Clozapine was one of the first drugs to have a “REMS” system in place to ensure safe use such that patients developing clozapine-induced severe neutropenia were precluded from getting the drug, which would do further damage, and, thus, avoiding potentially life-threatening scenarios.

Initially, the REMS program was independently operated by the innovator and, once the original generics were approved, each individual manufacturer developed and maintained its own REMS program.  Then the FDA moved towards a goal of a single REMS program and requested that firms develop and join a combined REMS program.  After a significant amount of negotiation, a single program was developed and approved, and all clozapine manufacturers now participate in that one, combined program.  The single program provides greater assurance that any patient who develops neutropenia will be well-monitored and, if it progresses to a certain severity, that they will no longer be eligible for continuation on that therapy regardless of which manufacturer’s drug is dispensed.  This REMS program was known as the “no blood, no drug” program, meaning that if you didn’t have a blood test showing your absolute neutrophil count, than you could not get the drug.  This was designed to protect the patients.

The modified, approved REMS program goes into effect on November 15, 2021 and requires action by healthcare providers to obtain recertification and also to reenroll all of their patients into the new program.  Failure to act by the November 15th deadline could result in a delay in providing patients their medications.  Healthcare providers that fail to recertify will have new prescriptions and refills denied for their patients.  Patients do not need to take any action.

The FDA notice of the program modification can be found here.  All healthcare providers are being notified of this modification, which the Agency spells out in detail, including all of the changes that are being made, the monitoring timeframes, and the removal of the “switch system,” which previously allowed telecommunication verification for safe-use determination.  As the FDA notes:

  • Pharmacies will no longer be able to use telecommunication verification (also known as the switch system) to verify safe-use conditions for clozapine. The authorization to dispense clozapine can be obtained either through the contact center or online via the REMS website.
    • Pharmacists will need to go to or call the Clozapine Contact Center to verify information and obtain a REMS dispense authorization to dispense clozapine.
  • There is a new patient status form to document monitoring for all outpatients. This form must be submitted monthly.
  • Patient monitoring must still continue per the prescribing information.

Please review the entire notice so your patients are not left in a difficult position when trying to fill or refill a prescription for clozapine.