Approved Risk Evaluation and Mitigation Strategies (REMS)

REMS that have more than one drug product but are not Shared System REMS will not display the product name and ingredient properly on this website due to database limitations. Please refer to the REMS document for the correct product names.

Tyruko (natalizumab-sztn)

BLA #761322

REMS last update: 08/24/2023

• View Tyruko's Regulatory Information at Drugs@FDA

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

What is the purpose of the REMS?

The goals of the TYRUKO REMS are:

1. To inform prescribers, infusion site healthcare providers, and patients about the risk of progressive multifocal leukoencephalopathy (PML) associated with TYRUKO including the increased risk of PML with the presence of anti-JCV antibodies, longer treatment duration, prior immunosuppressant use.
2. To warn against concurrent use with antineoplastic, immunosuppressant, or immunomodulating agents, and in patients who are immunocompromised.
3. To promote early diagnosis of progressive multifocal leukoencephalopathy and timely discontinuation of TYURKO in the event of suspected progressive multifocal leukoencephalopathy.

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

Health Care Providers who prescribe TYRUKO must:

To become certified to prescribe	Review the drug’s Prescribing Information. Review the following: Educational Slide Set, Overview and Helpful Information for Evaluation of New Neurological Symptoms in Patients Receiving TYRUKO (Multiple Sclerosis) or Understanding PML for Gastroenterologists (Crohn’s Disease). | Understanding PML for Gastroenterologists (Crohn’s Disease) | | Helpful Information for Evaluation of New Neurologic Symptoms in Patients Receiving TYRUKO (Multiple Sclerosis) | | Overview | | Educational Slide Set | Enroll in the REMS by completing the Prescriber Enrollment Form and submitting it to the REMS Program. | Prescriber Enrollment Form |
Before treatment initiation (first dose)	Counsel the patient using the Medication Guide and the Patient Enrollment Form – Multiple Sclerosis or Patient Enrollment Form – Crohn’s Disease. Provide a copy of the materials to the patient. | Medication Guide | | Patient Enrollment Form (Crohn’s Disease) | | Patient Enrollment Form (Multiple Sclerosis) | Enroll the patient by completing and submitting the Patient Enrollment Form – Multiple Sclerosis or Patient Enrollment Form – Crohn’s Disease to the REMS Program. | Patient Enrollment Form (Crohn’s Disease) | | Patient Enrollment Form (Multiple Sclerosis) | Assess the patient’s risk factors that increase the risk of progressive multifocal leukoencephalopathy.
During treatment; 3 months after the first infusion	Assess the patient’s signs, symptoms and risk factors for progressive multifocal leukoencephalopathy.
During treatment; 6 months after the first infusion and every 6 months thereafter	Assess the patient’s signs, symptoms and risk factors for progressive multifocal leukoencephalopathy and whether the patient should continue treatment. Document and submit the results to the REMS Program using the Patient Status Report and Reauthorization Questionnaire. | Patient Status Report and Reauthorization Questionnaire |
After treatment discontinuation; initially	Assess the patient’ s signs and symptoms for progressive multifocal leukoencephalopathy. Document and submit to the REMS Program using the Initial Discontinuation Questionnaire.
After treatment discontinuation; 6 months later	Assess the patient’s signs and symptoms for progressive multifocal leukoencephalopathy. Document and submit to the REMS Program using the 6-Month Discontinuation Questionnaire. | 6-Month Discontinuation Questionnaire |
At all times	Report cases of progressive multifocal leukoencephalopathy, hospitalizations due to opportunistic infection, or deaths to Sandoz.

Patients who are prescribed TYRUKO:

Before treatment initiation	Review the Medication Guide and the Patient Enrollment Form – Multiple Sclerosis or Patient Enrollment Form – Crohn’s Disease. | Medication Guide | | Patient Enrollment Form (Crohn’s Disease) | | Patient Enrollment Form (Multiple Sclerosis) | Receive counseling from the prescriber on the benefits and risks of treatment, and the need to promptly report any new or worsening symptoms that persist over several days, especially nervous system symptoms. Enroll in the REMS Program by completing the Patient Enrollment Form – Multiple Sclerosis or Patient Enrollment Form – Crohn’s Disease with the prescriber. Enrollment information will be provided to the REMS Program. | Patient Enrollment Form (Crohn’s Disease) | | Patient Enrollment Form (Multiple Sclerosis) | Be monitored for risk factors that increase the risk of progressive multifocal leukoencephalopathy.
During treatment, before each infusion	Review the Medication Guide. | Medication Guide | Have a list of medicines and treatments taken during the last month with you. Be monitored for signs, symptoms, and risk factors for progressive multifocal leukoencephalopathy.
During treatment; 3 months and 6 months after the first infusion, and every 6 months thereafter	Be monitored for signs, symptoms, and risk factors for progressive multifocal leukoencephalopathy and the appropriateness of continuing TYRUKO.
After treatment discontinuation; initially and 6 months later	Be monitored for signs and symptoms of progressive multifocal leukoencephalopathy.
At all times	Notify the REMS Program if you switch physicians or infusion sites. Inform the prescriber of new or worsening symptoms that last several days, especially nervous system symptoms including new or sudden change in thinking, eyesight, balance, or strength, and other new or worsening symptoms.

