Teplizumab-mzwv
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Parth Vikram Singh, MBBS[2]
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Overview
Teplizumab-mzwv is a CD3-directed antibody that is FDA approved for the treatment of delay the onset of Stage 3 type 1 diabetes (T1D) in adults and pediatric patients aged 8 years and older with Stage 2 T1D.. Common adverse reactions include lymphopenia, rash, leukopenia and headache..
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
TZIELD is indicated to delay the onset of Stage 3 type 1 diabetes in adults and pediatric patients 8 years of age and older with Stage 2 type 1 diabetes.
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: o At least two positive pancreatic islet cell autoantibodies o 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.
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 PrecautionsPrecautions o Lymphocyte count less than 1,000 lymphocytes/mcL o Hemoglobin less than 10 g/dL o Platelet count less than 150,000 platelets/mcL o Absolute neutrophil count less than 1,500 neutrophils/mcL o Elevated ALT or AST greater than 2 times the upper limit of normal (ULN) or bilirubin greater than 1.5 times ULN o Laboratory or clinical evidence of acute infection with Epstein-Barr virus (EBV) or cytomegalovirus (CMV) o Active serious infection or chronic active infection other than localized skin infections • Administer all age-appropriate vaccinations prior to starting TZIELD: o Administer live-attenuated (live) vaccines at least 8 weeks prior to treatment. o Administer inactivated (killed) vaccines or mRNA vaccines at least 2 weeks prior to treatment.
Important Preparation and Premedication Instructions
The following are important preparation and premedication instructions: • Must dilute TZIELD prior to use [see Dosage and Administration. • with: (1) a nonsteroidal anti-inflammatory drug (NSAID) or acetaminophen, (2) an antihistamine, and/or (3) an antiemetic .Administer additional doses of premedication if needed.
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.
Additional Preparation and Administration Instructions
The following are additional preparation and administration instructions:
• 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: o Sterile glass vial with 18 mL of 0.9% Sodium Chloride Injection or o 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.
Injection: 2 mg per 2 mL (1 mg/mL) clear and colorless solution in a single-dose vial.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Teplizumab-mzwv in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Teplizumab-mzwv in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Teplizumab-mzwv FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Teplizumab-mzwv in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Teplizumab-mzwv in pediatric patients.
Contraindications
None.
Warnings
Cytokine Release Syndrome
Cytokine release syndrome (CRS) has been observed in TZIELD-treated patients. In clinical trials, CRS was reported in 5% of TZIELD-treated patients compared to 0.8% of control-treated patients during the treatment period and through 28 days after the last study drug administration. CRS manifestations in TZIELD-treated patients included fever, nausea, fatigue, headache, myalgia, arthralgia, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), and increased total bilirubin. These manifestations typically occurred during the first 5 days of TZIELD treatment To mitigate CRS:
• Premedicate with antipyretics, antihistamines and/or antiemetics prior to TZIELD treatment. • Monitor liver enzymes during treatment. Discontinue TZIELD treatment in patients who develop elevated ALT or AST more than 5 times the upper limit of normal (ULN) or bilirubin more than 3 times ULN. • Treat symptoms of CRS with antipyretics, antihistamines and/or antiemetics. If severe CRS develops, consider temporarily pausing dosing for 1-2 days (and administer the remaining doses to complete the full 14-day course on consecutive days) or discontinuing treatment.
Serious Infections
- Bacterial and viral infections have occurred in TZIELD-treated patients. In clinical trials, TZIELD-treated patients had a higher rate of serious infections (3.5%) than control-treated patients (2%), including gastroenteritis, cellulitis, pneumonia, abscess, sepsis.
Use of TZIELD is not recommended in patients with active serious infection or chronic infection other than localized skin infections. Monitor patients for signs and symptoms of infection during and after TZIELD treatment. If serious infection develops, treat appropriately, and discontinue TZIELD.
Lymphopenia
- In clinical trials, 78% of TZIELD-treated patients developed lymphopenia compared to 11% of control-treated patients. For most TZIELD-treated patients who experienced lymphopenia, lymphocyte levels began to recover after the fifth day of treatment and returned to pre-treatment values within two weeks after treatment completion and without dose interruption. Severe lymphopenia (<500 cells per mcL) lasting 1 week or longer occurred in 0.9% of TZIELD-treated patients, and 0.5% of TZIELD-treated patients permanently discontinued TZIELD because of lymphopenia.
- Monitor white blood cell counts during the treatment period. If prolonged severe lymphopenia (<500 cells per mcL lasting 1 week or longer) develops, discontinue TZIELD.
