Revestive

1 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 

 



 

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This medicinal product is subject to additional monitoring. This will allow quick identification of 

new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 

See section 4.8 for how to report adverse reactions. 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Revestive 1.25 mg powder and solvent for solution for injection 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

One vial of powder contains 1.25 mg of teduglutide*. 

After reconstitution, each vial contains 1.25 mg teduglutide in 0.5 ml of solution, corresponding to a 

concentration of 2.5 mg/ml. 

 

*A glucagon-like peptide-2 (GLP-2) analogue produced in Escherichia coli cells by recombinant 
DNA technology. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Powder and solvent for solution for injection. 
The powder is white and the solvent is clear and colourless. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Revestive is indicated for the treatment of patients aged 1 year and above with Short Bowel Syndrome 

(SBS). Patients should be stable following a period of intestinal adaptation after surgery. 

 

4.2 Posology and method of administration 

 

Treatment should be initiated under the supervision of a medical professional with experience in the 

treatment of SBS. 

 

Treatment should not be initiated until it is reasonable to assume that a patient is stable following a 

period of intestinal adaptation. Optimisation and stabilisation of intravenous fluid and nutrition 

support should be performed before initiation of treatment. 

 

Clinical assessment by the physician should consider individual treatment objectives and patient 

preferences. Treatment should be stopped if no overall improvement of the patient condition is 

achieved. Efficacy and safety in all patients should be closely monitored on an ongoing basis 

according to clinical treatment guidelines. 

 

Posology 

Paediatric population (≥1 year) 
Treatment should be initiated under the supervision of a medical professional with experience in the 
treatment of paediatric SBS. 

 

The recommended dose of Revestive in children and adolescents (aged 1 to 17 years) is 0.05 mg/kg 

body weight once daily. The injection volume per body weight when using the 1.25 mg strength vial is 



 

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provided in Table 1 below. For paediatric patients with a body weight >20 kg, the 5 mg strength vial 

should be used. 

 

If a dose is missed, that dose should be injected as soon as possible on that day. A treatment period of 

6 months is recommended after which treatment effect should be evaluated. In children below the age 

of two years, treatment should be evaluated after 12 weeks. There are no data available in paediatric 

patients after 6 months (see section 5.1). 

 

Table 1 

 

Body weight 

1.25 mg strength 

Volume to be injected 

5-6 kg 0.10 ml 

7-8 kg 0.14 ml 

9-10 kg 0.18 ml 

11-12 kg 0.22 ml 

13-14 kg 0.26 ml 

15-16 kg 0.30 ml 

17-18 kg 0.34 ml 

19-20 kg 0.38 ml 

>20 kg Use the 5 mg strength vial 

 

The safety and efficacy of Revestive in children below 1 year of age have not been established. No 

data are available. 

 

Special populations 

Renal impairment 
No dose adjustment is necessary for paediatric patients with mild renal impairment. In 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% (see section 5.2). 

 

Hepatic impairment 
No dose adjustment is necessary for paediatric patients with mild and moderate hepatic impairment 

based on a study conducted in Child-Pugh grade B adult subjects. Revestive has not been studied in 

patients with severe hepatic impairment (see sections 4.4 and 5.2). 

 

Method of administration 

The reconstituted solution should be administered by subcutaneous injection once daily, alternating 

sites between 1 of the 4 quadrants of the abdomen. In case the injection into the abdomen is hampered 

by pain, scarring or hardening of the tissue, the thigh can also be used. Revestive should not be 

administered intravenously or intramuscularly. 

 

For instructions on reconstitution of the medicinal product before administration, see section 6.6. 

 

4.3 Contraindications  

 

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. 

 



 

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4.4 Special warnings and precautions for use 

 

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. These observations were not confirmed in clinical studies of more than one year duration. If 

a neoplasia is detected, it should be removed. In case of malignancy, Revestive 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 obstruction have been reported in clinical studies. In case of recurrent intestinal 

obstructions, the need for continued Revestive treatment should be reassessed. 

 

Fluid overload and Electrolyte Balance 
To avoid fluid overload or dehydration, careful adjustment of parenteral support is required in patients 

taking Revestive. Electrolyte balance and fluid status should be carefully monitored throughout 

treatment, especially during initial therapeutic response and discontinuation of Revestive treatment  

 

Fluid overload: 

Fluid overload has been observed in clinical trials. Fluid overload adverse events occurred most 
frequently during the first 4 weeks of therapy and decreased over time. 

 

Due to increased fluid absorption, patients with cardiovascular disease, such as cardiac insufficiency 

and hypertension, should be monitored with regard to fluid overload, especially during initiation of 

therapy. Patients should be advised to contact their physician in case of sudden weight gain, face 

swelling, swollen ankles and/or dyspnoea. In general, fluid overload can be prevented by appropriate 



 

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and timely assessment of parenteral nutrition needs. This assessment should be conducted more 

frequently within the first months of treatment. 

 

Congestive heart failure has been observed in clinical trials. In case of a significant deterioration of the 

cardiovascular disease, the need for continued treatment with Revestive should be reassessed. 

 

Dehydration: 

Patients with SBS are susceptible to dehydration that may lead to acute renal failure.  

In patients receiving Revestive, parenteral support should be reduced carefully and should not be 

discontinued abruptly. The patient’s fluid status should be evaluated following parenteral support 

reduction and corresponding adjustment performed, as needed. 

 

Concomitant medicinal products 

Patients receiving oral concomitant medicinal products requiring titration or with a narrow therapeutic 

index should be monitored closely due to potential increased absorption (see section 4.5). 

 

Special clinical conditions 

Revestive has not been studied in patients with severe, clinically unstable concomitant diseases, (e.g., 

cardiovascular, respiratory, renal, infectious, endocrine, hepatic, or CNS), or in patients with 

malignancies within the last five years (see section 4.3). Caution should be exercised when prescribing 

Revestive. 

 

Hepatic impairment 

Revestive has not been studied in patients with severe hepatic impairment. The data from use in 

subjects with moderate hepatic impairment do not suggest a need for restricted use. 

 

Discontinuation of treatment 
Due to the risk of dehydration, discontinuation of treatment with Revestive should be managed 

carefully. 

 

Paediatric population 

See also general precautions for adults under this section. 

 

Colo-rectal polyps/Neoplasia 
Prior to initiating treatment with Revestive, faecal occult blood testing should be done for all children 

and adolescents. Colonoscopy/sigmoidoscopy is required if there is evidence of unexplained blood in 

the stool. Subsequent faecal occult blood testing should be done annually in children and adolescents 

while they are receiving Revestive. 

 

Colonoscopy/sigmoidoscopy is recommended for all children and adolescents after one year of 

treatment, every 5 years thereafter while on continuous treatment with Revestive, and if they have new 

or unexplained gastrointestinal bleeding. 

 

Excipients 

Revestive contains less than 1 mmol sodium (23 mg) per dose. This means that it is essentially 

‘sodium-free’. 

 

Caution is needed when administering Revestive to persons with a known hypersensitivity to 

tetracycline (see section 4.3). 

 
4.5 Interaction with other medicinal products and other forms of interaction 

 

No clinical 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). 

 



 

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4.6 Fertility, pregnancy and lactation 

 

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. 

 

4.7 Effects on ability to drive and use machines 

 

Revestive has minor influence on the ability to drive, ride a bicycle, and use machines. However, cases 

of syncope have been reported in clinical studies (see section 4.8). Such events might impact the 

ability to drive, ride a bicycle, or use machines. 

 

4.8 Undesirable effects 

 

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 

 

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 

  



 

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Frequency 

 

System organ 

class  

Very common Common Uncommon Not known 

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 

Duodenal 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 

complications 

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. 
‡Includes the following preferred terms: Injection site haematoma, Injection site erythema, Injection sit e pain, 

Injection site swelling and Injection site haemorrhage. 

 

Description of selected adverse reactions 

Immunogenicity 

Consistent with the potentially immunogenic properties of medicinal products containing peptides, 

administration of Revestive 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 Revestive. 

 

Injection site reactions 
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, 



 

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injection site pain, injection site swelling and injection site haemorrhage (see also section 5.3). The 

majority of reactions were moderate in severity and no occurrences led to drug discontinuation. 

 

C-reactive protein 

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. 

 

Paediatric population 

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. 

 

Long-term safety data are not yet available for this paediatric population. No data are available for 

children under 1 year of age. 

 

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. 

 

4.9 Overdose 

 

The maximum dose of teduglutide studied during clinical development was 86 mg/day for 8 days. No 

unexpected systemic adverse reactions were seen (see section 4.8). 

 

In the event of an overdose, the patient should be carefully monitored by the medical professional. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1 Pharmacodynamic properties 

 

Pharmacotherapeutic group: Other alimentary tract and metabolism products, various alimentary tract 

and metabolism products, ATC code: A16AX08. 

 

Mechanism of action 

The naturally occurring human glucagon-like peptide-2 (GLP-2) is a peptide secreted by L cells of the 

intestine which is known to increase intestinal and portal blood flow, inhibit gastric acid secretion, and 

decrease intestinal motility. Teduglutide is an analogue of GLP-2. In several nonclinical studies, 

teduglutide has been shown to preserve mucosal integrity by promoting repair and normal growth of 

the intestine through an increase of villus height and crypt depth. 

 

Pharmacodynamic effects 
Similar to GLP-2, teduglutide is 33 amino acids in length with an amino acid substitution of alanine by 

glycine at the second position of the N-terminus. The single amino acid substitution relative to 

naturally occurring GLP-2 results in resistance to in vivo degradation by the enzyme dipeptidyl 
peptidase-IV (DPP-IV), resulting in an extended half-life. Teduglutide increases villus height and 

crypt depth of the intestinal epithelium. 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 

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Based on the findings derived from pre-clinical studies (see sections 4.4 and 5.3) and the proposed 

mechanism of action with the trophic effects on intestinal mucosa, there appears to be a risk for the 

promotion of small intestinal and/or colonic neoplasia. The clinical studies conducted could neither 

exclude nor confirm such an increased risk. Several cases of benign colorectal polyps occurred during 

the course of the trials, however, the frequency was not increased compared to placebo-treated 

patients. In addition to the need for a colonoscopy with removal of polyps by the time of the initiation 

of the treatment (see section 4.4.), every patient should be assessed for the need of an enhanced 

surveillance schedule based on the patient characteristics (e.g., age and underlying disease, previous 

occurrence of polyps etc.). 

 

Clinical efficacy 

Paediatric population 
The efficacy data presented are derived from 2 controlled studies in paediatric patients up to 24 weeks 

duration. These studies included 101 patients in the following age groups: 5 patients 1-2 years, 

56 patients 2 to <6 years, 32 patients 6 to <12 years, 7 patients 12 to <17 years, and 1 patient 17 to 

<18 years. Despite the limited sample size, which did not allow meaningful statistical comparisons, 

clinically meaningful, numerical reductions in the requirement for parenteral support were observed 

across all age groups. 

 

Teduglutide was studied in a 12-week, open-label, clinical study in 42 paediatric subjects aged 1 year 

through 14 years with SBS who were dependent on parenteral nutrition. The objectives of the study 

were to evaluate safety, tolerability, and efficacy of teduglutide compared to standard of care. Three 

(3) doses of teduglutide, 0.0125 mg/kg/day (n=8), 0.025 mg/kg/day (n=14), and 0.05 mg/kg/day 

(n=15), were investigated for 12 weeks. Five (5) subjects were enrolled in a standard of care cohort. 

 

Complete weaning 
Three subjects (3/15, 20%) on the recommended teduglutide dose were weaned off parenteral nutrition 

by Week 12. After a 4-week washout period, two of these patients had reinitiated parenteral nutrition 

support. 

 

Reduction in parenteral nutrition volume 

The mean change in parenteral nutrition volume from baseline at Week 12 in the ITT population, 

based on physician-prescribed data, was -2.57 (±3.56) l/week, correlating to a -39.11% (±40.79) mean 

decrease, compared to 0.43 (±0.75) l/week, correlating to a 7.38% (±12.76) increase in the standard of 

care cohort. At Week 16 (4 weeks following the end of treatment) parenteral nutrition volume 

reductions were still evident but less than observed at Week 12 when subjects were still on teduglutide 

(mean decrease of -31.80% (±39.26) compared to a 3.92% (±16.62) increase in the standard of care 

group). 

 

Reduction in parenteral nutrition calories 

At Week 12, there was a -35.11% (±53.04) mean change from baseline in parenteral nutrition calorie 

consumption in the ITT population based on physician-prescribed data. The corresponding change in 

the standard of care cohort was 4.31% (±5.36). At Week 16, the parenteral nutrition calories 

consumption continued to decrease with percentage mean changes from baseline of -39.15% (±39.08) 

compared to -0.87% (±9.25) for the standard of care cohort. 

 

Increases in enteral nutrition volume and enteral calories 
Based on prescribed data, the mean percentage change from baseline at Week 12 in enteral volume, in 

the ITT population, was 25.82% (±41.59) compared to 53.65% (±57.01) in the standard of care cohort. 

