What are the current guidelines for Clozaril (Clozapine) day supply in California now that the REMS (Risk Evaluation and Mitigation Strategy) program is no longer in place?

Current Clozaril (Clozapine) Day Supply Guidelines in California Without REMS Program

With the discontinuation of the REMS program in California, Clozaril (clozapine) can now be dispensed with up to a 30-day supply, though providers should still ensure regular blood monitoring is performed according to standard clinical protocols.

Background on Clozapine Monitoring Changes

Historically, clozapine was subject to one of the most stringent risk management programs due to its association with potentially fatal agranulocytosis. The Clozaril National Registry (CNR) was established to enforce a "no blood, no drug" policy that significantly reduced mortality associated with clozapine-induced agranulocytosis 1.

Prior to the discontinuation of the REMS program in California, clozapine dispensing was tightly controlled through:

• Mandatory white blood cell (WBC) count monitoring
• Registration in a centralized system
• Restricted dispensing based on monitoring results
• Limited day supply to ensure regular patient monitoring

Current Guidelines for Dispensing in California

Without the REMS program restrictions in California, the dispensing guidelines have changed in the following ways:

Day Supply Guidelines

• Standard dispensing can now be up to 30 days supply
• No mandatory registry enrollment for prescribers, pharmacies, or patients
• No centralized system restricting dispensing based on WBC results

Monitoring Recommendations

Despite the removal of the REMS program, clinical best practices still recommend:

• Regular WBC monitoring (typically weekly for the first 6 months)
• After 6 months of stable therapy, monitoring can be reduced to every 2 weeks 1
• Documentation of monitoring results in the patient's medical record

Clinical Considerations for Prescribers

While the regulatory requirements have changed, the clinical risks of clozapine remain the same. Providers should:

1. Maintain vigilant monitoring for agranulocytosis and other adverse effects
2. Document WBC counts before dispensing medication
3. Educate patients about the importance of adherence to monitoring schedules
4. Consider patient-specific factors when determining appropriate day supply:
   • Stability on medication
   • History of compliance with monitoring
   • Access to laboratory facilities
   • Risk of medication discontinuation

Potential Pitfalls and Caveats

• Loss of centralized protection: Without the CNR, there is no universal system preventing inappropriate rechallenge in patients who previously developed agranulocytosis 1
• Medication switching risks: Studies have shown that switching stable patients from branded Clozaril to generic clozapine has been associated with clinical worsening in some patients 2
• Monitoring compliance: Without mandatory monitoring tied to dispensing, there's increased responsibility on providers to ensure patients complete regular blood work
• Documentation importance: Thorough documentation of monitoring results becomes even more critical without a centralized registry

Conclusion

The removal of the REMS program in California represents a significant change in the regulatory approach to clozapine dispensing. While this allows for greater flexibility in prescribing and potentially improved access for patients, it places additional responsibility on healthcare providers to maintain appropriate monitoring protocols to ensure patient safety.