First FDA-Approved REMS for an Opioid

By William T. Koustas –

Last week, FDA announced the approval of Onsolis (fentanyl buccal soluble film) with a substantial Risk Evaluation and Mitigation Strategy ("REMS"), as well as a boxed warning.  Onsolis is a potent opioid that is administered through the mucous membranes of a patient’s mouth through a dissolvable film applied to the inner cheek.  Similar to other oral fentanyl products, Onsolis is only indicated for the “management of breakthrough pain in patients with cancer…who already use opioid pain medication around the clock and who need and are able to safely use high doses of an additional opioid medicine.”  However, FDA’s view of fentanyl’s potential for abuse/misuse has resulted in a REMS requirement under the FDA Amendments Act of 2007 (“FDAAA”).

Onsolis’ REMS are comprised of a medication guide, communication plan and elements to assure safe use (as well as a timetable to assessment and implementation system).  The medication guide will contain information useful to patients, such as important directions for safe use and potential adverse side effects, whereas the communication plan appears to consist of a letter to prescribers explaining the REMS.  The elements to assure safe use consist of a restrictive distribution scheme that requires prescribers, pharmacies and patients to be enrolled in the Full Ongoing Commitment to User Safety (“FOCUS”) Program.  Prescribers and patients must sign an enrollment form detailing the responsibilities of both, while pharmacies must, among other things, only dispense Onsolis via a courier to the patient’s home and not via a retail store. 

FDA has indicated that it intends to approve REMS for Actiq and Fentora (both already approved fentanyl products) in the “coming months.” 

The approval of Onsolis’ REMS raises the question of whether this creates a precedent for elements to be included in the wide-ranging extended-release opioid REMS (being developed by FDA).  FDA stresses that Onsolis is not an extended-release opioid product and is only to be prescribed to opioid tolerant patients, which FDA believes requires different and possibly more stringent REMS than what may be required for extended-release opioids that have the potential to be used by a broader patient population.  FDA claims that the Onsolis REMS is independent of the REMS currently being developed for extended-release opioids and therefore is not precedent setting.