The corresponding increase in enteral calories was 58.80% (±64.20), compared to 57.02% (±55.25) in 

the standard of care cohort. 

 

Reduction in infusion time 

The mean decrease from baseline at Week 12 in the number of days/week on parenteral nutrition, in 

the ITT population based on physician-prescribed data, was -1.36 (±2.37) days/week corresponding to 

a percentage decrease of -24.49% (±42.46). There was no change from baseline in the standard of care 



 

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cohort. Four subjects (26.7%) on the recommended teduglutide dose achieved at least a three-day 

reduction in parenteral nutrition needs. 

 

At Week 12, based on subject diary data, subjects showed mean percentage reductions of 

35.55% (±35.23) hours per day compared to baseline, which corresponded to reductions in the 

hours/day of parenteral nutrition usage of -4.18 (±4.08), while subjects in the standard of care cohort 

showed minimal change in this parameter at the same time point. 

 

An additional 24-week, randomised, double-blind, multicentre study was conducted in 59 paediatric 

subjects aged 1 year through 17 years who were dependent on parenteral support. The objective was to 

evaluate safety/tolerability, pharmacokinetics and efficacy of teduglutide. Two doses of teduglutide 

were studied: 0.025 mg/kg/day (n=24) and 0.05 mg/kg/day (n=26); 9 subjects were enrolled in a 

standard of care (SOC) arm. Randomisation was stratified by age across dose groups. Results below 

correspond to the ITT population at the recommended dose of 0.05 mg/kg/day. 

 

Complete weaning 
Three (3) paediatric subjects in the 0.05 mg/kg group achieved the additional endpoint of enteral 

autonomy by week 24. 

 

Reduction in parenteral nutrition volume 

Based on subject diary data, 18 (69.2%) subjects in the 0.05 mg/kg/day group achieved the 

primary endpoint of ≥20% reduction in PN/IV volume at end of treatment, compared to 

baseline; in the SOC arm, 1 (11.1%) subject achieved this endpoint. 

The mean change in parenteral nutrition volume from baseline at Week 24, based on subject 
diary data, was -23.30 (±17.50) mL/kg/day, corresponding to -41.57% (±28.90); the mean 

change in the SOC arm was -6.03 (±4.5) mL/kg/day (corresponding to a -10.21% [±13.59]). 

Reduction in infusion time 

At week 24, there was a decrease in the infusion time of -3.03 (±3.84) hours/day in the 0.05 mg/kg/day 

arm, corresponding to a percentage change of -26.09% (±36.14). The change from baseline in the SOC 

cohort was -0.21 (±0.69) hours/day (-1.75% [±5.89]). 

 

The mean decrease from baseline at Week 24 in the number of days/week on parenteral nutrition, 

based on subject diary data, was -1.34 (±2.24) days/week corresponding to a percentage decrease 

of -21.33% (±34.09). There was no reduction in PN/IV infusion days per week in the SOC arm. 

 

Adults 
Teduglutide was studied in 17 patients with SBS allocated to five treatment groups using doses 

of 0.03, 0.10 or 0.15 mg/kg teduglutide once daily, or 0.05 or 0.075 mg/kg bid in a 21-day open-label, 

multicenter, dose-ranging study. Treatment resulted in enhanced gastrointestinal fluid absorption of 

approximately 750-1000 ml/day with improvements in the absorption of macronutrients and 

electrolytes, decreased stomal or faecal fluid and macronutrients excretion, and enhanced key 

structural and functional adaptations in the intestinal mucosa. Structural adaptations were transient in 

nature and returned to baseline levels within three weeks of discontinuing the treatment. 

 

In the pivotal phase 3 double-blind, placebo-controlled study in patients with SBS, who required 

parenteral nutrition, 43 patients were randomised to a 0.05 mg/kg/day dose of teduglutide and 

43 patients to placebo for up to 24 weeks. 

 

The proportion of teduglutide-treated subjects achieving a 20% to 100% reduction of parenteral 

nutrition at Week 20 and 24 was statistically significantly different from placebo (27 out of 

43 subjects, 62.8% versus 13 out of 43 patients, 30.2%, p=0.002). Treatment with teduglutide resulted 
in a 4.4 l/week reduction in parenteral nutrition requirements (from a pre-treatment baseline of 

12.9 litres) versus 2.3 l/week (from a pre-treatment baseline of 13.2 litres) for placebo at 24 weeks. 
Twenty-one (21) patients treated with teduglutide (48.8%) versus 9 on placebo (20.9%) achieved at 

least a one day reduction in parenteral nutrition administration (p=0.008). 



 

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Ninety-seven percent (97%) of patients (37 out of 39 patients treated with teduglutide) that completed 

the placebo-controlled study entered a long-term extension study where all patients received 

0.05 mg/kg of Revestive daily for up to an additional 2 years. In total 88 patients participated in this 

extension study, thereof 39 treated with placebo and 12 enrolled, but not randomised, in the previous 

study; 65 of 88 patients completed the extension study. There continued to be evidence of increased 

response to treatment for up 2.5 years in all groups exposed to teduglutide in terms of parenteral 

nutrition volume reduction, gaining additional days off parenteral nutrition per week, and achieving 

weaning of parenteral support. 

 

Thirty (30) of the 43 teduglutide-treated patients from the pivotal study who entered the extension 

study completed a total of 30 months of treatment. Of these, 28 patients (93%) achieved a 20% or 

greater reduction of parenteral support. Of responders in the pivotal study who completed the 

extension study, 21 out of 22 (96%) sustained their response to teduglutide after an additional 2 years 

of continuous treatment. 

 

The mean reduction in parenteral nutrition (n=30) was 7.55 l/week (a 65.6% reduction from baseline). 

Ten (10) subjects were weaned off their parenteral support while on teduglutide treatment for 30 

months. Subjects were maintained on teduglutide even if no longer requiring parenteral nutrition. 

These 10 subjects had required parenteral nutrition support for 1.2 to 15.5 years, and prior to treatment 

with teduglutide had required between 3.5 l/week and 13.4 l/week of parenteral nutrition support. At 

the end of study, 21 (70%), 18 (60%) and 18 (60%) of the 30 completers achieved a reduction of 1, 2, 

or 3 days per week in parenteral support, respectively. 

 

Of the 39 placebo subjects, 29 completed 24 months of treatment with teduglutide. The mean 

reduction in parenteral nutrition was 3.11 l/week (an additional 28.3% reduction). Sixteen (16, 55.2%) 

of the 29 completers achieved a 20% or greater reduction of parenteral nutrition. At the end of study, 

14 (48.3%), 7 (24.1%) and 5 (17.2%) patients achieved a reduction of 1, 2, or 3 days per week in 

parenteral nutrition, respectively. Two (2) subjects were weaned off their parenteral support while on 

teduglutide. 

 

Of the 12 subjects not randomised in the pivotal study, 6 completed 24 months of treatment with 

teduglutide. The mean reduction in parenteral nutrition was 4.0 l/week (39.4% reduction from baseline 

– the start of the extension study) and 4 of the 6 completers (66.7%) achieved a 20% or greater 

reduction in parenteral support. At the end of study, 3 (50%), 2 (33%) and 2 (33%) achieved a 

reduction of 1, 2, or 3 days per week in parenteral nutrition, respectively. One subject was weaned off 

their parenteral support while on teduglutide. 

In another phase 3 double-blind, placebo-controlled study in patients with SBS, who required 

parenteral nutrition, patients received a 0.05 mg/kg/day dose (n=35), a 0.10 mg/kg/day dose (n=32) of 

teduglutide or placebo (n=16) for up to 24 weeks. 

 

The primary efficacy analysis of the study results showed no statistically significant difference 

between the group on teduglutide 0.10 mg/kg/day and the placebo group, while the proportion of 

subjects receiving the recommended teduglutide dose of 0.05 mg/kg/day achieving at least a 20% 

reduction of parenteral nutrition at Week 20 and 24 was statistically significantly different versus 
placebo (46% versus 6.3%, p<0.01). Treatment with teduglutide resulted in a 2.5 l/week reduction in 

parenteral nutrition requirements (from a pre-treatment baseline of 9.6 litres) versus 0.9 l/week (from a 
pre-treatment baseline of 10.7 litres) for placebo at 24 weeks. 

 

Teduglutide treatment induced expansion of the absorptive epithelium by significantly increasing 

villus height in the small intestine. 

 

Sixty-five (65) patients entered a follow-up SBS study for up to an additional 28 weeks of treatment. 

Patients on teduglutide maintained their previous dose assignment throughout the extension phase, 

while placebo patients were randomised to active treatment, either 0.05 or 0.10 mg/kg/day. 

 



 

12 

Of the patients who achieved at least a 20% reduction of parenteral nutrition at Weeks 20 and 24 in the 

initial study, 75% sustained this response on teduglutide after up to 1 year of continuous treatment. 

 

The mean reduction of weekly parenteral nutrition volume was 4.9 l/week (52% reduction from 

baseline) after one year of continuous teduglutide treatment. 

 

Two (2) patients on the recommended teduglutide dose were weaned off parenteral nutrition by 

Week 24. One additional patient in the follow-up study was weaned off parenteral nutrition. 

 

The European Medicines Agency has deferred the obligation to submit the results of studies with 

Revestive in one or more subsets of the paediatric population in the treatment of SBS (see section 4.2 

for information on paediatric use). 

 

5.2 Pharmacokinetic properties 

 

Absorption 

Teduglutide was rapidly absorbed from subcutaneous injection sites with maximum plasma levels 

occurring approximately 3-5 hours after dose administration at all dose levels. The absolute 

bioavailability of subcutaneous teduglutide is high (88%). No accumulation of teduglutide was 

observed following repeated subcutaneous administration. 

 

Distribution 

Following subcutaneous administration, teduglutide has an apparent volume of distribution of 26 litres 

in patients with SBS. 

 

Biotransformation 

The metabolism of teduglutide is not fully known. Since teduglutide is a peptide it is likely that it 

follows the principal mechanism for peptide metabolism. 

 

Elimination 

Teduglutide has a terminal elimination half-life of approximately 2 hours. Following intravenous 

administration teduglutide plasma clearance was approximately 127 ml/hr/kg which is equivalent to 

the glomerular filtration rate (GFR). Renal elimination was confirmed in a study investigating 

pharmacokinetics in subjects with renal impairment. No accumulation of teduglutide was observed 

following repeated subcutaneous administrations. 

 

Dose linearity 

The rate and extent of absorption of teduglutide is dose-proportional at single and repeated 

subcutaneous doses up to 20 mg. 

 

Pharmacokinetics in subpopulations 

Paediatric population 
Following subcutaneous administration, similar Cmax of teduglutide across age groups was 

demonstrated by population pharmacokinetics modelling. However, lower exposure (AUC) and 

shorter half-life were seen in paediatric patients 1 to 17 years of age, as compared with adults. The 

pharmacokinetic profile of Revestive in this paediatric population, as evaluated by clearance and 

volume of distribution, was different from that observed in adults after correcting for body weights. 

Specifically, clearance decreases with increasing age from 1 year old to adults. No data are available 

for paediatric patients with moderate to severe renal impairment and end-stage renal disease (ESRD). 

 

Gender 

No clinically relevant gender differences were observed in clinical studies. 
 

Elderly 

In a phase 1 study no difference in pharmacokinetics of teduglutide could be detected between healthy 

subjects younger than 65 years versus older than 65 years. Experience in subjects 75 years and above 

is limited. 



 

13 

 

Hepatic impairment 

In a phase 1 study the effect of hepatic impairment on the pharmacokinetics of teduglutide following 

subcutaneous administration of 20 mg teduglutide was investigated. The maximum exposure and the 

overall extent of exposure to teduglutide following single 20 mg subcutaneous doses were lower 

(10-15%) in subjects with moderate hepatic impairment relative to those in healthy matched controls. 

 

Renal impairment 
In a phase 1 study, the effect of renal impairment on the pharmacokinetics of teduglutide following 

subcutaneous administration of 10 mg teduglutide was investigated. With progressive renal 

impairment up to and including end-stage renal disease the primary pharmacokinetic parameters of 

teduglutide increased up to a factor of 2.6 (AUCinf) and 2.1 (Cmax) compared to healthy subjects. 

 

5.3 Preclinical safety data 

 

Hyperplasia in the gall bladder, hepatic biliary ducts, and pancreatic ducts were observed in 

subchronic and chronic toxicology studies. These observations were potentially associated with the 

expected intended pharmacology of teduglutide and were to a varying degree reversible within an 

8-13 week recovery period following chronic administration. 

 

Injection site reactions 

In pre-clinical studies, severe granulomatous inflammations were found associated with the injection 

sites. 

 

Carcinogenicity / mutagenicity 

Teduglutide was negative when tested in the standard battery of tests for genotoxicity. 

