Entyvio 300 mg powder for concentrate for solution for infusion
- Name:
Entyvio 300 mg powder for concentrate for solution for infusion
- Company:
Takeda Products Ireland Ltd
- Active Ingredients:
- Legal Category:
Product subject to medical prescription which may not be renewed (A)
Patient Information Leaflet Patient Information Leaflet last updated on medicines.ie: 17/11/20

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Takeda Products Ireland Ltd

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When a pharmaceutical company changes any document, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.
Updated on 17 November 2020 SPC
Reasons for updating
- Change to section 7 - Marketing authorisation holder
- Change to section 10 - Date of revision of the text
Legal category: Product subject to medical prescription which may not be renewed (A)
Free text change information supplied by the pharmaceutical company
In section 7:
New MAH address added:
Takeda Pharma A/S
Delta Park 45
2665 Vallensbaek Strand
Denmark
In section 10: date of revision updated to 21st October 2020
Updated on 17 November 2020 PIL
Reasons for updating
- Change to section 6 - marketing authorisation holder
- Change to section 6 - date of revision
Free text change information supplied by the pharmaceutical company
New MAH address added:
Takeda Pharma A/S
Delta Park 45
2665 Vallensbaek Strand
Denmark
Date of revision updated to October 2020
Updated on 11 May 2020 SPC
Reasons for updating
- Change to section 2 - Qualitative and quantitative composition
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.8 - Undesirable effects
- Change to section 10 - Date of revision of the text
Legal category: Product subject to medical prescription which may not be renewed (A)
Free text change information supplied by the pharmaceutical company
Change to section |
Details of change |
Various Format Changes |
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2 QUALITATIVE AND QUANTITATIVE COMPOSITION |
… Vedolizumab is a humanised IgG1 monoclonal antibody … |
4.4 Special warnings and precautions for use |
… All patients should be observed continuously during each infusion. For the first 2 infusions, they should also be observed for approximately 2 hours following completion of the infusion for signs and symptoms of acute hypersensitivity reactions. For all subsequent infusions, patients should be observed for approximately 1 hour following completion of the infusion.
Traceability
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Infusion‑related reactions and hypersensitivity reactions
In clinical studies, infusion‑related reactions (IRR) and hypersensitivity reactions have been reported, with the majority being mild to moderate in severity (see section 4.8).
…
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4.8 Undesirable effects |
Summary of the safety profile
The most commonly reported adverse reactions are infections (such as nasopharyngitis, upper respiratory tract infection, bronchitis, influenza and sinusitis), headache, nausea, pyrexia, fatigue, cough, arthralgia.
… … Infections
In GEMINI 1 and 2 controlled studies with intravenous vedolizumab, the rate of infections was 0.85 per patient‑year in the vedolizumab‑treated patients and 0.70 per patient‑year in the placebo‑treated patients. The infections consisted primarily of nasopharyngitis, upper respiratory tract infection, sinusitis, and urinary tract infections. Most patients continued on vedolizumab after the infection resolved.
In GEMINI 1 and 2 controlled studies with intravenous vedolizumab, the rate of serious infections was 0.07 per patient year in vedolizumab‑treated patients and 0.06 per patient year in placebo‑treated patients. Over time, there was no significant increase in the rate of serious infections.
In controlled and open‑label studies in adults with intravenous vedolizumab, serious infections have been reported, which include tuberculosis, sepsis (some fatal), salmonella sepsis, listeria meningitis, and cytomegaloviral colitis.
In clinical studies with intravenous vedolizumab, the rate of infections in vedolizumab-treated patients with BMI of 30 kg/m2 and above was higher than for those with BMI less than 30 kg/m2.
