Clozapine REMS 2021

Changes to the Clozapine REMS have been announced and are to be implemented on 11/15/2021. Additional information is available through the following FDA and CPNP resources:

December 16: FDA Listening Session

CPNP and its advocacy partners met with the FDA again on December 16. CPNP Past President Ray Love, PharmD, BCPP, presented the concerns of the coalition which members can also view here. Specific challenges were detailed out in the presentation and also provided to the FDA in writing. Stakeholders concluded by reiterating that the transition to the new clozapine REMS has placed unjustified burdens on health care providers and health care systems and continued requirements of questionable effectiveness. The risk the REMS puts on patients and the fact that it discourages use of an underutilized drug that could benefit even more patients was emphasized. In closing, the stakeholders respectfully asked the FDA to eliminate or modify the most problematic elements of the REMS, or at the very least, to engage in a constructive dialogue (not just listening sessions) with representatives of the stakeholders regarding alternative, less burdensome strategies to preserve patient safety. The stakeholders further requested that the FDA devise a scientific forum to hear the concerns regarding clozapine product labeling that have resulted in a complex, burdensome REMS that places patients at risk.

December 2, 2021: Listening Session with FDA

CPNP and fellow stakeholders had the opportunity to engage with the FDA on December 2, 2021 in a listening session related to the new Clozapine REMS. CPNP Past President Ray Love, PharmD, BCPP presented remarks on behalf of the stakeholders noting the continued challenges related to the new REMS and stakeholder recommendations below. CPNP and stakeholders have another listening session with the FDA on December 16 and will keep the CPNP membership apprised of the discussion and any outcomes.

  1. Permanently revoke the requirement for pharmacy enrollment and mandate extensive education for all wholesalers and all of their personnel regarding this issue;
  2. Declare a permanent end to the need for RDAs and Transition dispensing authorizations;
  3. Suspend the entire clozapine REMS Program until such time that it can undergo a comprehensive evaluation for the scope, necessity, benefits, risks and usability of the program; 
  4. Require that the REMS cannot be reinstituted until after the conduct of an extensive education program for all stakeholders including payers and wholesalers;
  5. Require website changes that inform users of mandatory versus optional data entry fields and/or provide improved instructions for users;
  6. Require website changes that make the patient’s current monitoring frequency more easily accessible and visible to pharmacists;
  7. Launch an immediate investigation into reimbursement issues or refer this matter to an appropriate agency to do so; and,
  8. Convene a discussion with PBMS, insurers and payers about clozapine reimbursement or refer this matter to an appropriate agency to do so.

Read the prepared statement here.

November 19, 2021: FDA Temporarily Suspending Certain Clozapine REMS Program Requirements to Ensure Continuity of Care for Patients Taking Clozapine

Health care professionals continue to alert FDA about ongoing difficulties with the Clozapine REMS program, including a high call volume and long call wait times for stakeholders since launch of the program on November 15, 2021. We understand that this has caused frustration and has led to patient access issues for clozapine. FDA takes these concerns seriously. Continuity of care, patient access to clozapine, and patient safety are our highest priorities. We are working closely with the Clozapine REMS program administrators to address these challenges and avoid interruptions in patient care. 

Due to problems with implementation and the potential impact to patient care, FDA is temporarily suspending certain Clozapine REMS program requirements:

  • Pharmacists may dispense clozapine without a REMS dispense authorization (RDA).
  • Wholesalers may continue to ship clozapine to pharmacies and health care settings without confirming enrollment in the REMS

Abrupt discontinuation of clozapine can result in significant complications for patient treatment. Health care professionals should use their clinical judgment with regard to prescribing and dispensing clozapine to patients with an absolute neutrophil count (ANC) within the acceptable range.

We encourage pharmacists and prescribers to continue working with the Clozapine REMS to complete certification and patient enrollment.

If you have questions or concerns about the Clozapine REMS Program or its website, please contact FDA at druginfo@fda.hhs.gov, 1-855-543-3784 or 301-796-3400.

November 19, 2021: Summary of FDA Meeting with Pharmacy Stakeholders Regarding Urgent Clozapine REMS Issues

November 12, 2021: 90-Day RDA Transition Period, Other Updates

On Friday, November 12, 2021, the FDA sent several communications to CPNP and the other stakeholders regarding the Clozapine REMS Program. One communication asked the stakeholders to hold a date for follow up meetings regarding the REMS in December. The second communication addressed several issues that the stakeholders had posed in our communications. 

