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Approved Risk Evaluation and Mitigation Strategies (REMS)

Xiaflex (collagenase clostridium histolyticum)
BLA #125338
REMS last update: 10/11/2024



What is the purpose of the REMS?

    1. The goal of the XIAFLEX REMS is to mitigate the risks of corporal rupture (penile fracture) and other serious penile injuries associated with the use of XIAFLEX for Peyronie’s disease by:
      1. Training healthcare providers in how to properly administer XIAFLEX.
      2. Informing healthcare providers about the risks of corporal rupture (penile fracture)and other serious injuries to the penis.
      3. Informing healthcare providers about the need to counsel patients to communicate that risks of corporal rupture and other serious penile injuries are associated with the use of XIAFLEX in treating Peyronie’s disease and that patient adherence to post-injection instructions is important for the drug’s safety and effectiveness.
      4. Ensuring that XIAFLEX is dispensed only in certified pharmacies or healthcare settings for the treatment of Peyronie’s disease.
      5. Informing patients about the risks of corporal rupture and other serious penile injuries associated with the use of XIAFLEX in treating Peyronie’s disease and that adherence to post-injection instructions is important for the drug’s safety and effectiveness.

What do participants need to know?

Below is a general overview of the REMS for all REMS participants (e.g., patients, pharmacies, and healthcare providers). See the application holder(s) REMS Website or the approved REMS materials for more information.

View application holder(s) REMS Website See Disclaimer page regarding links to external sites

Healthcare Providers who prescribe Xiaflex for Peyronie’s disease must:

To become certified to prescribe
  • Be able to manage male urological diseases.
  • Review the drug’s Prescribing Information.
  • Review the following: Education Program/Training Guide for Healthcare Providers or Training Video.
  • Enroll in the REMS by completing the Healthcare Provider Enrollment Form and submitting it to the REMS Program.
Before treatment initiation (first dose)
  • Counsel the patient on the risks, including corporal rupture and other serious penile injuries and the need to follow important post-injection instructions using the Patient Guide.
  • Provide the patient with a copy of Patient Guide.
During treatment, before each injection
  • Counsel the patient on the risks, including corporal rupture and other serious penile injuries and the need to follow important post-injection instructions using the Patient Guide.
  • Provide the patient with a copy of Patient Guide.

Patients who are prescribed Xiaflex for Peyronie’s disease:

Before treatment initiation
  • Review the Patient Guide
  • Receive counseling from the prescriber on the risks, including corporal rupture and other serious penile injuries and the need to follow important post-injection instructions using the Patient Guide.
Before administration
  • Receive counseling from the prescriber on the risks, including corporal rupture and other serious penile injuries and the need to follow important post-injection instructions using the Patient Guide.

Pharmacies and healthcare settings that dispense Xiaflex for Peyronie’s disease must:

To become certified to dispense
  • Designate an authorized representative to carry out the certification process and oversee implementation and compliance with the REMS Program on behalf of the healthcare setting.
  • Have the authorized representative enroll in the REMS Program by completing the Healthcare Settings Enrollment Form and submitting it to the REMS Program.
  • Establish processes and procedures to verify that the healthcare provider prescribing XIAFLEX for Peyronie’s disease is certified.
  • For healthcare settings: Establish processes and procedures to maintain a current list of certified healthcare providers affiliated with the healthcare setting.
Before dispensing
  • Verify the prescriber is certified through the processes and procedures established as a requirement of the REMS program.
To maintain certification to dispense
  • Have a new authorized representative enroll in the REMS Program by completing the Healthcare Settings Enrollment Form if the authorized representative changes.
To maintain certification to dispense, every 2 years
  • Have the authorized representative re-enroll in the REMS Program by completing the Healthcare Settings Enrollment Form.
At all times
  • Not distribute, transfer, loan, or sell Xiaflex.
  • Maintain records that all processes and procedures are in place and are being followed.
  • Maintain records of certified prescribers affiliated with your healthcare setting
  • Comply with audits carried out by Endo USA, Inc., and/or designated third party to ensure that all processes and procedures are in place and are being followed.

Wholesalers-distributors that distribute Xiaflex must:

To be able to distribute
  • Establish processes and procedures to ensure that the drug is distributed only to certified pharmacies and healthcare settings.
  • Train all relevant staff involved in ensure that the drug is distributed only to certified pharmacies and healthcare settings.
At all times
  • Distribute only to certified pharmacies and healthcare settings.
  • Maintain records of distribution.
  • Comply with audits carried out by Endo USA, Inc., and/or designated third party to ensure that all processes and procedures are in place and are being followed.

What materials are included in the REMS?

