TEGSEDI Solution for injection Ref.[10306] Active ingredients: Inotersen

2.1 Dosing Information

The recommended dose of TEGSEDI is 284 mg injected subcutaneously once weekly.

For consistency of dosing, patients should be instructed to give the injection on the same day every week.

If a dose is missed, patients should be instructed to take the missed dose as soon as possible, unless the next scheduled dose is within 2 days. In this situation, the patient should be directed to skip the missed dose and take the next scheduled dose on the scheduled day.

2.2 Administration

• TEGSEDI is intended for subcutaneous use only.
• The first injection administered by the patient or caregiver should be performed under the guidance of an appropriately qualified healthcare professional. Patients and/or caregivers should be trained in the subcutaneous administration of TEGSEDI in accordance with the Instructions for Use.
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit [see How Supplied/Storage and Handling (16)].
• Sites for injection include the abdomen, upper thigh region, or outer area of the upper arm. It is important to rotate sites for injection.
  • If injected in the upper arm, the injection should be administered by a person other than the patient. Injection should be avoided at the waistline and other sites where pressure or rubbing from clothing may occur.
  • TEGSEDI should not be injected into areas of skin disease or injury.
  • Tattoos and scars should also be avoided.
• TEGSEDI prefilled syringe should be allowed to reach room temperature prior to injection.
  • Remove from refrigerated storage at least 30 minutes prior to use.
  • Other warming methods should not be used.
• Use each prefilled syringe only once.

2.3 Assessment Prior to Initiating TEGSEDI

Measure platelet count, serum creatinine, estimated glomerular filtration rate (eGFR), urine protein to creatinine ratio (UPCR), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin, and perform urinalysis prior to treatment with TEGSEDI and as directed following treatment initiation [see Dosage and Administration (2.4) and Warnings and Precautions (5.1 and 5.2)].

2.4 Laboratory Testing and Monitoring to Assess Safety after Initiating TEGSEDI

Monitor platelet count, serum creatinine, estimated glomerular filtration rate (eGFR), urinalysis, urine protein to creatinine ratio (UPCR), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin during treatment with TEGSEDI, and for 8 weeks following discontinuation of treatment.

Platelet Count

Do not initiate TEGSEDI in patients with a platelet count less than 100 × 10⁹/L. Recommendations for platelet monitoring frequency and TEGSEDI dosing are specified in Table 1. If a patient develops signs or symptoms of thrombocytopenia, obtain a platelet count as soon as possible, and hold dosing until platelet count is confirmed. Recheck the platelet count as soon as possible if a platelet measurement is uninterpretable (e.g., clumped sample) [see Warnings and Precautions (5.8].

Table 1. TEGSEDI Monitoring and Treatment Recommendations for Platelet Count:

* It is strongly recommended that, unless the patient has a medical contraindication to receiving glucocorticoids, the patient receive glucocorticoid therapy to reverse the platelet decline [see Warnings and Precautions (5.1)].
# Additional risk factors for bleeding include age >60 years, receiving anticoagulant or antiplatelet medicinal products, or prior history of major bleeding events.
^† Patients who discontinue therapy with TEGSEDI because of platelet counts below 25 x10⁹/L should not reinitiate therapy.

Renal Monitoring

TEGSEDI should generally not be initiated in patients with a urine protein to creatinine ratio (UPCR) of 1000 mg/g or higher. Monitor serum creatinine, estimated glomerular filtration rate (eGFR), urinalysis, and UPCR every 2 weeks during treatment with TEGSEDI. Hold TEGSEDI in patients who develop a UPCR of 1000 mg/g or higher, or estimated glomerular filtration rate (eGFR) below 45 mL/minute/1.73 m², pending further evaluation of the cause.

If a dose is held, once eGFR increases to ≥45 mL/minute/1.73 m², UPCR decreases to below 1000 mg/g, or the underlying cause of the decline in renal function is corrected, weekly dosing may be reinitiated. In the case of UPCR of 2000 mg/g or higher, perform further evaluation for acute glomerulonephritis, as clinically indicated. If acute glomerulonephritis is confirmed, TEGSEDI should be permanently discontinued.

Liver Tests

Monitor alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin every four months during treatment with TEGSEDI; monitor monthly for patients who have received a liver transplant [see Warnings and Precautions (5.6)].