Hypersensitivity Reactions
- Acute hypersensitivity reactions including serum sickness, angioedema, urticaria, rash, vomiting and bronchospasm occurred in TZIELD-treated patients.If severe hypersensitivity reactions occur, discontinue use of TZIELD and treat promptly.
Vaccinations
The safety of immunization with live-attenuated vaccines in TZIELD-treated patients has not been studied. Additionally, TZIELD may interfere with the immune response to vaccination and decrease vaccine efficacy.
• Administer all age-appropriate vaccinations prior to starting TZIELD. • Inactivated or mRNA vaccinations are not recommended within the 2 weeks prior to TZIELD treatment, during treatment, or 6 weeks after completion of treatment. • Live-attenuated vaccinations are not recommended within the 8 weeks prior to TZIELD treatment, during treatment, or up to 52 weeks after treatment.
Adverse Reactions
Clinical Trials Experience
• Cytokine Release Syndrome. • Serious Infections. • Lymphopenia. • Hypersensitivity Reactions.
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Placebo-Controlled Study in Patients with Stage 2 Type 1 Diabetes
The data in Table 1 are derived from the placebo-controlled study (Study TN-10) in patients aged 8 years and older with Stage 2 type 1 diabetes (T1D). These data reflect exposure of 44 patients of whom 93% completed the full 14-day treatment course.
Pool of Five Controlled Clinical Studies in Stage 2 Type 1 Diabetes and in an Unapproved Population
Adverse reactions in TZIELD-treated patients were also evaluated in a larger pool of adult and pediatric patients who participated in five controlled clinical studies (including Study TN-10 described above):
• One study in patients with Stage 2 T1D (Study TN-10). • Three placebo-controlled studies in an unapproved population, • One open-label standard-of-care controlled study of TZIELD in an unapproved population. In this pool:
• 773 patients received TZIELD (44 patients with Stage 2 TID and 729 patients from an unapproved population), and • 245 patients received either placebo or standard of care control (32 patients with Stage 2 T1D and 213 patients from an unapproved population). In these studies, 436 patients received a 14-day dosing regimen of TZIELD with a total drug exposure that was comparable to the total drug exposure achieved with the recommended dosage, 168 patients received a 14-day course of TZIELD with a lower total TZIELD drug exposure, and 169 patients received a 6-day course of TZIELD with a lower total TZIELD drug exposure. The mean age of TZIELD-treated patients was 17.6 years (median 15 years), 62% were <18 years old (40% age 12 to 17; 21% age 8 to 11), and 64% were male. The population was 72% White, 26% Asian, 1% Black or African American, 1% were multiple or unknown race, and <1% American Indian or Alaska Native; 5% were Hispanic or Latino ethnicity. Common Adverse Reactions TABLE 1 presents common (≥ 5%) adverse reactions that occurred during treatment and through 28 days after the last study drug administration in Study TN-10. Adverse reactions observed in pediatric patients 8 years and older who received TZIELD were consistent with those reported in adult patients in this study.
Cytokine Release Syndrome (CRS)
In Study TN-10, CRS was reported in 2% of TZIELD-treated patients compared to 0% of placebo-treated patients. Of the 39 TZIELD-treated patients that developed CRS (5% of all TZIELD-treated patients) in the pool of 5 clinical trials, 13% of the CRS cases were serious adverse reactions. Liver transaminase elevations were observed in 56% of TZIELD-treated patients who experienced CRS: 64% were up to 2.5 times ULN, 32% were more than 2.5 to 5 times ULN, and 4.5% were 5-10 times ULN.
Serious Infections
In Study TN-10, serious infections (cellulitis, gastroenteritis, pneumonia, wound infection) were reported in 9% (4/44) of TZIELD-treated patients compared to 0% (0/32) of placebo-treated patients any time during or after the first dose of study treatment.
Rash and Hypersensitivity Reactions
Hypersensitivity reactions were reported with TZIELD in Study TN-10. Serum sickness was observed in 2% (1/44) of TZIELD-treated patients compared to 0% (0/32) of placebo-treated patients. The patient who developed serum sickness had a prior history of positive anti-nuclear antibody and presented with arthralgias and elevated c-reactive protein and low C4 complement five days after completing their course of TZIELD; illness resolved in 2.5 months. In the pool of 5 clinical trials of patients:
• Anaphylaxis (with hypoxia and bronchospasm) was observed in one TZIELD-treated patient who was hospitalized. • Angioedema (periorbital and facial) was observed in 0.3% TZIELD-treated patients, compared to 0% in control-treated patients. Peripheral and generalized edema was reported in 1.6% of TZIELD-treated patients and 0% of control-treated patients. • Rash was observed in 48% of TZIELD-treated patients compared to 15% in control-treated patients, with 33 excess cases of rash per 100 patients. The majority of rashes observed with TZIELD treatment were not serious and resolved without intervention; although 0.3% (2/773) of TZIELD-treated patients had a serious rash compared to 0% (0/245) of placebo- treated patients. • Urticaria was reported in 1.9% of TZIELD-treated patients and in 1.2% of control-treated patients. Immunogenicity: Anti-Drug Antibody-Associated Adverse Reactions In Study TN-10, rash occurred in 39% of TZIELD-treated patients who developed anti- teplizumab-mzwv antibodies and in 33% of TZIELD-treated patients who did not develop anti- teplizumab-mzwv antibodies.
