2.1 Patient Selection
Select adult patients and pediatric patients 8 years of age and older for TZIELD treatment who have a diagnosis of Stage 2 type 1 diabetes.
- Confirm Stage 2 type 1 diabetes by documenting:
- At least two positive pancreatic islet cell autoantibodies
- Dysglycemia without overt hyperglycemia using an oral glucose tolerance test (if an oral glucose tolerance test is not available, an alternative method for diagnosing dysglycemia without overt hyperglycemia may be appropriate)
- Ensure the clinical history of the patient does not suggest type 2 diabetes.
2.2 Laboratory Evaluation and Vaccination Prior to Initiation
- Prior to initiating TZIELD, obtain a complete blood count and liver enzyme tests.
- Use of TZIELD is not recommended in patients with [see Warnings and Precautions (5)]:
- Lymphocyte count less than 1,000 lymphocytes/mcL
- Hemoglobin less than 10 g/dL
- Platelet count less than 150,000 platelets/mcL
- Absolute neutrophil count less than 1,500 neutrophils/mcL
- Elevated ALT or AST greater than 2 times the upper limit of normal (ULN) or bilirubin greater than 1.5 times ULN
- Laboratory or clinical evidence of acute infection with Epstein-Barr virus (EBV) or cytomegalovirus (CMV)
- Active serious infection or chronic active infection other than localized skin infections
- Administer all age-appropriate vaccinations prior to starting TZIELD [see Warnings and Precautions (5.5)]:
- Administer live-attenuated (live) vaccines at least 8 weeks prior to treatment.
- Administer inactivated (killed) vaccines or mRNA vaccines at least 2 weeks prior to treatment.
2.3 Important Preparation and Premedication Instructions
The following are important preparation and premedication instructions:
- Must dilute TZIELD prior to use [see Dosage and Administration (2.5)].
- Premedicate prior to TZIELD infusion for the first 5 days of dosing with: (1) a nonsteroidal anti-inflammatory drug (NSAID) or acetaminophen, (2) an antihistamine, and/or (3) an antiemetic [see Warnings and Precautions (5.1)]. Administer additional doses of premedication if needed.
2.4 Recommended Dosage and Administration
Administer TZIELD by intravenous infusion (over a minimum of 30 minutes), using a body surface area-based dosing, once daily for 14 consecutive days as follows:
- Day 1: 65 mcg/m²
- Day 2: 125 mcg/m²
- Day 3: 250 mcg/m²
- Day 4: 500 mcg/m²
- Days 5 through 14: 1,030 mcg/m²
Do not administer two doses on the same day.
Recommendations Regarding Missed Dose(s)
If a planned TZIELD infusion is missed, resume dosing by administering all remaining doses on consecutive days to complete the 14-day treatment course.
2.5 Additional Preparation and Administration Instructions
The following are additional preparation and administration instructions [see Dosage and Administration (2.2, 2.3, 2.4)]:
- Inspect TZIELD visually before use (the supplied solution is clear and colorless). Do not use TZIELD if particulate matter or coloration is seen.
- Prepare TZIELD using aseptic technique. Each vial is intended for single dose only.
- Prepare a:
- Sterile glass vial with 18 mL of 0.9% Sodium Chloride Injection or
- Polyvinylchloride (PVC) infusion bag with 18 mL of 0.9% Sodium Chloride Injection.
- Remove 2 mL of TZIELD from the vial and slowly add to the 18 mL of 0.9% Sodium Chloride Injection. Mix gently by slowly inverting the vial or rocking the infusion bag. The resulting 20 mL diluted solution contains 100 mcg/mL of teplizumab-mzwv.
- Using an appropriately sized syringe (e.g., 5 mL), withdraw the volume of diluted TZIELD solution required for that day’s calculated dose from the 100 mcg/mL solution.
- Slowly add contents of the syringe containing the TZIELD dose to a 25 mL 0.9% Sodium Chloride Injection PVC infusion bag. Gently rock the infusion bag to ensure that the solution mixes sufficiently. Do not shake.
- Discard unused portion of remaining diluted TZIELD solution in the sterile glass vial or PVC infusion bag.
- Start the TZIELD infusion within 2 hours of preparation. If not used immediately, store the infusion solution at room temperature [15°C to 30°C (59°F to 86°F)] and complete infusion within 4 hours of the start of preparation. Discard the infusion solution if not administered within 4 hours of preparation.
