Drug Safety-related Labeling Changes (SrLC)

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Drug Safety-related Labeling Changes (SrLC) Database

ANDA	Abbreviated New Drug Application
BLA	Biologics License Application
CDER	Center for Drug Evaluation and Research
MG	Medication Guide
NDA	New Drug Application
PCI	Patient Counseling Information
PI	Patient Information
PLR	Physician Labeling Rule
PLLR	Pregnancy and Lactation Labeling Rule
Italics	For the most part, italics indicate an FDA comment such as: Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section.
Underlines	Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text.

Sections

BW	Box Warning
WP	Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format)
AR	Adverse Reactions (in pre-PLR format, this may be a subheading under precautions).
DI	Drug Interactions (in pre-PLR format, this may be a subheading under precautions).
USP	Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format.
PCI/PI/MG	Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events.

Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.

Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.

TZIELD (BLA-761183)

(TEPLIZUMAB-MZWV)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

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04/20/2026 (SUPPL-13)

Approved Drug Label (PDF)

Boxed Warning

Newly added subsection:

WARNING: Viral Reactivation

Serious, life-threatening cases of viral reactivation, including Epstein-Barr virus (EBV) and cytomegalovirus (CMV) reactivation have been reported with TZIELD. Patients who are immunocompromised are at increased risk. The majority of serious cases occurred in patients who continued TZIELD treatment despite persistent, severe lymphopenia. (5.1, 5.4)
Test patients for active EBV and CMV infection prior to starting treatment. TZIELD is not recommended in patients with laboratory or clinical evidence of active EBV or CMV infection. Adhere to lymphocyte count monitoring requirements and discontinuation recommendations. Monitor patients for signs and symptoms of viral reactivation following TZIELD treatment and for at least 2 months following the last infusion. If viral reactivation is suspected, discontinue TZIELD. (2.6, 5.1, 5.4)

5 Warnings and Precautions

5.1 Viral Reactivation

Newly added subsection:

Serious, life-threatening cases of viral reactivation, including EBV and CMV have been reported with TZIELD. During and within 2 months of TZIELD treatment, if primary infection or reactivation of EBV or CMV occurs, it may present with increased severity, including EBV-associated lymphoproliferative disease and organ failure. Patients who are immunocompromised, including patients with Down syndrome, may be at increased risk. The majority of serious viral reactivation cases occurred in patients who continued TZIELD despite persistent, severe lymphopenia [see Warnings and Precautions 5.4].

Prior to initiating treatment with TZIELD, evaluate patients for active EBV and CMV infection and confirm undetectable viral load (e.g., PCR testing). TZIELD is not recommended in patients with laboratory or clinical evidence of active EBV or CMV infection [see Dosage and Administration (2.2)].

During treatment with TZIELD, regularly monitor lymphocyte counts [see Dosage and Administration (2.6), Warnings and Precautions (5.4)] and monitor patients for signs and symptoms of viral reactivation during treatment and for at least 2 months following the last infusion. If viral reactivation is suspected, discontinue TZIELD and obtain viral load (e.g., PCR) promptly. Consider appropriate expert consultation for diagnostic testing recommendations as some diagnostic tests may give inaccurate results in immunosuppressed patients. If viral reactivation is confirmed, permanently discontinue TZIELD [see Dosage and Administration (2.6)]. Consider appropriate expert consultation for the management of severe viral reactivation.

5.2 Cytokine Release Syndrome

Additions and/or revisions underlined:

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 (with or without vomiting), fatigue, headache, myalgia, arthralgia, increased ALT, increased AST, and increased total bilirubin. These manifestations typically occurred during the first 5 days of TZIELD treatment [see Adverse Reactions (6.1)]. To mitigate CRS:

Premedicate with antipyretics, antihistamines and/or antiemetics prior to TZIELD treatment [see Dosage and Administration (2.3)].

Monitor liver enzymes and bilirubin 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 in TZIELD-treated patients with antipyretics, antihistamines and/or antiemetics. If severe CRS develops, consider:
- Temporarily pausing TZIELD dosing for 1-2 days and if symptoms have resolved or significantly improved, subsequently administering the remaining doses on consecutive days to complete the full 14-day course or
- Discontinuing TZIELD treatment.

5.4 Lymphopenia

Additions and/or revisions underlined:

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 [see Adverse Reactions (6.1)].

Obtain a CBC prior to starting TZIELD and monitor white blood cell counts during TZIELD treatment. If prolonged severe lymphopenia (<500 cells per mcL lasting 1 week or longer) develops, permanently discontinue TZIELD.