 

In a rat carcinogenicity study, treatment related benign neoplasms included tumours of the bile duct 

epithelium in males exposed to teduglutide plasma levels approximately 32- and 155-fold higher than 

obtained in patients administered the recommended daily dose (incidence of 1 out of 44 and 4 out 

of 48, respectively). Adenomas of the jejunal mucosa were observed in 1 out of 50 males and 5 out of 

50 males exposed to teduglutide plasma levels approximately 10- and 155-fold higher than obtained in 

patients administered the recommended daily dose. In addition, a jejunal adenocarcinoma was 

observed in a male rat administered the lowest dose tested (animal:human plasma exposure margin of 

approximately 10-fold). 

 

Reproductive and developmental toxicity 

Reproductive and developmental toxicity studies evaluating teduglutide have been carried out in rats 

and rabbits at doses of 0, 2, 10 and 50 mg/kg/day subcutaneously. Teduglutide was not associated with 

effects on reproductive performance, in utero or developmental parameters measured in studies to 

investigate fertility, embryo-foetal development and pre- and post-natal development. 

Pharmacokinetic data demonstrated that the teduglutide exposure of foetal rabbits and suckling rat 

pups was very low. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Powder 

L-histidine 

Mannitol 

Sodium phosphate monohydrate 

Disodium phosphate heptahydrate 

 



 

14 

Solvent 

Water for injections 

 

6.2 Incompatibilities 

 

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 

products. 

 

6.3 Shelf life 

 

Unopened vials 

4 years. 

 

Reconstituted product 

Chemical and physical in-use stablility has been demonstrated for 24 hours up to 25°C. 

 

From a microbiological point of view, unless the method of reconstitution precludes the risk of 

microbial contamination, the product should be used immediately. 

 

If not used immediately, in-use storage times and conditions are the responsibility of the user and 

would normally not be longer than 24 hours at 2 to 8°C, unless reconstitution has taken place in 

controlled and validated aseptic conditions. 

 

6.4 Special precautions for storage 

 

Store in a refrigerator (2°C – 8°C). Do not freeze. 

 

For storage conditions after reconstitution of the medicinal product, see section 6.3. 

 

6.5 Nature and contents of container 

 

Powder 

3 ml vial (glass) with rubber stopper (bromobutyl) containing 1.25 mg teduglutide. 

 

Solvent 

Pre-filled syringe (glass) with plungers (bromobutyl) containing 0.5 ml of solvent. 

 

Pack size of 28 vials of powder with 28 pre-filled syringes. 

 

6.6 Special precautions for disposal and other handling 

 

Determination of the number of vials needed for administration of one dose must be based on the 

individual patient’s weight and the recommended dose of 0.05 mg/kg/day. The physician should at 

each visit weigh the patient, determine the daily dose to be administered until next visit and inform the 

patient accordingly. 

 

A table with the injection volumes based on the recommended dose per body weight for paediatric 

patients is provided in section 4.2. 

 

The pre-filled syringe must be assembled with a reconstitution needle. 

 

The powder in the vial must then be dissolved by adding all the solvent from the pre-filled syringe. 
 

The vial should not be shaken, but can be rolled between the palms and gently turned upside-down 

once. Once a clear colourless solution is formed in the vial, the solution should be sucked up into a 

1 ml injection syringe (or 0.5 ml or smaller injection syringe for paediatric use) with scale intervals of 

0.02 ml or smaller (not included in the pack). 



 

15 

 

If two vials are needed, the procedure for the second vial must be repeated and the additional solution 

sucked up into the injection syringe containing the solution from the first vial. Any volume exceeding 

the prescribed dose in ml must be expelled and discarded. 

 

The solution must be injected subcutaneously into a cleaned area on the abdomen, or if this is not 

possible, on the thigh (see section 4.2 Method of administration) using a thin needle for subcutaneous 

injection suitable for paediatric use. 

 

Detailed instructions on the preparation and injection of Revestive are provided in the package leaflet. 

 

The solution must not be used if it is cloudy or contains particulate matter. 

 

For single use only. 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

All needles and syringes should be disposed of in a sharps disposal container. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Shire Pharmaceuticals Ireland Limited 

Block 2 & 3 Miesian Plaza 

50 – 58 Baggot Street Lower 

Dublin 2 

Ireland 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/12/787/003 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 
Date of first authorisation: 30 August 2012 

Date of latest renewal: 23 June 2017 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu. 

http://www.ema.europa.eu/


 

16 

This medicinal product is subject to additional monitoring. This will allow quick identification of 

new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 

See section 4.8 for how to report adverse reactions. 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Revestive 5 mg powder and solvent for solution for injection 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

One vial of powder contains 5 mg of teduglutide*. 

After reconstitution, each vial contains 5 mg teduglutide in 0.5 ml of solution, corresponding to a 

concentration of 10 mg/ml. 

 

*A glucagon-like peptide-2 (GLP-2) analogue produced in Escherichia coli cells by recombinant 
DNA technology. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Powder and solvent for solution for injection. 
The powder is white and the solvent is clear and colourless. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Revestive is indicated for the treatment of patients aged 1 year and above with Short Bowel Syndrome 

(SBS). Patients should be stable following a period of intestinal adaptation after surgery. 

 

4.2 Posology and method of administration 

 

Treatment should be initiated under the supervision of a medical professional with experience in the 

treatment of SBS. 

 

Treatment should not be initiated until it is reasonable to assume that a patient is stable following a 

period of intestinal adaptation. Optimisation and stabilisation of intravenous fluid and nutrition 

support should be performed before initiation of treatment. 

 

Clinical assessment by the physician should consider individual treatment objectives and patient 

preferences. Treatment should be stopped if no overall improvement of the patient condition is 

achieved. Efficacy and safety in all patients should be closely monitored on an ongoing basis 

according to clinical treatment guidelines. 

 

Posology 

Adults 
The recommended dose of Revestive is 0.05 mg/kg body weight once daily. The injection volume per 
body weight is provided below in Table 1. Due to the heterogeneity of the SBS population, a carefully 

monitored down-titration of the daily dose may be considered for some patients to optimise tolerability 

of the treatment. If a dose is missed, that dose should be injected as soon as possible on that day. 

 



 

17 

Treatment effect should be evaluated after 6 months. Limited data from clinical studies have shown 

that some patients may take longer to respond to treatment (i.e., those who still have presence of 

colon-in-continuity or distal/terminal ileum); if no overall improvement is achieved after 12 months, 

the need for continued treatment should be reconsidered. 

 

Continued treatment is recommended for patients who have weaned off parenteral nutrition. 

 

Table 1 

 

Body weight 

5 mg strength 

Volume to be injected 

38-41 kg 0.20 ml 

42-45 kg 0.22 ml 

46-49 kg 0.24 ml 

50-53 kg 0.26 ml 

54-57 kg 0.28 ml 

58-61 kg 0.30 ml 

62-65 kg 0.32 ml 

66-69 kg 0.34 ml 

70-73 kg 0.36 ml 

74-77 kg 0.38 ml 

78-81 kg 0.40 ml 

82-85 kg 0.42 ml 

86-89 kg 0.44 ml 

90-93 kg 0.46 ml 

 

Paediatric population (≥1 year) 
Treatment should be initiated under the supervision of a medical professional with experience in the 

treatment of paediatric SBS. 

 

The recommended dose of Revestive in children and adolescents (aged 1 to 17 years) is the same as 

for adults (0.05 mg/kg body weight once daily). The injection volume per body weight when using the 

5 mg strength vial is provided in Table 2 below. A 1.25 mg strength vial is also available for paediatric 

use (patients with a body weight <20 kg). 

 

If a dose is missed, that dose should be injected as soon as possible on that day. A treatment period of 

6 months is recommended after which treatment effect should be evaluated. In children below the age 

of two years, treatment should be evaluated after 12 weeks. There are no data available in paediatric 

patients after 6 months (see section 5.1). 

 

Table 2 

 

Body weight 

5 mg strength 

Volume to be injected 

10-11 kg 0.05 ml 

12-13 kg 0.06 ml 

14-17 kg 0.08 ml 

18-21 kg 0.10 ml 

22-25 kg 0.12 ml 

26-29 kg 0.14 ml 

30-33 kg 0.16 ml 

34-37 kg 0.18 ml 

38-41 kg 0.20 ml 



 

18 

 

Body weight 

5 mg strength 

Volume to be injected 

42-45 kg 0.22 ml 

46-49 kg 0.24 ml 

   ≥50 kg See Table 1 under “Adults” section. 

 

 

Special populations 
Elderly 

No dose adjustment is necessary in patients above the age of 65 years. 

 

Renal impairment 
No dose adjustment is necessary for adult or paediatric patients with mild renal impairment. 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% (see section 5.2). 

 

Hepatic impairment 

No dose adjustment is necessary for patients with mild and moderate hepatic impairment based on a 

study conducted in Child-Pugh grade B subjects. Revestive has not been studied in patients with 

severe hepatic impairment (see sections 4.4 and 5.2). 

 

Paediatric population 

The safety and efficacy of Revestive in children below 1 year of age have not been established. No 

data are available. 

 

Method of administration 

The reconstituted solution should be administered by subcutaneous injection once daily, alternating 

sites between 1 of the 4 quadrants of the abdomen. In case the injection into the abdomen is hampered 

by pain, scarring or hardening of the tissue, the thigh can also be used. Revestive should not be 

administered intravenously or intramuscularly. 

 

For instructions on reconstitution of the medicinal product before administration, see section 6.6. 

 

4.3 Contraindications  

 

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. 

 

4.4 Special warnings and precautions for use 

 

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 



 

19 

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. These observations were not confirmed in clinical studies of more than one year duration. If 

a neoplasia is detected, it should be removed. In case of malignancy, Revestive 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 obstruction have been reported in clinical studies. In case of recurrent intestinal 

obstructions, the need for continued Revestive treatment should be reassessed. 

 

Fluid overload and Electrolyte Balance 

To avoid fluid overload or dehydration, careful adjustment of parenteral support is required in patients 

taking Revestive. Electrolyte balance and fluid status should be carefully monitored throughout 

treatment, especially during initial therapeutic response and discontinuation of Revestive treatment  

 

Fluid overload: 

Fluid overload has been observed in clinical trials. Fluid overload adverse events occurred most 

frequently during the first 4 weeks of therapy and decreased over time. 

 

Due to increased fluid absorption, patients with cardiovascular disease, such as cardiac insufficiency 

and hypertension, should be monitored with regard to fluid overload, especially during initiation of 

therapy. Patients should be advised to contact their physician in case of sudden weight gain, face 

swelling, swollen ankles and/or dyspnoea. In general, fluid overload can be prevented by appropriate 

and timely assessment of parenteral nutrition needs. This assessment should be conducted more 

frequently within the first months of treatment. 

 

Congestive heart failure has been observed in clinical trials. In case of a significant deterioration of the 

cardiovascular disease, the need for continued treatment with Revestive should be reassessed. 

 

Dehydration: 

Patients with SBS are susceptible to dehydration that may lead to acute renal failure.  

In patients receiving Revestive, parenteral support should be reduced carefully and should not be 

discontinued abruptly. The patient’s fluid status should be evaluated following parenteral support 

reduction and corresponding adjustment performed, as needed. 

 



 

20 

Concomitant medicinal products 

Patients receiving oral concomitant medicinal products requiring titration or with a narrow therapeutic 

index should be monitored closely due to potential increased absorption (see section 4.5). 

 

Special clinical conditions 
Revestive has not been studied in patients with severe, clinically unstable concomitant diseases, (e.g., 

cardiovascular, respiratory, renal, infectious, endocrine, hepatic, or CNS), or in patients with 

malignancies within the last five years (see section 4.3). Caution should be exercised when prescribing 

Revestive. 

Hepatic impairment 

Revestive has not been studied in patients with severe hepatic impairment. The data from use in 

subjects with moderate hepatic impairment do not suggest a need for restricted use. 

 

Discontinuation of treatment 

Due to the risk of dehydration, discontinuation of treatment with Revestive should be managed 

carefully. 

 

Paediatric population 

See also general precautions for adults under this section. 

 

Colo-rectal polyps/Neoplasia 

Prior to initiating treatment with Revestive, faecal occult blood testing should be done for all children 

and adolescents. Colonoscopy/sigmoidoscopy is required if there is evidence of unexplained blood in 

the stool. Subsequent faecal occult blood testing should be done annually in children and adolescents 

while they are receiving Revestive. 

 

Colonoscopy/sigmoidoscopy is recommended for all children and adolescents after one year of 

treatment, every 5 years thereafter while on continuous treatment with Revestive, and if they have new 

or unexplained gastrointestinal bleeding. 

 

Excipients 

Revestive contains less than 1 mmol sodium (23 mg) per dose. This means that it is essentially 

‘sodium-free’. 

 

Caution is needed when administering Revestive to persons with a known hypersensitivity to 

tetracycline (see section 4.3). 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

No clinical 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). 

 

4.6 Fertility, pregnancy and lactation 

 

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. 

 



 

21 

Fertility 

There are no data on the effects of teduglutide on human fertility. Animal data do not indicate any 

impairment of fertility. 

 

4.7 Effects on ability to drive and use machines 

 

Revestive has minor influence on the ability to drive and use machines. However, cases of syncope 

have been reported in clinical studies (see section 4.8). Such events might impact the ability to drive 

and use machines. 

