(B26) Assessment of the U.S. Food and Drug Administration’s Risk Evaluation and Mitigation Strategy (REMS) for Prasugrel (Effient)

Publication Number: 638

Background: Prasugrel (Effient), a thienopyridine adenosine diphosphate receptor antagonist, was subject to a US Food and Drug Administration (FDA) Risk Evaluation and Mitigation Strategy (REMS) to mitigate the serious risk of bleeding.

Objectives: To characterize the design and assessment of prasugrel’s REMS program and explore the basis for the REMS’ discontinuation.

Methods: Qualitative analysis of 1041 pages of FDA documents obtained through a Freedom of Information Act request, including 1 REMS assessment report (2011), FDA evaluations of this report, and FDA-sponsor correspondence about safety issues. Each document was reviewed by two independent analysts and quantitative information was extracted from patient and health care provider (HCP) knowledge assessments of the REMS.

Results: The prasugrel REMS consisted of a medication guide and a communication plan that included a Dear Healthcare Provider Letter (DHCP) and Prescriber Brochure. Quantitative testing of patient and prescriber knowledge was conducted through questionnaires to assess the impact of the REMS. A total of 201 health care providers participated in the provider survey. A total of 4 out of 11 key risk messages did not meet the pre-defined level of comprehension (80%) with 3 regarding the circumstances under which prasugrel should or should not be discontinued and 1 regarding the maintenance dose for patients weighing less than 132 lbs. A total of 212 patients completed the patient knowledge assessment survey. Sixty-nine percent of respondents reported receiving a medication guide and 80% of these reported reading it. Only 16%-18% of patients demonstrated sufficient understanding of the medical conditions and concomitant medications that increase the risk of bleeding. FDA reviewed the 18-month REMS assessment and concluded that the medication guide, DHCP letter, and Prescriber’s Brochure were distributed per the commitment. However, they requested submission of a proposal to improve patient comprehension of the risk of using prasugrel with history of stroke or transient ischemic attack. The sponsor intended to conduct patient qualitative testing to identify factors associated with limited awareness of the contraindications. In June 2011 the FDA approved revisions made to the medication guide and Prescriber’s Brochure, but no follow-up reports or surveys were conducted. The FDA terminated the prasugrel REMS in March 2012.

Conclusions: Quantitative testing of patient and prescriber knowledge of prasugrel revealed a limited knowledge of risks arising from concomitant medications and contraindications. FDA requested a proposal to improve comprehension of the risk of using prasugrel but terminated the prasugrel REMS prior to implementing further action.