Entyvio

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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS



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1. NAME OF THE MEDICINAL PRODUCT

Entyvio 300 mg powder for concentrate for solution for infusion

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each vial contains 300 mg of vedolizumab.

After reconstitution, each mL contains 60 mg of vedolizumab.

Vedolizumab is a humanised IgG1 monoclonal antibody produced in Chinese hamster ovary (CHO) 
cells by recombinant DNA technology.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Powder for concentrate for solution for infusion.

White to off-white lyophilised cake or powder.

4. CLINICAL PARTICULARS

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.

4.2 Posology and method of administration

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.

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).



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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).

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.



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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.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Active severe infections such as tuberculosis (TB), sepsis, cytomegalovirus, listeriosis, and 
opportunistic infections such as Progressive Multifocal Leukoencephalopathy (PML) (see section 4.4).

4.4 Special warnings and precautions for use

Intravenous 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 
intravenous vedolizumab. 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).

If a severe IRR, anaphylactic reaction, or other severe reaction occurs, administration of Entyvio must 
be discontinued immediately and appropriate treatment initiated (e.g., epinephrine and antihistamines)
(see section 4.3).

If a mild to moderate IRR occurs, the infusion rate can be slowed or interrupted and appropriate 
treatment initiated. Once the mild or moderate IRR subsides, continue the infusion. Physicians should 
consider pre-treatment (e.g., with antihistamine, hydrocortisone and/or paracetamol) prior to the next 
infusion for patients with a history of mild to moderate IRR to vedolizumab, in order to minimize their 
risks (see section 4.8).

Infections

Vedolizumab is a gut-selective integrin antagonist with no identified systemic immunosuppressive 
activity (see section 5.1).

Physicians should be aware of the potential increased risk of opportunistic infections or infections for 
which the gut is a defensive barrier (see section 4.8). Vedolizumab treatment is not to be initiated in 
patients with active, severe infections until the infections are controlled, and physicians should 
consider withholding treatment in patients who develop a severe infection while on chronic treatment 
with vedolizumab. Caution should be exercised when considering the use of vedolizumab in patients 
with a controlled chronic severe infection or a history of recurring severe infections. Patients should be 
monitored closely for infections before, during and after treatment.
Vedolizumab is contraindicated in patients with active tuberculosis (see section 4.3). Before starting 
treatment with vedolizumab, patients must be screened for tuberculosis according to the local practice. 



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If latent tuberculosis is diagnosed, appropriate treatment must be started with anti-tuberculosis 
treatment in accordance with local recommendations, before beginning vedolizumab. In patients 
diagnosed with TB whilst receiving vedolizumab therapy, then vedolizumab therapy should be 
discontinued until the TB infection has been resolved.

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 specific to the gut. 
Although no systemic immunosuppressive effect was noted in healthy subjects the effects on systemic 
immune system function in patients with inflammatory bowel disease is not known. 

Healthcare professionals should monitor patients on vedolizumab for any new onset or worsening of 
neurological signs and symptoms as outlined in physician education materials, and consider 
neurological referral if they occur. The patient is to be given a Patient Alert Card (see section 4.2). If 
PML is suspected, treatment with vedolizumab must be withheld; if confirmed, treatment must be 
permanently discontinued.

Malignancies

The risk of malignancy is increased in patients with ulcerative colitis and Crohn’s disease. 
Immunomodulatory medicinal products may increase the risk of malignancy (see section 4.8).

Prior and concurrent use of biological products

No vedolizumab clinical trial data are available for patients previously treated with natalizumab or 
rituximab. Caution should be exercised when considering the use of vedolizumab in these patients.

Patients previously exposed to natalizumab should normally wait a minimum of 12 weeks prior to 
initiating therapy with vedolizumab, unless otherwise indicated by the patient’s clinical condition.

No clinical trial data for concomitant use of vedolizumab with biologic immunosuppressants are 
available. Therefore, the use of vedolizumab in such patients is not recommended.

Live and oral vaccines

In a placebo-controlled study of healthy volunteers, a single 750 mg dose of vedolizumab did not 
lower rates of protective immunity to hepatitis B virus in subjects who were vaccinated 
intramuscularly with 3 doses of recombinant hepatitis B surface antigen. Vedolizumab-exposed 
subjects had lower seroconversion rates after receiving a killed, oral cholera vaccine. The impact on 
other oral and nasal vaccines is unknown. It is recommended that all patients be brought up to date 
with all immunisations in agreement with current immunisation guidelines prior to initiating 
vedolizumab therapy. Patients receiving vedolizumab treatment may continue to receive non-live 
vaccines. There are no data on the secondary transmission of infection by live vaccines in patients 
receiving vedolizumab. Administration of the influenza vaccine should be by injection in line with 
routine clinical practice. Other live vaccines may be administered concurrently with vedolizumab only 
if the benefits clearly outweigh the risks.

Induction of remission in Crohn’s disease

Induction of remission in Crohn’s disease may take up to 14 weeks in some patients. The reasons for
this are not fully known and are possibly related to the mechanism of action. This should be taken into 
consideration, particularly in patients with severe active disease at baseline not previously treated with 
TNFα antagonists. (see also section 5.1.)

Exploratory subgroup analyses from the clinical trials in Crohn’s disease suggested that vedolizumab 
administered in patients without concomitant corticosteroid treatment may be less effective for 



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induction of remission in Crohn’s disease than in those patients already receiving concomitant 
corticosteroids (regardless of use of concomitant immunomodulators; see section 5.1).

4.5 Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed.

Vedolizumab has been studied in adult ulcerative colitis and Crohn’s disease patients with 
concomitant administration of corticosteroids, immunomodulators (azathioprine, 6-mercaptopurine, 
and methotrexate), and aminosalicylates. Population pharmacokinetic analyses suggest that 
co-administration of such agents did not have a clinically meaningful effect on vedolizumab 
pharmacokinetics. The effect of vedolizumab on the pharmacokinetics of commonly co-administered 
medicinal compounds has not been studied.

Vaccinations

Live vaccines, in particular live oral vaccines, should be used with caution concurrently with 
vedolizumab (see section 4.4).

4.6 Fertility, pregnancy and lactation

Women of childbearing potential

Women of childbearing potential should use adequate contraception to prevent pregnancy and to
continue its use for at least 18 weeks after the last treatment.

Pregnancy

There are limited amount of data from the use of vedolizumab in pregnant women.

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity 
(see section 5.3).

As a precautionary measure, it is preferable to avoid the use of vedolizumab during pregnancy unless 
the benefits clearly outweigh any potential risk to both the mother and foetus.

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.

Fertility

There are no data on the effects of vedolizumab on human fertility. Effects on male and female 
fertility have not been formally evaluated in animal studies (see section 5.3).

4.7 Effects on ability to drive and use machines

Vedolizumab has minor influence on the ability to drive and use machines, as dizziness has been 
reported in a small number of patients.



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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.

Infusion related reactions (with symptoms such as dyspnea, bronchospasm, urticaria, flushing, rash, 
and increased blood pressure and heart rate) have also been reported in patients treated with 
vedolizumab. 

Tabulated list of adverse reactions

The following listing of adverse reactions is based on clinical trial and post marketing experience and 
is displayed by system organ class. Within the system organ classes, adverse reactions are listed under 
headings of the following frequency categories: very common (≥ 1/10), common (≥ 1/100 to < 1/10),
uncommon (≥ 1/1,000 to < 1/100) and very rare (< 1/10,000). Within each frequency grouping, 
adverse reactions are presented in order of decreasing seriousness.

Table 1. Adverse reactions

System organ class Frequency Adverse reaction(s)

Infections and infestations Very common Nasopharyngitis
Common Bronchitis, 

Gastroenteritis, 
Upper respiratory tract infection, 
Influenza, 
Sinusitis, 
Pharyngitis

Uncommon Respiratory tract infection, 
Vulvovaginal candidiasis, 
Oral candidiasis, 
Herpes zoster

Very rare Pneumonia
Immune system disorders Very rare Anaphylactic reaction, 

Anaphylactic shock
Nervous system disorders Very common Headache

Common Paraesthesia
Eye disorders Very rare Blurred vision
Vascular disorders Common Hypertension
Respiratory, thoracic and 
mediastinal disorders

Common Oropharyngeal pain, 
Nasal congestion, 
Cough

Gastrointestinal disorders Common Anal Abscess, 
Anal fissure, 
Nausea, 
Dyspepsia, 
Constipation, 
Abdominal distension, 
Flatulence, 
Haemorrhoids



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Skin and subcutaneous tissue 
disorders

Common Rash, 
Pruritus, 
Eczema, 
Erythema, 
Night sweats, 
Acne

Uncommon Folliculitis
Musculoskeletal and connective 
tissue disorders

Very common Arthralgia
Common Muscle spasms, 

Back pain, 
Muscular weakness, 
Fatigue, 
Pain in the extremity

General disorders and 
administration site conditions

Common Pyrexia
Uncommon Infusion site reaction (including: Infusion site 

pain and Infusion site irritation), 
Infusion related reaction,
Chills, 
Feeling cold

Description of selected adverse reactions

Infusion-related reactions

In GEMINI 1 and 2 controlled studies, 4% of intravenous vedolizumab-treated patients and 3% of 
placebo-treated patients experienced an adverse reaction defined by the investigator as infusion-related 
reaction (IRR) (see section 4.4). No individual Preferred Term reported as an IRR occurred at a rate 
above 1%. The majority of IRRs were mild or moderate in intensity and < 1% resulted in 
discontinuation of study treatment. Observed IRRs generally resolved with no or minimal intervention 
following the infusion. Most infusion related reactions occurred within the first 2 hours. Of those 
patients who had infusion related reactions, those dosed with intravenous vedolizumab had more 
infusion related reactions with in the first 2 hours as compared to placebo patients with infusion 
related reactions. Most infusion related reactions were not serious and occurred during the infusion or 
within the first hour after infusion is completed.

One serious adverse reaction of IRR was reported in a Crohn’s disease patient during the second 
infusion (symptoms reported were dyspnoea, bronchospasm, urticaria, flushing, rash, and increased 
blood pressure and heart rate) and was successfully managed with discontinuation of infusion and 
treatment with antihistamine and intravenous hydrocortisone. In patients who received intravenous 
vedolizumab at weeks 0 and 2 followed by placebo, no increase in the rate of IRR was seen upon 
retreatment with intravenous vedolizumab after loss of response.

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.



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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.

Malignancy

Overall, results from the clinical program to date do not suggest an increased risk for malignancy with 
vedolizumab treatment; however, the number of malignancies was small and long-term exposure was 
limited. Long-term safety evaluations are ongoing.

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 the national reporting system 
listed in Appendix V.

4.9 Overdose

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.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: immunosuppressants, selective immunosuppressants, ATC code: 
L04AA33.

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.

In healthy subjects, ulcerative colitis patients, or Crohn’s disease patients, vedolizumab does not 
elevate neutrophils, basophils, eosinophils, B-helper and cytotoxic T lymphocytes, total memory T 



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helper lymphocytes, monocytes or natural killer cells, in the peripheral blood with no leukocytosis 
observed.

Vedolizumab did not affect immune surveillance and inflammation of the central nervous system in 
Experimental Autoimmune Encephalomyelitis in non-human primates, a model of multiple sclerosis. 
Vedolizumab did not affect immune responses to antigenic challenge in the dermis and muscle (see 
section 4.4). In contrast, vedolizumab inhibited an immune response to a gastrointestinal antigenic 
challenge in healthy human volunteers (see section 4.4).

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. 

Pharmacodynamic effects

In clinical trials with intravenous vedolizumab at doses ranging from 2 to 10 mg/kg, > 95% saturation 
of α4β7 receptors on subsets of circulating lymphocytes involved in gut immune surveillance was 
observed in patients.

Vedolizumab did not affect CD4+ and CD8+ trafficking into the CNS as evidenced by the lack of 
change in the ratio of CD4+/CD8+ in cerebrospinal fluid pre- and post-vedolizumab administration in 
healthy human volunteers. These data are consistent with investigations in nonhuman primates which 
did not detect effects on immune surveillance of the CNS.