 

4.8 Undesirable effects 

 

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. 

 

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 

 

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 

  



 

22 

Frequency 

 

System organ 

class  

Very common Common Uncommon Not known 

Gastrointestinal 

disorders 

Abdominal 

distension 

Abdominal pain 

Nausea 

Vomiting 

Colorectal polyp 

Colonic stenosis 

Flatulence 

Intestinal 

obstruction 

Pancreatic duct 

stenosis 

Pancreatitis† 

Small intestinal 

stenosis 

Duodenal 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 

complications 

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. 
‡Includes the following preferred terms: Injection site haematoma, Injection site erythema, Injection site pain, 

Injection site swelling and Injection site haemorrhage. 

 

Description of selected adverse reactions 

Immunogenicity 
Consistent with the potentially immunogenic properties of medicinal products containing peptides, 

administration of Revestive 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 Revestive. 

 

Injection site reactions 

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 (see also section 5.3). The 

majority of reactions were moderate in severity and no occurrences led to drug discontinuation. 

 

C-reactive protein 

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. 

 



 

23 

Paediatric population 

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. 

 

Long-term safety data are not yet available for this paediatric population. No data are available for 

children under 1 year of age. 

 

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. 

 

4.9 Overdose 

 

The maximum dose of teduglutide studied during clinical development was 86 mg/day for 8 days. No 

unexpected systemic adverse reactions were seen (see section 4.8). 

 

In the event of an overdose, the patient should be carefully monitored by the medical professional. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1 Pharmacodynamic properties 

 

Pharmacotherapeutic group: Other alimentary tract and metabolism products, various alimentary tract 

and metabolism products, ATC code: A16AX08. 

 

Mechanism of action 

The naturally occurring human glucagon-like peptide-2 (GLP-2) is a peptide secreted by L cells of the 

intestine which is known to increase intestinal and portal blood flow, inhibit gastric acid secretion, and 

decrease intestinal motility. Teduglutide is an analogue of GLP-2. In several nonclinical studies, 

teduglutide has been shown to preserve mucosal integrity by promoting repair and normal growth of 

the intestine through an increase of villus height and crypt depth. 

 

Pharmacodynamic effects 

Similar to GLP-2, teduglutide is 33 amino acids in length with an amino acid substitution of alanine by 

glycine at the second position of the N-terminus. The single amino acid substitution relative to 

naturally occurring GLP-2 results in resistance to in vivo degradation by the enzyme dipeptidyl 
peptidase-IV (DPP-IV), resulting in an extended half-life. Teduglutide increases villus height and 

crypt depth of the intestinal epithelium. 

 

Based on the findings derived from pre-clinical studies (see sections 4.4 and 5.3) and the proposed 

mechanism of action with the trophic effects on intestinal mucosa, there appears to be a risk for the 

promotion of small intestinal and/or colonic neoplasia. The clinical studies conducted could neither 

exclude nor confirm such an increased risk. Several cases of benign colorectal polyps occurred during 

the course of the trials, however, the frequency was not increased compared to placebo-treated 

patients. In addition to the need for a colonoscopy with removal of polyps by the time of the initiation 
of the treatment (see section 4.4.), every patient should be assessed for the need of an enhanced 

surveillance schedule based on the patient characteristics (e.g., age and underlying disease, previous 

occurrence of polyps etc.). 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 

24 

Clinical efficacy 

Adults 
Teduglutide was studied in 17 patients with SBS allocated to five treatment groups using doses 

of 0.03, 0.10 or 0.15 mg/kg teduglutide once daily, or 0.05 or 0.075 mg/kg bid in a 21-day open-label, 

multicenter, dose-ranging study. Treatment resulted in enhanced gastrointestinal fluid absorption of 

approximately 750-1000 ml/day with improvements in the absorption of macronutrients and 

electrolytes, decreased stomal or faecal fluid and macronutrients excretion, and enhanced key 

structural and functional adaptations in the intestinal mucosa. Structural adaptations were transient in 

nature and returned to baseline levels within three weeks of discontinuing the treatment. 

In the pivotal phase 3 double-blind, placebo-controlled study in patients with SBS, who required 

parenteral nutrition, 43 patients were randomised to a 0.05 mg/kg/day dose of teduglutide and 

43 patients to placebo for up to 24 weeks. 

 

The proportion of teduglutide-treated subjects achieving a 20% to 100% reduction of parenteral 

nutrition at Week 20 and 24 was statistically significantly different from placebo (27 out of 

43 subjects, 62.8% versus 13 out of 43 patients, 30.2%, p=0.002). Treatment with teduglutide resulted 
in a 4.4 l/week reduction in parenteral nutrition requirements (from a pre-treatment baseline of 

12.9 litres) versus 2.3 l/week (from a pre-treatment baseline of 13.2 litres) for placebo at 24 weeks. 

Twenty-one (21) patients treated with teduglutide (48.8%) versus 9 on placebo (20.9%) achieved at 
least a one day reduction in parenteral nutrition administration (p=0.008). 

 

Ninety-seven percent (97%) of patients (37 out of 39 patients treated with teduglutide) that completed 

the placebo-controlled study entered a long-term extension study where all patients received 

0.05 mg/kg of Revestive daily for up to an additional 2 years. In total 88 patients participated in this 

extension study, thereof 39 treated with placebo and 12 enrolled, but not randomised, in the previous 

study; 65 of 88 patients completed the extension study. There continued to be evidence of increased 

response to treatment for up 2.5 years in all groups exposed to teduglutide in terms of parenteral 

nutrition volume reduction, gaining additional days off parenteral nutrition per week, and achieving 

weaning of parenteral support. 

 

Thirty (30) of the 43 teduglutide-treated patients from the pivotal study who entered the extension 

study completed a total of 30 months of treatment. Of these, 28 patients (93%) achieved a 20% or 

greater reduction of parenteral support. Of responders in the pivotal study who completed the 

extension study, 21 out of 22 (96%) sustained their response to teduglutide after an additional 2 years 

of continuous treatment. 

 

The mean reduction in parenteral nutrition (n=30) was 7.55 l/week (a 65.6% reduction from baseline). 

Ten (10) subjects were weaned off their parenteral support while on teduglutide treatment for 30 

months. Subjects were maintained on teduglutide even if no longer requiring parenteral nutrition. 

These 10 subjects had required parenteral nutrition support for 1.2 to 15.5 years, and prior to treatment 

with teduglutide had required between 3.5 l/week and 13.4 l/week of parenteral nutrition support. At 

the end of study, 21 (70%), 18 (60%) and 18 (60%) of the 30 completers achieved a reduction of 1, 2, 

or 3 days per week in parenteral support, respectively. 

 

Of the 39 placebo subjects, 29 completed 24 months of treatment with teduglutide. The mean 

reduction in parenteral nutrition was 3.11 l/week (an additional 28.3% reduction). Sixteen (16, 55.2%) 

of the 29 completers achieved a 20% or greater reduction of parenteral nutrition. At the end of study, 

14 (48.3%), 7 (24.1%) and 5 (17.2%) patients achieved a reduction of 1, 2, or 3 days per week in 

parenteral nutrition, respectively. Two (2) subjects were weaned off their parenteral support while on 

teduglutide. 

 

Of the 12 subjects not randomised in the pivotal study, 6 completed 24 months of treatment with 

teduglutide. The mean reduction in parenteral nutrition was 4.0 l/week (39.4% reduction from baseline 

– the start of the extension study) and 4 of the 6 completers (66.7%) achieved a 20% or greater 

reduction in parenteral support. At the end of study, 3 (50%), 2 (33%) and 2 (33%) achieved a 

reduction of 1, 2, or 3 days per week in parenteral nutrition, respectively. One subject was weaned off 

their parenteral support while on teduglutide. 



 

25 

 

In another phase 3 double-blind, placebo-controlled study in patients with SBS, who required 

parenteral nutrition, patients received a 0.05 mg/kg/day dose (n=35), a 0.10 mg/kg/day dose (n=32) of 

teduglutide or placebo (n=16) for up to 24 weeks. 

 

The primary efficacy analysis of the study results showed no statistically significant difference 

between the group on teduglutide 0.10 mg/kg/day and the placebo group, while the proportion of 

subjects receiving the recommended teduglutide dose of 0.05 mg/kg/day achieving at least a 20% 

reduction of parenteral nutrition at Week 20 and 24 was statistically significantly different versus 
placebo (46% versus 6.3%, p<0.01). Treatment with teduglutide resulted in a 2.5 l/week reduction in 

parenteral nutrition requirements (from a pre-treatment baseline of 9.6 litres) versus 0.9 l/week (from a 

pre-treatment baseline of 10.7 litres) for placebo at 24 weeks. 

 

Teduglutide treatment induced expansion of the absorptive epithelium by significantly increasing 

villus height in the small intestine. 

 

Sixty-five (65) patients entered a follow-up SBS study for up to an additional 28 weeks of treatment. 

Patients on teduglutide maintained their previous dose assignment throughout the extension phase, 

while placebo patients were randomised to active treatment, either 0.05 or 0.10 mg/kg/day. 

 

Of the patients who achieved at least a 20% reduction of parenteral nutrition at Weeks 20 and 24 in the 

initial study, 75% sustained this response on teduglutide after up to 1 year of continuous treatment. 

 

The mean reduction of weekly parenteral nutrition volume was 4.9 l/week (52% reduction from 

baseline) after one year of continuous teduglutide treatment. 

 

Two (2) patients on the recommended teduglutide dose were weaned off parenteral nutrition by 

Week 24. One additional patient in the follow-up study was weaned off parenteral nutrition. 

 

Paediatric population 

The efficacy data presented are derived from 2 controlled studies in paediatric patients up to 24 weeks 

duration. These studies included 101 patients in the following age groups: 5 patients 1-2 years, 

56 patients 2 to <6 years, 32 patients 6 to <12 years, 7 patients 12 to <17 years, and 1 patient 17 to 

<18 years. Despite the limited sample size, which did not allow meaningful statistical comparisons, 

clinically meaningful, numerical reductions in the requirement for parenteral support were observed 

across all age groups. 

 

Teduglutide was studied in a 12-week, open-label, clinical study in 42 paediatric subjects aged 1 year 

through 14 years with SBS who were dependent on parenteral nutrition. The objectives of the study 

were to evaluate safety, tolerability, and efficacy of teduglutide compared to standard of care. Three 

(3) doses of teduglutide, 0.0125 mg/kg/day (n=8), 0.025 mg/kg/day (n=14), and 0.05 mg/kg/day 

(n=15), were investigated for 12 weeks. Five (5) subjects were enrolled in a standard of care cohort. 

 

Complete weaning 

Three subjects (3/15, 20%) on the recommended teduglutide dose were weaned off parenteral nutrition 

by Week 12. After a 4-week washout period, two of these patients had reinitiated parenteral nutrition 

support. 

 

Reduction in parenteral nutrition volume 
The mean change in parenteral nutrition volume from baseline at Week 12 in the ITT population, 

based on physician-prescribed data, was -2.57 (±3.56) l/week, correlating to a -39.11% (±40.79) mean 

decrease, compared to 0.43 (±0.75) l/week, correlating to a 7.38% (±12.76) increase in the standard of 

care cohort. At Week 16 (4 weeks following the end of treatment) parenteral nutrition volume 

reductions were still evident but less than observed at Week 12 when subjects were still on teduglutide 

(mean decrease of -31.80% (±39.26) compared to a 3.92% (±16.62) increase in the standard of care 

group). 

 



 

26 

Reduction in parenteral nutrition calories 

At Week 12, there was a -35.11% (±53.04) mean change from baseline in parenteral nutrition calorie 

consumption in the ITT population based on physician-prescribed data. The corresponding change in 

the standard of care cohort was 4.31% (±5.36). At Week 16, the parenteral nutrition calories 

consumption continued to decrease with percentage mean changes from baseline of -39.15% (±39.08) 

compared to -0.87% (±9.25) for the standard of care cohort. 

 

Increases in enteral nutrition volume and enteral calories 

Based on prescribed data, the mean percentage change from baseline at Week 12 in enteral volume, in 

the ITT population, was 25.82% (±41.59) compared to 53.65% (±57.01) in the standard of care cohort. 

The corresponding increase in enteral calories was 58.80% (±64.20), compared to 57.02% (±55.25) in 

the standard of care cohort. 

 

Reduction in infusion time 

The mean decrease from baseline at Week 12 in the number of days/week on parenteral nutrition, in 

the ITT population based on physician-prescribed data, was -1.36 (±2.37) days/week corresponding to 

a percentage decrease of -24.49% (±42.46). There was no change from baseline in the standard of care 

cohort. Four subjects (26.7%) on the recommended teduglutide dose achieved at least a three-day 

reduction in parenteral nutrition needs. 

 

At Week 12, based on subject diary data, subjects showed mean percentage reductions of 

35.55% (±35.23) hours per day compared to baseline, which corresponded to reductions in the 

hours/day of parenteral nutrition usage of -4.18 (±4.08), while subjects in the standard of care cohort 

showed minimal change in this parameter at the same time point. 

