Nearly a decade in the making, University of Maryland, Baltimore pharmacy and medical experts were instrumental in a groundbreaking vote in November to remove a longstanding barrier to patients being prescribed clozapine, a medication used to treat schizophrenia and schizoaffective disorder.  

A joint U.S. Food and Drug Administration (FDA) advisory committee — the Drug Safety and Risk Management Advisory Committee and the Psychopharmacologic Drugs Advisory Committee — voted overwhelmingly on Nov. 19 to eliminate the risk evaluation and mitigation strategy (REMS) program for clozapine.  

Deanna Kelly and Raymond Love

If the FDA implements the recommendation, this change will remove undue burden on patients, family members, caregivers, and medical professionals. 

Deanna Kelly, PharmD, BCPP, acting director of the Maryland Psychiatric Research Center at the University of Maryland School of Medicine (UMSOM), and Raymond Love, PharmD, BCPP, FASHP, professor emeritus of practice, sciences, and health outcomes research and former director of the University of Maryland School of Pharmacy's (UMSOP) Mental Health Program, provided testimony ahead of the vote.  

Megan Ehret, PharmD, MS, BCPP, professor of practice, sciences, and health outcomes research and co-director of UMSOP's Mental Health Program, and Gopal Vyas, DO, an adjunct faculty member with UMSOM, were ad hoc members of the committee. 

“I am hopeful that the FDA will now ease access to clozapine,” Love said. “Once it acts to modify or remove the REMS, it will take a concerted effort to communicate the change to health care providers. We will need to inform them about the administrative changes related to the REMS and educate them about the safe and effective use of clozapine. In this way, we can bring the promise of clozapine to additional patients and families.” 

As it stands now, the REMS requires patients on clozapine to undergo weekly blood tests for the first six months of treatment, followed by blood tests every two weeks until one year of treatment, followed by indefinite monthly tests. The tests are required because of the potential side effect of severe neutropenia, which is associated with an increased risk of serious and potentially fatal infections. 

The blood test results must be documented by prescribers to a national system.  Pharmacies then must get permission from this system to dispense the medication.  

“Prescribers should be completing the monitoring without the added step of documentation, and pharmacists should be able to dispense clozapine without verifying that prescribers are completing the monitoring,” Ehret said. “With the benefits of clozapine far outweighing the risks, I believe the REMS has created undue burden on patients and health care providers.” 

The REMS requirement, which was implemented in 2015, is especially burdensome to those with schizophrenia and their caregivers who are often members of vulnerable populations without easy access to labs for blood draws.  

Because of the blood test and documentation requirements, there can be an interruption in treatment and a worsening of the patient’s illness.  

“Last week, we were proud to take part in the historic call for an end to the burdensome REMS that has hobbled clozapine from the start,” Vyas said. “What has become clear is that the myriad harms from the clozapine REMS far outweigh any intended benefit. Without the REMS, we can appropriately utilize the only effective medicine in all of psychiatry for treatment-resistant schizophrenia and the only proven anti-suicidal medication for this patient group.” 

 Instead of decreasing the risk of neutropenia, the REMS created barriers to accessing the medication, leading patients to suffer from withdrawal and other severe side effects, including suicide attempts.  

 Research indicates severe neutropenia only occurs in a small percentage of patients prescribed clozapine. The joint committee found the current requirements for both prescribers and pharmacies unnecessary to ensure safe use of the medication.  

 The FDA still must vote on whether to remove the REMS requirement. And while it is not required to follow the committee’s recommendation, it often does.   

 If the FDA moves forward with the recommendation, it is likely other countries will follow suit.  

“Clozapine is vastly underused nationally, and our group has been actively researching it and trying to break down barriers for over 20 years,” Kelly said. “Nov. 19 was a very moving day at the FDA advisory board meeting, and I am grateful for the families and patients who testified at the meeting and shared their stories. Along with the anticipated changes to the clozapine REMS by the FDA, we plan to work diligently to expand clozapine use in Maryland and nationally.”