Revestive · 4.8 Undesirable effects · 1

HOS-155397 · has-adverse-reaction-information · PDF-Seite 7

Summary of the safety profile Adverse reactions were retrieved from 2 placebo-controlled clinical studies with teduglutide in 109 adult 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. Tabulated list of adverse reactions 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 Very common Common Uncommon Not known System organ class Infections and Respiratory tract Influenza-like illness infestations infection* Immune system Hypersensitivity disorders Metabolism and Decreased appetite nutrition disorders Fluid overload Psychiatric Anxiety disorders Insomnia Nervous system Headache disorders Cardiac disorders Congestive heart failure Vascular disorders Syncope Respiratory, Cough thoracic and Dyspnoea mediastinal disorde

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HOS-155403 · has-adverse-reaction-information · PDF-Seite 24

Summary of the safety profile 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. 24 Tabulated list of adverse reactions 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 Very common Common Uncommon Not known System organ class Infections and Respiratory tract Influenza-like illness infestations infection* Immune system Hypersensitivity disorders Metabolism and Decreased appetite nutrition disorders Fluid overload Psychiatric Anxiety disorders Insomnia Nervous system Headache disorders Cardiac disorders Congestive heart failure Vascular disorders Synco

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HOS-155393 · has-contraindication-information · PDF-Seite 4

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1, or trace residues of tetracycline. Active or suspected malignancy. Patients with a history of malignancies in the gastrointestinal tract, including the hepatobiliary system and pancreas within the last five years.

HOS-155399 · has-contraindication-information · PDF-Seite 21

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1, or trace residues of tetracycline. Active or suspected malignancy. Patients with a history of malignancies in the gastrointestinal tract, including the hepatobiliary system and pancreas within the last five years. 21

HOS-155398 · has-indication-information · PDF-Seite 19

Revestive is indicated for the treatment of patients 4 months corrected gestational age and above with Short Bowel Syndrome (SBS). Patients should be stable following a period of intestinal adaptation after surgery.

HOS-155392 · has-indication-information · PDF-Seite 2

Revestive is indicated for the treatment of patients 4 months corrected gestational age and above with Short Bowel Syndrome (SBS). Patients should be stable following a period of intestinal adaptation after surgery.

HOS-155401 · has-interaction-information · PDF-Seite 24

No clinical pharmacokinetic drug-drug interaction studies have been performed. An in vitro study indicates that teduglutide does not inhibit cytochrome P450 drug metabolising enzymes. Based upon the pharmacodynamic effect of teduglutide, there is a potential for increased absorption of concomitant medicinal products (see section 4.4).

HOS-155395 · has-interaction-information · PDF-Seite 6

No clinical pharmacokinetic drug-drug interaction studies have been performed. An in vitro study indicates that teduglutide does not inhibit cytochrome P450 drug metabolising enzymes. Based upon the pharmacodynamic effect of teduglutide, there is a potential for increased absorption of concomitant medicinal products (see section 4.4).

HOS-155396 · has-pregnancy-information · PDF-Seite 6

Pregnancy There are no data from the use of Revestive in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of Revestive during pregnancy. Breast-feeding 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 Revestive during breast-feeding. Fertility There are no data on the effects of teduglutide on human fertility. Animal data do not indicate any impairment of fertility.

HOS-155402 · has-pregnancy-information · PDF-Seite 24

Pregnancy There are no data from the use of Revestive in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of Revestive during pregnancy. Breast-feeding 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 Revestive during breast-feeding. Fertility There are no data on the effects of teduglutide on human fertility. Animal data do not indicate any impairment of fertility.