 

An additional 24-week, randomised, double-blind, multicentre study was conducted in 59 paediatric 

patients aged 1 year through 17 years who were dependent on parenteral support. The objective was to 

evaluate safety/tolerability, pharmacokinetics and efficacy of teduglutide. Two doses of teduglutide 

were studied: 0.025 mg/kg/day (n=24) and 0.05 mg/kg/day (n=26); 9 subjects were enrolled in a 

standard of care (SOC) arm. Randomisation was stratified by age across dose groups. Results below 

correspond to the ITT population at the recommended dose of 0.05 mg/kg/day. 

 

Complete weaning 

Three (3) paediatric subjects in the 0.05 mg/kg group achieved the additional endpoint of enteral 

autonomy by week 24. 

 

Reduction in parenteral nutrition volume 

Based on subject diary data, 18 (69.2%) subjects in the 0.05 mg/kg/day group achieved the 

primary endpoint of ≥20% reduction in PN/IV volume at end of treatment, compared to 

baseline; in the SOC arm, 1 (11.1%) subject achieved this endpoint. 

The mean change in parenteral nutrition volume from baseline at Week 24, based on subject 
diary data, was -23.30 (±17.50) mL/kg/day, corresponding to -41.57% (±28.90); the mean 

change in the SOC arm was -6.03 (±4.5) mL/kg/day (corresponding to a -10.21% [±13.59]). 

Reduction in infusion time 

At week 24, there was a decrease in the infusion time of -3.03 (±3.84) hours/day in the 0.05 mg/kg/day 

arm, corresponding to a percentage change of -26.09% (±36.14). The change from baseline in the SOC 

cohort was -0.21 (±0.69) hours/day (-1.75% [±5.89]). 

 

The mean decrease from baseline at Week 24 in the number of days/week on parenteral nutrition, 

based on subject diary data, was -1.34 (±2.24) days/week corresponding to a percentage decrease 

of -21.33% (±34.09). There was no reduction in PN/IV infusion days per week in the SOC arm. 

 

The European Medicines Agency has deferred the obligation to submit the results of studies with 

Revestive in one or more subsets of the paediatric population in the treatment of SBS (see section 4.2 

for information on paediatric use). 



 

27 

 

5.2 Pharmacokinetic properties 

 

Absorption 

Teduglutide was rapidly absorbed from subcutaneous injection sites with maximum plasma levels 

occurring approximately 3-5 hours after dose administration at all dose levels. The absolute 

bioavailability of subcutaneous teduglutide is high (88%). No accumulation of teduglutide was 

observed following repeated subcutaneous administration. 

 

Distribution 

Following subcutaneous administration, teduglutide has an apparent volume of distribution of 26 litres 

in patients with SBS. 

 

Biotransformation 

The metabolism of teduglutide is not fully known. Since teduglutide is a peptide it is likely that it 

follows the principal mechanism for peptide metabolism. 

 

Elimination 

Teduglutide has a terminal elimination half-life of approximately 2 hours. Following intravenous 

administration teduglutide plasma clearance was approximately 127 ml/hr/kg which is equivalent to 

the glomerular filtration rate (GFR). Renal elimination was confirmed in a study investigating 

pharmacokinetics in subjects with renal impairment. No accumulation of teduglutide was observed 

following repeated subcutaneous administrations. 

 

Dose linearity 

The rate and extent of absorption of teduglutide is dose-proportional at single and repeated 

subcutaneous doses up to 20 mg. 

 

Pharmacokinetics in subpopulations 

Paediatric population 

Following subcutaneous administration, similar Cmax of teduglutide across age groups was 

demonstrated by population pharmacokinetics modelling. However, lower exposure (AUC) and 
shorter half-life were seen in paediatric patients 1 to 17 years of age, as compared with adults. The 

pharmacokinetic profile of Revestive in this paediatric population, as evaluated by clearance and 

volume of distribution, was different from that observed in adults after correcting for body weights. 

Specifically, clearance decreases with increasing age from 1 year old to adults. No data are available 

for paediatric patients with moderate to severe renal impairment and end-stage renal disease (ESRD). 

 

Gender 
No clinically relevant gender differences were observed in clinical studies. 

 

Elderly 

In a phase 1 study no difference in pharmacokinetics of teduglutide could be detected between healthy 

subjects younger than 65 years versus older than 65 years. Experience in subjects 75 years and above 
is limited. 

 

Hepatic impairment 

In a phase 1 study the effect of hepatic impairment on the pharmacokinetics of teduglutide following 

subcutaneous administration of 20 mg teduglutide was investigated. The maximum exposure and the 

overall extent of exposure to teduglutide following single 20 mg subcutaneous doses were lower 

(10-15%) in subjects with moderate hepatic impairment relative to those in healthy matched controls. 

 

Renal impairment 

In a phase 1 study, the effect of renal impairment on the pharmacokinetics of teduglutide following 

subcutaneous administration of 10 mg teduglutide was investigated. With progressive renal 

impairment up to and including end-stage renal disease the primary pharmacokinetic parameters of 

teduglutide increased up to a factor of 2.6 (AUCinf) and 2.1 (Cmax) compared to healthy subjects. 



 

28 

 

5.3 Preclinical safety data 

 

Hyperplasia in the gall bladder, hepatic biliary ducts, and pancreatic ducts were observed in 

subchronic and chronic toxicology studies. These observations were potentially associated with the 

expected intended pharmacology of teduglutide and were to a varying degree reversible within an 

8-13 week recovery period following chronic administration. 

 

Injection site reactions 

In pre-clinical studies, severe granulomatous inflammations were found associated with the injection 

sites. 

 

Carcinogenicity / mutagenicity 

Teduglutide was negative when tested in the standard battery of tests for genotoxicity. 

 

In a rat carcinogenicity study, treatment related benign neoplasms included tumours of the bile duct 

epithelium in males exposed to teduglutide plasma levels approximately 32- and 155-fold higher than 

obtained in patients administered the recommended daily dose (incidence of 1 out of 44 and 4 out 

of 48, respectively). Adenomas of the jejunal mucosa were observed in 1 out of 50 males and 5 out of 

50 males exposed to teduglutide plasma levels approximately 10- and 155-fold higher than obtained in 

patients administered the recommended daily dose. In addition, a jejunal adenocarcinoma was 

observed in a male rat administered the lowest dose tested (animal:human plasma exposure margin of 

approximately 10-fold). 

 

Reproductive and developmental toxicity 

Reproductive and developmental toxicity studies evaluating teduglutide have been carried out in rats 

and rabbits at doses of 0, 2, 10 and 50 mg/kg/day subcutaneously. Teduglutide was not associated with 

effects on reproductive performance, in utero or developmental parameters measured in studies to 

investigate fertility, embryo-foetal development and pre- and post-natal development. 

Pharmacokinetic data demonstrated that the teduglutide exposure of foetal rabbits and suckling rat 

pups was very low. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Powder 

L-histidine 

Mannitol 

Sodium phosphate monohydrate 

Disodium phosphate heptahydrate 

Sodium hydroxide (pH adjustment) 

Hydrochloric acid (pH adjustment) 

 

Solvent 

Water for injections 

 

6.2 Incompatibilities 

 

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 

 

6.3 Shelf life 

 

Unopened vials 



 

29 

4 years. 

 

Reconstituted product 

Chemical and physical stability has been demonstrated for 3 hours at 25°C. 

 

From a microbiological point of view, unless the method of reconstitution precludes the risk of 

microbial contamination, the solution should be used immediately. 

 

If not used immediately, in-use storage times and conditions are the responsibility of the user and 

would normally not be longer than 24 hours at 2 to8°C, unless reconstitution has taken place in 

controlled and validated aseptic conditions. 

 

6.4 Special precautions for storage 

 

Store below 25°C. 

 

Do not freeze. 

 

For storage conditions after reconstitution of the medicinal product, see section 6.3. 

 

6.5 Nature and contents of container 

 

Powder 

3 ml vial (glass) with rubber stopper (bromobutyl) containing 5 mg teduglutide. 

 

Solvent 

Pre-filled syringe (glass) with plungers (bromobutyl) containing 0.5 ml of solvent. 

 

Pack sizes of 1 vial of powder with 1 pre-filled syringe or 28 vials of powder with 28 pre-filled 

syringes. 

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal and other handling 

 

Determination of the number of vials needed for administration of one dose must be based on the 

individual patient’s weight and the recommended dose of 0.05 mg/kg/day. The physician should at 

each visit weigh the patient, determine the daily dose to be administered until next visit and inform the 

patient accordingly. 

 

Tables with the injection volumes based on the recommended dose per body weight for both adults 

and paediatric patients are provided in section 4.2. 

 

The pre-filled syringe must be assembled with a reconstitution needle. 

 

The powder in the vial must then be dissolved by adding all the solvent from the pre-filled syringe. 

 

The vial should not be shaken, but can be rolled between the palms and gently turned upside-down 

once. Once a clear colourless solution is formed in the vial, the solution should be sucked up into a 

1 ml injection syringe (or 0.5 ml or smaller injection syringe for paediatric use) with scale intervals of 

0.02 ml or smaller (not included in the pack). 

 

If two vials are needed, the procedure for the second vial must be repeated and the additional solution 

sucked up into the injection syringe containing the solution from the first vial. Any volume exceeding 

the prescribed dose in ml must be expelled and discarded. 

 



 

30 

The solution must be injected subcutaneously into a cleaned area on the abdomen, or if this is not 

possible, on the thigh (see section 4.2 Method of administration) using a thin needle for subcutaneous 

injection. 

 

Detailed instructions on the preparation and injection of Revestive are provided in the package leaflet. 

 

The solution must not be used if it is cloudy or contains particulate matter. 

 

For single use only. 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

All needles and syringes should be disposed of in a sharps disposal container. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Shire Pharmaceuticals Ireland Limited 

Block 2 & 3 Miesian Plaza 

50 – 58 Baggot Street Lower 

Dublin 2 

Ireland 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/12/787/001 

EU/1/12/787/002 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 30 August 2012 

Date of latest renewal: 23 June 2017 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu. 

  

http://www.ema.europa.eu/


 

31 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE 

SUBSTANCE(S) AND MANUFACTURER(S) RESPONSIBLE 

FOR BATCH RELEASE 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARDS TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 

PRODUCT 

 

 

 

 



 

32 

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND 

MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer of the biological active substance 

 

Boehringer Ingelheim RCV GmbH & Co KG 

Dr. Boehringer-Gasse 5-11 

A-1121 Vienna 

Austria 

 

Name and address of the manufacturer responsible for batch release 

 

Shire Pharmaceuticals Ireland Limited 

Block 2 & 3 Miesian Plaza 

50 – 58 Baggot Street Lower 

Dublin 2 

Ireland 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 

Characteristics, section 4.2). 

 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

• Periodic Safety Update Reports 

 

The requirements for submission of periodic safety update reports for this medicinal product are set 

out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 

2001/83/EC and any subsequent updates published on the European medicines web-portal. 

 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARDS TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

• Risk Management Plan (RMP) 

 

The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 

agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 

updates of the RMP. 

 

An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 

• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 

an important (pharmacovigilance or risk minimisation) milestone being reached. 

 

 
• Obligations to conduct post-authorisation measures 

 
The MAH shall complete, within the stated timeframe, the below measures: 

 



 

33 

Description Due date 

International Short Bowel Syndrome Registry 

Non-interventional study (NIS) to gather further safety data, in order to 

further elucidate the potential and identified risk as outlined in the RMP, 

based on a CHMP approved protocol. 

 

 

 

Interim data for the NIS should be provided every second year. 

 

 

 

 

 

 

Final study report 

Four interim reports 

will be provided 

within six months 

after the data lock 

points (i.e., Q4 

2016, Q4 2018, Q4 

2020, and Q4 2022). 

 

Q3 2031 

 

 

  



 

34 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

 

  



 

35 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 

 

  



 

36 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Revestive 1.25 mg powder and solvent for solution for injection 

teduglutide 

For children and adolescents 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One vial of powder contains 1.25 mg of teduglutide. After reconstitution, each vial contains 1.25 mg 

of teduglutide in 0.5 ml of solution, corresponding to a concentration of 2.5 mg/ml. 

 

 

3. LIST OF EXCIPIENTS 

 

Powder: L-histidine, mannitol, sodium phosphate monohydrate, disodium phosphate heptahydrate. 

Solvent: Water for injections. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder and solvent for solution for injection 

28 vials of powder containing 1,25 mg teduglutide 

28 pre-filled syringes containing 0.5 ml of solvent 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Subcutaneous use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. Do not freeze. 

After reconstitution, the solution should be used immediately. 



 

37 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Shire Pharmaceuticals Ireland Limited 

Block 2 & 3 Miesian Plaza 

50 – 58 Baggot Street Lower 

Dublin 2 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/12/787/003 28 vials 

 

 

13. BATCH NUMBER 

 

Lot 

 
 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Revestive 1.25 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 

PC: 

SN: 

NN: 

 

 



 

38 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Revestive 5 mg powder and solvent for solution for injection 

teduglutide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One vial of powder contains 5 mg of teduglutide. After reconstitution, each vial contains 5 mg of 

teduglutide in 0.5 ml of solution, corresponding to a concentration of 10 mg/ml. 

