Chemical formula: C₁₆₄H₂₅₂N₄₄O₅₅S Molecular mass: 3,750.803 g/mol
Teduglutide interacts in the following cases:
Patients receiving oral concomitant medicinal products requiring titration or with a narrow therapeutic index should be monitored closely due to potential increased absorption.
In adult or paediatric patients with moderate and severe renal impairment (creatinine clearance less than 50 ml/min), and end-stage renal disease, the daily dose should be reduced by 50%.
Teduglutide has not been studied in patients with severe hepatic impairment.
There are no data from the use of teduglutide in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of teduglutide during pregnancy.
It is unknown whether teduglutide is excreted in human milk. In rats, mean teduglutide concentration in milk was less than 3% of the maternal plasma concentration following a single subcutaneous injection of 25 mg/kg. A risk to the breast-fed newborn/infant cannot be excluded. As a precautionary measure it is preferable to avoid the use of teduglutide during breast-feeding.
There are no data on the effects of teduglutide on human fertility. Animal data do not indicate any impairment of fertility.
Teduglutide has minor influence on the ability to drive and use machines. However, cases of syncope have been reported in clinical studies. Such events might impact the ability to drive and use machines.
Adverse reactions were retrieved from 2 placebo-controlled clinical studies with teduglutide in 109 patients with SBS treated with doses of 0.05 mg/kg/day and 0.10 mg/kg/day for up to 24 weeks. Approximately 52% of the patients treated with teduglutide experienced adverse reactions (versus 36% of the patients given placebo). The most commonly reported adverse reactions were abdominal pain and distension (45%), respiratory tract infections (28%) (including nasopharyngitis, influenza, upper respiratory tract infection, and lower respiratory tract infection), nausea (26%), injection site reactions (26%), headache (16%), and vomiting (14%). Approximately 38% of the treated patients with a stoma experienced gastrointestinal stoma complications. The majority of these reactions were mild or moderate.
No new safety signals have been identified in patients exposed to 0.05 mg/kg/day of teduglutide for up to 30 months in a long-term open-label extension study.
Adverse reactions are listed below by MedDRA system organ class and by frequency. Frequencies are defined as 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 available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
All adverse reactions identified in post-marketing experience are italicised.
| Frequency System organ class | Very common | Common | Uncommon | Not known |
|---|---|---|---|---|
| Infections and infestations | Respiratory tract infection* | Influenza-like illness | ||
| Immune system disorders | Hypersensitivity | |||
| Metabolism and nutrition disorders | Decreased appetite Fluid overload | |||
| Psychiatric disorders | Anxiety Insomnia | |||
| Nervous system disorders | Headache | |||
| Cardiac disorders | Congestive heart failure | |||
| Vascular disorders | Syncope | |||
| Respiratory, thoracic and mediastinal disorders | Cough Dyspnoea | |||
| Gastrointestinal disorders | Abdominal distension Abdominal pain Nausea Vomiting | Colorectal polyp Colonic stenosis Flatulence Intestinal obstruction Pancreatic duct stenosis Pancreatitis† Small intestinal stenosis | Small intestinal polyp‡ | Gastric polyp |
| Hepatobiliary disorders | Cholecystitis Cholecystitis acute | |||
| General disorders and administration site conditions | Injection site reaction§ | Oedema peripheral | Fluid retention | |
| Injury, poisoning and procedural complcations | Gastrointestinal stoma complication |
* Includes the following preferred terms: Nasopharyngitis, Influenza, Upper respiratory tract infection, and Lower respiratory tract infection.
† Includes the following preferred terms: Pancreatitis, Pancreatitis acute, and Pancreatitis chronic.
‡ Locations include duodenum, jejunum, and ileum.
§ Includes the following preferred terms: Injection site haematoma, Injection site erythema, Injection site pain, Injection site swelling and Injection site haemorrhage.
Consistent with the potentially immunogenic properties of medicinal products containing peptides, administration of teduglutide may potentially trigger the development of antibodies. Based on integrated data from two trials in adults with SBS (a 6-month randomised placebo-controlled trial, followed by a 24-month open-label trial), the development of anti-teduglutide antibodies in subjects who received subcutaneous administration of 0.05 mg/kg teduglutide once daily was 3% (2/60) at Month 3, 17% (13/77) at Month 6, 24% (16/67) at Month 12, 33% (11/33) at Month 24, and 48% (14/29) at Month 30. In phase 3 studies with SBS patients who received teduglutide for ≥2 years, 28% of patients developed antibodies against E. coli protein (residual host cell protein from the manufacture). The antibody formation has not been associated with clinically relevant safety findings, reduced efficacy or changed pharmacokinetics of teduglutide.
Injection site reactions occurred in 26% of SBS patients treated with teduglutide, compared to 5% of patients in the placebo arm. The reactions included injection site haematoma, injection site erythema, injection site pain, injection site swelling and injection site haemorrhage. The majority of reactions were moderate in severity and no occurrences led to drug discontinuation.
Modest increases of C-reactive protein of approximately 25 mg/l have been observed within the first seven days of teduglutide treatment, which decreased continuously under ongoing daily injections. After 24 weeks of teduglutide treatment, patients showed small overall increase in C-reactive protein of approximately 1.5 mg/l on average. These changes were neither associated with any changes in other laboratory parameters nor with any reported clinical symptoms. There were no clinically relevant mean increases of C-reactive protein from baseline following long-term treatment with teduglutide for up to 30 months.
In two completed clinical trials, there were 87 paediatric subjects (aged 1 to 17 years) enrolled and exposed to teduglutide for a duration of up to 6 months. No subject discontinued the studies due to an adverse event. Overall, the safety profile of teduglutide (including type and frequency of adverse reactions, and immunogenicity) in children and adolescents (ages 1-17 years) was similar to that in adults.
In three completed clinical studies in paediatric subjects (aged 4 to <12 months corrected gestational age), the safety profile reported in these studies was consistent with the safety profile seen in the previous paediatric studies and no new safety issues were identified.
Limited long-term safety data is available for the paediatric population. No data are available for children under 4 months of age.
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