ENTYVIO 300 mg Powder for concentrate for solution for infusion Ref.[8936] Active ingredients: Vedolizumab

Treatment should be initiated and supervised by specialist healthcare professionals experienced in the diagnosis and treatment of ulcerative colitis, Crohn’s disease or pouchitis (see section 4.4). Patients should be given the package leaflet.

Posology

Ulcerative colitis

The recommended dose regimen of intravenous vedolizumab is 300 mg administered by intravenous infusion at 0, 2 and 6 weeks and then every 8 weeks thereafter.

Therapy for patients with ulcerative colitis should be discontinued if no evidence of therapeutic benefit is observed by week 10 (see section 5.1).

Some patients who have experienced a decrease in their response may benefit from an increase in dosing frequency to intravenous vedolizumab 300 mg every 4 weeks.

In patients who have responded to treatment with vedolizumab, corticosteroids may be reduced and/or discontinued in accordance with standard of care.

Retreatment

If therapy is interrupted and there is a need to restart treatment with intravenous vedolizumab, dosing at every 4 weeks may be considered (see section 5.1). The treatment interruption period in clinical trials extended up to 1 year. Efficacy was regained with no evident increase in adverse reactions or infusion-related reactions during retreatment with vedolizumab (see section 4.8).

Crohn’s disease

The recommended dose regimen of intravenous vedolizumab is 300 mg administered by intravenous infusion at 0, 2 and 6 weeks and then every 8 weeks thereafter.

Patients with Crohn’s disease, who have not shown a response may benefit from a dose of intravenous vedolizumab at week 10 (see section 4.4). Therapy should be continued every 8 weeks from week 14 in responding patients. Therapy for patients with Crohn’s disease should be discontinued if no evidence of therapeutic benefit is observed by week 14 (see section 5.1).

Some patients who have experienced a decrease in their response may benefit from an increase in dosing frequency to intravenous vedolizumab 300 mg every 4 weeks. In patients who have responded to treatment with vedolizumab, corticosteroids may be reduced and/or discontinued in accordance with standard of care.

Retreatment

If therapy is interrupted and there is a need to restart treatment with intravenous vedolizumab, dosing at every 4 weeks may be considered (see section 5.1). The treatment interruption period in clinical trials extended up to 1 year. Efficacy was regained with no evident increase in adverse reactions or infusion-related reactions during retreatment with vedolizumab (see section 4.8).

Pouchitis

The recommended dose regimen of intravenous vedolizumab is 300 mg administered by intravenous infusion at 0, 2 and 6 weeks and then every 8 weeks thereafter.

Treatment with vedolizumab should be initiated in parallel with standard of care antibiotic (e.g., fourweek of ciprofloxacin) (see section 5.1).

Discontinuation of treatment should be considered if no evidence of therapeutic benefit is observed by 14 weeks of treatment with vedolizumab.

Retreatment

There are no retreatment data available in patients with pouchitis.

Special populations

Elderly patients

No dose adjustment is required in elderly patients. Population pharmacokinetic analyses showed no effect of age (see section 5.2).

Patients with renal or hepatic impairment

Vedolizumab has not been studied in these patient populations. No dose recommendations can be made.

Paediatric population

The safety and efficacy of vedolizumab in children aged 0 to 17 years old have not been established. No data are available.

Method of administration

Entyvio 300 mg powder for concentrate for solution for infusion is for intravenous use only. It is to be reconstituted and further diluted prior to intravenous administration.

Entyvio 300 mg powder for concentrate for solution for infusion is administered as an intravenous infusion over 30 minutes. Patients should be monitored during and after infusion (see section 4.4).

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

Doses up to 10 mg/kg (approximately 2.5 times the recommended dose) have been administered intravenously in clinical trials. No dose-limiting toxicity was seen in clinical trials.

3 years.

In-use stability of the reconstituted solution in the vial has been demonstrated for 8 hours at 2°C-8°C. In-use stability of the diluted solution in sodium chloride 9 mg/mL (0.9%) solution for injection in infusion bag has been demonstrated for 12 hours at 20°C-25°C or 24 hours at 2°C-8°C.

The combined in-use stability of vedolizumab in the vial and infusion bag with sodium chloride 9 mg/mL (0.9%) solution for injection is a total of 12 hours at 20°C-25°C or 24 hours at 2°C-8°C. A 24 hour period may include up to 8 hours at 2°C-8°C for reconstituted solution in the vial and up to 12 hours at 20°C-25°C for diluted solution in the infusion bag but the infusion bag must be stored in the refrigerator (2°C-8°C) for the rest of the 24 hour period.

Do not freeze the reconstituted solution in the vial or the diluted solution in the infusion bag.

¹ Up to 30 minutes are allowed for reconstitution.
² This time assumes the reconstituted solution is immediately diluted in the sodium chloride 9 mg/mL (0.9%) solution for injection and held in the infusion bag only. Any time that the reconstituted solution was held in the vial should be subtracted from the time the solution may be held in the infusion bag.
³ This period may include up to 12 hours at 20°C-25°C.

Store in a refrigerator (2°C-8°C). Keep the vial in the outer carton in order to protect from light.

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

Powder for concentrate for solution for infusion in Type 1 glass vial (20 mL) fitted with rubber stopper and aluminium crimp protected by a plastic cap.

Each pack contains 1 vial.

Instructions for reconstitution and infusion:

1. Use aseptic technique when preparing Entyvio solution for intravenous infusion.
2. Remove flip-off cap from the vial and wipe with alcohol swab. Reconstitute vedolizumab with 4.8 mL of sterile water for injections at room temperature (20°C-25°C), using a syringe with a 21-25 gauge needle.
3. Insert the needle into the vial through the centre of the stopper and direct the stream of liquid to the wall of the vial to avoid excessive foaming.
4. Gently swirl the vial for at least 15 seconds. Do not vigorously shake or invert.
5. Let the vial sit for up to 20 minutes at room temperature (20°C-25°C), to allow for reconstitution and for any foam to settle; the vial can be swirled and inspected for dissolution during this time. If not fully dissolved after 20 minutes, allow another 10 minutes for dissolution.
6. Inspect the reconstituted solution visually for particulate matter and discolouration prior to dilution. Solution should be clear or opalescent, colourless to light yellow and free of visible particulates. Reconstituted solution with uncharacteristic colour or containing particulates must not be administered.
7. Once dissolved, gently invert vial 3 times.
8. Immediately withdraw 5 mL (300 mg) of reconstituted Entyvio using a syringe with a 21-25 gauge needle.
9. Add the 5 mL (300 mg) of reconstituted Entyvio to 250 mL of sterile sodium chloride 9 mg/mL (0.9%) solution for injection, and gently mix the infusion bag (5 mL of sodium chloride 9 mg/mL (0.9%) solution for injection does not have to be withdrawn from the infusion bag prior to adding Entyvio). Do not add other medicinal products to the prepared infusion solution or intravenous infusion set. Administer the infusion solution over 30 minutes (see section 4.2).

Once reconstituted, the infusion solution should be used as soon as possible.

Do not store any unused portion of the reconstituted solution or infusion solution for reuse.

Each vial is for single-use only.

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