Clinical efficacy and safety

Ulcerative colitis

The efficacy and safety of intravenous vedolizumab for the treatment of adult patients with moderately 
to severely active ulcerative colitis (Mayo score 6 to 12 with endoscopic sub score ≥ 2) was 
demonstrated in a randomised, double-blind, placebo-controlled study evaluating efficacy endpoints at 
week 6 and week 52 (GEMINI 1). Enrolled patients had failed at least one conventional therapy, 
including corticosteroids, immunomodulators, and/or the TNFα antagonist infliximab (including 
primary non-responders). Concomitant stable doses of oral aminosalicylates, corticosteroids and/or 
immunomodulators were permitted. 

For the evaluation of the week 6 endpoints, 374 patients were randomised in a double-blind fashion 
(3:2) to receive vedolizumab 300 mg or placebo at week 0 and week 2. Primary endpoint was the 
proportion of patients with clinical response (defined as reduction in complete Mayo score of 
 3 points and  30% from baseline with an accompanying decrease in rectal bleeding subscore of 
 1 point or absolute rectal bleeding subscore of ≤ 1 point) at week 6. Table 2 shows the results from 
the primary and secondary endpoints evaluated.



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Table 2. Week 6 efficacy results of GEMINI 1

Endpoint
Placebo
n = 149

Vedolizumab IV
n = 225

Clinical response 26% 47%*

Clinical remission§ 5% 17%†

Mucosal healing¶ 25% 41%‡

*p < 0.0001
†p ≤ 0.001
‡p < 0.05
§Clinical remission: Complete Mayo score of ≤ 2 points and no individual subscore > 1 point
¶Mucosal healing: Mayo endoscopic subscore of ≤ 1 point

The beneficial effect of vedolizumab on clinical response, remission and mucosal healing was 
observed both in patients with no prior TNF antagonist exposure as well as in those who had failed 
prior TNF antagonist therapy.

In GEMINI 1, 2 cohorts of patients received vedolizumab at week 0 and week 2: cohort 1 patients 
were randomised to receive either vedolizumab 300 mg or placebo in a double-blind fashion, and 
cohort 2 patients were treated with open-label vedolizumab 300 mg. To evaluate efficacy at week 52, 
373 patients from cohort 1 and 2 who were treated with vedolizumab and had achieved clinical 
response at week 6 were randomised in a double-blind fashion (1:1:1) to one of the following 
regimens beginning at week 6: vedolizumab 300 mg every 8 weeks, vedolizumab 300 mg every 
4 weeks, or placebo every 4 weeks. Beginning at week 6, patients who had achieved clinical response 
and were receiving corticosteroids were required to begin a corticosteroid-tapering regimen. Primary 
endpoint was the proportion of patients in clinical remission at week 52. Table 3 shows the results 
from the primary and secondary endpoints evaluated.

Table 3. Week 52 efficacy results of GEMINI 1

Endpoint
Placebo
n = 126*

Vedolizumab IV
every 8 weeks

n = 122

Vedolizumab IV
every 4 weeks

n = 125

Clinical remission 16% 42%† 45%†

Durable clinical response¶ 24% 57%† 52%†

Mucosal healing 20% 52%† 56%†

Durable clinical remission# 9% 20%§ 24%‡

Corticosteroid-free clinical remission♠ 14% 31%§ 45%†

*The placebo group includes those subjects who received vedolizumab at week 0 and week 2, and were 
randomised to receive placebo from week 6 through week 52.

†p < 0.0001
‡p < 0.001
§p < 0.05
¶Durable clinical response: Clinical response at weeks 6 and 52
#Durable clinical remission: Clinical remission at weeks 6 and 52
♠Corticosteroid-free clinical remission: Patients using oral corticosteroids at baseline who had discontinued 
corticosteroids beginning at week 6 and were in clinical remission at week 52. Patient numbers were n = 72 
for placebo, n = 70 for vedolizumab every 8 weeks, and n = 73 for vedolizumab every 4 weeks

Exploratory analyses provide additional data on key subpopulations studied. Approximately one-third 
of patients had failed prior TNF antagonist therapy. Among these patients, 37% receiving 
vedolizumab every 8 weeks, 35% receiving vedolizumab every 4 weeks, and 5% receiving placebo 
achieved clinical remission at week 52. Improvements in durable clinical response (47%, 43%, 16%), 
mucosal healing (42%, 48%, 8%), durable clinical remission (21%, 13%, 3%) and corticosteroid-free 
clinical remission (23%, 32%, 4%) were seen in the prior TNFα antagonist failure population treated 
with vedolizumab every 8 weeks, vedolizumab every 4 weeks and placebo, respectively.



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Patients who failed to demonstrate response at week 6 remained in the study and received 
vedolizumab every 4 weeks. Clinical response using partial Mayo scores was achieved at week 10 and 
week 14 by greater proportions of vedolizumab patients (32% and 39%, respectively) compared with 
placebo patients (15% and 21%, respectively).

Patients who lost response to vedolizumab when treated every 8 weeks were allowed to enter an 
open-label extension study and receive vedolizumab every 4 weeks. In these patients, clinical 
remission was achieved in 25% of patients at week 28 and week 52.

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 4 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 196 weeks.

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 generic 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). 

Crohn’s disease

The efficacy and safety of intravenous vedolizumab for the treatment of adult patients with moderately 
to severely active Crohn’s disease (Crohn’s Disease Activity Index [CDAI] score of 220 to 450) were 
evaluated in 2 studies (GEMINI 2 and 3). Enrolled patients have failed at least one conventional 
therapy, including corticosteroids, immunomodulators, and/or TNFα antagonists (including primary 
non-responders). Concomitant stable doses of oral corticosteroids, immunomodulators, and antibiotics 
were permitted.

The GEMINI 2 Study was a randomised, double-blind, placebo-controlled study evaluating efficacy 
endpoints at week 6 and week 52. Patients (n = 368) were randomised in a double-blind fashion (3:2) 
to receive 2 doses of vedolizumab 300 mg or placebo at week 0 and week 2. The 2 primary endpoints 
were the proportion of patients in clinical remission (defined as CDAI score ≤ 150 points) at week 6 
and the proportion of patients with enhanced clinical response (defined as a ≥ 100-point decrease in 
CDAI score from baseline) at week 6 (see Table 4). 

GEMINI 2 contained 2 cohorts of patients that received vedolizumab at weeks 0 and 2: 
cohort 1 patients were randomised to receive either vedolizumab 300 mg or placebo in a double-blind 
fashion, and cohort 2 patients were treated with open-label vedolizumab 300 mg. To evaluate efficacy 
at week 52, 461 patients from cohorts 1 and 2, who were treated with vedolizumab and had achieved 
clinical response (defined as a ≥ 70-point decrease in CDAI score from baseline) at week 6, were 
randomised in a double-blind fashion (1:1:1) to one of the following regimens beginning at week 6: 
vedolizumab 300 mg every 8 weeks, vedolizumab 300 mg every 4 weeks, or placebo every 4 weeks. 
Patients showing clinical response at week 6 were required to begin corticosteroid tapering. Primary 
endpoint was the proportion of patients in clinical remission at week 52 (see Table 5).

The GEMINI 3 Study was a second randomised, double-blind, placebo-controlled study that evaluated 
efficacy at week 6 and week 10 in the subgroup of patients defined as having failed at least 
1 conventional therapy and failed TNF antagonist therapy (including primary non-responders) as 
well as the overall population, which also included patients who failed at least 1 conventional therapy 
and were naïve to TNF antagonist therapy. Patients (n = 416), which included approximately 75% 
TNF antagonist failures patients, were randomised in a double-blind fashion (1:1) to receive either 



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vedolizumab 300 mg or placebo at weeks 0, 2, and 6. The primary endpoint was the proportion of 
patients in clinical remission at week 6 in the TNF antagonist failure subpopulation. As noted in 
Table 4, although the primary endpoint was not met, exploratory analyses show that clinically 
meaningful results were observed. 

Table 4. Efficacy results for GEMINI 2 and 3 studies at week 6 and week 10
Study

Endpoint Placebo Vedolizumab IV

GEMINI 2 Study

Clinical remission, week 6

Overall 7% (n = 148) 15%* (n = 220)

TNFα Antagonist(s) Failure 4% (n = 70) 11% (n = 105)

TNFα Antagonist(s) Naïve 9% (n = 76) 17% (n = 109)

Enhanced clinical response, week 6

Overall 26% (n = 148) 31%† (n = 220)

TNFα Antagonist(s) Failure 23% (n = 70) 24% (n = 105)

TNFα Antagonist(s) Naïve 30% (n = 76) 42% (n = 109)

Serum CRP change from baseline to week 6, 
median (mcg/mL)

Overall‡ -0.5 (n = 147) -0.9 (n = 220)

GEMINI 3 Study

Clinical remission, week 6

Overall‡ 12% (n = 207) 19% (n = 209)

TNFα Antagonist(s) Failure¶ 12% (n = 157) 15%§ (n = 158)

TNFα Antagonist(s) Naïve 12% (n = 50) 31% (n = 51)

Clinical remission, week 10

Overall 13% (n = 207) 29% (n = 209)

TNFα Antagonist(s) Failure¶,‡ 12% (n = 157) 27% (n = 158)

TNFα Antagonist(s) Naïve 16% (n = 50) 35% (n = 51)

Sustained clinical remission#,¶

Overall 8% (n = 207) 15% (n = 209)

TNFα Antagonist(s) Failure¶,‡ 8% (n = 157) 12% (n = 158)

TNFα Antagonist(s) Naïve 8% (n = 50) 26% (n = 51)

Enhanced clinical response, week 6

Overall^ 23% (n = 207) 39% (n = 209)

TNFα Antagonist(s) Failure‡ 22% (n = 157) 39% (n = 158)

TNFα Antagonist(s) Naïve^ 24% (n = 50) 39% (n = 51)

*p < 0.05
†not statistically significant
‡secondary endpoint to be viewed as exploratory by pre-specified statistical testing procedure
§not statistically significant, the other endpoints were therefore not tested statistically
¶n = 157 for placebo and n = 158 for vedolizumab
#Sustained clinical remission: clinical remission at weeks 6 and 10
^Exploratory Endpoint



14

Table 5. Efficacy results for GEMINI 2 at week 52

Placebo
n = 153*

Vedolizumab IV
every 8 weeks

n = 154

Vedolizumab IV
every 4 weeks

n = 154

Clinical remission 22% 39%† 36%‡

Enhanced clinical response 30% 44%‡ 45%‡

Corticosteroid-free clinical remission§ 16% 32%‡ 29%‡

Durable clinical remission¶ 14% 21% 16%

*The placebo group includes those subjects who received vedolizumab at week 0 and week 2, and were 
randomised to receive placebo from week 6 through week 52.

†p < 0.001
‡p < 0.05
§Corticosteroid-free clinical remission: Patients using oral corticosteroids at baseline who had discontinued 
corticosteroids beginning at week 6 and were in clinical remission at week 52. Patient numbers were n = 82 
for placebo, n = 82 for vedolizumab every 8 weeks, and n = 80 for vedolizumab every 4 weeks 

¶Durable clinical remission: Clinical remission at ≥ 80% of study visits including final visit (week 52)

Exploratory analyses examined the effects of concomitant corticosteroids and immunomodulators on 
induction of remission with vedolizumab. Combination treatment, most notably with concomitant 
corticosteroids, appeared to be more effective in inducing remission in Crohn’s disease than 
vedolizumab alone or with concomitant immunomodulators, which showed a smaller difference from 
placebo in the rate of remission. Clinical remission rate in GEMINI 2 at week 6 was 10% (difference 
from placebo 2%, 95% CI: -6, 10) when administered without corticosteroids compared to 20% 
(difference from placebo 14%, 95% CI: -1, 29) when administered with concomitant corticosteroids. 
In GEMINI 3 at week 6 and 10 the respective clinical remission rates were 18% (difference from 
placebo 3%, 95% CI: -7, 13) and 22% (difference from placebo 8%, 95% CI: -3, 19) when 
administered without corticosteroids compared to 20% (difference from placebo 11%, 95% CI: 2, 20) 
and 35% (difference from placebo 23%, 95% CI: 12, 33) respectively when administered with 
concomitant corticosteroids. These effects were seen whether or not immunomodulators were also 
concomitantly administered.

