Approved Risk Evaluation and Mitigation Strategies (REMS)

Tegsedi (Inotersen)

NDA #211172

REMS last update: 05/11/2020

View Tegsedi's Regulatory Information at Drugs@FDA

Goals
Summary
REMS Materials
Update history

What is the purpose of the REMS?

The goal of the Tegsedi REMS is to mitigate the risk of serious bleeding with severe thrombocytopenia and the risk of glomerulonephritis associated with Tegsedi by:

Ensuring prescribers are educated on the risk of serious bleeding with severe thrombocytopenia and the risk of glomerulonephritis associated with Tegsedi.

Ensuring prescribers are educated and adhere to the following:
- Counsel patients on how to recognize and respond to signs and symptoms of serious bleeding and glomerulonephritis.
- Enroll patients in the Tegsedi REMS Program.
- Submit documentation that periodic monitoring of patients is being done to identify severe thrombocytopenia, serious bleeding with severe thrombocytopenia, and glomerulonephritis.
Ensuring patients are informed on the following:
- How to recognize and respond to signs and symptoms of serious bleeding and glomerulonephritis.
- The need to have their platelet count and renal function monitored.
Enrollment of all patients in a registry to further support long-term safety and safe use of Tegsedi.

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 Tegsedi must

To become certified to prescribe	Review the drug's Prescribing Information. Review the following: Prescriber Training and Program Overview. Successfully complete the Prescriber Knowledge Assessment and submit it to the REMS Program. Enroll in the REMS by completing the Prescriber Enrollment Form and submitting it to the REMS Program.
Before treatment initiation (first dose)	Enroll in the REMS by completing the Prescriber Enrollment Form and submitting it to the REMS Program. Provide the patient with the Patient Guide and Wallet Card. Assess the patient's platelet count and apppropriateness of initiating treatment. Document and submit to the REMS Program using the Patient Enrollment Form. Assess the patient's estimated glomerular filtration rate (eGFR), urinalysis, and urine protein to creatinine ratio (UPCR) and appropriateness of initiating treatment. Document and submit to the REMS Program using the Patient Enrollment Form. Enroll the patient by completing and submitting the Patient Enrollment Form to the REMS Program. Provide a completed copy of the form to the patient.
During treatment; weekly or more frequently as described in the Prescribing Information	Assess the patient's platelet count and appropriateness of continuing treatment.
During treatment; every two weeks	Assess the patient's estimated glomerular filtration rate (eGFR), urinalysis, and urine protein to creatinine ratio (UPCR) and appropriateness of continuing treatment.
During treatment; every 90 days	Assess the patient's platelet count, signs and symptoms of thrombocytopenia, and appropriateness of continuing treatment. Document and submit to the REMS Program using the Patient Status Form. Assess the patient's estimated glomerular filtration rate (eGFR), urinalysis, urine protein to creatinine ratio (UPCR), signs and symptoms of renal toxicity, and appropriateness of continuing treatment. Document and submit to the REMS Program using the Patient Status Form.
After treatment discontinuation; weekly for 8 weeks or more frequently as described in the Prescribing Information	Assess the patient's platelet count.
After treatment discontinuation; every 2 weeks for 8 weeks	Assess the patient's estimated glomerular filtration rate (eGFR), urinalysis, urine protein to creatinine ratio (UPCR), and signs and symptoms of renal toxicity. Document and submit to the REMS Program using the Patient Status Form.
After treatment discontinuation; at 8 weeks	Assess the patient’s platelet count and signs and symptoms of thrombocytopenia. Document and submit to the REMS Program using the Patient Status Form. Assess the patient’s estimated glomerular filtration rate (eGFR), urinalysis, urine protein to creatinine ratio (UPCR), and signs and symptoms of renal toxicity. Document and submit to the REMS Program using the Patient Status Form.
At all times	Report events of severe thrombocytopenia, serious bleeding with severe thrombocytopenia, and glomerulonephritis to the REMS Program. Report treatment discontinuation or transfer of care to the REMS Program using the Patient Status Form.

Patients who are prescribed Tegsedi

Before treatment initiation (first dose)	Review the Patient Guide and Wallet Card. Enroll in the REMS Program by completing the Patient Enrollment Form with the prescriber. Enrollment information will be provided to the REMS Program. Get a blood test to check your platelet count and blood and urine tests to check your kidneys. Receive counseling from the prescriber on the risk of serious bleeding, the risk of kidney inflammation (glomerulonephritis), and the need to complete the appropriate laboratory testing using the Patient Guide and Wallet Card.
During treatment; every week or more often as directed by your prescriber	Get a blood test to check your platelet count.
During treatment; every two weeks	Get blood and urine tests to check your kidneys.
After treatment discontinuation; weekly for 8 weeks or more often as directed by your prescriber	Get a blood test to check your platelet count.
After treatment discontinuation; every 2 weeks for 8 weeks	Get blood and urine tests to check your kidneys.
At all times	Inform the prescriber if you have serious bleeding or signs and symptoms of kidney inflammation. Have the Wallet Card with you. Inform all of your healthcare providers about this treatment.