5.6 Vaccinations

Additions and/or revisions underlined:

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 [see Dosage and Administration (2.2)].
Inactivated or mRNA vaccinations are not recommended within the 2 weeks prior to TZIELD treatment, during treatment, or up to 6 weeks after completion of treatment.
Live-attenuated vaccinations are not recommended within the 8 weeks prior to starting TZIELD treatment, during treatment, or up to 52 weeks after treatment.

6 Adverse Reactions

Addition of the following to the bulleted line listing:

· Viral Reactivation [see Warnings and Precautions (5.1)]

6.2 Clinical Trials Experience

Additions and/or revisions underlined:

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 Adult and Pediatric Patients Aged 8 Years and Older with Stage 2 T1D

The data in Table 1 are derived from the placebo-controlled study (Study TN-10) in adult and pediatric patients aged 8 years and older with Stage 2 T1D [see Clinical Studies (14)]. 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 T1D and for an Unapproved Use

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):

…

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 [see Clinical Pharmacology (12.6)].

Open Label Study in Pediatric Patients Age 1 to Less Than 8 Years with Stage 2 T1D

The safety of TZIELD was evaluated in a non-randomized, single arm, open-label, multicenter study in 23 pediatric patients age 1 to less than 8 years with Stage 2 T1D (PETITE-T1D Study; NCT05757713)[see Clinical Pharmacology (12.3)]. In this trial, 87% completed the full 14-day treatment course. The median age was 4.9 years (1 patient was less than 2 years old; 52% were 2 to less than 5 years old; 44% were 5 to less than 8 years old; range 1.7 to 6.8 years) and 52% were female. The majority of the population (96%) was White and one patient (4%) was Asian; 3 patients (13%) were Hispanic or Latino ethnicity. At baseline, 87% of participants had a first-degree relative with T1D. The majority (87%) were positive for 3 or more diabetes-related autoantibodies. The most common autoantibodies were anti-insulin (87%), anti-ICA (85%), anti-GAD65 (83%), anti-ZnT8 (74%), and anti-IA2 (68%). The median HbA1c was 5.5%.

Overall, the safety profile of TZIELD observed in pediatric patients less than 8 years of age with Stage 2 T1D was consistent with that observed in patients 8 years of age and older with Stage 2 T1D. The most common adverse reactions that occurred in patients less than 8 years of age were vomiting (52%) and diarrhea (30%).

Other Adverse Reactions in Adult and Pediatric Patients Age 1 Year and Older with Stage 2 T1D

…

Procedure-Related Venous Thrombosis

Venous thrombus and thrombophlebitis have been reported in patients receiving teplizumab intravenously administered via peripherally inserted central catheter (PICC). In the pool of 5 clinical trials of patients, deep vein thrombus was reported in 0.4% of TZIELD-treated patients compared to 0 placebo-treated patients. One teplizumab-treated patient (4.3%) in the PETITE-T1D study experienced a deep vein thrombosis.

…

8 Use in Specific Populations

8.1 Pregnancy

Additions and/or revisions underlined:

Risk Summary

Available case reports from clinical trials with TZIELD are insufficient to identify a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Although there are no data on teplizumab-mzwv in nonclinical studies, monoclonal antibodies can be actively transported across the placenta, and TZIELD may cause immunosuppression in the utero-exposed infant (see Clinical Considerations). To minimize exposure to a fetus, avoid use of TZIELD during pregnancy and at least 30 days prior to planned pregnancy.

TZIELD is not active in rodents. In animal reproduction studies, mice were given a surrogate anti-mouse CD3 antibody subcutaneously during organogenesis through lactation. Pups born to dams administered the murine surrogate antibody during pregnancy showed a reduction in the adaptive immune response consistent with the expected pharmacology (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively.

Report pregnancies to Provention Bio, Inc.’s Adverse Event reporting line at 1-800-633-1610 or visit https://ae.reporting.sanofi.

…

8.4 Pediatric Use

Additions and/or revisions underlined:

The safety and effectiveness of TZIELD have been established to delay the onset of Stage 3 T1D in pediatric patients 1 year of age and older with Stage 2 T1D.

Use of TZIELD for this indication is supported by evidence from an adequate and well-controlled study (Study TN-10) in adult and pediatric patients 8 years of age and older (including 29 pediatric patients) with Stage 2 T1D and from additional pharmacokinetic and safety data in 23 pediatric patients aged 1 to less than 8 years of age with Stage 2 T1D (PETITE T1D) [see Adverse Reactions (6.1), Clinical Pharmacology (12.3) and Clinical Studies (14)].

Adverse reactions observed in pediatric patients 1 year of age and older who received TZIELD were consistent with those reported in adults [see Adverse Reactions (6.1)].