HOS-155394 · has-warning-information · PDF-Seite 4

It is strongly recommended that every time Revestive is administered to a patient, the name and lot number of the product are recorded in order to maintain a link between the patient and the lot of the product. Adults Colo-rectal polyps A colonoscopy with removal of polyps should be performed at the time of starting treatment with Revestive. Once yearly follow-up colonoscopies (or alternate imaging) are recommended during the first 2 years of Revestive treatment. Subsequent colonoscopies are recommended at a minimum of five year intervals. An individual assessment whether increased frequency of surveillance is necessary should be performed based on the patient characteristics (e.g., age, underlying disease). See also section 5.1. If a polyp is found, adherence to current polyp follow-up guidelines is recommended. In case of malignancy, Revestive therapy must be discontinued (see section 4.3). Gastrointestinal neoplasia including hepatobiliary tract In the rat carcinogenicity study, benign tumours were found in the small bowel and the extrahepatic bile ducts. Development of small intestinal polyps has also been observed in human SBS patients within several months after start of teduglutide treatment. Because of this, upper gastro-intestinal endoscopy or other imaging is recommended before and during the treatment with teduglutide. If a neoplasia is detected, it should be removed. In case of malignancy, teduglutide treatment must be discontinued (see sections 4.3 and 5.3). Gallbladder and bile ducts Cases of cholecystitis, cholangitis, and cholelithiasis have been reported in clinical studies. In case of gallbladder or bile duct-related symptoms, the need for continued Revestive treatment should be reassessed. Pancreatic diseases Pancreatic adverse events such as chronic and acute pancreatitis, pancreatic duct stenosis, pancreas infection and increased blood amylase and lipase have been reported in clinical studies. In case of pancreatic adverse events, the need for continued Revestive treatment should be reassessed. Monitoring of small bowel, gallbladder and bile ducts, and pancreas SBS patients are to be kept under close surveillance according to clinical treatment guidelines. This usually includes the monitoring of small bowel function, gallbladder and bile ducts, and pancreas for 4 signs and symptoms, and, if indicated, additional laboratory investigations and appropriate imaging technique

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HOS-155400 · has-warning-information · PDF-Seite 22

It is strongly recommended that every time Revestive is administered to a patient, the name and lot number of the product are recorded in order to maintain a link between the patient and the lot of the product. Adults Colo-rectal polyps A colonoscopy with removal of polyps should be performed at the time of starting treatment with Revestive. Once yearly follow-up colonoscopies (or alternate imaging) are recommended during the first 2 years of Revestive treatment. Subsequent colonoscopies are recommended at a minimum of five year intervals. An individual assessment whether increased frequency of surveillance is necessary should be performed based on the patient characteristics (e.g., age, underlying disease). See also section 5.1. If a polyp is found, adherence to current polyp follow-up guidelines is recommended. In case of malignancy, Revestive therapy must be discontinued (see section 4.3). Gastrointestinal neoplasia including hepatobiliary tract In the rat carcinogenicity study, benign tumours were found in the small bowel and the extrahepatic bile ducts. Development of small intestinal polyps has also been observed in human SBS patients within several months after start of teduglutide treatment. Because of this, upper gastro-intestinal endoscopy or other imaging is recommended before and during the treatment with teduglutide. If a neoplasia is detected, it should be removed. In case of malignancy, teduglutide treatment must be discontinued (see sections 4.3 and 5.3). Gallbladder and bile ducts Cases of cholecystitis, cholangitis, and cholelithiasis have been reported in clinical studies. In case of gallbladder or bile duct-related symptoms, the need for continued Revestive treatment should be reassessed. Pancreatic diseases Pancreatic adverse events such as chronic and acute pancreatitis, pancreatic duct stenosis, pancreas infection and increased blood amylase and lipase have been reported in clinical studies. In case of pancreatic adverse events, the need for continued Revestive treatment should be reassessed. Monitoring of small bowel, gallbladder and bile ducts, and pancreas SBS patients are to be kept under close surveillance according to clinical treatment guidelines. This usually includes the monitoring of small bowel function, gallbladder and bile ducts, and pancreas for signs and symptoms, and, if indicated, additional laboratory investigations and appropriate imaging techniques. Intestinal obstruction Cases of intestinal obstructi

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