department of Health was used to illustrate the frequency of the co-prescription for opioids and benzodiazepines.

“Among all patients dispensed an opioid in the state, 27 percent also were dispensed a benzodiazepine at least once within 30 days of receiving an opioid,” the supporting document said. In turn, the document continued, “Of those dispensed a benzodiazepine, 59 percent were also dispensed an opioid at least once with in 30 days of receiving a benzodiazepine.”

One of the common clinical scenarios for co-prescription of opioids and benzodiazepines is the patient with chronic pain, despite little evidence for therapeutic benefit, according to the draft petition.

Further, the draft petition identified what it called “hazards” of this clinical practice. “Concurrent benzodiazepine use [by] opioid users is not associated with improved symptoms; instead daily benzodiazepine users have reported higher pain severity and less coping with their pain,” the draft petition said.

Alexander-Scott has taken the lead in working with states, while Wen has taken the lead in working with cities, in developing a working coalition around the petition to the FDA.

The Rhode Island strategy
In Rhode Island, benzodiazepines were involved in one-third of all confirmed deaths in 2014-2015 – some 126 deaths, according to the R.I. Department of Health. Further, Rhode Island ranked fourth in the U.S. for benzodiazepine use per capita, according the most recent national statistics.

To give an indication of the size of the problem, by the numbers, in October of 2015, there were 5,662,003 doses of benzodiazepine prescriptions dispensed in Rhode Island, according to the R.I. Department of Health.

During the same time period of October of 2015, there were 3,092,881 doses of opioid prescriptions dispensed [except buprenorphine] in Rhode Island, according to the R.I. Department of Health.

In the strategic plan on addiction and overdose in Rhode Island prepared by the state Task Force on Overdose Prevention and Intervention, the third leg of the plan focused on safer prescribing and dispensing, targeting the lethal mix of prescriptions of opioids and benzodiazepines.

The strategy included the following steps:

• Reorient the Prescription Monitoring Program to structure “alert” messages to prescribers and pharmacists when a patient’s medications currently include a combination of opioids and benzodiazepines.

• Encourage a standardized use of urine drug testing that can identify “co-ingestion” of both kinds of medications at opioid treatment programs and other health care settings.

• Provide a prescription for naloxone as risk mitigation.

• Educate both prescribers and patients about the dangers of mixed use with aggressive safety messaging. This strategy seeks to reduce dangerous prescribing of benzodiazepines, which combine with opioids to impair breathing and cause death.

The last detailed step, of course, is precisely the aim of the national petition to the FDA to create a black box warning.

Alexander-Scott described the national strategy of the black box warning as being congruent with the state’s prevention strategies. “We wanted to design the most aggressive, high impact way to get the message out to patients and providers in every state in the country,” she told ConvergenceRI in a phone interview. “Black box messages tend to stand out and patients pay attention.”

In perspective
The overarching goal of the state’s strategic plan is to reduce the number of overdose deaths by one-third over the next three years. The petition to the FDA to create a black box warning label certainly promises to help reach that goal by raising awareness by both patients and providers about the dangers of mixing opioids and benzodiazepines promises be an important tool, both nationally and statewide.

Another key strategic tool, in terms of public outreach and engagement, is the creation of a dashboard, an online “indicator panel of relevant data to provide of a snapshot of problems and progress, including the key metrics for all the strategy initiatives.

The preview of that dashboard is scheduled to make its debut in early March, according to Green, one of the authors of the state’s strategy.

The dashboard, Alexander-Scott said, was an important tool in capturing the metrics and numbers to demonstrate the achievements of the treatment, recovery, prevention and reversal strategies moving forward.