Teplizumab-mzwv (Monograph)

Brand name: Tzield
Drug class: Antidiabetic Agents, Miscellaneous

Medically reviewed by Drugs.com on May 10, 2024. Written by ASHP.

Introduction

CD3-directed humanized IgG₁ kappa antibody.

Uses for Teplizumab-mzwv

Delay of Onset of Stage 3 Type 1 Diabetes

Used for the delay of onset of Stage 3 type 1 diabetes (T1D) in adults and pediatric patients ≥8 years of age with Stage 2 T1D.

Insulin remains the mainstay treatment for T1D.

American Diabetes Association recommends considering use of teplizumab to delay the onset of symptomatic T1D (stage 3) in selected individuals ≥8 years of age with stage 2 T1D. Administration of teplizumab should occur in a specialized setting with appropriately trained personnel.

Teplizumab-mzwv Dosage and Administration

General

Pretreatment Screening

Confirm Stage 2 type 1 diabetes (T1D) by documenting at least 2 positive pancreatic islet cell autoantibodies in those who have dysglycemia without overt hyperglycemia using an oral glucose tolerance test (OGTT) or alternative method if appropriate and OGTT is not available.
In patients who meet criteria for a diagnosis of Stage 2 T1D, ensure the clinical history of the patient does not suggest type 2 diabetes.
Prior to initiating teplizumab-mzwv, obtain a CBC and liver enzyme tests.
Confirm the absence of acute infection with Epstein-Barr virus, cytomegalovirus, or other active infection other than localized skin infections.

Patient Monitoring

Monitor liver enzymes.
Monitor for signs and symptoms of infection.
Monitor for white blood cell counts for lymphopenia.

Premedication and Prophylaxis

Ensure all age-appropriate vaccinations prior to starting therapy. Administer live-attenuated vaccines at least 8 weeks prior to treatment. Administer inactivated or mRNA vaccines at least 2 weeks prior to treatment.
Premedicate with: (1) a nonsteroidal anti-inflammatory agent (NSAIA) or acetaminophen, (2) an antihistamine, and/or (3) an antiemetic before each infusion for at least the first 5 days of the 14-day treatment course.

Administration

Available as a clear, colorless solution for IV infusion after dilution. Do not use if particulate matter or coloration is present.

Do not administer 2 doses on the same day. If a dose is missed, resume dosing by administering all remaining doses on consecutive days to complete the 14-day treatment course.

Start infusion within 2 hours of preparation. If not used immediately, store at 15–30°C and complete infusion within 4 hours of preparation. Discard if not administered within 4 hours of preparation.

Dilution

Remove 2 mL of drug solution from vial and add to 18 mL of 0.9% sodium chloride injection (in either a sterile glass vial or polyvinyl chloride [PVC] infusion bag). Mix solution gently. Diluted solution contains 100 mcg/mL of teplizumab-mzwv.

Withdraw calculated dose with an appropriately sized syringe and add contents to a 25 mL 0.9% sodium chloride PVC infusion bag. Mix solution but do not shake. Discard unused diluted solution.

Rate of Administration

Administer over a minimum of 30 minutes.

Dosage

Pediatric Patients

Delay of Onset of Stage 3 Type 1 Diabetes

IV

In pediatric patients ≥8 years of age, administer once daily for 14 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.

Adults

Delay of Onset of Stage 3 Type 1 Diabetes

IV

Administer once daily for 14 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.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No specific dosage recommendations.

Cautions for Teplizumab-mzwv

Contraindications

None.

Warnings/Precautions

Cytokine Release Syndrome

Cytokine release syndrome (CRS) reported. Symptoms include fever, nausea, fatigue, headache, myalgia, arthralgia, increased ALT, increased AST, and increased total bilirubin and typically occur during the first 5 days of teplizumab-mzwv treatment.

Premedicate with antipyretics, antihistamines, and/or antiemetics prior to teplizumab-mzwv treatment. Monitor liver enzymes during treatment. Discontinue treatment in patients who develop elevated ALT or AST more than 5 times 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 reported. Monitor patients for signs and symptoms of infection during and after treatment. If serious infection develops, treat appropriately and discontinue teplizumab-mzwv.

Lymphopenia

In clinical trials, 78% of patients treated with teplizumab-mzwv developed lymphopenia compared to 11% of controls. Return of lymphocyte levels to pre-treatment values occurred within 2 weeks after treatment completion and did not require treatment interruption. Severe lymphopenia (<500 cells/mm³) lasting 1 week or longer occurred in 0.9% of teplizumab-treated patients, and 0.5% of these patients permanently discontinued therapy because of lymphopenia.

Monitor WBC counts during treatment. If prolonged severe lymphopenia (<500 cells/mm³ lasting ≥1 week) develops, discontinue teplizumab-mzwv.

Hypersensitivity Reactions

Acute hypersensitivity reactions including serum sickness, angioedema, urticaria, rash, vomiting, and bronchospasm may occur. If severe hypersensitivity reactions occur, discontinue use and treat promptly.

Vaccinations

Safety of immunization with live-attenuated vaccines in patients treated with teplizumab-mzwv not studied. Additionally, teplizumab-mzwv may interfere with immune response to vaccination and decrease vaccine efficacy.

