The Food and Drug Administration is issuing strong new warnings that the combined use of opioid medications and benzodiazepines, a class of anti-anxiety medications better known by such commercial names as Xanax and Ativan, can dangerously suppress breathing and cause coma or death.
The drug safety agency is recommending that physicians take extra care in prescribing medication regimens that mix the two classes of drugs. And it is alerting people who use — or abuse — such drugs to the “serious risks” of taking them together.
The new FDA order calls for some 400 products to carry one of several “black box warnings.” Those aim to alert physicians and patients to the dangers of mixing opioids with benzodiazepines and other drugs — including insomnia medications, muscle relaxants, antipsychotic drugs and alcohol — that depress the central nervous system.
The new warnings tell physicians and patients that the combined use of drugs that reduce the reflexive urge to breathe can cause dizziness, extreme sleepiness, slowed or difficult breathing, and unresponsiveness.
Products that must carry the new warnings include not only benzodiazepines and narcotic pain relievers, but also medications such as cough syrup that contains codeine, an opioid that acts as a cough suppressant.
The FDA says the number of patients who were prescribed both an opioid analgesic and benzodiazepine increased by 41% from 2002 to 2014, which translates to an increase of more than 2.5 million opioid analgesic patients receiving benzodiazepines.
From 2004 to 2011, the agency said, emergency department visits involving nonmedical use of both drug classes also increased significantly. During that period, the agency cited a tripling of overdose deaths among people taking prescribed or greater-than-prescribed doses of both drug classes.
“It is nothing short of a public health crisis when you see a substantial increase of avoidable overdose and death related to two widely used drug classes being taken together,” said Dr. Robert Califf, the FDA commissioner.
The move also came in response to a citizen petition presented to the FDA by a group of city and state health officials from around the country. In their petition, health officers noted that nearly 1 in 3 unintentional overdose deaths from prescription opioids also involves benzodiazepines.
In February, health officials from 17 states and territories and 13 cities called existing warnings on the concurrent use of opioids and benzodiazepines “inconsistent, infrequent and insufficient." The officials cited statistics showing that in the decade leading up to 2010, there was a nearly sixfold increase in addiction treatment admissions for people hooked on both benzodiazepines and opioids. During the same period, admissions due to all other substance use disorders decreased by almost 10%, the petition said.
On Wednesday, Baltimore City Health Commissioner Leana Wen thanked the FDA for its response, but asked whether more lives could have been saved if the agency had acted sooner.
“As an emergency physician, I have seen that in medical training and practice, it is common to prescribe opioid painkillers to a patient taking benzodiazepines for anxiety, and vice versa,” Wen said. Physicians who do so, she said, are typically acting out of habit and not considering the few benefits and substantial risks that such a combination offers to patients, she said. But, she added, that could change.
“Doctors notice black box warnings,” Wen said in February in calling for the FDA to require the new language on prescription drug packaging.
The FDA on Wednesday stopped short of requiring a new black box warning on drugs such as methadone used to wean people addicted to opioids from those drugs. The agency said it is continuing to examine available evidence regarding the safety of using benzodiazepines and opioids in medication-assisted therapy treatment.
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