Exploratory analyses provide additional data on key subpopulations studied. In GEMINI 2, 
approximately half of patients had previously failed TNFα antagonist therapy. Among these patients, 
28% receiving vedolizumab every 8 weeks, 27% receiving vedolizumab every 4 weeks, and 13% 
receiving placebo achieved clinical remission at week 52. Enhanced clinical response was achieved in 
29%, 38%, 21%, respectively, and corticosteriod-free clinical remission was achieved in 24%, 16%, 
0%, respectively. 

Patients who failed to demonstrate response at week 6 in GEMINI 2 were retained in the study and 
received vedolizumab every 4 weeks. Enhanced clinical response was observed at week 10 and 
week 14 for greater proportions of vedolizumab patients 16% and 22%, respectively, compared with 
placebo patients 7% and 12%, respectively. There was no clinically meaningful difference in clinical 
remission between treatment groups at these time points. Analyses of week 52 clinical remission in 
patients who were non-responders at week 6 but achieved response at week 10 or week 14 indicate 
that non-responder CD patients may benefit from a dose of vedolizumab at week 10.

Patients who lost response to vedolizumab when treated every 8 weeks in GEMINI 2 were allowed to 
enter an open-label extension study and received vedolizumab every 4 weeks. In these patients, 
clinical remission was achieved in 23% of patients at week 28 and 32% of patients at week 52.

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 4 weeks. In these patients, clinical remission was 
achieved in 46% of patients by 28 weeks and 41% of patients by 52 weeks.



15

In this open-label extension study, clinical remission and clinical response were observed in patients 
for up to 196 weeks.

Exploratory analysis showed clinically meaningful improvements were observed for the vedolizumab 
every 4 weeks and every 8 weeks groups in GEMINI 2 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.

Paediatric population

The European Medicines Agency has deferred the obligation to submit the results of studies with 
vedolizumab in one or more subsets of the paediatric population in ulcerative colitis and Crohn’s 
disease (see section 4.2 for information on paediatric use).

5.2 Pharmacokinetic properties

The single and multiple dose pharmacokinetics of vedolizumab have been studied in healthy subjects 
and in patients with moderate to severely active ulcerative colitis or Crohn’s disease. 

In patients administered 300 mg vedolizumab as a 30 minute intravenous infusion on weeks 0 and 2, 
mean serum trough concentrations at week 6 were 27.9 mcg/mL (SD ± 15.51) in ulcerative colitis 
and 26.8 mcg/mL (SD ± 17.45) in Crohn’s disease. In studies with intravenous vedolizumab, starting 
at week 6, patients received 300 mg intravenous vedolizumab every 8 or 4 weeks. In patients with 
ulcerative colitis, mean steady-state serum trough concentrations were 11.2 mcg/mL (SD ± 7.24) 
and 38.3 mcg/mL (SD ± 24.43), respectively. In patients with Crohn's disease mean steady-state serum 
trough concentrations were 13.0 mcg/mL (SD ± 9.08) and 34.8 mcg/mL (SD ± 22.55), respectively.

Distribution

Population pharmacokinetic analyses indicate that the distribution volume of vedolizumab is 
approximately 5 litres. The plasma protein binding of vedolizumab has not been evaluated. 
Vedolizumab is a therapeutic monoclonal antibody and is not expected to bind to plasma proteins.

Vedolizumab does not pass the blood brain barrier after intravenous administration. Vedolizumab 
450 mg administered intravenously was not detected in the cerebrospinal fluid of healthy subjects.

Elimination

Population pharmacokinetic analyses indicate that vedolizumab has a total body clearance of 
approximately 0.169 L/day and a serum half-life of 24 days. The exact elimination route of 
vedolizumab is not known. Population pharmacokinetic analyses suggest that while low albumin, 
higher body weight and prior treatment with anti-TNF drugs may increase vedolizumab clearance, the 
magnitude of their effects is not considered to be clinically relevant.

Linearity

Vedolizumab exhibited linear pharmacokinetics at serum concentrations greater than 1 mcg/mL.

Special populations

Age does not impact the vedolizumab clearance in ulcerative colitis and Crohn’s disease patients 
based on the population pharmacokinetic analyses. No formal studies have been conducted to examine 
the effects of either renal or hepatic impairment on the pharmacokinetics of vedolizumab.



16

5.3 Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction
and development. 

Long-term animal studies with vedolizumab to assess its carcinogenic potential have not been 
conducted because pharmacologically responsive models to monoclonal antibodies do not exist. In a 
pharmacologically responsive species (cynomolgus monkeys), there was no evidence of cellular 
hyperplasia or systemic immunomodulation that could potentially be associated with oncogenesis in 
13- and 26-week toxicology studies. Furthermore, no effects were found of vedolizumab on the 
proliferative rate or cytotoxicity of a human tumour cell line expressing the α4β7 integrin in vitro.

No specific fertility studies in animals have been performed with vedolizumab. No definitive 
conclusion can be drawn on the male reproductive organs in cynomolgus monkey repeated dose 
toxicity study. Given the lack of binding of vedolizumab to male reproductive tissue in monkey and 
human, and the intact male fertility observed in β7 integrin-knockout mice, it is not expected that 
vedolizumab will affect male fertility.

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. 

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

L-histidine
L-histidine monohydrochloride
L-arginine hydrochloride
Sucrose
Polysorbate 80

6.2 Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products.

6.3 Shelf life

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. 



17

Storage condition
Refrigerator (2°C-8°C) 20°C-25°C

Reconstituted solution in the vial 8 hours Do not hold1

Diluted solution in sodium chloride 9 mg/mL 
(0.9%) solution for injection

24 hours2,3 12 hours2

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.

6.4 Special precautions for storage

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.

6.5 Nature and contents of container

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.

6.6 Special precautions for disposal and other handling

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.



18

Each vial is for single use only. 

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

7. MARKETING AUTHORISATION HOLDER

Takeda Pharma A/S
Delta Park 45
2665 Vallensbaek Strand
Denmark

8. MARKETING AUTHORISATION NUMBER(S) 

EU/1/14/923/001

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 22 May 2014
Date of latest renewal: 12 December 2018

10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu



19

1. NAME OF THE MEDICINAL PRODUCT

Entyvio 108 mg solution for injection in pre-filled syringe
Entyvio 108 mg solution for injection in pre-filled pen 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Entyvio 108 mg solution for injection in pre-filled syringe

Each pre-filled syringe contains 108 mg of vedolizumab in 0.68 mL.

Entyvio 108 mg solution for injection in pre-filled pen

Each pre-filled pen contains 108 mg of vedolizumab in 0.68 mL.

Vedolizumab is a humanised IgG1 monoclonal antibody produced in Chinese hamster ovary (CHO) 
cells by recombinant DNA technology.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Solution for injection (injection).

Colourless to yellow solution.

4. CLINICAL PARTICULARS

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.

4.2 Posology and method of administration

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.

Posology

Ulcerative colitis and Crohn’s disease

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



20

2 weeks. The first subcutaneous dose should be administered in place of the next scheduled 
intravenous dose and every 2 weeks thereafter.
For the intravenous dose regimen, see section 4.2 of the Entyvio 300 mg powder for concentrate for 
solution for infusion SmPC.

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.

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

Retreatment and missed dose(s)
If treatment with subcutaneous vedolizumab is interrupted or if a patient misses a scheduled dose(s) of 
subcutaneous vedolizumab, patient should be advised to inject the next subcutaneous dose as soon as 
possible and then every 2 weeks thereafter. The treatment interruption period in clinical trials extended 
up to 46 weeks with no evident increase in adverse reactions or injection site reactions during 
re-initiation of treatment with subcutaneous vedolizumab (see section 4.8).

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 solution for injection (in a pre-filled syringe or a pre-filled pen) is for subcutaneous injection 
only.

After proper training on correct subcutaneous injection technique, a patient or caregiver may inject 
with subcutaneous vedolizumab if their physician determines it is appropriate. Comprehensive 
instructions for administration using the pre-filled syringe or the pre-filled pen are given in the 
respective package leaflet.

For further instructions on preparation and special precautions for handling, see section 6.6.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Active severe infections such as tuberculosis (TB), sepsis, cytomegalovirus, listeriosis, and 
opportunistic infections such as Progressive Multifocal Leukoencephalopathy (PML) (see section 4.4).



21

4.4 Special warnings and precautions for use

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.

Hypersensitivity reactions

In clinical studies, hypersensitivity reactions have been reported, with the majority being mild to 
moderate in severity (see section 4.8).

If an anaphylactic reaction, or other severe reaction occurs, administration of vedolizumab must be 
discontinued immediately and appropriate treatment initiated (see section 4.3).

Infections

Vedolizumab is a gut-selective integrin antagonist with no identified systemic immunosuppressive 
activity (see section 5.1).

Physicians should be aware of the potential increased risk of opportunistic infections or infections for 
which the gut is a defensive barrier (see section 4.8). Treatment is not to be initiated in patients with 
active, severe infections until the infections are controlled, and physicians should consider withholding 
treatment in patients who develop a severe infection while on chronic treatment with vedolizumab. 
Caution should be exercised when considering the use of vedolizumab in patients with a controlled 
chronic severe infection or a history of recurring severe infections. Patients should be monitored 
closely for infections before, during and after treatment.
Vedolizumab is contraindicated in patients with active tuberculosis (see section 4.3). Before starting 
treatment with vedolizumab, patients must be screened for tuberculosis according to the local practice. 
If latent tuberculosis is diagnosed, appropriate treatment must be started with anti-tuberculosis 
treatment in accordance with local recommendations, before beginning vedolizumab. In patients 
diagnosed with TB whilst receiving vedolizumab therapy, then vedolizumab therapy should be 
discontinued until the TB infection has been resolved.

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 specific to the gut. 
Although no systemic immunosuppressive effect was noted in healthy subjects the effects on systemic 
immune system function in patients with inflammatory bowel disease is not known.

Healthcare professionals should monitor patients on vedolizumab for any new onset or worsening of 
neurological signs and symptoms as outlined in physician education materials, and consider 
neurological referral if they occur. If PML is suspected, treatment with vedolizumab must be withheld; 
if confirmed, treatment must be permanently discontinued.

Malignancies

The risk of malignancy is increased in patients with ulcerative colitis and Crohn’s disease. 
Immunomodulatory medicinal products may increase the risk of malignancy (see section 4.8).

Prior and concurrent use of biological products

No vedolizumab clinical trial data are available for patients previously treated with natalizumab or 
rituximab. Caution should be exercised when considering the use of vedolizumab in these patients.



22

Patients previously exposed to natalizumab should normally wait a minimum of 12 weeks prior to 
initiating therapy with vedolizumab, unless otherwise indicated by the patient’s clinical condition.
No clinical trial data for concomitant use of vedolizumab with biologic immunosuppressants are 
available. Therefore, the use of vedolizumab in such patients is not recommended.

Live and oral vaccines

In a placebo-controlled study of healthy volunteers, a single 750 mg dose of vedolizumab did not 
lower rates of protective immunity to hepatitis B virus in subjects who were vaccinated 
intramuscularly with 3 doses of recombinant hepatitis B surface antigen. Vedolizumab-exposed 
subjects had lower seroconversion rates after receiving a killed, oral cholera vaccine. The impact on
other oral and nasal vaccines is unknown. It is recommended that all patients be brought up to date 
with all immunisations in agreement with current immunisation guidelines prior to initiating 
vedolizumab therapy. Patients receiving vedolizumab treatment may continue to receive non-live 
vaccines. There are no data on the secondary transmission of infection by live vaccines in patients 
receiving vedolizumab. Administration of the influenza vaccine should be by injection in line with 
routine clinical practice. Other live vaccines may be administered concurrently with vedolizumab only 
if the benefits clearly outweigh the risks.

Induction of remission in Crohn’s disease

Induction of remission in Crohn’s disease may take up to 14 weeks in some patients. The reasons for 
this are not fully known and are possibly related to the mechanism of action. This should be taken into 
consideration, particularly in patients with severe active disease at baseline not previously treated with 
TNFα antagonists (see also section 5.1.).

