Clozapine REMS Program – Is The End Coming?

For decades, the clozapine REMS program was one of the most well-known safety initiatives done by the FDA. The program was designed to reduce the risk of severe neutropenia. This REMS program has also been a popular target for board exam questions. But is the clozapine REMS program coming to an end?

Why Does Clozapine Have Restrictions?

Clozapine carries a risk of severe neutropenia, with the risk being greatest in the first 18 weeks of treatment. FDA committee members stated that the current rules were overly burdensome on patients, providers, and pharmacies, and currently limited access to an imperative treatment in treatment-resistant schizophrenia. Multiple committee members stated the REMS program was a large barrier to patients receiving their medication in a timely manner and many had experienced delays in obtaining medication due to the requirements of the program. Committee members also stated that physicians should be trusted to be appropriately educated on the risks of this medication and should do their due diligence in monitoring when the risk is the highest.

Review of the Program

In mid-November, the FDA held a joint meeting with two different committees to discuss the REMS program for clozapine products. At the end of the discussion involving a review of the data surrounding neutropenia and safe clozapine use, members reviewed four basic domains.

How reassured or concerned are you that current and potential clozapine healthcare providers have sufficient knowledge or access to resources about the risk of neutropenia and the need for absolute neutrophil count (ANC) monitoring?
How reassured or concerned are you that current and potential clozapine healthcare providers will perform ANC monitoring without the requirements of the REMS program?
Are the requirements for the prescriber to document ANC results and the pharmacy to verify the ANC results through REMS necessary to ensure safety?
Is the requirement to educate health care providers through the REMS about the risk of severe neutropenia and the need for ANC monitoring necessary to ensure safety? Yes or No

The results for both questions 3 and 4 were an overwhelming vote for “No.” That being said, this is only a step in the change of the REMS program as now FDA officials will consider the votes and decide on the next steps.

The Votes

Committee members voted against continuing documentation requirements for patients’ ANC results through REMS by both pharmacies and physicians. They stated that monitoring should continue as directed on the medication’s label (frequency dependent on ANC level) but voted against additional reporting of ANC values. Additionally, members voted against requiring education from physicians about ANC monitoring requirements and the risk of neutropenia to patients. They stated that psychiatrists should be allowed to practice medicine without these barriers in place that limit access to a disease-modifying medication.

While REMS programs may have the patient’s best interest at heart, many health care professionals have discussed the barriers these rules can present in medication access and timeliness which have direct negative effects on the intended population the REMS program was designed to protect, patients.

Do you have strong opinions about REMS programs? Are they effective in serving the needs of our patients? Do you think the FDA will move forward in changing the clozapine REMS program?

Clozapine has more risks than just neutropenia, here are the five boxed warnings associated with this medication.

This article was written by Emma Carlberg, PharmD Candidate in collaboration with Eric Christianson, PharmD, BCPS, BCGP

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