Pharmacies that dispense Tegsedi 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 Program Overview. Have the authorized representative enroll in the REMS Program by completing the Pharmacy Enrollment Form and submitting it to the REMS Program. Establish processes and procedures to dispense no more than a 30-days' supply. Establish processes and procedures to report severe thrombocytopenia, serious bleeding with severe thrombocytopenia, and glomerulonephritis events to the REMS Program. Train all relevant staff involved in the dispensing of Tegsedi on the program requirements using the Program Overview.
Before dispensing	Obtain authorization to dispense each prescription by contacting the REMS Program to verify the prescriber is certified and the patient is enrolled and authorized to receive the drug. Dispense no more than a 30 days' supply.
At all times	Report severe thrombocytopenia, serious bleeding with severe thrombocytopenia, and glomerulonephritis events to the REMS Program. Not distribute, transfer, loan, or sell Tegsedi, except to certified dispensers. Maintain records documenting staff's completion of REMS training. Maintain records that all REMS processes and procedures are in place and are being followed. Comply with audits carried out by Ionis Pharmaceuticals or a third party acting on behalf of Ionis Pharmaceuticals to ensure all processes and procedures are in place and are being followed.

Wholesaler-distributors that distribut Tegsedi must

To be able to distribute	Establish processes and procedures to ensure the drug is distributed only to certified pharma Train all relevant staff involved in distributing on the program requirements.
At all times	Distribute only to certified pharmacies. Maintain records of all distributions. Comply with audits carried out by Ionis Pharmaceuticals or a third party acting on behalf of Ionis Pharmaceuticals to ensure 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 Tegsedi REMS, see the DailyMed link(s).

Material Name	Material Name Link
Patient Enrollment Form (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tegsedi_2020_05_11_Patient_Enrollment_Form.pdf
Patient Guide (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tegsedi_2020_05_11_Patient_Guide.pdf
Patient Status Form (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tegsedi_2020_05_11_Patient_Status_Form.pdf
Patient Wallet Card (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tegsedi_2020_05_11_Patient_Wallet_Card.pdf
Pharmacy Enrollment Form (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tegsedi_2020_05_11_Pharmacy_Enrollment_Form.pdf
Prescriber Enrollment Form (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tegsedi_2020_05_11_Prescriber_Enrollment_Form.pdf
Prescriber Knowledge Assessment (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tegsedi_2020_05_11_Prescriber_Knowledge_Assessment.pdf
Prescriber Training (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tegsedi_2020_05_11_Prescriber_Training.pdf
REMS Document (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tegsedi_2020_05_11_REMS_Document.pdf
REMS Full (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tegsedi_2020_05_11_REMS_Full.pdf
REMS Program Overview (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tegsedi_2020_05_11_REMS_Program_Overview.pdf
REMS Website Screenshots (PDF)	https://www.accessdata.fda.gov/drugsatfda_docs/rems/Tegsedi_2020_05_11_REMS_Website_Screenshots.pdf

What updates have been made to the REMS?

Date	Summary of change
05/11/2020	Modified to make: Changes to the Prescriber Enrollment Form that include the addition of name and contact information fields related to prescriber delegates. Updates to the Patient Status Form including a section that indicates the form may be submitted by a prescriber delegate and the ability of the prescriber to choose from a range of platelet counts to further clarify the level of thrombocytopenia that led to discontinuation. Updates to the Prescriber Knowledge Assessment to revise the answer to one of the questions. Revised to make editorial changes.
10/05/2018	Approval of REMS. Revised to reflect change in ownership.

Date

Summary of change

05/11/2020

Modified to make:

Changes to the Prescriber Enrollment Form that include the addition of name and contact information fields related to prescriber delegates.

Updates to the Patient Status Form including a section that indicates the form may be submitted by a prescriber delegate and the ability of the prescriber to choose from a range of platelet counts to further clarify the level of thrombocytopenia that led to discontinuation.

Updates to the Prescriber Knowledge Assessment to revise the answer to one of the questions.

Revised to make editorial changes.

10/05/2018

Approval of REMS. Revised to reflect change in ownership.

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.

Tegsedi (Inotersen) NDA #211172 REMS last update: 05/11/2020