In clinical studies with intravenous vedolizumab, a slightly higher incidence of serious infections was reported in vedolizumab-treated patients who had prior exposure to TNFα antagonist therapy compared to patients who were naïve to previous TNFα antagonist therapy. … |
10. Date of revision of the text |
Updated text in red:
28 April 2020 |
Updated on 11 May 2020 PIL
Reasons for updating
- Change to section 4 - possible side effects
- Change to section 6 - date of revision
- Correction of spelling/typing errors
Updated on 30 April 2020 Ed-HCP
Reasons for updating
- Add New Doc
Updated on 30 April 2020 Ed-Ptnt
Reasons for updating
- Add New Doc
Updated on 6 March 2019 PIL
Reasons for updating
- Change to section 2 - pregnancy, breast feeding and fertility
- Change to section 4 - possible side effects
- Change to section 6 - date of revision
Updated on 6 March 2019 SPC
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.6 - Pregnancy and lactation
- Change to section 4.8 - Undesirable effects
- Change to section 5.1 - Pharmacodynamic properties
- Change to section 5.2 - Pharmacokinetic properties
- Change to section 5.3 - Preclinical safety data
- Change to section 10 - Date of revision of the text
Legal category: Product subject to medical prescription which may not be renewed (A)
Free text change information supplied by the pharmaceutical company
Change to section |
Details of change |
4.2 Posology and method of administration |
… Posology Ulcerative colitis The recommended dose regimen of Entyvio is 300 mg administered by intravenous infusion at zero, two and six weeks and then every eight weeks thereafter.
Some patients who have experienced a decrease in their response may benefit from an increase in dosing frequency to Entyvio 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. …
… Crohn's disease The recommended dose regimen of Entyvio 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 Entyvio at week 10 (see section 4.4). Therapy should be continued every eight weeks from week 14 in responding patients. Therapy for patients with Crohn's disease should Some patients who have experienced a decrease in their response may benefit from an increase in dosing frequency to Entyvio 300 mg every four weeks. … |
4.4 Special warnings and precautions for use |
…
Infections … Some integrin antagonists and some systemic immunosuppressive agents have been associated with progressive multifocal leukoencephalopathy (PML), which is a rare and often fatal opportunistic infection caused by the John Cunningham (JC) virus. By binding to the α4β7 integrin expressed on gut-homing lymphocytes, vedolizumab exerts an immunosuppressive effect
…
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4.6 Fertility, pregnancy and lactation |
…
Breast-feeding Vedolizumab has been detected in human milk. The effect of vedolizumab on infants is unknown. The use of vedolizumab in lactating women should take into account the benefit of therapy to the mother and potential risks to the infant.
… |
4.8 Undesirable effects |
… Herpes zoster added to the Infections and infestations section of Table 1 (Adverse Reactions) as an Uncommon side effect. …
…
… |
5.1 Pharmacodynamic properties |
… Mechanism of action Vedolizumab is a gut-selective immunosuppressive biologic. It is a humanised monoclonal antibody that binds specifically to the α4β7 integrin, which is preferentially expressed on gut homing T helper lymphocytes. By binding to α4β7 on certain lymphocytes, vedolizumab inhibits adhesion of these cells to mucosal addressin cell adhesion molecule-1 (MAdCAM-1), but not to vascular cell adhesion molecule-1 (VCAM-1). MAdCAM-1 is mainly expressed on gut endothelial cells and plays a critical role in the homing of T lymphocytes to tissues within the gastrointestinal tract. Vedolizumab does not bind to, nor inhibit function of, the α4β1 and αEβ7 integrins. The α4β7 integrin is expressed on a discrete subset of memory T helper lymphocytes which preferentially migrate into the gastrointestinal (GI) tract and cause inflammation that is characteristic of ulcerative colitis and Crohn's disease, both of which are chronic inflammatory immunologically mediated conditions of the GI tract. Vedolizumab reduces gastrointestinal inflammation in UC and CD patients. Inhibiting the interaction of α4β7 with MAdCAM-1 with vedolizumab prevents transmigration of gut-homing memory T helper lymphocytes across the vascular endothelium into parenchymal tissue in nonhuman primates and induced a reversible 3-fold elevation of these cells in peripheral blood. The murine precursor of vedolizumab alleviated gastrointestinal inflammation in colitic cotton-top tamarins, a model of ulcerative colitis. …
… Immunogenicity
Antibodies to vedolizumab may develop during vedolizumab treatment most of which are neutralising. The formation of anti‑vedolizumab antibodies is associated with increased clearance of vedolizumab and lower rates of clinical remission.
