Source: European Medicines Agency (EU) Revision Year: 2020 Publisher: Shire Pharmaceuticals Ireland Limited, Block 2 & 3 Miesian Plaza, 50–58 Baggot Street Lower, Dublin 2, Ireland
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.
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.
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.
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 |
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 |
| 42-45 kg | 0.22 ml |
| 46-49 kg | 0.24 ml |
| ≥50 kg | See Table 1 under “Adults” section |
No dose adjustment is necessary in patients above the age of 65 years.
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).
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).
The safety and efficacy of Revestive in children below 1 year of age have not been established. No data are available.
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.
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.
Unopened vials: 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 to 8°C, unless reconstitution has taken place in controlled and validated aseptic conditions.
Store below 25°C.
Do not freeze.
For storage conditions after reconstitution of the medicinal product, see section 6.3.
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.
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.
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.
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