 

 

3. LIST OF EXCIPIENTS 

 

Powder: L-histidine, mannitol, sodium phosphate monohydrate, disodium phosphate heptahydrate, 

sodium hydroxide (pH adjustment), hydrochloric acid (pH adjustment). 

Solvent: Water for injections. 

 
 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder and solvent for solution for injection 

1 vial of powder containing 5 mg teduglutide 

1 pre-filled syringe containing 0.5 ml of solvent 

28 vials of powder containing 5 mg teduglutide 

28 pre-filled syringes containing 0.5 ml of solvent 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Subcutaneous use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 



 

39 

9. SPECIAL STORAGE CONDITIONS 

 

Store below 25°C. 

Do not freeze. 

After reconstitution, the solution should be used immediately. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Shire Pharmaceuticals Ireland Limited 

Block 2 & 3 Miesian Plaza 

50 – 58 Baggot Street Lower 

Dublin 2 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/12/787/002 1 vial 

EU/1/12/787/001 28 vials 

 

 

13. BATCH NUMBER 

 

Lot 

 
 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Revestive 5 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

  



 

40 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Revestive 1.25 mg powder for solution for injection 

teduglutide 

Subcutaneous use 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 
 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

1.25 mg 

 

 

6. OTHER 

 

 



 

41 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Revestive 5 mg powder for solution for injection 

teduglutide 

Subcutaneous use 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP 
 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

5 mg 

 

 

6. OTHER 

 

 



 

42 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

SOLVENT PREFILLED SYRINGE LABEL 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Solvent for Revestive 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

0.5 ml 

 

 

6. OTHER 

 

For reconstitution 

 

  



 

43 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 

  



 

44 

Package leaflet: Information for the patient 

 

Revestive 1.25 mg powder and solvent for solution for injection 

Teduglutide 

For children and adolescents 

 

This medicine is subject to additional monitoring. This will allow quick identification of new 

safety information. You can help by reporting any side effects you may get. See the end of section 4 

for how to report side effects. 

 

Read all of this leaflet carefully before you start using this medicine because it contains 

important information for you. 

 

- Keep this leaflet. You may need to read it again. 

- If you have any further questions, ask your child’s doctor, pharmacist or nurse. 
- This medicine has been prescribed for your child only. Do not pass it on to others. It may harm 

them, even if their signs of illness are the same. 

- If the child gets any side effects, talk to your child’s doctor, pharmacist or nurse. This includes 
any possible side effects not listed in this leaflet. See section 4. 

 

 

What is in this leaflet 

 

1. What Revestive is and what it is used for 

2. What you need to know before you use Revestive 

3. How to use Revestive 

4. Possible side effects 

5 How to store Revestive 

6. Contents of the pack and other information 

 

 

1. What Revestive is and what it is used for 

 

Revestive contains the active substance teduglutide. It improves the absorption of nutrients and fluid 

from your child’s remaining gastrointestinal tract (gut). 

Revestive is used to treat children and adolescents (aged 1 year and above) with Short Bowel 

Syndrome. Short Bowel Syndrome is a disorder arising from an inability to absorb food nutrients and 

fluid across the gut. It is often caused by surgical removal of all or part of the small intestine. 

 

 

2. What you need to know before you use Revestive 

 

Do not use Revestive 

 

- if your child is allergic to teduglutide or any of the other ingredients of this medicine (listed in 

section 6) or trace residues of tetracycline. 

- if your child has or is suspected to have cancer. 

- if your child has had cancer in the gastrointestinal tract, including liver, gallbladder or bile 

ducts, and pancreas within the last five years. 

 

Warnings and precautions 

 

Talk to your child’s doctor before using Revestive: 

- if your child has severely decreased liver function. The doctor will consider this when 

prescribing this medicine. 

- if your child suffers from certain cardiovascular diseases (affecting the heart and/or blood 

vessels) such as high blood pressure (hypertension) or has a weak heart (cardiac insufficiency). 



 

45 

The signs and symptoms include sudden weight gain, face swelling, swollen ankles and/or 

shortness of breath. 

- if your child has other severe diseases that are not well controlled. The doctor will consider this 

when prescribing this medicine. 

- if your child has decreased kidney function. The doctor may need to give your child a lower 

dose of this medicine. 

 

When starting and while getting treated with Revestive, the doctor may adjust the amount of 

intravenous fluids or nutrition your child receives. 

Medical check-ups before and during treatment with Revestive 

Before starting treatment with this medicine, your child will have a test done to see if there is blood in 

the stool. Your child will also have a colonoscopy done (a procedure to see inside their colon and 

rectum to check for the presence of polyps (small abnormal growths) and have them removed) if they 

have unexplained blood in their bowel movements (stools). If polyps are found before treatment with 

Revestive, the doctor will decide whether your child should use this medicine. Revestive should not be 

used if a cancer is detected during colonoscopy. The doctor will perform further colonoscopies if your 

child continues treatment with Revestive. The doctor will monitor your child’s body fluids and 

electrolytes as an imbalance may cause fluid overload or dehydration. 

 

The doctor will take special care and monitor your child’s small bowel function and monitor for signs 

and symptoms indicating problems with the gallbladder, bile ducts and pancreas. 

 

Children and adolescents 

 

Children below 1 year of age 

This medicine should not be used in children under 1 year of age. This is because there is no 

experience with Revestive in this age group. 

 

Other medicines and Revestive 

 

Tell the doctor, pharmacist or nurse if your child is using, has recently used or might use any other 

medicines. 

 

Revestive may affect how other medicines are absorbed from the gut and therefore how well they 

work. The doctor may have to change your child’s dose of other medicines. 

 

Pregnancy and breast-feeding 

 

If your child is pregnant or breast-feeding, the use of Revestive is not recommended. 

If your child is pregnant or breast-feeding, may be pregnant or is planning to have a baby, ask the 

doctor, pharmacist or nurse for advice before using this medicine. 

 

Driving, cycling and using machines 

 

This medicine may cause your child to feel dizzy. If this happens to your child, they should not drive, 

ride a bicycle or use machines until they feel better. 

 

Important information about some of the ingredients in Revestive 

 

This medicine contains less than 1 mmol sodium (23 mg) per dose. This means that it is essentially 

‘sodium-free’. 

Caution is needed if your child is hypersensitive to tetracycline (see “Do not use Revestive” section). 

 

 



 

46 

3. How to use Revestive 

 

Always use this medicine exactly as the doctor has told you. Check with your child’s doctor, 

pharmacist or nurse if you are not sure. 

 

Dose 

The recommended daily dose for your child is 0.05 mg per kg body weight. The dose will be given 

in millilitres (ml) of solution. 

 

The doctor will choose the dose that is right for your child, depending on their body weight. The 

doctor will tell you which dose to inject. If you are not sure, ask the doctor, pharmacist or nurse. 

 

How to use Revestive 

Revestive is injected under the skin (subcutaneously) once daily. The injection can be 

self-administered or given by another person, for example your child’s doctor, his/her assistant or your 

child’s home nurse. If you, or the carer, are injecting the medicine, you or the carer must receive 

adequate training by the doctor or nurse. You will find detailed instructions for injections at the end of 

this leaflet. 

 

It is strongly recommended that every time your child receives a dose of Revestive, the name and lot 

number of the product are recorded in order to maintain a record of the lots used. 

 

If you use more Revestive than you should 

 

If you inject more Revestive than you are told to by your child’s doctor, you should contact the doctor, 

pharmacist or nurse. 

 

If you forget to use Revestive 

 

If you forget to inject this medicine (or cannot inject it at the usual time), use it as soon as possible on 

that day. Never use more than one injection in the same day. Do not inject a double dose to make up 

for a forgotten dose. 

 

If you stop using Revestive 

 

Keep using this medicine for as long as your child’s doctor prescribes it for them. Do not stop using 

this medicine without consulting the doctor, as a sudden stop can cause changes in your child’s fluid 

balance. 

 

If you have any further questions on the use of this medicine, ask your child’s doctor, pharmacist or 

nurse. 

 

 

4. Possible side effects 

 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

Seek immediate medical attention if any of the following side effects occur: 

 

Common (may affect up to 1 in 10 people): 

- Congestive heart failure. Contact the doctor if your child experiences tiredness, shortness of 

breath or swelling of ankles or legs or face swelling. 

- Inflammation of the pancreas (pancreatitis). Contact the doctor or the emergency unit if your 

child experiences severe stomach ache and fever 

- Intestinal obstruction (blockage of the bowel). Contact the doctor or the emergency unit if your 

child experiences severe stomach ache, vomiting and constipation 



 

47 

- Reduced flow of bile from the gallbladder and/or inflammation of the gallbladder. Contact the 

doctor or the emergency unit if your child experiences yellowing of the skin and the whites in 

the eyes, itching, dark urine and light-coloured stools or pain in the upper right side or middle of 

the stomach area 

 

Uncommon (may affect up to 1 in 100 people): 

- Fainting. If heart rate and breathing is normal and your child awakens fast, speak to the doctor. 

In other cases, seek help as soon as possible 

 

Other side effects include: 

 

Very common (may affect more than 1 in 10 people): 

- Respiratory tract infection (any infection of the sinuses, throat, airways or lungs) 

- Headache 

- Stomach pain, bloated stomach, feeling sick (nausea), swelling of stoma (an artificial opening 

for waste removal), vomiting 

- Reddening, pain or swelling at the site of the injection 

 

Common (may affect up to 1 in 10 people): 

- Flu (influenza) or flu-like symptoms 

- Decreased appetite 

- Swelling of hands and/or feet 

- Problems sleeping, anxiety 

- Cough, shortness of breath 

- Polyps (small abnormal growths) in your child’s large bowel 

- Passing gas (flatulence) 

- Narrowing or blockage of your child’s pancreatic duct, which may cause inflammation of the 

pancreas 

- Inflammation of the gallbladder 

 

Uncommon (may affect up to 1 in 100 people) 

- Polyps (small abnormal growths) in your child’s small bowel 

 

Not known (frequency cannot be estimated from the available data): 

- Allergic reaction (hypersensitivity) 

- Fluid retention 

- Polyps (small abnormal growths) in your child’s stomach 

 

Use in children and adolescents 

 

In general, the side effects in children and adolescents are similar to those seen in adults. 

 

There is no experience in children under 1 year of age. 

 

Reporting of side effects 

 

If your child gets any side effects, talk to your child’s doctor or pharmacist. This includes any possible 

side effects not listed in this leaflet. You can also report side effects directly via the national reporting 

system listed in Appendix V. 

 

By reporting side effects you can help provide more information on the safety of this medicine. 
 

 

5. How to store Revestive 

 

Keep this medicine out of the sight and reach of children. 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 

48 

Do not use this medicine after the expiry date which is stated on the carton, the vial and the pre-filled 

syringe after EXP. The expiry date refers to the last day of that month. 

 

Store in a refrigerator (2°C – 8°C). Do not freeze. 

 

After reconstitution, from a microbiological point of view, the solution should be used immediately. 

However, chemical and physical stability has been demonstrated for 24 hours at 25°C. 

 

Do not use this medicine if you notice that the solution is cloudy or contains particulate matter. 

 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 

throw away medicines you no longer use. These measures will help protect the environment. 

Dispose of all needles and syringes in a sharps disposal container. 

 

 

6. Contents of the pack and other information 

 

What Revestive contains 

 

- The active substance is teduglutide. One vial of powder contains 1.25 mg of teduglutide. After 

reconstitution, each vial contains 1.25 mg teduglutide in 0.5 ml of solution, corresponding to a 

concentration of 2.5 mg/ml. 

- The other ingredients are L-histidine, mannitol, sodium phosphate monohydrate, disodium 

phosphate heptahydrate. 

- The solvent contains water for injections. 

 

What Revestive looks like and contents of the pack 

 

Revestive is a powder and solvent for solution for injection (1.25 mg teduglutide in vial, 0.5 ml 

solvent in pre-filled syringe). 

 

The powder is white and the solvent is clear and colourless. 

 

Revestive comes in pack sizes of 28 vials of powder with 28 pre-filled syringes. 

 

Marketing Authorisation Holder and Manufacturer 

 

Shire Pharmaceuticals Ireland Limited 

Block 2 & 3 Miesian Plaza 

50 – 58 Baggot Street Lower 

Dublin 2 

Ireland 

Tel: +44(0)1256 894 959 

E-mail: medinfoEMEA@shire.com 

 

This leaflet was last revised  

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu. There are also links to other websites about rare diseases and treatments. 
  

http://www.ema.europa.eu/


 

49 

Instructions for preparing and injecting Revestive 

 

Important information: 

 

- Read the Package Leaflet before using Revestive. 
- Revestive is for injection under the skin (subcutaneous injection). 

- Do not inject Revestive into a vein (intravenously) or muscle (intramuscularly). 

- Keep Revestive out of the sight and reach of children. 

- Do not use Revestive after the expiry date which is stated on the carton, the vial and the 
pre-filled syringe. The expiry date refers to the last day of that month. 

