FDA committees strike down monitoring requirements for schizophrenia drug

Two FDA committees overwhelmingly voted to strike down monitoring requirements under a Risk Evaluation and Mitigation Strategy, or REMS, program for clozapine, a medication for individuals with treatment-resistant schizophrenia.

According to the FDA, clozapine can cause severe neutropenia, where the body produces an unusually low number of white blood cells called neutrophils, which may lead to a compromised immune system and serious or fatal infections.

In 2015, the agency approved the REMS clozapine program to ensure prescribers regularly monitor patients’ absolute neutrophil count (ANC) while on the medication.

On Nov. 19, the Drug Safety and Risk Management Advisory Committee and Psychopharmacologic Drugs Advisory Committee held a joint meeting to consider key questions pertaining to the standard of care in management of clozapine:

Are the requirements for the prescriber to document ANC results and the pharmacy to verify the ANC results through the REMS program necessary to ensure safe use?

Is the requirement to educate health care providers through the REMS program about the risk for severe neutropenia and the need for ANC monitoring necessary to ensure safe use?

The vote on both questions was 14 no, 1 yes.

Both votes in favor of the REMS requirements were by Walter Dunn, MD, PhD, a staff psychiatrist at the Veterans Administration Greater Los Angeles Healthcare System. He said his vote on the first question was based on the potential risk within the 18-week window where a REMS could be useful to provide monitoring guidance, as well as a need to streamline communication between patients, prescribers and pharmacies.

Regarding the second question, Dunn pointed out that an “educational component” is needed for other antipsychotic medications, such as ketamine, for which registration is required by both provider and pharmacy.

“No doubt, [clozapine] is a life-saving drug,” he averred. “This is pretty much our only option for treatment-resistant schizophrenia. But clearly it has more management issues than some of our other antipsychotics.”

The main rationale cited by panel members who voted against the requirements centered around reducing the bureaucratic burden on health care professionals as well as removing a barrier to prescribing the drug, particularly for patients who require an emergency supply.

In her vote against the first question, Sascha Dublin, MD, PhD, affiliate professor in the department of epidemiology at the University of Washington School of Public Health acknowledged the need for monitoring clozapine. However, she noted, “I do not believe the REMS approach to documenting and enforcing that is serving the health of the patient, the needs of the community or the well-being of providers.”

Explaining her “no” vote on the second question, Maryann Amirshahi, PharmD, MD, MPH, emergency medicine physician at MedStar Washington Hospital Center, disputed the notion that certification should be required from a physician or pharmacy to prescribe clozapine.

Citing an unnecessary burden on patients who need the medication when in danger of low supply, she said, “I think this would be one less barrier to prevent people from falling through the cracks and decompensating.”

Reference:

• Information on clozapine. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/information-clozapine. Accessed Nov. 19, 2024.