Infusion related reactions after vedolizumab infusion are reported in subjects with anti‑vedolizumab antibodies. …
… Patients who achieved a clinical response after receiving vedolizumab at week 0 and 2 and were then randomised to placebo (for 6 to 52 weeks) and lost response were allowed to enter the open-label extension study and receive vedolizumab every four weeks. In these patients, clinical remission was achieved in 45% of patients by 28 weeks and 36% of patients by 52 weeks. In this open-label extension study, the benefits of vedolizumab treatment as assessed by partial Mayo score, clinical remission, and clinical response were shown for up to Health-related quality of life (HRQOL) was assessed by Inflammatory Bowel Disease Questionnaire (IBDQ), a disease specific instrument, and SF-36 and EQ-5D, which are general measures. Exploratory analysis show clinically meaningful improvements were observed for vedolizumab groups, and the improvements were significantly greater as compared with the placebo group at week 6 and week 52 on EQ-5D and EQ-5D VAS scores, all subscales of IBDQ (bowel symptoms, systemic function, emotional function and social function), and all subscales of SF-36 including the Physical Component Summary (PCS) and Mental Component Summary (MCS). …
… Patients who achieved a clinical response after receiving vedolizumab at week 0 and 2 and were then randomised to placebo (for 6 to 52 weeks) and lost response were allowed to enter the open-label extension study and receive vedolizumab every four weeks. In these patients, clinical remission was achieved in 46% of patients by 28 weeks and 41% of patients by 52 weeks. In this open-label extension study, clinical remission and clinical response were observed in patients for up to Exploratory analysis showed clinically meaningful improvements were observed for the vedolizumab every four weeks and every eight weeks groups in GEMINI II and the improvements were significantly greater as compared with the placebo group from baseline to week 52 on EQ-5D and EQ-5D VAS scores, total IBDQ score, and IBDQ subscales of bowel symptoms and systemic function. … |
5.2 Pharmacokinetic properties |
… Elimination Population pharmacokinetic analyses indicate that vedolizumab has a total body clearance of approximately 0.157 L/day and a serum half-life of 25 days. The exact elimination route of vedolizumab is not known. Population pharmacokinetic analyses suggest that while low albumin, higher body weight and … |
5.3 Preclinical safety data |
… Administration of vedolizumab to pregnant cynomolgus monkeys during most of gestation resulted in no evidence of effects on teratogenicity, prenatal or postnatal development in infants up to 6 months of age. Low levels (< 300 mcg/L) of vedolizumab were detected on post-partum day 28 in the milk of 3 of 11 cynomolgus monkeys treated 100 mg/kg of vedolizumab dosed every 2 weeks and not in any animals that received 10 mg/kg. … |
10. Date of revision of the text |
Updated text in red:
20th February 2019 |
Updated on 21 December 2018 PIL
Reasons for updating
- Change to section 3 - how to take/use
- Removal of Black Inverted Triangle
- Improved presentation of PIL
Updated on 21 December 2018 SPC
Reasons for updating
- Change to section 2 - Qualitative and quantitative composition
- Change to section 4.6 - Pregnancy and lactation
- Change to section 4.7 - Effects on ability to drive and use machines
- Change to section 4.8 - Undesirable effects
- Change to section 5.3 - Preclinical safety data
- Change to section 10 - Date of revision of the text
- Improved presentation of SPC
- Removal of Black Inverted Triangle
Legal category: Product subject to medical prescription which may not be renewed (A)
Updated on 6 September 2018 PIL
Reasons for updating
- Change to section 4 - possible side effects
- Change to section 6 - date of revision
Updated on 6 September 2018 SPC
Reasons for updating
- Change to section 4.8 - Undesirable effects
- Change to section 10 - Date of revision of the text
Legal category: Product subject to medical prescription which may not be renewed (A)
Free text change information supplied by the pharmaceutical company
In section 4.8 (undesirable effects), anaphylactic reaction and anaphylactice shock have been added as a very rare adverse reaction.