- Store in a refrigerator (2°C – 8°C). 

- Do not freeze. 
- After reconstitution, from a microbiological point of view, the solution should be used 

immediately. However, chemical and physical stability has been demonstrated for 24 hours at 

25ºC. 

- Do not use Revestive if you notice that the solution is cloudy or contains particulate matter. 
- Do not throw away any medicines via wastewater or household waste. Ask your pharmacist 

how to throw away medicines you no longer use. These measures will help protect the 

environment. 

- Dispose of all needles and syringes in a sharps disposal container. 
 

 
 

Materials provided in the pack: 

- 28 vials with 1.25 mg teduglutide as a powder 
- 28 pre-filled syringes with solvent 

 

Materials needed but not included in the pack: 

- Reconstitution needles (size 22G, length 1½" (0.7 x 40 mm)) 

- 0.5 or 1 ml injection syringes (with scale intervals of 0.02 ml or smaller). For children, a 0.5 ml 
(or smaller) injection syringe may be used 

- Thin injection needles for subcutaneous injection (e.g., size 26G, length 5/8" (0.45 x 16 mm), or 
smaller needles for children, as appropriate) 

- Alcohol wipes 
- Alcohol swabs 
- A puncture-proof container for safe disposal of the used syringes and needles 

 

NOTE: Before you start, make sure you have a clean work surface and that you have washed your 

hands before proceeding. 

 

 

1. Assemble the pre-filled syringe 

 

Once you have all the materials ready, you need to assemble the pre-filled syringe. The following 

procedure shows how you do this. 

 

 

1.1 Take the pre-filled syringe with solvent and flip off the top part 

of the white plastic cap so that it is ready for the reconstitution needle to 

be attached. 



 

50 

 

1.2 Attach the reconstitution needle (22G, 1½" (0.7 x 40 mm)) to 

the assembled pre-filled syringe by screwing it on in a clockwise 

direction. 

 

 

2. Dissolve the powder 

 

Now you are ready to dissolve the powder with the solvent. 

 

 
 

2.1 Remove the blue flip-off button from the powder vial, wipe the 

top with an alcohol wipe and allow to dry. Do not touch the top of the 

vial. 

 
 

2.2 Uncap the reconstitution needle on the assembled pre-filled 

syringe with solvent without touching the tip of the needle. 

 
 

2.3 Taking the powder vial, insert the reconstitution needle 

attached to the assembled pre-filled syringe into the centre of the rubber 

stopper and gently push the plunger all the way down to inject all the 

solvent into the vial. 

 
 

2.4 Leave the reconstitution needle and empty syringe in the vial. 

Let the vial rest for approximately 30 seconds. 

 

2.5 Gently roll the vial between your palms for about 15 seconds. 

Then gently turn the vial upside-down once with the reconstitution 

needle and empty syringe still in the vial. 

 

NOTE: Do not shake the vial. Shaking the vial may produce foam, which makes it difficult to extract 

the solution from the vial. 

 



 

51 

 
 

2.6 Let the vial rest for about two minutes. 

2.7 Observe the vial for any undissolved powder. If any powder remains, repeat steps 2.5 and 2.6. 

Do not shake the vial. If there is still some undissolved powder, discard the vial and start the 

preparation again from the beginning with a new vial. 

 

NOTE: The final solution should be clear. If the solution is cloudy or contains particulate matter, do 

not inject it. 

 

NOTE: Once prepared, the solution should be used immediately. It should be kept below 25°C and 

maximum storage time is twenty-four hours. 

 

 

3. Prepare the injection syringe 

 

 
 

3.1 Remove the reconstitution syringe from the reconstitution 

needle which is still in the vial and discard the reconstitution syringe. 

 
 

3.2 Take the injection syringe and attach it to the reconstitution 

needle which is still in the vial. 

 

3.3 Turn the vial upside down, slide the tip of the reconstitution 

needle close to the stopper and allow all the medicine to fill the syringe 

by pulling the plunger back gently. 

 

NOTE: If your child’s doctor has told you that you need two vials, prepare a second pre-filled syringe 

with solvent and a second powder vial as shown in the main steps 1 and 2. Withdraw the solution from 

the second vial into the same injection syringe by repeating step 3. 

 

 
 

3.4 Remove the injection syringe from reconstitution needle 

leaving the needle in the vial. Discard the vial and reconstitution needle 

together into the sharps disposal container. 



 

52 

 
 

3.5 Take the injection needle, but do not remove the plastic needle 

cap. Attach the needle to the injection syringe containing the medicine. 

 
 

3.6 Check for air bubbles. If air bubbles are present, gently tap the 

syringe until they rise to the top. Then gently push up the plunger to 

expel the air. 

 

3.7 Your child’s dose in ml has been calculated by the doctor. 

Expel any excessive volume from the syringe with the needle cap still 

on until your dose is reached. 

 

 

4. Inject the solution 

 

  

4.1 Find an area on your child’s belly, or if 

they have pain or hardening of the tissue on 

their belly, on your child’s thigh where it is easy 

for you to give the injection (see the diagram). 

 

NOTE: Do not use the same area each day for each injection - rotate sites (use upper, lower, and left 

and right side of your child’s belly) to avoid discomfort. Avoid areas that are inflamed, swollen, 

scarred or covered by a mole, birthmark or other lesion. 

 

 
 

4.2 Clean the intended site of injection on your child’s skin with an 

alcohol swab, using a circular motion, working outwards. Allow the 

area to air-dry. 

 

4.3 Remove the plastic cap from the needle of the prepared 

injection syringe. Gently grasp the cleaned skin at the injection site 

with one hand. With the other hand, hold the syringe as you would with 

a pencil. Bend your wrist back and quickly insert the needle at a 

45° angle. 

 

 

4.4 Pull back the plunger slightly. If you see any blood in the syringe, withdraw the needle and 

replace the needle on the injection syringe with a clean one of the same size. You can still use the 

medicine that is already in the syringe. Try to inject in another place in the cleaned skin area. 



 

53 

 

4.5 Inject the medicine slowly by pushing steadily on the plunger until all the medicine is injected 

and the syringe is empty. 

 

4.6 Pull the needle straight out of the skin and discard the needle and syringe together into the 

sharps disposal container. A small amount of bleeding may occur. If necessary, press gently on the 

injection site with an alcohol swab or 2x2 gauze until any bleeding has stopped. 

 

4.7 Dispose all needles and syringes in a sharps disposal container or hard-walled container (for 

example, a detergent bottle with a lid). This container must be puncture proof (top and sides). If you 

need a sharps disposal container, please contact your child’s doctor. 



 

54 

Package leaflet: Information for the patient 

 

Revestive 5 mg powder and solvent for solution for injection 

Teduglutide 

 

This medicine is subject to additional monitoring. This will allow quick identification of new safety 

information. You can help by reporting any side effects you may get. See the end of section 4 for how 

to report side effects. 

 

Read all of this leaflet carefully before you start using this medicine because it contains 

important information for you. 

 

- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 

- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 
even if their signs of illness are the same as yours. 

- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 

 
 

What is in this leaflet 

 

1. What Revestive is and what it is used for 

2. What you need to know before you use Revestive 

3. How to use Revestive 

4. Possible side effects 

5 How to store Revestive 

6. Contents of the pack and other information 

 

 

1. What Revestive is and what it is used for 

 

Revestive contains the active substance teduglutide. It improves the absorption of nutrients and fluid 

from your remaining gastrointestinal tract (gut). 

Revestive is used to treat adults, children and adolescents (aged 1 year and above) with Short Bowel 

Syndrome. Short Bowel Syndrome is a disorder arising from an inability to absorb food nutrients and 

fluid across the gut. It is often caused by surgical removal of all or part of the small intestine. 

 

 

2. What you need to know before you use Revestive 

 

Do not use Revestive 

 

- if you are allergic to teduglutide or any of the other ingredients of this medicine (listed in 

section 6) or trace residues of tetracycline. 

- if you have or are suspected to have cancer. 

- if you have had cancer in the gastrointestinal tract, including liver, gallbladder or bile ducts, and 

pancreas within the last five years. 

 

Warnings and precautions 

 

Talk to your doctor before using Revestive: 
- if you have severely decreased liver function. Your doctor will consider this when prescribing 

this medicine. 

- if you suffer from certain cardiovascular diseases (affecting the heart and/or blood vessels) such 

as high blood pressure (hypertension) or have a weak heart (cardiac insufficiency). The signs 



 

55 

and symptoms include sudden weight gain, face swelling, swollen ankles and/or shortness of 

breath. 

- if you have other severe diseases that are not well controlled. Your doctor will consider this 

when prescribing this medicine. 

- if you have decreased kidney function. Your doctor may need to give you a lower dose of this 

medicine. 

 

When starting and while getting treated with Revestive, your doctor may adjust the amount of 

intravenous fluids or nutrition you receive. 

 

Medical check-ups before and during treatment with Revestive 

Before you start treatment with this medicine, your doctor will need to perform a colonoscopy (a 

procedure to see inside your colon and rectum) to check for the presence of polyps (small abnormal 

growths) and remove them. It is recommended that your doctor performs these examinations once a 

year during the first 2 years after starting treatment, and then at a minimum of five-year intervals. If 

polyps are found either before or during your treatment with Revestive, your doctor will decide 

whether you should continue using this medicine. Revestive should not be used if a cancer is detected 

during your colonoscopy. The doctor will monitor your body fluids and electrolytes as an imbalance 

may cause fluid overload or dehydration. 

 

Your doctor will take special care and monitor your small bowel function and monitor for signs and 

symptoms indicating problems with your gallbladder, bile ducts and pancreas. 

 

Children and adolescents 

 

Medical check-ups before and during treatment with Revestive 

Before you start treatment with this medicine, you will need to have a test done to see if there is blood 

in the stool. You will also have a colonoscopy done (a procedure to see inside your colon and rectum 

to check for the presence of polyps (small abnormal growths) and have them removed) if you have 

unexplained blood in your bowel movements (stools). If polyps are found before your treatment with 

Revestive, your doctor will decide whether you should use this medicine. Revestive should not be 

used if a cancer is detected during your colonoscopy. Your doctor will perform further colonoscopies 

if you continue treatment with Revestive. The doctor will monitor your child’s body fluids and 

electrolytes as an imbalance may cause fluid overload or dehydration  

 

Children below 1 year of age 

This medicine should not be used in children under 1 year of age. This is because there is no 

experience with Revestive in this age group. 

 

Other medicines and Revestive 

 

Tell your doctor, pharmacist or nurse if you are using, have recently used or might use any other 

medicines. 

 

Revestive may affect how other medicines are absorbed from the gut and therefore how well they 

work. Your doctor may have to change your dose of other medicines. 

 

Pregnancy and breast-feeding 

 

If you are pregnant or breast-feeding, the use of Revestive is not recommended. 

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 

your doctor, pharmacist or nurse for advice before using this medicine. 

 



 

56 

Driving and using machines 

 

This medicine may cause you to feel dizzy. If this happens to you, do not drive or use machines until 

you feel better. 

 

Important information about some of the ingredients in Revestive 

 

This medicine contains less than 1 mmol sodium (23 mg) per dose. This means that it is essentially 

‘sodium-free’. 

Caution is needed if you are hypersensitive to tetracycline (see “Do not use Revestive” section). 

 

 

3. How to use Revestive 

 

Always use this medicine exactly as your doctor has told you. Check with your doctor, pharmacist or 

nurse if you are not sure. 

 

Dose 

The recommended daily dose is 0.05 mg per kg body weight. The dose will be given in millilitres (ml) 

of solution. 

 

Your doctor will choose the dose that is right for you depending on your body weight. Your doctor 

will tell you which dose to inject. If you are not sure, ask your doctor, pharmacist or nurse. 

 

Use in children and adolescents 

Revestive can be used in children and adolescents (aged 1 year and above). Use this medicine exactly 

as your doctor has told you. 

 

How to use Revestive 

Revestive is injected under the skin (subcutaneously) once daily. The injection can be 

self-administered or given by another person, for example your doctor, his/her assistant or your home 

nurse. If you, or your carer, are injecting the medicine, you or your carer must receive adequate 

training by your doctor or nurse. You will find detailed instructions for injections at the end of this 

leaflet. 

 

It is strongly recommended that every time you or your child receive a dose of Revestive, the name 

and lot number of the product are recorded in order to maintain a record of the lots used. 

 

If you use more Revestive than you should 

 

If you inject more Revestive than you are told to by your doctor, you should contact your doctor, 

pharmacist or nurse. 

 

If you forget to use Revestive 

 

If you forget to inject this medicine (or cannot inject it at your usual time), use it as soon as possible 

on that day. Never use more than one injection in the same day. Do not inject a double dose to make 

up for a forgotten dose. 

 

If you stop using Revestive 

 

Keep using this medicine for as long as your doctor prescribes it for you. Do not stop using this 

medicine without consulting your doctor, as a sudden stop can cause changes in your fluid balance. 

