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FDA Advisory Committee Considers Tweaking Opioid-related REMS

Posted 06 August 2018 | By Ana Mulero 

FDA Advisory Committee Considers Tweaking Opioid-related REMS

An advisory committee convened Friday by the US Food and Drug Administration (FDA) received questions on discrepancies in the data obtained on the Risk Evaluation and Mitigation Strategy (REMS) regarding transmucosal immediate-release fentanyl (TIRF) products.
Following the committee meeting, FDA Commissioner Scott Gottlieb said on Twitter “there are gaps in data on use of these products and adverse events. We need to use every tool available to examine real-world impact of these drugs and the REMS program, and align our approach to strike better balance between access and safety.”
Data discussed by the advisory committee showed the number of patients with dispensed TIRF prescriptions saw a 80% decrease since the REMS with Elements to Assure Safe Use (ETASU) for TIRF products received approval in 2011—from 24,000 in 2010, down to 5,000 in 2017.
Yet the decline in TIRF prescriptions under FDA’s REMS can be explained, at least in part, by the downward trends among active patients (from 15,922 in 2015 vs. the current total of 6,984) and enrolled prescribers, totaling 8,151 last year compared to 9,096 in 2016. The 10 TIRFs with FDA approval can only be dispensed with the REMS program in place, despite being the only medicines indicated for treatment of breakthrough cancer pain.
Further, the data also showed 569 unique cases of adverse events between 2016 and 2017 linked to the use of TIRF products. Most (549 or 96.7%) of the cases reported patient deaths, followed by overdoses (6%), addiction (1.8%) and pediatric exposure (0.2%).
Adverse events also “showed increases in rates of abuse, intentional misuse, unintentional therapeutic errors, emergency department visits and hospitalizations, and deaths/ major medical outcomes, pre-to-post REMS, after adjusting for product utilization,” FDA wrote in a report.

Based on a review of a 60-month REMS assessment from October 2015 to 2016, FDA concluded that the program was "only partially meeting its goals because the included surveillance data appeared to indicate that for most outcomes assessed, event rates for TIRF medicines increased over time per number of prescriptions dispensed.”
Members of the TIRF REMS industry group, which include Insys Therapeutics, Mylan and Teva Pharmaceuticals, argued that many of the adverse events could be attributed to the use of illicit fentanyl products, but the lack of data makes it difficult to reach such conclusions. They also pointed to China as the supplier responsible for the current illicit fentanyl problem in the US.
Still, the concerns around the spike in adverse events reported resulted in several changes proposed by the group for what would be the 5th modification to the TIRF REMS. The program was last modified in 2017 for alignment with class product labeling data requested by FDA.
As part of the continued efforts to deter inappropriate prescribing and unnecessary burden on the healthcare delivery system, the proposed changes include updating education materials and revising the patient-prescriber agreement form to include an attestation of opioid tolerance.
Other proposed modifications relate to revising the pharmacy enrollment form to potentially increase the pool of inpatient pharmacies and updating the prescriber noncompliance protocol to raise flags earlier in the patient enrollment process.
On ensuring appropriate prescribing, the group plans on further validating the claim-based algorithm based on data from electronic medical records. It also endorsed co-prescribing TIRF medicines with naloxone and the launch of a registry dedicated to TIRF data.

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