REVESTIVE 1.25 mg Powder and solvent for solution for injection Ref.[113910] Active ingredients: Teduglutide

Source: European Medicines Agency (EU)  Revision Year: 2024  Publisher: Takeda Pharmaceuticals International AG Ireland Branch, Block 2 Miesian Plaza, 50 – 58 Baggot Street Lower, Dublin 2, D02 HW68, Ireland, medinfoEMEA@takeda.com

4.1. Therapeutic indications

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

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 (≥4 months)

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 4 months corrected gestational age 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 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.

Table 1. Injection volume per body weight for paediatric population (≥4 months):

Body weight1.25 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

* For paediatric patients weighing more than 20 kg, the 5 mg strength vial should be used. Refer to the Summary of Product Characteristics of Revestive 5 mg powder and solvent for solution for injection for dosing information.

Adults

The recommended dose of Revestive for adults is 0.05 mg/kg body weight once daily. For adults patients, the 5 mg strength vial should be used. Refer to the Summary of Product Characteristics of Revestive 5 mg powder and solvent for solution for injection for dosing information.

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).

Paediatric population (<4 months)

There are currently no available data in children below 4 months corrected gestational age.

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.

4.9. 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.

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).

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.

© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.