TEIZEILD Concentrate for solution for infusion Ref.[116513] Active ingredients: Teplizumab

Source: European Medicines Agency (EU)  Revision Year: 2026  Publisher: Sanofi Winthrop Industrie, 82 avenue Raspail, 94250 Gentilly, France

4.3. Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4. Special warnings and precautions for use

Cytokine release syndrome

Cytokine release syndrome (CRS) has been observed in clinical studies in patients treated with teplizumab during the treatment period and through 28 days after the last administration (see section 4.8). CRS symptoms included fever, nausea, fatigue, headache, myalgia, arthralgia, increased ALT, increased AST, and increased total bilirubin. These symptoms typically occurred during the first 5 days of treatment (see section 4.8).

To mitigate CRS:

  • antipyretics, antihistamines and/or antiemetics should be administered prior to treatment (see section 4.2).
  • liver enzymes and bilirubin should be monitored during treatment, more frequently within the first week. Treatment should be discontinued 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.
  • Symptoms of CRS should be treated with antipyretics, antihistamines and/or antiemetics. If severe CRS develops, temporarily pausing dosing for 1-2 days should be considered (and the remaining doses to complete the full 14-day course should be administered on consecutive days). If CRS does not improve or if CRS recurs despite the pause, discontinuing treatment may be warranted.

Serious infections

Bacterial and viral infections have occurred in patients treated with Teizeild, including gastroenteritis, cellulitis, pneumonia, abscess, sepsis (see section 4.8). Use of Teizeild is not recommended in patients with active serious infection or chronic infection other than localised skin infections. Patients should be monitored for signs and symptoms of infection during and after treatment. If serious infection develops, appropriate treatment should be provided and Teizeild should be discontinued.

Lymphopenia

In clinical studies, 75% of patients treated with Teizeild developed lymphopenia. For most 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 (see section 4.8).

White blood cell counts should be monitored during the treatment period. If prolonged severe lymphopenia (<0.5 x 109 cells/L lasting 1 week or longer) develops, treatment should be discontinued (see section 4.8).

Hypersensitivity reactions

Acute hypersensitivity reactions including serum sickness, angioedema, urticaria, rash, vomiting and bronchospasm occurred in patients treated with Teizeild. Generalised cutaneous reactions and anaphylaxis have occurred in at least one patient (see section 4.8). If severe hypersensitivity reactions occur, Teizeild should be discontinued and treatment should be provided promptly.

Vaccinations

The safety of immunisation with live-attenuated vaccines in patients treated with Teizeild has not been studied. Additionally, Teizeild may interfere with the immune response to vaccination and decrease vaccine efficacy.

  • All age-appropriate vaccinations should be administered prior to starting Teizeild (see section 4.2).
  • Inactivated or mRNA vaccinations are not recommended within the 2 weeks prior to 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 treatment, during treatment, or up to 52 weeks after completion of treatment.

Glucose monitoring

Blood glucose as well as signs and symptoms of hypoglycaemia or hyperglycaemia should be monitored and diabetes managed according to current practice guidelines.

Other considerations

Patients must not have type 2 diabetes (T2D) or secondary dysglycaemia related to a condition other than T1D (e.g. diabetes secondary to medicinal products or surgery, monogenic diabetes).

Educational/Safety advice tools

Healthcare professionals involved in the management of patients treated with Teizeild must be familiar with the guides available for the safe use of this medicinal product and inform patients about the potential risks associated with the use of Teizeild.

  • Guide for risk minimisation for Healthcare Professionals: Healthcare Professional Guide
  • Guide for risk minimisation for Patients: Patient Guide – to be provided to patients by healthcare professionals

Excipients with known effect

Sodium

This medicinal product contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially 'sodium-free'. Teizeild is administered in 0.9% sodium chloride intravenous solution (see section 6.6).

Polysorbate 80

This medicinal product contains 0.10 mg of polysorbate 80 in each vial which is equivalent to 0.05 mg/mL. Polysorbates may cause allergic reactions.

4.5. Interaction with other medicinal products and other forms of interaction

No drug interaction studies have been performed.

Teizeild should be administered with caution in patients with concomitant medicinal products that are associated with significant liver abnormalities, cytopenias and other immune modulators.

Cytokine release syndrome accompanied by a slight and transient increase in IL-6 concentrations may occur with Teizeild.

Teizeild is not expected to have any relevant cytochrome P450 mediated drug-drug interactions.

Teizeild may interfere with the immune response to vaccination (see section 4.4).

4.6. Fertility, pregnancy and lactation

Women of childbearing potential

Women of childbearing potential have to use effective contraception during treatment with teplizumab and for 30 days after the last dose of treatment. Teizeild is not recommended in women of childbearing potential not using contraception.

Pregnancy

There are no available data from the use of teplizumab in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Teizeild is not recommended during pregnancy.

Breast-feeding

It is unknown whether teplizumab is excreted in human milk. Toxicological data in animals suggest excretion of teplizumab in milk of lactating mice (see section 5.3). A risk to the newborns/infants cannot be excluded. Breast-feeding should be discontinued during treatment with Teizeild and for 30 days after the last dose of treatment.

Fertility

There are no clinical data available for teplizumab on the effects on fertility. Fertility and reproductive performance were unaffected in female and male mice treated with a surrogate anti-mouse CD3 antibody (see section 5.3).

4.7. Effects on ability to drive and use machines

Teizeild has a minor influence on the ability to drive and use machines. Fatigue has been reported (see section 4.8).

4.8. Undesirable effects

Summary of safety profile

The most frequently reported adverse reactions were lymphopenia (75%), leukopenia (58%), neutropenia (37%), and rash (36%). The most frequent serious adverse reaction was cytokine release syndrome (0.9%). Other serious adverse reactions included alanine aminotransferase increased (0.2%), aspartate aminotransferase increased (0.2%), lymphopenia (0.2%), neutropenia (0.2%), and infection (0.2%).

