ENTYVIO POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION 300MG/VIAL

4.1 Therapeutic indications

Ulcerative Colitis

Entyvio is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumour necrosis factor-alpha (TNFα) antagonist.

Crohn’s Disease

Entyvio is indicated for the treatment of adult patients with moderately to severely active Crohn’s disease who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumour necrosis factor-alpha (TNFα) antagonist.

4.3 Contraindications

Hypersensitivity (such as dyspnea, bronchospasm, urticaria, flushing and increased heart rate) to the active substance or to any of the excipients listed in section 6.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

Active severe infections such as tuberculosis, sepsis, cytomegalovirus, listeriosis, and opportunistic infections such as Progressive Multifocal Leukoencephalopathy (PML) (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

4.2 Posology and method of administration

Entyvio treatment should be initiated and supervised by specialist healthcare professionals experienced in the diagnosis and treatment of ulcerative colitis or Crohn’s disease.

Posology – Intravenous Administration

Ulcerative Colitis

The recommended dose regimen of intravenous vedolizumab is 300 mg administered by intravenous infusion at zero, two and six weeks and then every eight weeks thereafter.

Therapy for patients with ulcerative colitis should not be continued if no evidence of therapeutic benefit is observed by Week 14 (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

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

In patients who have responded to treatment with Entyvio, 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 four weeks may be considered (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). The treatment interruption period in clinical studies extended up to one year. Efficacy was regained with no evident increase in adverse events or infusion-related reactions during retreatment with intravenous vedolizumab (see section 4.8 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Crohn’s disease

The recommended dose regimen of intravenous vedolizumab is 300 mg administered by intravenous infusion at zero, two and six weeks and then every eight 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 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Continue therapy every eight weeks from Week 14 in responding patients. Therapy for patients with Crohn’s disease should not be continued if no evidence of therapeutic benefit is observed by Week 14 (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

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

In patients who have responded to treatment with Entyvio, 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 four weeks may be considered (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). The treatment interruption period in clinical studies extended up to one year. Efficacy was regained with no evident increase in adverse events or infusion-related reactions during retreatment with intravenous vedolizumab (see section 4.8 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Posology – Subcutaneous Administration

Ulcerative Colitis and Crohn’s Disease

The recommended dose regimen of subcutaneous vedolizumab as a maintenance treatment, following at least two intravenous infusions, is 108 mg administered by subcutaneous injection once every 2 weeks.

The first subcutaneous maintenance dose should be administered in place of the next scheduled intravenous dose and every 2 weeks thereafter. See Intravenous Administration section above for intravenous dosing schedule.

Insufficient data are available to determine if patients who experience a decrease in response on maintenance treatment with subcutaneous vedolizumab would benefit from an increase in dosing frequency.

There are no data on transition of patients from subcutaneous vedolizumab to intravenous vedolizumab during maintenance treatment.

Missed Dose(s)

If treatment with subcutaneous vedolizumab is interrupted or if a patient misses a scheduled dose(s) of subcutaneous vedolizumab, advise the patient to inject the next subcutaneous dose as soon as possible and then every 2 weeks thereafter. The treatment interruption period in clinical studies extended up to 46 weeks with no evident increase in adverse events or injection site reactions during reinitiation of treatment with subcutaneous vedolizumab.

Corticosteroids

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

Paediatric population

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

Elderly patients

No dose adjustment is required in elderly patients. Population pharmacokinetic analyses showed no effect of age (see section 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Patients with renal or hepatic impairment

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

Method of administration – Intravenous Administration

Intravenous vedolizumab is for intravenous use only. It is to be reconstituted and further diluted prior to intravenous administration, for instructions see section 6.5 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

Intravenous vedolizumab is administered as an intravenous infusion over 30 minutes. Do not administer as an intravenous push or bolus. Vedolizumab lyophilized powder must be reconstituted with sterile water for injection and diluted in 250 mL of sterile 0.9% sodium chloride solution or 250mL of sterile Lactated Ringer’s solution prior to administration. After the infusion is complete, flush with 30 mL of sterile 0.9% sodium chloride solution or 30mL of sterile Lactated Ringer’s solution. Patients should be monitored during and after infusion (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Method of Administration – Subcutaneous Administration

Vedolizumab in a prefilled pen/autoinjector is for subcutaneous injection only.

After proper training on correct subcutaneous injection technique, a patient or caregiver may inject subcutaneous vedolizumab if their physician determines it is appropriate. Inspect the solution visually for particulate matter and discoloration prior to administration. The solution should be colorless to yellow. Do not use prefilled pen/autoinjector with visible particulate matter or discoloration.