New requirements roll out on Nov. 15

The FDA issued a reminder that it is modifying the Risk Evaluation and Mitigation Strategy (REMS) for the schizophrenia drug clozapine, effective Nov. 15.

The new requirements, which the agency first announced at the end of July 2021, are intended to further protect patients from the risk of severe neutropenia associated with use of the drug, the agency explained.

“The modifications were necessary to ensure safe use of clozapine while maintaining patient access,” the FDA wrote. “The Clozapine Products Manufacturers Group proposed a modification to the REMS to remove the use of telecommunication verification (the switch system) for pharmacies to verify safe use conditions. After Nov. 15, 2021, pharmacies will need to contact the REMS Program by phone or online to verify safe use conditions. The removal of the switch necessitated a modification of the REMS. Changes were also made to improve the process for a prescriber to submit absolute neutrophil count (ANC) results. Depending on the patient’s monitoring frequency, this could require daily, weekly, biweekly, or monthly documentation of the ANC. In order to reduce the burden on prescribers and minimize unintended treatment interruption for patients, the documentation of ANC will now be submitted monthly.”

The agency emphasized that they are not modifying REMS requirements for patients currently taking clozapine, and patients do not need to take any action. However, due to the significant changes being made, prescribers will have to re-enroll their patients by Nov. 15 in order to continue treatment with the drug. As for patients who are starting clozapine between now and the Nov. 15 update, physicians will need to enroll those individuals in both the current REMS program and the updated program.

All pharmacies will also need to re-certify in the REMS before dispensing clozapine to patients, the agency noted, and pharmacy management systems that currently rely on the switch system might need to develop new processes and procedures to be able to continue dispensing clozapine.

“The Pre-Dispense Authorization (PDA) will be replaced by a REMS Dispense Authorization (RDA),” the FDA wrote. “For outpatient pharmacies, RDA of the first dispense will verify that the pharmacy is certified, patient is enrolled, and patient’s treatment is not interrupted or discontinued. RDA for subsequent dispensings will verify that that pharmacy is certified, patient is enrolled, a Patient Status Form has been completed in the last 37 days, and patient’s treatment is not interrupted or discontinued.”

There will be no changes to the requirements for pharmacies that dispense clozapine for inpatient use, the agency added.

The FDA announcement contains specific instructions for prescribers and authorized pharmacy representatives to re-certify and re-enroll in the REMS program for clozapine; to reach the new REMS website:

In addition to the risk for severe neutropenia, clozapine also carries a boxed label warning for orthostatic hypotension, brachycardia, and syncope; seizure; myocarditis, cardiomyopathy, and mitral valve incompetence; and increased mortality in elderly patients with dementia-related psychosis, for which the drug is not approved.

John McKenna, Associate Editor, BreakingMED™

Cat ID: 57

Topic ID: 87,57,730,192,57,725,925