The REMS includes a REMS Document. In addition, the REMS includes the following materials intended for patients and healthcare providers. For a specific Medication Guide of a product in the Xiaflex REMS, see the DailyMed link(s).
Material Name Material Name Link
Education Program/Training Guide for Healthcare Providers (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xiaflex_2024_10_11_Education_Program_Training_Guide_for_Healthcare_Providers.pdf
Healthcare Provider Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xiaflex_2024_10_11_Healthcare_Provider_Enrollment_Form.pdf
Healthcare Setting Enrollment Form (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xiaflex_2024_10_11_Healthcare_Setting_Enrollment_Form.pdf
REMS Document (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xiaflex_2024_10_11_REMS_Document.pdf
REMS Full (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xiaflex_2024_10_11_REMS_Full.pdf
REMS Website (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xiaflex_2024_10_11_REMS_Website.pdf
Training Video (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xiaflex_2024_10_11_Training_Video.pdf
What You Need To Know About Xiaflex Treatment: A Patient Guide (PDF) https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xiaflex_2024_10_11_What_You_Need_To_Know_About_Xiaflex_Treatment_A_Patient_Guide.pdf
Assessment Plan

This webpage provides REMS assessment plan measures, metrics, and indicators for drug and biological products with a REMS. The REMS assessment plan measures, metrics, and indicators are part of the overall REMS assessment plan used by FDA to evaluate the performance of a REMS and are included in FDA approval letters. The current REMS assessment plan measures, metrics, and indicators are extracted from regulatory letters that contain REMS information, including FDA approval letters, and posted here as they become available.

What updates have been made to the REMS?

Date Summary of change
10/11/2024 Modified to:

1) Update REMS materials due to changes in the REMS Administrator; and

2) Change the REMS website to enhance operational flow and accommodate technical capabilities of the REMS Administrator; and

3) Include editorial revisions of layout and incorporation of Endo USA, Inc. and updated Endo logo across REMS materials.

11/02/2022 Modified to:

  1. Convert the REMS Document to the new, standardized format
  2. Make changes to the Patient Counseling Tool based on the results from qualitative testing studies
  3. Improve website functionality due to a change in REMS administrator
06/09/2022 Modified to remove the mail-in option for healthcare provider and pharmacy/healthcare setting enrollment and other minor updates due to a REMS administrator change.
01/11/2022 Modified to update the REMS materials to reflect the safety labeling changes that were recently approved on August 19, 2021 and approved labeling regarding penile hematoma.
10/30/2018 Revised to reflect minor editorial changes.
09/26/2018 Modified to revise REMS educational materials to align with safety labeling changes.
07/10/2018 Revised to reflect a change in ownership.
01/25/2017 Revised to correct a typographical error (s).
11/28/2016

  1. Modified the REMS for the treatment of Dupuytren’s contracture to:
    1. Remove the communication plan from the REMS.
    2. Release the REMS requirements.
  2. Modified the REMS for the treatment of Peyronie’s disease to:
    1. Change to the Prescriber Material, “Training Guide for the Administration of Xiaflex for Peyronie’s Disease”
    2. Change to the Patient Counseling Tool, “What You Need to Know About XIAFLEX Treatment for Peyronie’s Disease: A Patient Guide”
    3. Align the Training Video with the Prescriber Material.
    4. Align the Xiaflex REMS Program website with the Prescriber Material.
    5. Remove information related to the communication plan.
10/20/2014

  1. Modified the REMS for the treatment of Dupuytren’s contracture to:
  1. Include the following change to information in the dosing regimen: two concurrent injections of Xiaflex into palpable cords affecting multiple joints in the same hand in adult patients with Dupuytren’s contracture with finger extension procedure 24 to 72 hours after injection; and
  2. Include the risk of skin laceration requiring skin graft in patients treated with Xiaflex (collagenase clostridium histolyticum) in the communication plan materials (Dear Healthcare Provider Letter; Training Guide for the Administration of Xiaflex; and Xiaflex Procedure Training Video).
12/06/2013 Modified to ensure that the benefits of the drug outweigh the risk of corporal fracture (penile fracture) and other serious penile injuries by ensuring that healthcare providers who prescribe XIAFLEX (collagenase clostridium histolyticum) for Peyronie’s disease are specially certified, and that pharmacies or healthcare settings that dispense XIAFLEX (collagenase clostridium histolyticum) for Peyronie’s disease are specially certified.
02/24/2012 Modified to:

  1. Eliminate the requirement for the Medication Guide as an element of the REMS.
  2. Address the requirements in our June 1, 2011 REMS Modification Notification letter to revise some of the communication plan materials to more effectively educate prescribers about the risks when injecting Xiaflex into a cord of the proximal interphalangeal joint of the fifth finger.
02/02/2010 Approval of the REMS.

Disclaimer: This webpage provides general information about REMS programs to various REMS participants (e.g., patients, pharmacies, and healthcare providers). The summary information provided herein is not comprehensive and may not include all of the information relevant to REMS participants. This webpage does not constitute a replacement, modification, or revision of the approved REMS document, including any appended REMS materials. Refer to the approved REMS document for complete information on the REMS requirements for each approved application.

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