Exploratory subgroup analyses from the clinical trials in Crohn’s disease suggested that vedolizumab 
administered in patients without concomitant corticosteroid treatment may be less effective for 
induction of remission in Crohn’s disease than in those patients already receiving concomitant 
corticosteroids (regardless of use of concomitant immunomodulators; see section 5.1).

Sodium content

This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially 
‘sodium-free’.

4.5 Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed.

Vedolizumab has been studied in adult ulcerative colitis and Crohn’s disease patients with 
concomitant administration of corticosteroids, immunomodulators (azathioprine, 6-mercaptopurine, 
and methotrexate), and aminosalicylates. Population pharmacokinetic analyses suggest that 
co-administration of such agents did not have a clinically meaningful effect on vedolizumab 
pharmacokinetics. The effect of vedolizumab on the pharmacokinetics of commonly co-administered 
medicinal compounds has not been studied.

Vaccinations

Live vaccines, in particular live oral vaccines, should be used with caution concurrently with 
vedolizumab (see section 4.4).



23

4.6 Fertility, pregnancy and lactation

Women of childbearing potential

Women of childbearing potential should use adequate contraception to prevent pregnancy and to 
continue its use for at least 18 weeks after the last treatment.

Pregnancy

There are limited amount of data from the use of vedolizumab in pregnant women.

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity 
(see section 5.3).

As a precautionary measure, it is preferable to avoid the use of vedolizumab during pregnancy unless 
the benefits clearly outweigh any potential risk to both the mother and foetus.

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.

Fertility

There are no data on the effects of vedolizumab on human fertility. Effects on male and female 
fertility have not been formally evaluated in animal studies (see section 5.3).

4.7 Effects on ability to drive and use machines

Vedolizumab has minor influence on the ability to drive and use machines, as dizziness has been 
reported in a small number of patients.

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.

No clinically relevant differences in the overall safety profile and adverse reactions were observed in 
patients who received subcutaneous vedolizumab compared to the safety profile observed in clinical 
studies with intravenous vedolizumab with the exception of injection site reactions (with subcutaneous 
administration). 

Tabulated list of adverse reactions

The following listing of adverse reactions is based on clinical trial and post marketing experience and 
is displayed by system organ class. Within the system organ classes, adverse reactions are listed under 
headings of the following frequency categories: very common (≥ 1/10), common (≥ 1/100 to < 1/10), 
uncommon (≥ 1/1,000 to < 1/100) and very rare (< 1/10,000). Within each frequency grouping, 
adverse reactions are presented in order of decreasing seriousness.



24

Table 1. Adverse reactions

System organ class Frequency* Adverse reaction(s)

Infections and infestations Very common Nasopharyngitis
Common Bronchitis, 

Gastroenteritis, 
Upper respiratory tract infection,
Influenza, 
Sinusitis, 
Pharyngitis

Uncommon Respiratory tract infection, 
Vulvovaginal candidiasis, 
Oral candidiasis, 
Herpes zoster

Very rare Pneumonia
Immune system disorders Very rare Anaphylactic reaction, 

Anaphylactic shock
Nervous system disorders Very common Headache

Common Paraesthesia
Eye disorders Very rare Blurred vision
Vascular disorders Common Hypertension
Respiratory, thoracic and 
mediastinal disorders

Common Oropharyngeal pain, 
Nasal congestion, 
Cough

Gastrointestinal disorders Common Anal Abscess, 
Anal fissure, 
Nausea, 
Dyspepsia, 
Constipation, 
Abdominal distension, 
Flatulence, 
Haemorrhoids

Skin and subcutaneous tissue 
disorders

Common Rash, 
Pruritus, 
Eczema, 
Erythema, 
Night sweats, 
Acne

Uncommon Folliculitis
Musculoskeletal and connective 
tissue disorders

Very common Arthralgia
Common Muscle spasms, 

Back pain, 
Muscular weakness, 
Fatigue, 
Pain in the extremity

General disorders and 
administration site conditions

Common Pyrexia
Injection site reactions#

Uncommon Infusion site reaction (including: Infusion site 
pain and Infusion site irritation), 
Infusion related reaction, 
Chills, 
Feeling cold

*Frequency is based on clinical trial data with intravenous administration except where noted.
#Subcutaneous administration only.



25

Description of selected adverse reactions

Injection site reactions

Injection site reactions (including pain, oedema, erythema or pruritus) were reported in 5.1% of 
patients receiving subcutaneous vedolizumab (pooled safety analysis). None resulted in 
discontinuation of study treatment or changes to the dosing schedule. The majority of injection site 
reactions resolved within 1-4 days. There were no reports of anaphylaxis following subcutaneous 
vedolizumab administration.

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 subcutaneous vedolizumab, the rate of infections was 0.26 per patient year in 
vedolizumab-treated patients. The most frequent infections were nasopharyngitis, upper respiratory 
tract infection, bronchitis and influenza.

In clinical studies with subcutaneous vedolizumab, the rate of serious infections was 0.02 per patient 
year in subcutaneous vedolizumab-treated patients.

In clinical studies with intravenous and subcutaneous 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 and subcutaneous 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.

Malignancy

Overall, results from the clinical program to date do not suggest an increased risk for malignancy with 
vedolizumab treatment; however, the number of malignancies was small and long-term exposure was 
limited. Long-term safety evaluations are ongoing.

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 the national reporting system 
listed in Appendix V.



26

4.9 Overdose

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.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: immunosuppressants, selective immunosuppressants, ATC code: 
L04AA33.

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.

In healthy subjects, ulcerative colitis patients, or Crohn’s disease patients, vedolizumab does not 
elevate neutrophils, basophils, eosinophils, B-helper and cytotoxic T lymphocytes, total memory T 
helper lymphocytes, monocytes or natural killer cells, in the peripheral blood with no leukocytosis 
observed.

Vedolizumab did not affect immune surveillance and inflammation of the central nervous system in 
Experimental Autoimmune Encephalomyelitis in non-human primates, a model of multiple sclerosis. 
Vedolizumab did not affect immune responses to antigenic challenge in the dermis and muscle (see 
section 4.4). In contrast, vedolizumab inhibited an immune response to a gastrointestinal antigenic 
challenge in healthy human volunteers (see section 4.4).

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. 

Pharmacodynamic effects

In clinical trials with intravenous vedolizumab at doses ranging from 2 to 10 mg/kg, > 95% saturation 
of α4β7 receptors on subsets of circulating lymphocytes involved in gut immune surveillance was 
observed in patients.



27

Vedolizumab did not affect CD4+ and CD8+ trafficking into the CNS as evidenced by the lack of 
change in the ratio of CD4+/CD8+ in cerebrospinal fluid pre- and post-vedolizumab administration in 
healthy human volunteers. These data are consistent with investigations in nonhuman primates which 
did not detect effects on immune surveillance of the CNS.

Clinical efficacy and safety

Ulcerative colitis - vedolizumab for intravenous administration

The efficacy and safety of intravenous vedolizumab for the treatment of adult patients with moderately 
to severely active ulcerative colitis (Mayo score 6 to 12 with endoscopic sub score ≥ 2) was 
demonstrated in a randomised, double-blind, placebo-controlled study evaluating efficacy endpoints at 
week 6 and week 52 (GEMINI 1). Enrolled patients had failed at least 1 conventional therapy, 
including corticosteroids, immunomodulators, and/or the TNFα antagonist infliximab (including 
primary non-responders). Concomitant stable doses of oral aminosalicylates, corticosteroids and/or 
immunomodulators were permitted. 

For the evaluation of the week 6 endpoints, 374 patients were randomised in a double-blind fashion 
(3:2) to receive vedolizumab 300 mg or placebo at week 0 and week 2. Primary endpoint was the 
proportion of patients with clinical response (defined as reduction in complete Mayo score of 
 3 points and  30% from baseline with an accompanying decrease in rectal bleeding subscore of 
 1 point or absolute rectal bleeding subscore of ≤ 1 point) at week 6. Table 2 shows the results from 
the primary and secondary endpoints evaluated.

Table 2. Week 6 efficacy results of GEMINI 1

Endpoint
Placebo
n = 149

Vedolizumab
n = 225

Clinical response 26% 47%*
Clinical remission§ 5% 17%†

Mucosal healing¶ 25% 41%‡

*p < 0.0001
†p ≤ 0.001
‡p < 0.05
§Clinical remission: Complete Mayo score of ≤ 2 points and no individual subscore > 1 point
¶Mucosal healing: Mayo endoscopic subscore of ≤ 1 point

The beneficial effect of vedolizumab on clinical response, remission and mucosal healing was 
observed both in patients with no prior TNF antagonist exposure as well as in those who had failed 
prior TNF antagonist therapy.

In GEMINI 1, 2 cohorts of patients received vedolizumab at week 0 and week 2: cohort 1 patients 
were randomised to receive either vedolizumab 300 mg or placebo in a double-blind fashion, and 
cohort 2 patients were treated with open-label vedolizumab 300 mg. To evaluate efficacy at week 52, 
373 patients from cohort 1 and 2 who were treated with vedolizumab and had achieved clinical 
response at week 6 were randomised in a double-blind fashion (1:1:1) to 1 of the following regimens 
beginning at week 6: vedolizumab 300 mg every 8 weeks, vedolizumab 300 mg every 4 weeks, or 
placebo every 4 weeks. Beginning at week 6, patients who had achieved clinical response and were 
receiving corticosteroids were required to begin a corticosteroid-tapering regimen. Primary endpoint 
was the proportion of patients in clinical remission at week 52. Table 3 shows the results from the 
primary and secondary endpoints evaluated.



28

Table 3. Week 52 efficacy results of GEMINI 1

Endpoint
Placebo
n = 126*

Vedolizumab IV
every 8 weeks

n = 122

Vedolizumab IV
every 4 weeks

n = 125

Clinical remission 16% 42%† 45%†

Durable clinical response¶ 24% 57%† 52%†

Mucosal healing 20% 52%† 56%†

Durable clinical remission# 9% 20%§ 24%‡

Corticosteroid-free clinical remission♠ 14% 31%§ 45%†

*The placebo group includes those subjects who received vedolizumab at week 0 and week 2, and were 
randomised to receive placebo from week 6 through week 52.

†p < 0.0001
‡p < 0.001
§p < 0.05
¶Durable clinical response: Clinical response at weeks 6 and 52
#Durable clinical remission: Clinical remission at weeks 6 and 52
♠Corticosteroid-free clinical remission: Patients using oral corticosteroids at baseline who had 
discontinued corticosteroids beginning at week 6 and were in clinical remission at week 52. Patient 
numbers were n = 72 for placebo, n = 70 for vedolizumab every 8 weeks, and n = 73 for vedolizumab 
every 4 weeks

Exploratory analyses provide additional data on key subpopulations studied. Approximately one-third 
of patients had failed prior TNF antagonist therapy. Among these patients, 37% receiving 
vedolizumab every 8 weeks, 35% receiving vedolizumab every 4 weeks, and 5% receiving placebo 
achieved clinical remission at week 52. Improvements in durable clinical response (47%, 43%, 16%), 
mucosal healing (42%, 48%, 8%), durable clinical remission (21%, 13%, 3%) and corticosteroid-free 
clinical remission (23%, 32%, 4%) were seen in the prior TNFα antagonist failure population treated 
with vedolizumab every 8 weeks, vedolizumab every 4 weeks and placebo, respectively.

Patients who failed to demonstrate response at week 6 remained in the study and received 
vedolizumab every 4 weeks. Clinical response using partial Mayo scores was achieved at week 10 and 
week 14 by greater proportions of vedolizumab patients (32% and 39%, respectively) compared with 
placebo patients (15% and 21%, respectively).

Patients who lost response to vedolizumab when treated every 8 weeks were allowed to enter an 
open-label extension study and receive vedolizumab every 4 weeks. In these patients, clinical 
remission was achieved in 25% of patients at week 28 and week 52.

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 4 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 196 weeks.

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 generic 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).