Pharmacies that dispense TYRUKO 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 pharmacy. Have the authorized representative review the Educational Slide Set. | Educational Slide Set | Have the authorized representative enroll in the REMS Program by completing the Pharmacy Enrollment Form and submitting it to the REMS Program. | Pharmacy Enrollment Form | Establish processes and procedures to verify that the infusion site is authorized.
Before dispensing	Verify that the infusion site is authorized through the processes and procedures established as a requirement of the REMS Program.
At all times	Maintain records of the pharmacy’s Site Authorization Confirmation. Comply with audits carried out by Sandoz or a third party acting on behalf of Sandoz to ensure that all processes and procedures are in place and are being followed.

Infusion sites that dispense TYRUKO 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 infusion site. Have the authorized representative review the Educational Slide Set. | Educational Slide Set | Have the authorized representative enroll in the REMS Program by completing the Infusion Site Enrollment Form and submitting it to the REMS Program.Have the authorized representative enroll in the REMS Program by completing the Infusion Site Enrollment Form and submitting it to the REMS Program. | Infusion Site Enrollment Form |
Before administering	Obtain authorization to dispense each infusion for administration by contacting the REMS Program or confirm receipt of a Notice of Patient Authorization and no Notice of Patient Discontinuation to verify the patient is authorized to receive the drug. Provide the patient with the Medication Guide. | Medication Guide | Assess the patients’ health status for signs, symptoms and risk factors of progressive multifocal leukoencephalopathy. Document using the Pre-Infusion Patient Checklist. | Pre-Infusion Patient Checklist |
During treatment; within 1 business day of the patient visit for infusion	Submit the Pre-Infusion Patient Checklist to the REMS Program regardless of whether the patient receives the infusion. | Pre-Infusion Patient Checklist |
At all times	Maintain records of the infusion site’s Site Authorization Confirmation. Comply with audits carried out by Sandoz or a third party acting on behalf of Sandoz to ensure that all processes and procedures are in place and are being followed.

Wholesalers-distributors that distribute TYRUKO must:

To be able to distribute	Establish processes and procedures to ensure that the drug is distributed only to certified pharmacies and infusion sites. Train all relevant staff involved in distributing on the REMS Program requirements.
At all times	Distribute only to certified pharmacies and infusion sites. Maintain records to support that all processes and procedures are in place and being followed. Comply with audits carried out by Sandoz or a third party acting on behalf of Sandoz to ensure that all processes and procedures are in place and 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 Tyruko REMS, see the DailyMed link(s).

Material Name	Material Name Link
6-Month Discontinuation Questionnaire (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tyruko_2023_08_24_6-Month_Discontinuation_Questionnaire.pdf
Change Prescriber Authorization Form (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tyruko_2023_08_24_Change_in_Prescriber_Authorization_Form.pdf
Educational Slide Set (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tyruko_2023_08_24_Educational_Slide_Set.pdf
Helpful Information for Evaluation of New Neurologic Symptoms in Patients Receiving TYRUKO (Multiple Sclerosis) (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tyruko_2023_08_24_Helpful_Information_for_Evaluation of New Neurologic_Symptoms_in_Patients_Receiving_TYRUKO_(MS).pdf
Infusion Site Enrollment Form (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tyruko_2023_08_24_Infusion_Site_Enrollment_Form.pdf
Initial Discontinuation Questionnaire (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tyruko_2023_08_24_Initial_Discontinuation_Questionnaire.pdf
Medication Guide (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tyruko_2023_08_24_Medication_Guide.pdf
Overview (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tyruko_2023_08_24_Overview.pdf
Patient Enrollment Form (Crohn’s Disease) (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tyruko_2023_08_24_Patient_Enrollment_Form-CD.pdf
Patient Enrollment Form (Multiple Sclerosis) (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tyruko_2023_08_24_Patient_Enrollment_Form-MS.pdf
Patient Status Report and Reauthorization Questionnaire (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tyruko_2023_08_24_Patient_Status_Report_and_Reauthorization_Questionnaire.pdf
Pharmacy Enrollment Form (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tyruko_2023_08_24_Pharmacy_Enrollment_Form.pdf
Pre-Infusion Patient Checklist (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tyruko_2023_08_24_Pre-infusion_Patient_Checklist.pdf
Prescriber Enrollment Form (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tyruko_2023_08_24_Prescriber_Enrollment_Form.pdf
REMS Document (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tyruko_2023_08_24_REMS_Document.pdf
REMS Full (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tyruko_2023_08_24_REMS_Full.pdf
REMS Program Website (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tyruko_2023_08_24_REMS_Program_Website.pdf
Understanding PML for Gastroenterologists (Crohn’s Disease) (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tyruko_2023_08_24_Understanding_PML_for_Gastroenterologists_(CD).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
08/24/2023	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.