Association of a Risk Evaluation and Mitigation Strategy Program with Transmucosal Fentanyl Prescribing

Importance: Transmucosal immediate-release fentanyl (TIRF) drugs are potent, rapid-acting opioids approved to treat breakthrough pain in patients with cancer who are tolerant to other around-the-clock opioid analgesics. In March 2012, a US Food and Drug Administration-approved Risk Evaluation and Mitigation Strategy (REMS) was implemented, mandating prescribers, distributors, pharmacies, and patients to enroll in the REMS to prescribe, dispense, or receive TIRF drugs. Objective: To evaluate the association of the TIRF-REMS Access Program with TIRF prescribing. Design, Setting, and Participants: Cohort study using an interrupted time series analysis of TIRF prescriptions to Medicare Part D beneficiaries nationwide from 2010 to 2014. Data were analyzed from August 2017 through July 2018. Main Outcomes and Measures: Prescribing of TIRF per 100000 Medicare Part D beneficiaries, overall and stratified by cancer status; percentage of TIRF prescriptions for patients without cancer, overall and by brand; and percentage of TIRF prescriptions for patients without known opioid tolerance, defined as patients prescribed at least 60 morphine milligram equivalents per day, overall and by brand. Results: There were 99601 TIRF prescriptions written by 8619 clinicians to 10472 patients. Most of the patients (79%) were younger than 65 years (mean [SD] age, 56 [13] years), and most (67%) did not have cancer. Implementation of TIRF-REMS was associated with a 26.7% relative level decrease in TIRF prescribing (95% CI, -33.3% to -19.4%; P <.001) but was followed by 2.0% monthly increases in prescribing (95% CI, 1.3% to 2.7%; P <.001). Sensitivity analyses that accounted for overall opioid prescribing trends were consistent with these findings. Furthermore, there were no significant changes associated with REMS implementation in the level (0.47%; 95% CI, -5.36% to 4.69%; P =.85) or trend (0.16%; 95% CI, -0.06% to 0.37%; P =.15) of the percentage of prescriptions for patients without cancer. However, a sensitivity analysis that used a broader cancer definition found implementation was associated with a 7.2% (95% CI, -13.5% to -0.48%; P =.04) level decrease in the percentage of TIRF prescriptions for patients without cancer. Lastly, the TIRF-REMS was associated with a 22.5% level decline in the percentage of TIRF prescriptions for patients without known opioid tolerance (95% CI, -36.1% to -5.95%; P =.01) followed by 1.98% monthly decreases (95% CI, -3.19% to -0.80%; P =.001). Conclusions and Relevance: Implementation of the TIRF-REMS Access Program, a restrictive drug distribution program, was associated with a temporary reduction in the rate of TIRF prescribing to Medicare Part D beneficiaries, and with a sustained decrease in the percentage of TIRF prescriptions for patients without known opioid tolerance. Implementation may have also been associated with a temporary decrease in the percentage of TIRF prescriptions for patients without cancer.