29

Ulcerative colitis - vedolizumab for subcutaneous administration

The efficacy and safety of subcutaneous vedolizumab for the treatment of adult patients with 
moderately to severely active ulcerative colitis (Mayo score 6 to 12 with endoscopic sub score ≥ 2) 
was demonstrated in a randomised, double-blind, placebo-controlled study evaluating efficacy 
endpoints at week 52 (VISIBLE 1). In VISIBLE 1, enrolled patients (n = 383) had failed at least 
1 conventional therapy, including corticosteroids, immunomodulators, and/or TNFα antagonists 
(including primary non responders). Concomitant stable doses of oral aminosalicylates, corticosteroids 
and/or immunomodulators were permitted.

Patients who achieved clinical response to open-label treatment with intravenous vedolizumab at 
week 6 were eligible to be randomised For the evaluation of the week 52 endpoints, 216 (56.4%) 
patients were randomised and treated in a double-blind fashion (2:1:1) to 1 of the following regimens: 
subcutaneous vedolizumab 108 mg every 2 weeks, intravenous vedolizumab 300 mg every 8 weeks, or 
placebo.
The baseline demographics were similar for patients in vedolizumab and placebo groups. The baseline 
Mayo score was between 9 to 12 (severe ulcerative colitis) in about 62% and 6 to 8 (moderate 
ulcerative colitis) in about 38% of the overall study population.

Primary study endpoint clinical remission was defined as a complete Mayo score of ≤ 2 points and no 
individual subscore > 1 point at 52 weeks in patients who had achieved a clinical response at week 6 
of intravenous vedolizumab induction treatment. Clinical response was defined as a reduction in 
complete Mayo score of ≥ 3 points and ≥ 30% from baseline with an accompanying decrease in rectal 
bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 2 points and no individual 
subscore >1 point.

Table 4 shows the evaluated results from the primary and secondary endpoints.

Table 4. Week 52 efficacy results of VISIBLE I

Endpointa
Placebob

n = 56

Vedolizumab 
SC 108 mg

every 2 weeks
n = 106

Vedolizumab 
IV

300 mg
every 8 weeks

n = 54

Estimatec of 
treatment 
difference 
(95% CI) 

Vedolizumab SC 
vs. Placebo

P-valuec

Clinical remissiond 14.3% 46.2% 42.6% 32.3 (19.7, 45.0) p < 0.001

Mucosal healinge 21.4% 56.6% 53.7% 35.7 (22.1, 49.3) p < 0.001

Durable clinical 
responsef

28.6% 64.2% 72.2% 36.1 (21.2, 50.9) p < 0.001

Durable clinical 
remissiong

5.4% 15.1% 16.7% 9.7 (-6.6, 25.7)
p = 0.076

(NS)

Corticosteroid-free 
remissionh

8.3% 28.9% 28.6% 20.6 (-4.5, 43.7)
p = 0.067

(NS)
aEndpoints are presented in the order that fixed-sequence testing was performed for control of Type 1 error at 5%
bThe placebo group includes those subjects who received intravenous vedolizumab at week 0 and week 2, and 
were randomised to receive placebo from week 6 through week 52.
cEstimate of treatment difference and the p-value for all endpoints is based on the Cochrane-Mantel-Haenszel 
method
dClinical remission: Complete Mayo score of ≤ 2 points and no individual subscore > 1 point at week 52
eMucosal healing: Mayo endoscopic subscore of ≤ 1 point
fDurable clinical response: Clinical response at weeks 6 and 52
gDurable clinical remission: Clinical remission at weeks 6 and 52
hCorticosteroid-free clinical remission: Patients using oral corticosteroids at baseline who had discontinued 
corticosteroids and were in clinical remission at week 52. Patient numbers using oral corticosteroids at baseline 
were n = 24 for placebo, n = 45 for subcutaneous vedolizumab and n = 21 for intravenous vedolizumab
NS = non significant (2-tailed p-value > 0.05)



30

The primary and secondary endpoints were analysed in subgroups of patients who had failed prior 
TNFα antagonist therapy (37%; n = 80) and patients who were naïve to previous TNFα antagonist 
therapy (63%; n = 136). Results of study patients treated with placebo and subcutaneous vedolizumab 
in these subgroups are presented in Table 5.

Table 5. VISIBLE 1 Study results at week 52 analysed by response to prior previous TNFα 
antagonist therapy

Treatment once every 2 weeks
Placebo Vedolizumab SC 108 mg

Failure prior TNFα antagonist therapy n = 19 n = 39

Clinical remission 5.3% 33.3%

Mucosal healing 5.3% 46.2%

Durable clinical response 15.8% 66.7%

Durable clinical remission 0% 2.6%

Corticosteroid free clinical remissiona 8.3% 27.3%

Naive TNFα antagonist therapy n = 37 n = 67

Clinical remission 18.9% 53.7%

Mucosal healing 29.7% 62.7%

Durable clinical response 35.1% 62.7%

Durable clinical remission 8.1% 22.4%

Corticosteroid free clinical remissionb 8.3% 30.4%
a Patients who had failed prior TNFα antagonist therapy and using oral corticosteroids at baseline were n = 12 for 
placebo and n = 22 for subcutaneous vedolizumab
b Patients who were naïve to prior TNFα antagonist therapy and using oral corticosteroids at baseline were 
n = 12 for placebo and n = 23 for subcutaneous vedolizumab

Health related quality of life (HRQOL) was assessed by Inflammatory Bowel Disease Questionnaire 
(IBDQ), a disease specific instrument, and EuroQol-5 Dimension (EQ-5D, including EQ 5D VAS), 
which is a generic measure. Work productivity was assessed by work productivity and activity 
impairment questionnaire (WPAI-UC). Patients treated with subcutaneous vedolizumab maintained 
improvements in IBDQ, EQ-5D and WPAI-UC scores at week 52 to a greater extent than patients who 
received placebo.

Patients who completed VISIBLE 1 were eligible to enrol in an ongoing, open-label extension study to 
evaluate long-term safety and efficacy of subcutaneous vedolizumab treatment in patients with 
ulcerative colitis or Crohn’s disease.

Patients in VISIBLE 1 who did not achieve clinical response at week 6 received a third dose of
vedolizumab 300 mg by intravenous infusion at week 6. Of patients who received a third dose of 
vedolizumab 300 mg by intravenous infusion at week 6, 79.7% (114/143) achieved a clinical response 
at week 14. Patients who achieved a clinical response at week 14 were eligible to enter the open-label 
extension study and receive subcutaneous vedolizumab 108 mg every 2 weeks. Clinical remission as 
assessed by the partial Mayo score (a standardised measure that includes 3 of the 4 scored subscales of 
the complete Mayo score: stool frequency, rectal bleeding, and physician global assessment) was 
achieved by 39.2% (40/102) of these patients at week 40 after transitioning to subcutaneous 
vedolizumab in the open-label extension study.

Patients randomised to intravenous vedolizumab treatment group in VISIBLE 1 received vedolizumab 
300 mg intravenously at weeks 0, 2, and 6 and every 8 weeks thereafter until week 52. At week 52, 
these patients entered the open-label extension study and received subcutaneous vedolizumab 108 mg 
every 2 weeks. Clinical remission as assessed by the partial Mayo score was maintained in 77% of 



31

patients at 24 weeks after transitioning to subcutaneous vedolizumab in the open-label extension 
study.

Crohn’s disease – vedolizumab for intravenous administration 

The efficacy and safety of intravenous vedolizumab for the treatment of adult patients with moderately 
to severely active Crohn’s disease (Crohn’s Disease Activity Index [CDAI] score of 220 to 450) were 
evaluated in 2 studies (GEMINI 2 and 3). Enrolled patients have failed at least 1 conventional therapy, 
including corticosteroids, immunomodulators, and/or TNFα antagonists (including primary 
non-responders). Concomitant stable doses of oral corticosteroids, immunomodulators, and antibiotics 
were permitted.

The GEMINI 2 Study was a randomised, double-blind, placebo-controlled study evaluating efficacy 
endpoints at week 6 and week 52. Patients (n = 368) were randomised in a double-blind fashion (3:2) 
to receive 2 doses of vedolizumab 300 mg or placebo at week 0 and week 2. The 2 primary endpoints 
were the proportion of patients in clinical remission (defined as CDAI score ≤ 150 points) at week 6 
and the proportion of patients with enhanced clinical response (defined as a ≥ 100-point decrease in 
CDAI score from baseline) at week 6 (see Table 6).

GEMINI 2 contained 2 cohorts of patients that received vedolizumab at weeks 0 and 2: 
cohort 1 patients were randomised to receive either vedolizumab 300 mg or placebo in a double-blind 
fashion, and cohort 2 patients were treated with open-label vedolizumab 300 mg. To evaluate efficacy 
at week 52, 461 patients from cohorts 1 and 2, who were treated with vedolizumab and had achieved 
clinical response (defined as a ≥ 70-point decrease in CDAI score from baseline) at week 6, were 
randomised in a double-blind fashion (1:1:1) to 1 of the following regimens beginning at week 6: 
vedolizumab 300 mg every 8 weeks, vedolizumab 300 mg every 4 weeks, or placebo every 4 weeks. 
Patients showing clinical response at week 6 were required to begin corticosteroid tapering. Primary 
endpoint was the proportion of patients in clinical remission at week 52 (see Table 7).

The GEMINI 3 Study was a second randomised, double-blind, placebo-controlled study that evaluated 
efficacy at week 6 and week 10 in the subgroup of patients defined as having failed at least 
1 conventional therapy and failed TNF antagonist therapy (including primary non-responders) as 
well as the overall population, which also included patients who failed at least 1 conventional therapy 
and were naïve to TNF antagonist therapy. Patients (n = 416), which included approximately 75% 
TNF antagonist failures patients, were randomised in a double-blind fashion (1:1) to receive either 
vedolizumab 300 mg or placebo at weeks 0, 2, and 6. The primary endpoint was the proportion of 
patients in clinical remission at week 6 in the TNF antagonist failure subpopulation. As noted in 
Table 6, although the primary endpoint was not met, exploratory analyses show that clinically 
meaningful results were observed.



32

Table 6. Efficacy results for GEMINI 2 and 3 studies at week 6 and week 10
Study

Endpoint Placebo Vedolizumab IV

GEMINI 2 Study

Clinical remission, week 6

Overall 7% (n = 148) 15%* (n = 220)

TNFα Antagonist(s) Failure 4% (n = 70) 11% (n = 105)

TNFα Antagonist(s) Naïve 9% (n = 76) 17% (n = 109)

Enhanced clinical response, week 6

Overall 26% (n = 148) 31%† (n = 220)

TNFα Antagonist(s) Failure 23% (n = 70) 24% (n = 105)

TNFα Antagonist(s) Naïve 30% (n = 76) 42% (n = 109)

Serum CRP change from baseline to 
week 6, median (mcg/mL)

Overall‡ -0.5 (n = 147) -0.9 (n = 220)

GEMINI 3 Study

Clinical remission, week 6

Overall‡ 12% (n = 207) 19% (n = 209)

TNFα Antagonist(s) Failure¶ 12% (n = 157) 15%§ (n = 158)

TNFα Antagonist(s) Naïve 12% (n = 50) 31% (n = 51)

Clinical remission, week 10

Overall 13% (n = 207) 29% (n = 209)

TNFα Antagonist(s) Failure¶,‡ 12% (n = 157) 27% (n = 158)

TNFα Antagonist(s) Naïve 16% (n = 50) 35% (n = 51)

Sustained clinical remission#,¶

Overall 8% (n = 207) 15% (n = 209)

TNFα Antagonist(s) Failure¶,‡ 8% (n = 157) 12% (n = 158)

TNFα Antagonist(s) Naïve 8% (n = 50) 26% (n = 51)

Enhanced clinical response, week 6

Overall^ 23% (n = 207) 39% (n = 209)

TNFα Antagonist(s) Failure‡ 22% (n = 157) 39% (n = 158)

TNFα Antagonist(s) Naïve^ 24% (n = 50) 39% (n = 51)

*p < 0.05
†not statistically significant
‡secondary endpoint to be viewed as exploratory by pre-specified statistical testing procedure
§not statistically significant, the other endpoints were therefore not tested statistically
¶n = 157 for placebo and n = 158 for vedolizumab
#
Sustained clinical remission: clinical remission at weeks 6 and 10

^Exploratory Endpoint



33

Table 7. Efficacy results for GEMINI 2 at week 52

Placebo
n = 153*

Vedolizumab IV
every 8 weeks

n = 154

Vedolizumab IV
every 4 weeks

n = 154

Clinical remission 22% 39%† 36%‡

Enhanced clinical response 30% 44%‡ 45%‡

Corticosteroid-free clinical remission§ 16% 32%‡ 29%‡

Durable clinical remission¶ 14% 21% 16%

*The placebo group includes those subjects who received vedolizumab at week 0 and week 2, and were 
randomised to receive placebo from week 6 through week 52.