The safety and effectiveness of TZIELD have not been established in pediatric patients younger than 1 year of age.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

Additions and/or revisions underlined:

What is the most important information I should know about TZIELD? TZIELD may cause serious side effects, including:

Viral Reactivation. Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are common viruses that may stay inactive in your body after an initial infection. TZIELD may cause these viruses to become active again which, especially in patients with a weakened immune system, can become serious and potentially life-threatening. These viral reactivations can happen during treatment with TZIELD and up to 2 months after your last dose. Your healthcare provider will test you for active EBV and CMV infections before treatment with TZIELD. Contact your healthcare provider right away if you develop symptoms of an infection during or after treatment with TZIELD (such as fever, swollen glands, or fatigue).

Cytokine Release Syndrome (CRS). Signs and symptoms of CRS problems may include:

…

?nausea with or without vomiting

…

Your healthcare provider will do blood tests to check for active infections, verify your liver function and your complete blood counts before you start treatment and during treatment with TZIELD. During and after your treatment with TZIELD, your healthcare provider will check for serious side effects, as well as other side effects, and treat you as needed. Your healthcare provider may temporarily or completely stop your treatment with TZIELD, if you develop liver problems, have a serious infection or viral reactivation, or if your blood counts stay too low.

…

What is TZIELD?

TZIELD is a prescription medicine used to delay the onset of Stage 3 type 1 diabetes, which is when your body can not make enough insulin on its own and may require insulin injections. TZIELD is for adults and children 1 year of age and older who have Stage 2 type 1 diabetes. This means that they have tested positive for 2 or more type 1 diabetes-related autoantibodies, have abnormal blood sugar levels and do not have type 2 diabetes or other forms of diabetes.

It is not known if TZIELD is safe and effective in children under 1 years of age.

Before or after receiving TZIELD, tell your healthcare provider about all your medical conditions, including if you:

have any of the conditions or symptoms listed in the section “What is the most important information I should know about TZIELD?”
have a weakened immune system, including if you have Down syndrome.
have a serious infection or an infection that does not go away or that keeps coming back (chronic).
have recently received or are scheduled to receive an immunization (vaccine). TZIELD may affect how well a vaccine works. Tell your healthcare provider that you are receiving treatment with TZIELD before receiving a vaccine.

are pregnant or plan to become pregnant. TZIELD may harm your unborn baby. Do not receive TZIELD during pregnancy and at least 30 days before a planned pregnancy.

If you become pregnant while taking TZIELD, you are encouraged to report your pregnancy to the Provention Bio’s Adverse Event reporting line at 1-800-633-1610 or visit https://ae.reporting.sanofi.

…

How will I receive TZIELD?

TZIELD is given by a healthcare provider through a needle placed in a vein (intravenous infusion) in the arm.
TZIELD is received as an infusion one-time a day, every day, for 14 days.
- Each TZIELD infusion will last at least 30 minutes if you are an adult or your child is 8 years of age or older.
- Each TZIELD infusion will last at least 2 hours if your child is 1 to less than 8 years of age.
For the first 5 days of treatment, your healthcare provider will give medicines to be taken by mouth before starting the TZIELD infusion. These medicines include pain relievers (such as ibuprofen, naproxen or acetaminophen), an antihistamine, and possibly an anti-nausea medicine. These medicines may help reduce symptoms of CRS such as fever, headache, muscle and joint pain, or nausea, with or without vomiting. Vomiting and diarrhea may occur more frequently in children less than 8 years of age.
If a scheduled infusion is missed, your healthcare provider will continue the treatment on the next scheduled day. Two infusions are not given on the same day.
…
What are the possible side effects of TZIELD? TZIELD may cause serious side effects including:

See “What is the most important information I should know about TZIELD?” The most common side effects of TZIELD include:
decrease in white blood cell counts
vomiting
rash
diarrhea
headache

These are not all of the possible side effects of TZIELD. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects to Provention Bio at 1-800-633-1610 or visit https://ae.reporting.sanofi.

…

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Viral Reactivation

Inform patients that TZIELD may cause viral reactivation, including serious cases of EBV and CMV. Instruct patients to contact their healthcare provider if they develop any symptoms of viral reactivation (such as fever, swollen glands, or fatigue) [see Warnings and Precautions (5.1)].

…

Pregnancy

Advise patients to inform their healthcare provider of a known or suspected pregnancy. Advise patients who are exposed to TZIELD during pregnancy to contact Provention Bio, Inc.’s Adverse Event reporting line at 1-800-633-1610 or visit https://ae.reporting.sanofi [see Use in Specific Populations (8.1)].

Lactation

Advise a lactating woman that she may interrupt breastfeeding and pump and discard breast milk during treatment and for 20 days after TZIELD administration to minimize drug exposure to a breastfed child [see Use in Specific Populations (8.2)].