Nearly half of the patients prescribed high potent transmucosal immediate-release fentanyl (TIRF) reserved to treat breakthrough pain in cancer patients already on round-the-clock opioid therapy, were given the drugs off-label. Yet, when this evidence surfaced, the Food and Drug Administration (FDA) dragged its feet on addressing the problem. And when it did, the agency only made a “few substantive changes” to its Risk Evaluation Mitigation Strategy (REMS), according to a study published in JAMA.
The REMS for TIRF drugs was approved by the FDA on Dec. 28, 2011, because the medications were very potent and there was a high risk for overdose. TIRF drugs are a class of short-acting fentanyl products that are delivered through tablets that dissolve under the tongue or in the cheek, lozenges, and sprays.
The REMS requires drug manufacturers to ensure that outpatient prescribers and dispensing pharmacies are specially certified, that distributors deliver the drugs only to certified pharmacies, and that patients that are treated with them are enrolled in the REMS. Doctors prescribing the TIRF drugs must also attest that they understand the risks the drugs pose.
Despite these restrictions, “Not only did we see that large numbers of patients were unsafely prescribed these products, but we also found that the FDA and manufacturers missed opportunities to revise the program once these deficiencies were identified,” Johns Hopkins Bloomberg School of Public Health G. Caleb Alexander, M.D., told MedPage Today. “Rather than having rapid, iterative assessments and revisions to the program to ensure safe use, we found that the identification of unsafe, off-label prescribing was delayed; it didn’t occur until three years in. And even when it occurred, even the FDA and manufacturers failed to substantially overhaul the program.”
FDA-approved TIRF drugs include Abstral, Actique, Fentora, Lazanda, Onsolis as well as Subsys, manufactured by Insys Therapeutics. During the study period, Insys was found to have paid kickbacks to doctors to increase sales of its Subsys spray, and misled insurance companies to cover the cost of the drug for off-label uses. Seven executives of the company face criminal indictments by the U.S. Attorney’s Office in the District of Massachusetts. To date, two have pled guilty.
“But there’s a thread that suggests the problem is not just with Insys,” Alexander cautioned.