†p < 0.001
‡p < 0.05
§Corticosteroid-free clinical remission: Patients using oral corticosteroids at baseline who had discontinued 
corticosteroids beginning at week 6 and were in clinical remission at week 52. Patient numbers were n = 82 
for placebo, n = 82 for vedolizumab every 8 weeks, and n = 80 for vedolizumab every 4 weeks 

¶Durable clinical remission: Clinical remission at ≥ 80% of study visits including final visit (week 52)

Exploratory analyses examined the effects of concomitant corticosteroids and immunomodulators on 
induction of remission with vedolizumab. Combination treatment, most notably with concomitant 
corticosteroids, appeared to be more effective in inducing remission in Crohn’s disease than 
vedolizumab alone or with concomitant immunomodulators, which showed a smaller difference from 
placebo in the rate of remission. Clinical remission rate in GEMINI 2 at week 6 was 10% (difference 
from placebo 2%, 95% CI: -6, 10) when administered without corticosteroids compared to 20% 
(difference from placebo 14%, 95% CI: -1, 29) when administered with concomitant corticosteroids. 
In GEMINI 3 at week 6 and 10 the respective clinical remission rates were 18% (difference from 
placebo 3%, 95% CI: -7, 13) and 22% (difference from placebo 8%, 95% CI: -3, 19) when 
administered without corticosteroids compared to 20% (difference from placebo 11%, 95% CI: 2, 20) 
and 35% (difference from placebo 23%, 95% CI: 12, 33) respectively when administered with 
concomitant corticosteroids. These effects were seen whether or not immunomodulators were also 
concomitantly administered.

Exploratory analyses provide additional data on key subpopulations studied. In GEMINI 2, 
approximately half of patients had previously failed TNFα antagonist therapy. Among these patients, 
28% receiving vedolizumab every 8 weeks, 27% receiving vedolizumab every 4 weeks, and 13% 
receiving placebo achieved clinical remission at week 52. Enhanced clinical response was achieved in 
29%, 38%, 21%, respectively, and corticosteriod-free clinical remission was achieved in 24%, 16%, 
0%, respectively.

Patients who failed to demonstrate response at week 6 in GEMINI 2 were retained in the study and 
received vedolizumab every 4 weeks. Enhanced clinical response was observed at week 10 and 
week 14 for greater proportions of vedolizumab patients 16% and 22%, respectively, compared with 
placebo patients 7% and 12%, respectively. There was no clinically meaningful difference in clinical 
remission between treatment groups at these time points. Analyses of week 52 clinical remission in 
patients who were non-responders at week 6 but achieved response at week 10 or week 14 indicate 
that non-responder CD patients may benefit from a dose of vedolizumab at week 10.

Patients who lost response to vedolizumab when treated every 8 weeks in GEMINI 2 were allowed to 
enter an open-label extension study and received vedolizumab every 4 weeks. In these patients, 
clinical remission was achieved in 23% of patients at week 28 and 32% of patients at week 52.

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 4 weeks. In these patients, clinical remission was 
achieved in 46% of patients by 28 weeks and 41% of patients by 52 weeks.



34

In this open-label extension study, clinical remission and clinical response were observed in patients 
for up to 196 weeks.

Exploratory analysis showed clinically meaningful improvements were observed for the vedolizumab 
every 4 weeks and every 8 weeks groups in GEMINI 2 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.

Crohn’s disease - vedolizumab for subcutaneous administration

The efficacy and safety of subcutaneous vedolizumab for the treatment of adult patients with 
moderately to severely active Crohn’s disease (CDAI score of 220 to 450) was demonstrated in a 
randomised, double-blind, placebo-controlled study evaluating efficacy endpoints at 
week 52 (VISIBLE 2). In VISIBLE 2, enrolled patients (n = 644) had inadequate response to, loss of 
response to, or intolerance to one conventional therapy, including corticosteroids, immunomodulators, 
and/or TNFα antagonists (including primary non-responders). Concomitant stable doses of oral 
aminosalicylates, corticosteroids and/or immunomodulators were permitted.

Patients who achieved clinical response to open-label treatment with intravenous vedolizumab at 
week 6 were eligible to be randomised. For the evaluation of the week 52 endpoints, 409 (64%) 
patients were randomised and treated in a double-blind fashion (2:1) to receive subcutaneous 
vedolizumab 108 mg (n = 275) or subcutaneous placebo (n = 134) every 2 weeks.

The baseline demographics were similar for patients in vedolizumab and placebo groups. The baseline 
CDAI was > 330 (severe Crohn’s disease) in about 41% and ≤ 330 (moderate Crohn’s disease) in 
about 59% of the overall study population.

Beginning at week 6, patients who had achieved clinical response (defined as a ≥ 70-point decrease in 
the CDAI score from baseline) and were receiving corticosteroids were required to begin a 
corticosteroid tapering regimen. Primary endpoint was the proportion of patients with clinical 
remission (CDAI score ≤ 150) at week 52. The secondary endpoints were the proportion of patients 
with enhanced clinical response ( ≥ 100 point decrease in CDAI score from baseline) at week 52, the 
proportion of patients with corticosteroid-free remission (patients using oral corticosteroids at baseline 
who had discontinued corticosteroids and were in clinical remission) at week 52, and the proportion of 
TNFα antagonist naïve patients who achieved clinical remission (CDAI score ≤ 150) at week 52.

Table 8 shows the evaluated results from the primary and secondary endpoints.



35

Table 8. Week 52 efficacy results of VISIBLE 2

Endpoint*
Placebo†

n = 134

Vedolizumab 
SC 108 mg

every 2 weeks
n = 275

Estimate‡ of 
treatment difference 

(95% CI) 
Vedolizumab SC vs. 

Placebo

P-value‡

Clinical remission§ 34.3% 48.0% 13.7 (3.8, 23.7) p = 0.008

Enhanced clinical response# 44.8% 52.0% 7.3 (-3.0, 17.5)
p = 0.167

(NS)

Corticosteroid-free 
remission**

18.2% 45.3% 27.1 (11.9, 42.3) p = 0.002‡‡

Clinical remission in TNFα 
antagonist naïve patients††

42.9% 48.6% 4.3 (-11.6, 20.3) p = 0.591‡‡

*Endpoints are presented in the order that fixed-sequence testing was performed for control of Type 1 error at 
5%
†The placebo group includes those subjects who received intravenous vedolizumab at week 0 and week 2, and 
were randomised to receive placebo from week 6 through week 52.
‡Estimate of treatment difference and the p-value for all endpoints is based on the Cochrane-Mantel-Haenszel 
method
§Clinical remission: CDAI score ≤ 150, at week 52 
#Enhanced clinical response: ≥ 100-point decrease in CDAI score from baseline (week 0), at week 52
**Corticosteroid-free clinical remission: Patients using oral corticosteroids at baseline who had discontinued 
corticosteroids and were in clinical remission at week 52. Patient numbers using oral corticosteroids at 
baseline were n = 44 for placebo and n = 95 for subcutaneous vedolizumab. 
†† Clinical remission (CDAI score ≤ 150, at week 52) in TNFα antagonist naïve patients (n = 63 placebo; 
n = 107 subcutaneous vedolizumab
‡‡ nominal p-value
NS = non significant (2-tailed p-value > 0.05)

The primary and secondary endpoints were analysed in subgroups of patients who were naïve to prior 
TNFα antagonist therapy (42%; n = 170), patients who had failed prior TNFα antagonist therapy 
(51%; n = 210), and patients who had exposure to prior TNFα antagonist therapy but did not 
experience treatment failure (7%; n = 29). Results of study patients treated with placebo and 
subcutaneous vedolizumab in these subgroups are presented in Tables 9 and 10.

Table 9. Week 52 efficacy results in TNFα antagonist naïve patients in VISIBLE 2

Endpoint
Placebo
n = 63

Vedolizumab SC 108 mg
every 2 weeks

n = 107

Treatment difference 
(95% CI) 

Vedolizumab SC vs. 
Placebo

Clinical remission 42.9% 48.6% 4.3 (-11.6, 20.3)

Enhanced clinical response 47.6% 54.2% 4.4 (-11.6, 20.3)

Corticosteroid-free remission** 18.2% 41.0% 22.8 (-3.2, 46.8)
** Patients who were naïve to prior TNFα antagonist therapy and using oral corticosteroids at baseline were 
n = 22 for placebo and n = 39 for subcutaneous vedolizumab



36

Table 10. Week 52 efficacy results in patients who failed TNFα antagonist therapy in VISIBLE 2

Endpoint
Placebo
n = 59

Vedolizumab SC 108 mg
every 2 weeks

n = 151

Treatment difference 
(95% CI) 

Vedolizumab SC vs. 
Placebo

Clinical remission 28.8% 46.4% 17.6 (3.8, 31.4)

Enhanced clinical response 45.8% 49.0% 3.2 (-11.8, 18.2)

Corticosteroid-free remission** 15.0% 46.2% 31.2 (5.2, 54.5)
** Patients who had failed prior TNFα antagonist therapy and using oral corticosteroids at baseline were n = 20 
for placebo and n = 52 for subcutaneous vedolizumab

HRQOL was assessed by IBDQ, a disease specific instrument, and EQ-5D (including EQ-5D VAS), 
which is a generic measure. Work productivity was assessed by WPAI-CD. Patients treated with 
subcutaneous vedolizumab maintained improvements in IBDQ, EQ-5D and WPAI-CD scores at 
week 52 to a greater extent than patients who received placebo.
Patients who completed VISIBLE 2 were eligible to enrol in an ongoing, open-label extension study to 
evaluate long-term safety and efficacy of subcutaneous vedolizumab treatment in patients with 
ulcerative colitis or Crohn’s disease.

Paediatric population

The European Medicines Agency has deferred the obligation to submit the results of studies with 
vedolizumab in 1 or more subsets of the paediatric population in ulcerative colitis and Crohn’s disease 
(see section 4.2 for information on paediatric use).

5.2 Pharmacokinetic properties

The single and multiple dose pharmacokinetics of vedolizumab have been studied in healthy subjects 
and in patients with moderate to severely active ulcerative colitis or Crohn’s disease.

Absorption

In patients administered 300 mg intravenous vedolizumab as a 30 minute intravenous infusion on 
weeks 0 and 2, mean serum trough concentrations at week 6 were 27.9 mcg/mL (SD ± 15.51) in 
ulcerative colitis and 26.8 mcg/mL (SD ± 17.45) in Crohn’s disease. In studies with intravenous 
vedolizumab, starting at week 6, patients received 300 mg intravenous vedolizumab every 8 or 
4 weeks. In patients with ulcerative colitis, mean steady-state serum trough concentrations were 
11.2 mcg/mL (SD ± 7.24) and 38.3 mcg/mL (SD ± 24.43), respectively. In patients with Crohn's 
disease mean steady-state serum trough concentrations were 13.0 mcg/mL (SD ± 9.08) 
and 34.8 mcg/mL (SD ± 22.55), respectively.

In studies in patients with ulcerative colitis or Crohn’s disease receiving subcutaneous vedolizumab, 
starting at week 6, patients received 108 mg subcutaneous vedolizumab every 2 weeks. The mean 
steady state serum trough concentrations were 35.8 mcg/mL (SD ± 15.2) in patients with ulcerative 
colitis and 31.4 mcg/mL (SD ± 14.7) in patients with Crohn’s disease. The bioavailability of 
vedolizumab following single-dose subcutaneous administration of 108 mg relative to single-dose 
intravenous administration was approximately 75%. The median time to reach maximum serum 
concentration (tmax) was 7 days (range 3 to 14 days), and the mean maximum serum concentration 
(Cmax) was 15.4 mcg/mL (SD ± 3.2).

