Approved Risk Evaluation and Mitigation Strategies (REMS)

Xiaflex (collagenase clostridium histolyticum)

BLA #125338

REMS last update: 11/02/2022

• View the Xiaflex Prescribing Information and Medication Guide at DailyMed.
• View Xiaflex's Regulatory Information at Drugs@FDA

• Goals
• Summary
• REMS Materials
• Assessment Plan
• Update history

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

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. | REMS Training Guide for Administering Xiaflex for Peyronie's Disease | | Training Video for Administering Xiaflex for Peyronie's Disease | Enroll in the REMS by completing the Healthcare Provider Enrollment Form and submitting it to the REMS Program. | Healthcare Provider Enrollment Form for Peyronie's Disease |
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. | What You Need to Know About Xiaflex A Patient Guide | Provide the patient with a copy of Patient Guide. | What You Need to Know About Xiaflex A 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. | What You Need to Know About Xiaflex A Patient Guide | Provide the patient with a copy of Patient Guide. | What You Need to Know About Xiaflex A Patient Guide |

Patients who are prescribed Xiaflex for Peyronie’s disease:

Before treatment initiation	Review the Patient Guide | What You Need to Know About Xiaflex A 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. | What You Need to Know About Xiaflex A 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. | What You Need to Know About Xiaflex A Patient Guide |

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

To become certified to dispense and oversee implementation and compliance with the REMS Program on behalf of the healthcare setting.	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. | Pharmacy/Healthcare Setting Enrollment Form for Peyronie's Disease | 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. | Pharmacy/Healthcare Setting Enrollment Form for Peyronie's Disease |
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. | Pharmacy/Healthcare Setting Enrollment Form for Peyronie's Disease |
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 Pharmaceuticals, 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 Pharmaceuticals, 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
Healthcare Provider Enrollment Form for Peyronie's Disease (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xiaflex_2022_11_02_Healthcare_Provider_Enrollment_Form_for_Peyronie's_Disease.pdf
Pharmacy/Healthcare Setting Enrollment Form for Peyronie's Disease (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xiaflex_2022_11_02_Pharmacy_Healthcare_Setting_Enrollment_Form_for_Peyronie's_Disease.pdf
Program Website Screenshots (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xiaflex_2022_11_02_Program_Website_Screenshots.pdf
REMS Document (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xiaflex_2022_11_02_REMS_Document.pdf
REMS Full (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xiaflex_2022_11_02_REMS_Full.pdf
REMS Training Guide for Administering Xiaflex for Peyronie's Disease (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xiaflex_2022_11_02_REMS_Training_Guide_for_Administering_Xiaflex_for_Peyronie's_Disease.pdf
Training Video for Administering Xiaflex for Peyronie's Disease (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xiaflex_2022_11_02_Training_Video_for_Administering_Xiaflex_for_Peyronie's_Disease.pdf
What You Need to Know About Xiaflex A Patient Guide (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Xiaflex_2022_11_02_What_You_Need_to_Know_About_Xiaflex_A_Patient_Guide.pdf

What assessment is available to the REMS?

Assessment Plan
REMS assessment plan unavailable for posting at this time.

What updates have been made to the REMS?

Date	Summary of change
11/02/2022	Modified to: Convert the REMS Document to the new, standardized format Make changes to the Patient Counseling Tool based on the results from qualitative testing studies 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	Modified the REMS for the treatment of Dupuytren’s contracture to: Remove the communication plan from the REMS. Release the REMS requirements. Modified the REMS for the treatment of Peyronie’s disease to: Change to the Prescriber Material, “Training Guide for the Administration of Xiaflex for Peyronie’s Disease” Change to the Patient Counseling Tool, “What You Need to Know About XIAFLEX Treatment for Peyronie’s Disease: A Patient Guide” Align the Training Video with the Prescriber Material. Align the Xiaflex REMS Program website with the Prescriber Material. Remove information related to the communication plan.
10/20/2014	Modified the REMS for the treatment of Dupuytren’s contracture to: 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 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: Eliminate the requirement for the Medication Guide as an element of the REMS. 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.