 

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 

 

 



 

57 

4. Possible side effects 

 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

Seek immediate medical attention if any of the following side effects occur: 

 

Common (may affect up to 1 in 10 people): 

- Congestive heart failure. Contact your doctor if you experience tiredness, shortness of breath or 

swelling of ankles or legs or face swelling. 

- Inflammation of the pancreas (pancreatitis). Contact your doctor or the emergency unit if you 

experience severe stomach ache and fever 

- Intestinal obstruction (blockage of the bowel). Contact your doctor or the emergency unit if you 

experience severe stomach ache, vomiting and constipation 

- Reduced flow of bile from the gallbladder and/or inflammation of the gallbladder. Contact your 

doctor or the emergency unit if you experience yellowing of the skin and the whites in the eyes, 

itching, dark urine and light-coloured stools or pain in the upper right side or middle of the 

stomach area 

 

Uncommon (may affect up to 1 in 100 people): 

- Fainting. If heart rate and breathing is normal and you awaken fast, speak to your doctor. In 

other cases, seek help as soon as possible 

 

Other side effects include: 

 

Very common (may affect more than 1 in 10 people): 

- Respiratory tract infection (any infection of the sinuses, throat, airways or lungs) 

- Headache 

- Stomach pain, bloated stomach, feeling sick (nausea), swelling of stoma (an artificial opening 

for waste removal), vomiting 

- Reddening, pain or swelling at the site of the injection 

 

Common (may affect up to 1 in 10 people): 

- Flu (influenza) or flu-like symptoms 

- Decreased appetite 

- Swelling of hands and/or feet 

- Problems sleeping, anxiety 

- Cough, shortness of breath 

- Polyps (small abnormal growths) in your large bowel 

- Passing gas (flatulence) 

- Narrowing or blockage of your pancreatic duct, which may cause inflammation of the pancreas 

- Inflammation of the gallbladder 

 

Uncommon (may affect up to 1 in 100 people) 

- Polyps (small abnormal growths) in your small bowel 

 

Not known (frequency cannot be estimated from the available data): 

- Allergic reaction (hypersensitivity) 

- Fluid retention 

- Polyps (small abnormal growths) in your stomach 

 

Use in children and adolescents 

 

In general, the side effects in children and adolescents are similar to those seen in adults. 

 

There is no experience in children under 1 year of age. 

 



 

58 

Reporting of side effects 

 

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 

not listed in this leaflet. You can also report side effects directly via the national reporting system 

listed in Appendix V. 

 

By reporting side effects you can help provide more information on the safety of this medicine. 

 

 

5. How to store Revestive 

 

Keep this medicine out of the sight and reach of children. 

 

Do not use this medicine after the expiry date which is stated on the carton, the vial and the pre-filled 

syringe after EXP. The expiry date refers to the last day of that month. 

 

Store below 25°C. 

 

Do not freeze. 

 

After reconstitution, from a microbiological point of view, the solution should be used immediately. 

However, chemical and physical stability has been demonstrated for 3 hours at 25°C. 

 

Do not use this medicine if you notice that the solution is cloudy or contains particulate matter. 

 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 

throw away medicines you no longer use. These measures will help protect the environment. 

Dispose of all needles and syringes in a sharps disposal container. 

 

 

6. Contents of the pack and other information 

 

What Revestive contains 

 

- The active substance is teduglutide. One vial of powder contains 5 mg of teduglutide. After 

reconstitution, each vial contains 5 mg teduglutide in 0.5 ml of solution, corresponding to a 

concentration of 10 mg/ml. 

- The other ingredients are L-histidine, mannitol, sodium phosphate monohydrate, disodium 

phosphate heptahydrate, sodium hydroxide (pH adjustment), hydrochloric acid (pH adjustment). 

- The solvent contains water for injections. 

 

What Revestive looks like and contents of the pack 

 

Revestive is a powder and solvent for solution for injection (5 mg teduglutide in vial, 0.5 ml solvent in 

pre-filled syringe). 

 

The powder is white and the solvent is clear and colourless. 

 

Revestive comes in pack sizes of 1 vial of powder with 1 pre-filled syringe or 28 vials of powder with 

28 pre-filled syringes. 

 

Not all pack sizes may be available. 
 

Marketing Authorisation Holder and Manufacturer 

 

Shire Pharmaceuticals Ireland Limited 

Block 2 & 3 Miesian Plaza 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 

59 

50 – 58 Baggot Street Lower 

Dublin 2 

Ireland 

Tel: +44(0)1256 894 959 

E-mail: medinfoEMEA@shire.com 

 

This leaflet was last revised  

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu. There are also links to other websites about rare diseases and treatments. 

  

mailto:medinfoEMEA@shire.com
http://www.ema.europa.eu/


 

60 

Instructions for preparing and injecting Revestive 

 

Important information: 

 

- Read the Package Leaflet before using Revestive. 
- Revestive is for injection under the skin (subcutaneous injection). 

- Do not inject Revestive into a vein (intravenously) or muscle (intramuscularly). 

- Keep Revestive out of the sight and reach of children. 

- Do not use Revestive after the expiry date which is stated on the carton, the vial and the 
pre-filled syringe. The expiry date refers to the last day of that month. 

- Store below 25°C. 

- Do not freeze. 
- After reconstitution, from a microbiological point of view, the solution should be used 

immediately. However, chemical and physical stability has been demonstrated for 3 hours at 

25ºC. 

- Do not use Revestive if you notice that the solution is cloudy or contains particulate matter. 
- Do not throw away any medicines via wastewater or household waste. Ask your pharmacist 

how to throw away medicines you no longer use. These measures will help protect the 

environment. 

- Dispose of all needles and syringes in a sharps disposal container. 
 

 

Materials provided in the pack: 

- 1 or 28 vials with 5 mg teduglutide as a powder 
- 1 or 28 pre-filled syringes with solvent 

 

 

Materials needed but not included in the pack: 

- Reconstitution needles (size 22G, length 1½" (0.7 x 40 mm)) 

- 0.5 or 1 ml injection syringes (with scale intervals of 0.02 ml or smaller). For children, a 0.5 ml 
(or smaller) injection syringe may be used 

- Thin injection needles for subcutaneous injection (e.g., size 26G, length 5/8" (0.45 x 16 mm), or 
smaller needles for children, as appropriate) 

- Alcohol wipes 
- Alcohol swabs 
- A puncture-proof container for safe disposal of the used syringes and needles 

 

NOTE: Before you start, make sure you have a clean work surface and that you have washed your 

hands before proceeding. 

 

 

1. Assemble the pre-filled syringe 

 

Once you have all the materials ready, you need to assemble the pre-filled syringe. The following 

procedure shows how you do this. 

 

 
 

1.1 Take the pre-filled syringe with the solvent and flip off the top 

part of the white plastic cap on the pre-filled syringe so that it is ready 

for the reconstitution needle to be attached. 



 

61 

 

1.2 Attach the reconstitution needle (22G, 1½" (0.7 x 40 mm)) to 

the assembled pre-filled syringe by screwing it on in a clockwise 

direction. 

 

 

2. Dissolve the powder 

 

Now you are ready to dissolve the powder with the solvent. 

 

 
 

2.1 Remove the green flip-off button from the powder vial, wipe 

the top with an alcohol wipe and allow to dry. Do not touch the top of 

the vial. 

 
 

2.2 Uncap the reconstitution needle on the assembled pre-filled 

syringe with solvent without touching the tip of the needle. 

 
 

2.3 Taking the powder vial, insert the reconstitution needle 

attached to the assembled pre-filled syringe into the centre of the rubber 

stopper and gently push the plunger all the way down to inject all the 

solvent into the vial. 

 
 

2.4 Leave the reconstitution needle and empty syringe in the vial. 

Let the vial rest for approximately 30 seconds. 

 

2.5 Gently roll the vial between your palms for about 15 seconds. 

Then gently turn the vial upside-down once with the reconstitution 

needle and empty syringe still in the vial. 

 

NOTE: Do not shake the vial. Shaking the vial may produce foam, which makes it difficult to extract 

the solution from the vial. 

 



 

62 

 
 

2.6 Let the vial rest for about two minutes. 

2.7 Observe the vial for any undissolved powder. If any powder remains, repeat steps 2.5 and 2.6. 

Do not shake the vial. If there is still some undissolved powder, discard the vial and start the 

preparation again from the beginning with a new vial. 

 

NOTE: The final solution should be clear. If the solution is cloudy or contains particulate matter, do 

not inject it. 

 

NOTE: Once prepared, the solution should be used immediately. It should be kept below 25°C and 

maximum storage time is three hours. 

 

 

3. Prepare the injection syringe 

 

 
 

3.1 Remove the reconstitution syringe from the reconstitution 

needle which is still in the vial and discard the reconstitution syringe. 

 
 

3.2 Take the injection syringe and attach it to the reconstitution 

needle which is still in the vial. 

 

3.3 Turn the vial upside down, slide the tip of the reconstitution 

needle close to the stopper and allow all the medicine to fill the syringe 

by pulling the plunger back gently. 

 

NOTE: If your doctor has told you that you need two vials, prepare a second pre-filled syringe with 

solvent and a second powder vial as shown in the main steps 1 and 2. Withdraw the solution from the 

second vial into the same injection syringe by repeating step 3. 

 

 
 

3.4 Remove the injection syringe from reconstitution needle 

leaving the needle in the vial. Discard the vial and reconstitution needle 

together into the sharps disposal container. 



 

63 

 
 

3.5 Take the injection needle, but do not remove the plastic needle 

cap. Attach the needle to the injection syringe containing the medicine. 

 
 

3.6 Check for air bubbles. If air bubbles are present, gently tap the 

syringe until they rise to the top. Then gently push up the plunger to 

expel the air. 

 

3.7 Your dose in ml has been calculated by your doctor. Expel any 

excessive volume from the syringe with the needle cap still on until 

your dose is reached. 

 

 

4. Inject the solution 

 

  

4.1 Find an area on your belly, or if you 

have pain or hardening of the tissue on your 

belly, on your thigh where it is easy for you to 

give the injection (see the diagram). 

 

NOTE: Do not use the same area each day for each injection - rotate sites (use upper, lower, and left 

and right side of your belly) to avoid discomfort. Avoid areas that are inflamed, swollen, scarred or 

covered by a mole, birthmark or other lesion. 

 

 
 

4.2 Clean the intended site of injection on your skin with an 

alcohol swab, using a circular motion, working outwards. Allow the 

area to air-dry. 

 

4.3 Remove the plastic cap from the needle of the prepared 

injection syringe. Gently grasp the cleaned skin at the injection site 

with one hand. With the other hand, hold the syringe as you would with 

a pencil. Bend your wrist back and quickly insert the needle at a 

45° angle. 

 

4.4 Pull back the plunger slightly. If you see any blood in the syringe, withdraw the needle and 

replace the needle on the injection syringe with a clean one of the same size. You can still use the 

medicine that is already in the syringe. Try to inject in another place in the cleaned skin area. 

 



 

64 

4.5 Inject the medicine slowly by pushing steadily on the plunger until all the medicine is injected 

and the syringe is empty. 

 

4.6 Pull the needle straight out of the skin and discard the needle and syringe together into the 

sharps disposal container. A small amount of bleeding may occur. If necessary, press gently on the 

injection site with an alcohol swab or 2x2 gauze until any bleeding has stopped. 

 

4.7 Dispose all needles and syringes in a sharps disposal container or hard-walled container (for 

example, a detergent bottle with a lid). This container must be puncture proof (top and sides). If you 

need a sharps disposal container, please contact your doctor. 

  



 

65 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX IV 

SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE 

TERMS OF THE MARKETING AUTHORISATION(S) 

 

 

 

 

 

 



 

66 

Scientific conclusions 

Taking into account the PRAC Assessment Report on the PSUR(s) for teduglutide, the scientific 

conclusions of CHMP are as follows:  

Based on cumulative data on renal disorders from registry TED-R13-002, literature, post-marketing 

and clinical studies chronic renal disorders are an underlying complication of patients with short 

bowel syndrome (SBS) receiving parenteral nutrition. Whilst not directly related to the treatment 

with teduglutide, also acute and renal failure (ARF) which is a serious condition occurs frequently in 

the post-marketing setting. ARF appears to be due to dehydration and other metabolic stressors such 

as infection, intestinal obstruction and during the postoperative period. In general, dehydration can be 

prevented by appropriate and timely monitoring for fluid and electrolyte imbalance, and subsequent 

adjustment of parenteral fluid and electrolytes. Considering the seriousness of ARF and its 

preventability, the warning on the risks of dehydration and fluid imbalances was strengthened and 

the package leaflet was updated accordingly.   

 

The CHMP agrees with the scientific conclusions made by the PRAC. 

 

Grounds for the variation to the terms of the marketing authorisation(s) 

On the basis of the scientific conclusions for teduglutide the CHMP is of the opinion that the 

benefit-risk balance of the medicinal product(s) containing teduglutide is unchanged subject to the 

proposed changes to the product information 

The CHMP recommends that the terms of the marketing authorisation(s) should be varied. 

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARDS TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET
	SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMS OF THE MARKETING AUTHORISATION(S)