Distribution

Population pharmacokinetic analyses indicate that the distribution volume of vedolizumab is 
approximately 5 litres. The plasma protein binding of vedolizumab has not been evaluated. 
Vedolizumab is a therapeutic monoclonal antibody and is not expected to bind to plasma proteins.



37

Vedolizumab does not pass the blood brain barrier after intravenous administration. Vedolizumab 
450 mg administered intravenously was not detected in the cerebrospinal fluid of healthy subjects.

Elimination

Population pharmacokinetic analyses indicate that vedolizumab has a total body clearance of 
approximately 0.169 L/day and a serum half-life of 24 days. The exact elimination route of 
vedolizumab is not known. Population pharmacokinetic analyses suggest that while low albumin, 
higher body weight and prior treatment with anti-TNF drugs may increase vedolizumab clearance, the 
magnitude of their effects is not considered to be clinically relevant.

Linearity

Vedolizumab exhibited linear pharmacokinetics at serum concentrations greater than 1 mcg/mL.

Special populations

Age does not impact the vedolizumab clearance in ulcerative colitis and Crohn’s disease patients 
based on the population pharmacokinetic analyses. No formal studies have been conducted to examine 
the effects of either renal or hepatic impairment on the pharmacokinetics of vedolizumab.

5.3 Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction 
and development.

Long-term animal studies with vedolizumab to assess its carcinogenic potential have not been 
conducted because pharmacologically responsive models to monoclonal antibodies do not exist. In a 
pharmacologically responsive species (cynomolgus monkeys), there was no evidence of cellular 
hyperplasia or systemic immunomodulation that could potentially be associated with oncogenesis in 
13- and 26-week toxicology studies. Furthermore, no effects were found of vedolizumab on the 
proliferative rate or cytotoxicity of a human tumour cell line expressing the α4β7 integrin in vitro.

No specific fertility studies in animals have been performed with vedolizumab. No definitive 
conclusion can be drawn on the male reproductive organs in cynomolgus monkey repeated dose 
toxicity study. Given the lack of binding of vedolizumab to male reproductive tissue in monkey and 
human, and the intact male fertility observed in β7 integrin-knockout mice, it is not expected that 
vedolizumab will affect male fertility.

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.



38

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Citric acid monohydrate
Sodium citrate dihydrate
L-histidine
L-histidine monohydrochloride
L-arginine hydrochloride
Polysorbate 80
Water for injections

6.2 Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products.

6.3 Shelf life

24 months

6.4 Special precautions for storage

Store in a refrigerator (2 °C-8 °C). Keep the pre-filled syringe or pre-filled pen in the outer carton in 
order to protect from light.
Do not freeze.

If needed, the pre-filled syringe and pre-filled pen can be left out of the refrigerator in its original 
carton at room temperature (up to 25 °C) for up to 7 days. Do not use the pre-filled syringe or 
pre-filled pen if left out of the refrigerator for more than 7 days.

6.5 Nature and contents of container

Entyvio 108 mg solution for injection in pre-filled syringe

Solution for injection in a Type I glass 1 mL syringe with a fixed 27 gauge thin wall, 1.27 cm needle. 
The syringe has a rubber needle cover encased in a plastic shell and rubber stopper.
The subcutaneous vedolizumab pre-filled syringe is a single dose, disposable drug delivery system 
with manual injection operation. Each pre-filled syringe is equipped with a safety device that activates 
to extend and lock a guard over the needle once the injection is completed.

Packs of 1 pre-filled syringe, and multipacks of 2 (2 packs of 1) or 6 (6 packs of 1) pre-filled syringes. 

Entyvio 108 mg solution for injection in pre-filled pen

Solution for injection in a pre-filled pen in a Type I glass 1 mL syringe and a fixed 27 gauge thin wall, 
1.27 cm needle. The syringe has a rubber needle cover encased in a plastic shell and rubber stopper.
The subcutaneous vedolizumab pre-filled pen is a single dose, disposable drug delivery system with 
mechanical injection operation. Each pre-filled pen is equipped with an automated needle shield to 
extend and lock over the needle once the device is removed from the injection site.

Packs of 1 pre-filled pen, and multipacks of 2 (2 packs of 1) or 6 (6 packs of 1) pre-filled pens.

Not all pack sizes may be marketed.



39

6.6 Special precautions for disposal and other handling

Instructions for administration

After removing the pre-filled syringe or pre-filled pen from the refrigerator, wait 30 minutes before 
injecting to allow the solution to reach room temperature. 

Do not leave the pre-filled syringe or pre-filled pen in direct sunlight.

Do not freeze. Do not use if it has been frozen.

Inspect the solution visually for particulate matter and discoloration prior to administration. The 
solution should be colourless to yellow. Do not use pre-filled syringe or pre-filled pen with visible 
particulate matter or discoloration.

Each pre-filled syringe or pre-filled pen is for single use only.

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

7. MARKETING AUTHORISATION HOLDER

Takeda Pharma A/S
Delta Park 45
2665 Vallensbaek Strand
Denmark

8. MARKETING AUTHORISATION NUMBER(S)

Entyvio 108 mg solution for injection in pre-filled syringe

EU/1/14/923/002 1 pre-filled syringe
EU/1/14/923/003 Multipack: 2 (2 packs of 1) pre-filled syringes
EU/1/14/923/004 Multipack: 6 (6 packs of 1) pre-filled syringes

Entyvio 108 mg solution for injection in pre-filled pen

EU/1/14/923/005 1 pre-filled pen
EU/1/14/923/006 Multipack: 2 (2 packs of 1) pre-filled pens
EU/1/14/923/007 Multipack: 6 (6 packs of 1) pre-filled pens

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 22 May 2014
Date of latest renewal: 12 December 2018

10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu



40

ANNEX II

A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE 
SUBSTANCE AND MANUFACTURERS RESPONSIBLE 
FOR BATCH RELEASE

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 
AND USE

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO
THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT



41

A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 
MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturers of the biological active substance

AbbVie Bioresearch Center
100 Research Drive
Worcester, MA
01605-4314
USA

Abbvie Biotechnology, Ltd
Road #2 Km 59.2
PO Box 2191
Barceloneta
Puerto Rico 00617

Lonza Biologics, Inc.
101 International Drive
Portsmouth
NH 03801
USA

Name and address of the manufacturers responsible for batch release

Delpharm Novara S.r.l.
Via Crosa, 86
28065 Cerano (NO)
Italy

Takeda Austria GmbH
St. Peter-Straße 25
4020 Linz
Austria

The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch.

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2).

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION

 Periodic safety update reports (PSURs)

The requirements for submission of PSURs for this medicinal product are set out in the list of 
Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC
and any subsequent updates published on the European medicines web-portal.



42

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT

 Risk management plan (RMP)

The marketing authorisation holder (MAH) shall perform the required pharmacovigilance 
activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of the 
marketing authorisation and any agreed subsequent updates of the RMP.

An updated RMP should be submitted:
 At the request of the European Medicines Agency;
 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached.

If the dates for submission of a PSUR and the update of a RMP coincide, they can be submitted at the 
same time.

 Additional risk minimisation measures

The Marketing Authorisation Holder (MAH) shall ensure that, prior to launch, all physicians 
who are expected to prescribe/use Entyvio are provided with a physician pack containing the 
following:

 Summary of Product Characteristics and Package Leaflet
 Physician’s Educational Material 
 Patient alert card when treatment with vedolizumab is first initiated (with Entyvio 300 mg 

powder for concentrate for solution for infusion), 

The Physican’s Educational Material should contain the following key messages:

 Consider the patient’s full medical history, including any prior or concurrent biological 
medicine use

 There is no clinical trial experience with Entyvio in patients previously treated with 
natalizumab. Given the known risk of PML development in patients with previous natalizumab 
exposure, physicians should normally wait 12 weeks after the last natalizumab dose prior to 
initiating Entyvio treatment.

 Patients treated with Entyvio should be monitored for any new onset or worsening of 
neurological signs and symptoms such as those listed below:
o Progressive weakness on one side of the body or clumsiness of limbs
o Disturbance of vision
o Changes in thinking, memory, and orientation, leading to confusion and personality 

changes
 Any patients with new onset or worsening signs and symptoms suggestive of PML should be 

considered for neurological referral at a center equipped to diagnose PML.



43

ANNEX III

LABELLING AND PACKAGE LEAFLET



44

A. LABELLING



45

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARTON (300 mg)

1. NAME OF THE MEDICINAL PRODUCT

Entyvio 300 mg powder for concentrate for solution for infusion
vedolizumab

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each vial contains 300 mg of vedolizumab.
After reconstitution each mL contains 60 mg of vedolizumab.

3. LIST OF EXCIPIENTS

Excipients: Sucrose, L-histidine, L-histidine monohydrochloride, L-arginine hydrochloride,
polysorbate 80.

4. PHARMACEUTICAL FORM AND CONTENTS

Powder for concentrate for solution for infusion
1 vial 

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
For intravenous use after reconstitution and dilution.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Store in a refrigerator. Keep the vial in the outer carton in order to protect from light.



46

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Takeda Pharma A/S
Delta Park 45
2665 Vallensbaek Strand
Denmark

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/14/923/001

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Justification for not including Braille accepted.

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN



47

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

VIAL LABEL (300 mg)

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Entyvio 300 mg powder for concentrate for solution for infusion
vedolizumab 
For intravenous use after reconstitution and dilution.

2. METHOD OF ADMINISTRATION

For intravenous use after reconstitution and dilution.

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

300 mg

6. OTHER



48

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARTON (WITH BLUE BOX) – PRE-FILLED SYRINGE (108 mg)
(EXCLUDING MULTIPACKS)

1. NAME OF THE MEDICINAL PRODUCT

Entyvio 108 mg solution for injection in pre-filled syringe
vedolizumab

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each pre-filled syringe contains 108 mg of vedolizumab.

3. LIST OF EXCIPIENTS

Excipients: citric acid monohydrate, sodium citrate dihydrate, L-histidine, L-histidine 
monohydrochloride, L-arginine hydrochloride, polysorbate 80, water for injections. See the package 
leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

Solution for injection
1 pre-filled syringe

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Subcutaneous use
For single use only.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Store in a refrigerator.



49

Do not freeze.
Keep the pre-filled syringe in the outer carton in order to protect from light.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Takeda Pharma A/S
Delta Park 45
2665 Vallensbaek Strand
Denmark

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/14/923/002

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Entyvio 108 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN



50

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER CARTON FOR MULTIPACK (WITH BLUE BOX) (108 mg)
(2x1 AND 6x1 PRE-FILLED SYRINGES)

1. NAME OF THE MEDICINAL PRODUCT

Entyvio 108 mg solution for injection in pre-filled syringe
vedolizumab

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each pre-filled syringe contains 108 mg of vedolizumab.

3. LIST OF EXCIPIENTS

Excipients: citric acid monohydrate, sodium citrate dihydrate, L-histidine, L-histidine 
monohydrochloride, L-arginine hydrochloride, polysorbate 80, water for injections. See the package 
leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

Solution for injection

Multipack: 2 (2 packs of 1) pre-filled syringes
Multipack: 6 (6 packs of 1) pre-filled syringes

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Subcutaneous use
For single use only.
Read the package leaflet before use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP



51

9. SPECIAL STORAGE CONDITIONS

Store in a refrigerator.
Do not freeze.
Keep the pre-filled syringe in the outer carton in order to protect from light.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Takeda Pharma A/S
Delta Park 45
2665 Vallensbaek Strand
Denmark

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/14/923/003 (2x1 pre-filled syringes)
EU/1/14/923/004 (6x1 pre-filled syringes)

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Entyvio 108 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN



52

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

INTERMEDIATE CARTON OF MULTIPACK (WITHOUT BLUE BOX) – PRE-FILLED 
SYRINGES (108 mg)

1. NAME OF THE MEDICINAL PRODUCT

Entyvio 108 mg solution for injection in pre-filled syringe
vedolizumab

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each pre-filled syringe contains 108 mg of vedolizumab.