Tabulated list of adverse reactions

The adverse reactions occurring in patients in the pooled safety analysis of clinical studies and post- marketing setting are shown in Table 1 per MedDRA System Organ Class presented by frequency categories: very common: (≥1/10), common: (≥1/100 to <1/10), uncommon: (≥1/1 000 to <1/100), rare: (≥1/10 000 to <1/1 000), very rare: (<1/10 000), not known: (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.

Table 1. Adverse reactions:

System organ classFrequency
Very commonCommonUncommonNot known
Infections and infestations  Infections1Epstein-Barr
virus
reactivation
Blood and lymphatic
system disorders
Lymphopenia,
Thrombocytopenia,
Leukopenia,
Neutropenia,
Haemoglobin
decreased
Eosinophilia  
Immune system disorders Cytokine
release
syndrome
Hypersensitivity1 
Nervous system disordersHeadache   
Gastrointestinal disordersVomiting, NauseaDiarrhoea,
Abdominal
pain
  
Hepatobiliary disordersAlanine
aminotransferase
increased, Aspartate
aminotransferase
increased
Bilirubin
increased
  
Skin and subcutaneous
tissue disorders
Rash, PruritusRash
maculo-
papular,
Rash
pruritic,
Urticaria,
Skin
exfoliation
  
General disorders and
administration site
conditions
Pyrexia, FatigueChills Pain, Illness

1 Reported as serious – see "Description of selected adverse reactions".

Description of selected adverse reactions

Cytokine release syndrome (CRS)

In study TN-10, CRS was reported in 2% of patients treated with Teizeild.

In the pool of 7 clinical studies, 6% of patients treated with Teizeild developed CRS. In 14% of these patients, CRS was reported as serious (see section 4.4). Liver transaminase elevations were observed more frequently in patients treated with Teizeild who experienced CRS.

Serious infections

In study TN-10, serious infections (cellulitis, gastroenteritis, pneumonia, wound infection) were reported in 9% of patients treated with Teizeild.

In the pool of 7 clinical studies, serious infections were reported in 3.1% of patients treated with Teizeild, including gastroenteritis, cellulitis, pneumonia, abscess, sepsis, and infectious mononucleosis.

Lymphopenia

In study TN-10, lymphopenia was reported in 73% of patients treated with Teizeild. The average lymphocyte count nadir occurred at day 5 of treatment, with recovery and return to baseline by week 6 (see section 4.4).

In the pool of 7 clinical studies, severe lymphopenia (<0.5 x 109 cells/L) lasting 1 week or longer occurred in 2% of patients treated with Teizeild and 0.5% of patients permanently discontinued treatment because of lymphopenia.

Rash and hypersensitivity reactions

Hypersensitivity reactions were reported with Teizeild in study TN-10. Serum sickness was observed in 2% of patients treated with Teizeild.

In the pool of 7 clinical studies of patients:

  • Anaphylaxis (with hypoxia and bronchospasm) was observed in one patient treated with Teizeild who was hospitalised.
  • Angioedema (periorbital and facial) was observed in 0.2% patients treated with Teizeild,
  • Peripheral and generalised oedema was reported in 1.2% of patients treated with Teizeild.
  • Rash was observed in 36% of patients treated with Teizeild. 0.3% of patients treated with Teizeild had a serious rash.
  • Urticaria was reported in 2.7% of patients treated with Teizeild.
  • Hypersensitivity reactions were reported in 1% of patients treated with Teizeild. Less than 0.1% of patients treated with Teizeild had a serious hypersensitivity reaction.

Haemoglobin decreased and thrombocytopenia

In the pool of 7 clinical studies, haemoglobin decreased was reported in 23% of patients treated with Teizeild and thrombocytopenia was reported in 17% of patients treated with Teizeild; recovery occurred within 2 to 4 weeks of treatment. In clinical studies, 1.2% of patients treated with Teizeild discontinued treatment due to haemoglobin less than 85 g/L (or a decrease of more than 20 g/L to a value less than 100 g/L), and 1% discontinued Teizeild due to platelet count less than 50 x 109 platelets/L.

Liver enzyme and bilirubin elevations

Liver enzyme and bilirubin elevations were observed in patients treated with Teizeild, both in the context of CRS and in patients without CRS. On laboratory analysis, 7.8% of patients treated with Teizeild experienced a peak ALT more than 3 times the ULN. For AST, 5.3% of patients treated with Teizeild experienced a peak AST more than 3 times the ULN. Most liver enzyme elevations were transient and resolved 1-2 weeks after treatment.

Immunogenicity

The observed incidence of anti-drug antibodies (ADA) is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies.

In the placebo-controlled study in patients aged 8 years of age and older with stage 2 T1D (study TN-10) (see section 5.1), approximately 57% of patients treated with Teizeild developed treatment emergent anti-teplizumab antibodies, 46% of whom developed neutralising antibodies.

Based on the available data, no definitive conclusion can be made to characterise the effects of ADA on pharmacokinetics, pharmacodynamics, or effectiveness of Teizeild.

Paediatric population

Immunogenicity data in children younger than 8 years of age have not been established.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

6.2. Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products. Teizeild should not be infused concomitantly in the same intravenous line with other medicinal products.

Incompatible materials:

  • Ethylene-propylene copolymer (EPC) and polypropylene (PP) intravenous infusion bags
  • Light protected infusion sets
  • For Teizeild dose <68 micrograms: polyethylene (PE) and polyolefin (PO) blend.

This medicinal product should be prepared and administered as instructed in section 4.2 and section 6.6.

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