Administer all age-appropriate vaccinations prior to starting teplizumab-mzwv.

Do not administer inactivated or mRNA vaccinations within the 2 weeks prior to teplizumab-mzwv treatment, during treatment, or 6 weeks after completion of treatment.

Do not administer live-attenuated vaccinations within the 8 weeks prior to teplizumab-mzwv treatment, during treatment, or up to 52 weeks after treatment.

Immunogenicity

In a study of patients with stage 2 T1D, approximately 57% of patients treated with teplizumab-mzwv developed antibodies, of whom 46% developed neutralizing antibodies. Higher incidence of rash observed in patients who developed antibodies.

Specific Populations

Pregnancy

Inadequate data regarding use in pregnant women to establish risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Potential for fetal exposure because human IgG crosses the placenta. Avoid use of teplizumab-mzwv during pregnancy and for at least 30 days (6 half-lives) prior to planned pregnancy. Consider risks and benefits prior to administering live vaccines to infants exposed to teplizumab-mzwv in utero.

Report pregnancies to Provention Bio, Inc.’s Adverse Event reporting line at 1-844-778-2246.

Lactation

Not known whether teplizumab-mzwv distributes into human or animal milk, affects milk production, or affects breast-fed infants. Maternal IgG and monoclonal antibodies are present in breast milk. Effects of local GI and limited systemic exposure in the breast-fed infant unknown.

Consider benefits of breast-feeding and importance of the drug to the woman; also consider any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition. May interrupt breastfeeding and pump and discard breast milk during treatment and for 20 days after teplizumab-mzwv administration to minimize drug exposure to a breastfed child.

Pediatric Use

Safety and effectiveness of teplizumab-mzwv established in pediatric patients ≥8 years of age with Stage 2 T1D. Use of teplizumab-mzwv for this indication is supported by a study in adults and pediatric patients ≥8 years of age (including 29 pediatric patients). Adverse reactions observed in pediatric patients ≥8 years of age were consistent with those reported in adult patients.

Safety and effectiveness not established in pediatric patients <8 years of age.

Geriatric Use

Clinical studies of teplizumab-mzwv to delay the onset of Stage 3 T1D did not include patients ≥65 years of age.

Common Adverse Effects

Most common adverse reactions (>10%) were lymphopenia, rash, leukopenia, headache.

Drug Interactions

Vaccinations

Inactivated or mRNA Vaccines

Teplizumab-mzwv may interfere with immune response and decrease vaccine efficacy; do not administer inactivated or mRNA vaccinations within the 2 weeks prior to teplizumab-mzwv treatment, during treatment, or 6 weeks after completion of treatment.

Live-attenuated Vaccines

Unknown safety with concomitant use; do not administer live-attenuated vaccinations within the 8 weeks prior to teplizumab-mzwv treatment, during treatment, or up to 52 weeks after treatment.

Teplizumab-mzwv Pharmacokinetics

Absorption

Steady-state concentrations not expected to be achieved during the 14-day treatment course.

Distribution

Extent

Not known whether distributed into human milk.

Elimination

Metabolism

Expected to be degraded into small peptides via catabolic pathways.

Half-life

4.5 days.

Special Populations

No differences in pharmacokinetics observed based on age, biologic sex, or racial groups (white, Asian).

Stability

Storage

Parenteral

Injection

2–8°C; do not freeze. Store upright. Store in original carton to protect from light until use.

Store diluted solution (if not used immediately) at 15–30°C; complete infusion within 4 hours of start of infusion solution preparation.

Actions

Teplizumab-mzwv binds to CD3 (a cell surface antigen present on T lymphocytes).
Partial agonistic signaling and deactivation of pancreatic beta cell autoreactive T lymphocytes.
Increases the proportion of regulatory T cells and of exhausted CD8+ T cells in peripheral blood.

Advice to Patients

Advise the patient to read the FDA-approved patient labeling.
Inform patients about the signs and symptoms of cytokine release syndrome (CRS).
Inform patients that teplizumab-mzwv may lower the ability of the immune system to fight infections. Instruct patients to contact their health care provider if they develop any symptoms of infection.
Inform patients that liver enzyme monitoring is necessary during treatment.
Inform patients that although most teplizumab-mzwv-treated patients had mild lymphopenia, monitoring is required. Few patients had severe lymphopenia that required stopping teplizumab-mzwv.
Advise patients of the symptoms of hypersensitivity reactions and instruct them to stop taking teplizumab-mzwv and seek medical attention promptly if such symptoms occur.
Advise patients to receive all age-appropriate vaccinations prior to starting teplizumab-mzwv and avoid concurrent use of live, inactivated, and mRNA vaccines.
Advise patients to inform their health care provider of a known or suspected pregnancy. Advise patients who are exposed to teplizumab-mzwv during pregnancy to contact Provention Bio, Inc.’s Adverse Event reporting line at 1-844-778-2246.
Advise a lactating woman that she may interrupt breastfeeding and pump and discard breast milk during treatment and for 20 days after teplizumab-mzwv administration to minimize drug exposure to a breastfed infant.
Inform clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.