Other Adverse Reactions
- Lymphopenia
In Study TN-10, lymphopenia was reported in 73% of TZIELD-treated patients compared to 6% of placebo-treated patients. The average lymphocyte count nadir occurred at Day 5 of treatment, with recovery and return to baseline by Week 6.
- Neutropenia
In Study TN-10, neutropenia was observed in 7% of TZIELD-treated patients compared to 3% of placebo-treated patients.
- Anemia and Thrombocytopenia
In the pool of 5 clinical trials of patients, anemia was reported in 27% of TZIELD-treated patients compared to 21% of placebo-treated patients, and thrombocytopenia was reported in 13% of TZIELD-treated patients compared to 5% of placebo-treated patients during the 14-day treatment course; recovery occurred within 2 to 4 weeks of treatment. In clinical trials, 1.8% of TZIELD-treated patients discontinued treatment due to hemoglobin less than 8.5 g/dL (or a decrease of more than 2 g/dL to a value less than 10 g/dL), and 1% discontinued TZIELD due to platelet count less than 50,000 platelets/mcL.
- Liver Enzyme Elevations
Liver enzyme elevations were observed in TZIELD-treated patients, both in the context of CRS and in patients without CRS. In the pool of 5 clinical trials, elevated aminotransferases were reported in 25% of TZIELD-treated patients compared to 11% of placebo-treated patients during the 14-day treatment course. On laboratory analysis, 5.1% of TZIELD-treated patients experienced a peak ALT more than 3 times the ULN compared to 0.8% of control-treated patients. Most liver enzyme elevations were transient and resolved 1-2 weeks after treatment; 98% resolved by follow-up week 14.
- Other Laboratory Abnormalities
In the pool of 5 clinical trials, other laboratory abnormalities including decreased bicarbonate (15% in TZIELD-treated patients, compared to 7% in placebo-treated patients) and decreased blood calcium (19% in TZIELD-treated patients, compared to 13% in placebo-treated patients) were noted.
Postmarketing Experience
There is limited information regarding Teplizumab-mzwv Postmarketing Experience in the drug label.
Drug Interactions
There is limited information regarding Teplizumab-mzwv Drug Interactions in the drug label.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Teplizumab-mzwv in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Teplizumab-mzwv in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Teplizumab-mzwv during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Teplizumab-mzwv in women who are nursing.
Pediatric Use
There is no FDA guidance on the use of Teplizumab-mzwv in pediatric settings.
Geriatic Use
There is no FDA guidance on the use of Teplizumab-mzwv in geriatric settings.
Gender
There is no FDA guidance on the use of Teplizumab-mzwv with respect to specific gender populations.
Race
There is no FDA guidance on the use of Teplizumab-mzwv with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Teplizumab-mzwv in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Teplizumab-mzwv in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Teplizumab-mzwv in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Teplizumab-mzwv in patients who are immunocompromised.
Administration and Monitoring
Administration
There is limited information regarding Teplizumab-mzwv Administration in the drug label.
Monitoring
There is limited information regarding Teplizumab-mzwv Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Teplizumab-mzwv and IV administrations.
Overdosage
There is limited information regarding Teplizumab-mzwv overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Teplizumab-mzwv Pharmacology in the drug label.
Mechanism of Action
There is limited information regarding Teplizumab-mzwv Mechanism of Action in the drug label.
Structure
There is limited information regarding Teplizumab-mzwv Structure in the drug label.
Pharmacodynamics
There is limited information regarding Teplizumab-mzwv Pharmacodynamics in the drug label.
Pharmacokinetics
There is limited information regarding Teplizumab-mzwv Pharmacokinetics in the drug label.
Nonclinical Toxicology
There is limited information regarding Teplizumab-mzwv Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Teplizumab-mzwv Clinical Studies in the drug label.
How Supplied
There is limited information regarding Teplizumab-mzwv How Supplied in the drug label.
Storage
There is limited information regarding Teplizumab-mzwv Storage in the drug label.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
There is limited information regarding Teplizumab-mzwv Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Teplizumab-mzwv interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Teplizumab-mzwv Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Teplizumab-mzwv Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.