In their response, the FDA indicates that there will not be a delay in the implementation of the REMS. However, they do indicate that there will be a transition period that will allow a pharmacist to obtain a REMS Dispense Authorization (RDA) even if the patient has not been enrolled in the REMS. Depending on the specifics, this would be an important comprise. The problem is that they supply no details on how this will work and whether it will work for unenrolled community pharmacies. We will probably not find out until Monday, November 15, 2021. They also indicate that they will continue this transition policy regarding RDAs longer than 90 days if necessary.

CPNP urges any members who learn more about these changes to the RDA system on Monday, November 15, 2021 to share their experiences by emailing info@cpnp.org.

The FDA asserts that the RDA “ensures providers are monitoring patients and documenting their absolute neutrophil count and risk/benefit analysis for continuing treatment.” The stakeholders have stated that a 37-day retrospective view using a Patient Status Form (PSF) does not ensure this in a manner that promotes patient safety. It also inappropriately assigns pharmacists roles as “enforcers” rather than collaborative team members.

CPNP is aware that many pharmacists were unaware of any prior policy limiting clozapine discharge supplies from hospital pharmacies to seven days. The FDA says that this a carryover policy. They are willing to further discuss this matter. They are also willing to discuss the issue of classification of pharmacies.

Finally, they note that the REMS has made changes to the designee system. They ask for further information regarding the problems with pharmacists and prescribers also fulfilling roles as designees. CPNP will respond to this request for information in coordination with the other stakeholders in the coming days.

CPNP has taken a leading role in addressing the challenges of this new Clozapine REMS. Please continue to send us your questions and experiences so that we may share them with both the FDA and our colleague stakeholder organizations. The information that you have provided has helped lead to the changes we have seen pre-implementation. It will be essential as we continue meeting with the FDA.

November 10, 2021: Guidance on Prescriber Desginees

As part of our ongoing dialogue with the FDA regarding the New Clozapine REMS (NCR), we have received further guidance on the issue of prescriber designees. In the initial release of the NCR, there were many important components of the current system that were problematic. In particular:

  • The designation of a prescriber designee had to be initiated by the prescriber rather than the designee.
  • A single individual could only serve as a prescriber designee for a single prescriber (unless they utilized a separate email address for each prescriber).

Details regarding a recent update to the REMS addresses these two issues. A many-prescriber to many-prescriber-designee relationship can now be established. And, a potential prescriber designee can now initiate the prescriber-prescribe designee relationship. However, they need the prescriber's NPI to initiate this process. This is accomplished by a new prescriber designee account creation process. Meanwhile, the prescriber uses the "Manage Personnel" button on the prescriber page to deal with their designees.

One CPNP member who tested this system notes that the prescriber is not actively informed of the prescriber designee request, but has to check the through the "Manage Personnel" button for new designee requests.

To the best of our knowledge, this change still does not allow an individual enrolled in NCR as a pharmacist to serve as a prescriber designee without the use of a second email address.

November 10, 2021: Email to FDA Concerning Unresolved Clozapine REMS Issues

September 15, 2021: CPNP Recommendations to FDA and CPMG

Clozapine in Practice

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Clozapine is the medication of choice for those with treatment-resistant schizophrenia. Clozapine is also FDA approved for the reduction in suicidal behavior in schizophrenia or schizoaffective disorder and effective for treatment-resistant mood disorders. Despite the clinical benefits of clozapine, hesitancy to prescribe the medication is not uncommon based on perceived dangers and rigorous monitoring parameters. One method to overcome barriers of clozapine use includes ensuring adequate education about the medication.

As an update to the 2011 toolkit in the MHC, this version contains important clozapine-related drug information such as:

  • Considerations when starting clozapine 
  • Baseline screening parameters  
  • Ongoing monitoring 
  • Drug interactions 
  • Potential adverse reactions with prevention and management strategies    
  • An introduction to clozapine-augmentation strategies 

Authored by CPNP members Jonathan G. Leung, PharmD, BCPS, BCPP, Greg Deardorff, PharmD, BCPP, Megan Trout, PharmD, and Robin Hieber, PharmD, BCPP, this toolkit is intended to highlight both the evidence base available as well as strategies of clinical decision making used by expert clinicians.