Navigating the New Clozapine REMS

Bret S. Stetka, MD; Mitchell Mathis, MD


December 04, 2015

Editorial Collaboration

Medscape &

Components of the New REMS

Medscape: What are the components of the new REMS program, and how is it different from the previous programs?

Dr Mathis: The new shared clozapine REMS program has similar components to the previous registries in that prescribers, pharmacies, and patients must be enrolled to prescribe, dispense, or receive clozapine. Prescribers and pharmacists are still required to check a patient's ANC on the basis of the patient's monitoring schedule, to make sure it is current and within the acceptable range as described in the prescribing information before dispensing.

There are also many differences in the clozapine REMS program from the previous registries that have been put in place to support the changes to the prescribing information. For example:

  • Patients with benign ethnic neutropenia(BEN), who previously were not eligible for clozapine treatment, will now be able to receive the medicine. Prescribers can identify patients with BEN in the new program, which places those patients on a different monitoring algorithm with lower ANC thresholds than the thresholds for the general population.

  • Prescribers have greater flexibility to make individualized treatment decisions about continuing and resuming treatment in patients who experience moderate to severe neutropenia if they determine that the risk for psychiatric illness is greater than the risk for moderate to severe neutropenia. The decision to continue treatment needs to be documented with the clozapine REMS program before an outpatient can continue treatment.

The prescribing information with regard to how to monitor neutropenia and manage clozapine treatment have become more complex. It includes two different monitoring algorithms and increased flexibility to continue or resume treatment in patients. For this reason, the clozapine REMS program was designed with an enhanced infrastructure, which was determined necessary to support communication between prescribers and pharmacists.

Once fully operational, the clozapine REMS program will require a "predispense authorization" (PDA) in order for pharmacists to dispense clozapine in an outpatient setting. The PDA is an electronic code indicating that the program's safe use requirements are verified (electronically) and it is safe to dispense the drug. Outpatient pharmacies have a choice as to how to obtain the PDA, and some pharmacies are incorporating this verification step into their pharmacy management systems, so that this verification is done at the same time (and in a similar way) as electronic insurance claim adjudication is taking place.

In the previous registries, prescribers and pharmacists enrolled as a "treatment team," which meant patients had to continue to fill their clozapine with a specific pharmacy. In the new program, prescribers and pharmacies are not linked, and a patient can fill his or her clozapine prescription at any pharmacy that is enrolled. Similarly, any certified prescriber can write a prescription for a patient.

Medscape: What does this mean for existing patients currently receiving clozapine? Do they have to be reregistered?

Dr Mathis: Patients who were previously treated with clozapine were automatically transferred to the new clozapine REMS program. We do understand that there were some challenges with migrating all previous patients, especially those who had incomplete information or different information across multiple registries. The clozapine manufacturers continue to work through these data reconciliation issues. To resolve the issues, it often requires contacting the call center to speak to a representative directly.

Because of data issues like this, the clozapine REMS call center has been extremely busy. Wait times are improving, but this has been a source of frustration for healthcare providers.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: