FDA Issues Guidance on Abuse Deterrent Opioids

By Pat Anson, Editor

The U.S. Food and Drug Administration has released its long-awaited guidance on abuse-deterrent opioids, beating a Congressional deadline and a potential loss of $20 million in funding.

The document “Guidance for Industry: Abuse-Deterrent Opioids – Evaluation and Labeling” explains the FDA’s current thinking about abuse-deterrent properties and recommends to drug makers how clinical studies should be conducted to evaluate their effectiveness.

Abuse deterrent formulas are intended to make it harder for drug abusers to crush or liquefy a narcotic painkiller for snorting or injecting. But the evidence is mixed that they actually work.

“It should be noted that these technologies have not yet proven successful at deterring the most common form of abuse — swallowing a number of intact capsules or tablets to achieve a feeling of euphoria. Moreover, the fact that a product has abuse -deterrent properties does not mean that there is no risk of abuse.  It means, rather, that the risk of abuse is lower than it would be without such properties. Because opioid products must in the end be able to deliver the opioid to the patient, there may always be some abuse of these products,” the FDA said in its report.

The agency has been under pressure from Congress to move faster in developing guidelines for abuse deterrence. An appropriations bill passed late last year would have moved $20 million in funding from the FDA’s Commissioner’s office if the guidance wasn’t released by June 30.

“The science of abuse-deterrent medication is rapidly evolving, and the FDA is eager to engage with manufacturers to help make these medications available to patients who need them,” said FDA Commissioner Margaret Hamburg, MD. “We feel this is a key part of combating opioid abuse. We have to work hard with industry to support the development of new formulations that are difficult to abuse but are effective and available when needed.”

So far only four opioids have been approved with abuse-deterrent formulas, OxyContin, Embeda, Targiniq and Hysingla. The latter was recently introduced by Purdue Pharma as the only “pure” hydrocodone extended release product with abuse-deterrence.

Purdue’s reformulated version of OxyContin was the first opioid to have abuse deterrence. It was introduced in 2010, at a time when the painkiller was widely being abused.

A recent study by researchers at Washington University’s School of Medicine in St. Louis found that over a quarter of drug abusers entering treatment facilities admitted they still abused OxyContin. About a third of the abusers said they had found a way to inhale or inject it. The rest took the painkiller orally.

One unintended consequence of reformulating OxyContin is that 70% of the drug abusers who stopped using it and who switched to other narcotics started using heroin.

"The newer formulations are less attractive to abusers, but the reality is -- and our data demonstrate this quite clearly -- it's naïve to think that by making an abuse-deterrent pill we can eliminate drug abuse. There are people who will continue to use, no matter what the drug makers do, and until we focus more on why people use these drugs, we won't be able to solve this problem,” said senior investigator Theodore J. Cicero, PhD, a professor of neuropharmacology in psychiatry.

Some patients believe the reformulated version of OxyContin is less effective as a pain reliever and causes gastrointestinal problems because it is harder to digest.

The FDA said it would take “a flexible, adaptive approach” to the future evaluation and labeling of abuse-deterrent products.

“Development of abuse-deterrent products is a priority for the FDA, and we hope this guidance will lead to more approved drugs with meaningful abuse-deterrent properties,” said Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research.

“While abuse-deterrent formulations do not make an opioid impossible to abuse and cannot wholly prevent overdose and death, they are an important part of the effort to reduce opioid misuse and abuse.”

Over 16,500 deaths in the U.S. were linked to opioids in 2010. According to the National Institutes of Health, only about 5% of patients taking opioids as directed for a year end up with an addiction problem.