In section 10, date of revision is 23 August 2018
Updated on 11 June 2018 SPC
Reasons for updating
- Change to section 6.3 - Shelf life
- Change to section 6.6 - Special precautions for disposal and other handling
- Change to section 10 - Date of revision of the text
Legal category: Product subject to medical prescription which may not be renewed (A)
Updated on 11 June 2018 PIL
Reasons for updating
- Change to section 5 - how to store or dispose
Updated on 16 February 2018 SPC
Reasons for updating
- New SPC for new product
Legal category: Product subject to medical prescription which may not be renewed (A)
Updated on 16 February 2018 SPC
Reasons for updating
- Change to section 10 - Date of revision of the text
Legal category: Product subject to medical prescription which may not be renewed (A)
Free text change information supplied by the pharmaceutical company
Change to section |
Details of change |
10. Date of revision of the text |
Updated text in red:
|
Updated on 15 February 2018 PIL
Reasons for updating
- Change to section 6 - date of revision
Updated on 15 February 2018 PIL
Reasons for updating
- New PIL for new product
Updated on 8 January 2018 SPC
Reasons for updating
- Change to section 4.8 - Undesirable effects
- Change to Section 4.8 – Undesirable effects - how to report a side effect
- Change to section 10 - Date of revision of the text
Legal category: Product subject to medical prescription which may not be renewed (A)
Free text change information supplied by the pharmaceutical company
Change to section |
Details of change |
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4.8 Undesirable effects |
Text in blue removed and text in red added:
… Tabulated list of adverse reactions The following listing of adverse reactions is based on …
…
…
… 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 HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.
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10. Date of revision of the text |
Updated text in red:
14 December 2017 |
Updated on 4 January 2018 PIL
Reasons for updating
- Change to section 4 - possible side effects
- Change to section 6 - date of revision
- Change to section 4 - how to report a side effect
Updated on 10 November 2016 PIL
Reasons for updating
- Change to section 6 - manufacturer
Updated on 13 January 2016 PIL
Reasons for updating
- Addition of manufacturer
Updated on 3 September 2015 SPC
Reasons for updating
- Change to section 4.2 - Posology and method of administration
- Change to section 4.4 - Special warnings and precautions for use
- Change to section 4.8 - Undesirable effects
- Change to section 10 - Date of revision of the text
Legal category: Product subject to medical prescription which may not be renewed (A)
Free text change information supplied by the pharmaceutical company
Change to section |
Details of change |
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 (see section 4.4). Patients should be given the package leaflet and the Patient Alert Card. |
4.4. Special warnings and precautions for use |
Vedolizumab should be administered in a healthcare setting equipped to allow management of acute hypersensitivity reactions including anaphylaxis, if they occur. Appropriate monitoring and medical support measures should be available for immediate use when administering vedolizumab. |
4.8. Undesirable Effects |
Summary of safety profile “……eight weeks or every four weeks from Week 6 for up to 52 weeks, and 297 patients receiving placebo for up to 52 weeks, adverse events….” Muscle spasms, Back pain, Muscular weakness, Fatigue, Pain in the extremity – has been added as “common” under “Musculoskeletal and connective tissue disorders” |
10. DATE OF REVISION OF THE TEXT |
Changed to: 20th August 2015 |
Updated on 26 August 2015 PIL
Reasons for updating
- Change to side-effects
- Change to date of revision
- Addition of information on reporting a side effect.
Updated on 3 August 2015 PIL
Reasons for updating
- Change to dosage and administration
Updated on 1 June 2015 PIL
Reasons for updating
- Change to name of manufacturer
Updated on 12 September 2014 SPC
Reasons for updating
- New SPC for new product
Legal category: Product subject to medical prescription which may not be renewed (A)
Free text change information supplied by the pharmaceutical company
Updated on 4 September 2014 PIL
Reasons for updating
- New PIL for new product
Entyvio (vedolizumab) HCP Educational BrochureRisk Minimisation Materials
(Click to Download)
Educational Materials for Medicines
Educational Materials for Medicines
Entyvio (vedolizumab) Patient Alert CardRisk Minimisation Materials
(Click to Download)
Educational Materials for Medicines
Educational Materials for Medicines