Patient Advocacy Groups Demand Significant Changes to Clozapine REMS

Rachel Streiff is legal guardian for an adult woman who has been prescribed the antipsychotic clozapine for treatment-resistant schizophrenia, and—like the patients who rely on clozapine and their parents and caretakers featured in the vignettes above—she is furious.

“She has had her clozapine interrupted multiple times with tragic consequences—prolonged hospitalizations, symptoms of cholinergic rebound, and severe setbacks to her recovery,” Streiff told Psychiatric News. “If you’re prescribed clozapine, your life depends on it. Even 24 hours without the drug will have significant consequences.”

Streiff is a leader and founding member of The Angry Moms, a coalition of hundreds of parents and patient advocates who are … well … angry. They say treatment interruptions have in every case been the result of a cautionary protocol imposed on the prescription of clozapine by the Food and Drug Administration (FDA)—the Risk Evaluation and Mitigation Strategy, or REMS. A total of 73 drugs approved by the FDA are accompanied by a REMS because of health risks that are deemed serious enough to merit a higher degree of oversight and monitoring by prescribers and dispensing pharmacists.

The FDA requires the Clozapine REMS to manage the risk of severe neutropenia—known as agranulocytosis—associated with clozapine treatment. Originally instituted in September 2015, the REMS actually stems from a blood-monitoring requirement imposed by the drug’s manufacturers as a condition of its approval 30 years ago in 1990 (see “‘Godfather of Clozapine’ Calls for End to REMS,” p. 21). The REMS applies to all clozapine medicines on the market and comes with a set of requirements known as “elements to assure safe use” (ETASU) that include lifetime regular blood monitoring of patients and the use of a centralized system in which prescribers and pharmacists are mandated to report blood monitoring.

Streiff noted that there is no official database for recording the kind of bad outcomes (reported in The Angry Moms’ “Negligence of the Week”) that stem from treatment disruptions caused by REMS. She added that when those disruptions do occur, it is potentially dangerous for caregivers and the surrounding community, as well as for the patient.

Of the woman for whom she is guardian, Streiff said: “She has never missed a blood test, never had a low value. She is not at risk for agranulocytosis from clozapine. There is absolutely no reason why her treatment has been interrupted the way it has.”