3. LIST OF EXCIPIENTS

Excipients: citric acid monohydrate, sodium citrate dihydrate, L-histidine, L-histidine 
monohydrochloride, L-arginine hydrochloride, polysorbate 80, water for injections. See the package 
leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

Solution for injection
1 pre-filled syringe

Component of a multipack, cannot be sold separately.

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Subcutaneous use
For single use only.
Read the package leaflet before use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP



53

9. SPECIAL STORAGE CONDITIONS

Store in a refrigerator.
Do not freeze.
Keep the pre-filled syringe in the outer carton in order to protect from light.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Takeda Pharma A/S
Delta Park 45
2665 Vallensbaek Strand
Denmark

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/14/923/003 (2x1 pre-filled syringe)
EU/1/14/923/004 (6x1 pre-filled syringe)

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Entyvio 108 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA



54

MINIMUM PARTICULARS TO APPEAR ON BLISTER OR STRIPS

LIDDING (PRE-FILLED SYRINGE) (108 mg)

1. NAME OF THE MEDICINAL PRODUCT

Entyvio 108 mg solution for injection in pre-filled syringe
vedolizumab

2. NAME OF THE MARKETING AUTHORISATION HOLDER

Takeda Pharma A/S (as Takeda logo)

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER

For single use only.



55

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

SYRINGE LABEL (108 mg)

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Entyvio 108 mg injection
vedolizumab
SC

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

0.68 mL

6. OTHER



56

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARTON (WITH BLUE BOX) – PRE-FILLED PEN (108 mg)
(EXCLUDING MULTIPACKS)

1. NAME OF THE MEDICINAL PRODUCT

Entyvio 108 mg solution for injection in pre-filled pen
vedolizumab

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each pre-filled pen contains 108 mg of vedolizumab.

3. LIST OF EXCIPIENTS

Excipients: citric acid monohydrate, sodium citrate dihydrate, L-histidine, L-histidine 
monohydrochloride, L-arginine hydrochloride, polysorbate 80, water for injections. See the package 
leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

Solution for injection
1 pre-filled pen

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Subcutaneous use
Read the package leaflet before use.
For single use only.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP



57

9. SPECIAL STORAGE CONDITIONS

Store in a refrigerator.
Do not freeze.
Keep the pre-filled pen in the outer carton in order to protect from light.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Takeda Pharma A/S
Delta Park 45
2665 Vallensbaek Strand
Denmark

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/14/923/005

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Entyvio 108 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN



58

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER CARTON FOR MULTIPACK (WITH BLUE BOX) (108 mg)
(2x1 AND 6x1 PRE-FILLED PENS)

1. NAME OF THE MEDICINAL PRODUCT

Entyvio 108 mg solution for injection in pre-filled pen
vedolizumab

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each pre-filled pen contains 108 mg of vedolizumab.

3. LIST OF EXCIPIENTS

Excipients: citric acid monohydrate, sodium citrate dihydrate, L-histidine, L-histidine 
monohydrochloride, L-arginine hydrochloride, polysorbate 80, water for injections. See the package 
leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

Solution for injection

Multipack: 2 (2 packs of 1) pre-filled pens
Multipack: 6 (6 packs of 1) pre-filled pens

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Subcutaneous use
For single use only.
Read the package leaflet before use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP



59

9. SPECIAL STORAGE CONDITIONS

Store in a refrigerator.
Do not freeze.
Keep the pre-filled pen in the outer carton in order to protect from light.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Takeda Pharma A/S
Delta Park 45
2665 Vallensbaek Strand
Denmark

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/14/923/006 (2x1 pre-filled pens)
EU/1/14/923/007 (6x1 pre-filled pens)

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Entyvio 108 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN



60

PARTICULARS TO APPEAR ON THE OUTER PACKAGING
INTERMEDIATE CARTON OF MULTIPACK (WITHOUT BLUE BOX) – PRE-FILLED 
PEN (108 mg)

1. NAME OF THE MEDICINAL PRODUCT

Entyvio 108 mg solution for injection in pre-filled pen
vedolizumab

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each pre-filled pen contains 108 mg of vedolizumab.

3. LIST OF EXCIPIENTS

Excipients: citric acid monohydrate, sodium citrate dihydrate, L-histidine, L-histidine 
monohydrochloride, L-arginine hydrochloride, polysorbate 80, water for injections. See the package 
leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

Solution for injection
1 pre-filled pen 

Component of a multipack, cannot be sold separately.

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Subcutaneous use
For single use only.
Read the package leaflet before use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP



61

9. SPECIAL STORAGE CONDITIONS

Store in a refrigerator.
Do not freeze.
Keep the pre-filled pen in the outer carton in order to protect from light.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Takeda Pharma A/S
Delta Park 45
2665 Vallensbaek Strand
Denmark

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/14/923/006 (2x1 pre-filled pen)
EU/1/14/923/007 (6x1 pre-filled pen)

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Entyvio 108 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA



62

MINIMUM PARTICULARS TO APPEAR ON BLISTER OR STRIPS

LIDDING (PRE-FILLED PEN) (108 mg)

1. NAME OF THE MEDICINAL PRODUCT

Entyvio 108 mg solution for injection in pre-filled pen
vedolizumab 

2. NAME OF THE MARKETING AUTHORISATION HOLDER

Takeda Pharma A/S (as Takeda logo)

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. OTHER

For single use only.



63

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

PEN LABEL (108 mg)

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Entyvio 108 mg injection
vedolizumab
SC

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

0.68 mL

6. OTHER



64

B. PACKAGE LEAFLET



65

Package leaflet: Information for the patient

Entyvio 300 mg powder for concentrate for solution for infusion
vedolizumab

Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you.
 Keep this leaflet. You may need to read it again.
 If you have any further questions, ask your doctor or nurse.
 If you get any side effects, talk to your doctor or nurse. This includes any possible side effects

not listed in this leaflet. See section 4.
 Your doctor will also give you a Patient Alert Card for you to keep with you at all times.

What is in this leaflet

1. What Entyvio is and what it is used for
2. What you need to know before you are given Entyvio
3. How Entyvio will be given
4. Possible side effects
5. How to store Entyvio
6. Contents of the pack and other information

1. What Entyvio is and what it is used for

What Entyvio is
Entyvio contains the active substance ‘vedolizumab’. Vedolizumab belongs to a group of biological 
medicines called monoclonal antibodies (MAbs). 

How Entyvio works
Entyvio works by blocking a protein on the surface of white blood cells that cause the inflammation in 
ulcerative colitis and Crohn’s disease. This reduces the amount of inflammation.

What Entyvio is used for
Entyvio is used to treat the signs and symptoms in adults of:
 moderately to severely active ulcerative colitis
 moderately to severely active Crohn’s disease.

Ulcerative colitis
Ulcerative colitis is a disease that causes inflammation of the large bowel. If you have ulcerative 
colitis, you will first be given other medicines. If you do not respond well enough or cannot tolerate
these medicines, your doctor may give you Entyvio to reduce the signs and symptoms of your disease.

Crohn’s disease
Crohn’s disease is a disease that causes inflammation of the digestive system. If you have Crohn’s 
disease you will first be given other medicines. If you do not respond well enough or cannot tolerate
these medicines, your doctor may give you Entyvio to reduce the signs and symptoms of your disease.

2. What you need to know before you are given Entyvio

Do not use Entyvio
 if you are allergic to vedolizumab or any of the other ingredients of this medicine (listed in 

section 6).
 if you have an active severe infection - such as TB (tuberculosis), blood poisoning, severe 

diarrhoea and vomiting (gastroenteritis), nervous system infection.



66

Warnings and precautions
Talk to your doctor or nurse before being given Entyvio.

Tell your doctor or nurse immediately when you first receive this medicine, during treatment, and
between doses:

 if you experience blurred, loss of or double vision, difficulty speaking, weakness in an arm or a 
leg, a change in the way you walk or problems with your balance, persistent numbness, 
decreased sensation or loss of sensation, memory loss or confusion. These may all be symptoms 
of a serious and potentially fatal brain condition known as progressive multifocal 
leukoencephalopathy (PML).

 if you have an infection, or think you have an infection - signs include chills, shivering, 
persistent cough or a high fever. Some infections may become serious and possibly even 
life-threatening if left untreated.

 if you experience signs of an allergic reaction or other reaction to the infusion such as 
wheezing, difficulty breathing, hives, itching, swelling or dizziness. These could occur during or 
after the infusion. For more detailed information, see infusion and allergic reactions in section 4.

 if you are going to receive any vaccination or have recently had a vaccination. Entyvio may 
affect the way you respond to a vaccination.

 if you have cancer, tell your doctor. Your doctor will have to decide if you can still be given 
Entyvio.

 if you are not feeling any better as vedolizumab may take up to 14 weeks to work in some 
patients with very active Crohn’s disease.

Children and adolescents
Entyvio is not recommended for use in children or adolescents (under 18 years of age) due to the lack 
of information regarding the use of this medicine in this age group.

Other medicines and Entyvio
Tell your doctor or nurse if you are taking, have recently taken or might take any other medicines.

 Entyvio should not be given with other biologic medicines that suppress your immune system as 
the effect of this is not known.

Tell your doctor if you have previously taken:
 natalizumab (a medicine for multiple sclerosis) or 
 rituximab (a medicine for certain types of cancer and rheumatoid arthritis).
Your doctor will decide if you can be given Entyvio. 

Pregnancy and breast-feeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor for advice before taking this medicine.

Pregnancy
The effects of Entyvio in pregnant women are not known. Therefore, this medicine is not
recommended for use during pregnancy. You and your doctor should decide if the benefit to you 
clearly outweighs the potential risk to yourself and your baby.

If you are a woman of childbearing potential, you are advised to avoid becoming pregnant while using
Entyvio. You should use adequate contraception during treatment and for at least 4.5 months after the 
last treatment. 



67

Breast-feeding
Tell your doctor if you are breast-feeding or planning to breast-feed. Entyvio passes into breast milk. 
There is not enough information on what effect this may have on your baby. A decision must be made 
whether to stop breast-feeding or to stop using from Entyvio therapy taking into account the benefit of 
breast-feeding for your child and the benefit of therapy for you.

Driving and using machines
This medicine has a minor effect on your ability to drive or use tools or machines. A small number of 
patients have felt dizzy after receiving Entyvio. If you feel dizzy, do not drive or use tools or 
machines.

3. How Entyvio will be given

How much Entyvio you will receive
Treatment with Entyvio is the same for ulcerative colitis and Crohn’s disease.

The recommended dose is 300 mg of Entyvio given as follows (see table below):

Treatment (infusion) number Timing of treatment (infusion)
Treatment 1 0 weeks
Treatment 2 2 weeks after Treatment 1
Treatment 3 6 weeks after Treatment 1

Further treatments Every 8 weeks

Your doctor may decide to alter this treatment schedule depending on how well Entyvio works for 
you.

 The infusion will be given to you, by your doctor or nurse, through a drip in 1 of the veins in 
your arm (intravenous infusion) over about 30 minutes.

 For your first 2 infusions, your doctor or nurse will monitor you closely during the infusion and 
for approximately 2 hours after you have completed the infusion. For all subsequent infusions 
(after the first 2), you will be monitored during the infusion and for approximately 1 hour after 
you have completed the infusion.

If you forget or miss your Entyvio infusion
If you forget or miss an appointment to receive the infusion, make another appointment as soon as 
possible.

If you stop using Entyvio
Do not stop using Entyvio without talking with your doctor first.

If you have any further questions on the use of this medicine, ask your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects although not everybody gets them.

Serious side effects
Tell your doctor immediately if you notice any of the following:
 allergic reactions (may affect up to 1 in 100 people) - the signs may include: wheezing or 

difficulty breathing, hives, itching of the skin, swelling, feeling sick, pain at the infusion site, 
redness of skin and

 infections (may affect up to 1 in 10 people) - the signs may include: chills or shivering, high 
fever or rash



68

Other side effects
Tell your doctor as soon as possible if you notice any of the following:

Very common side effects (may affect more than 1 in 10 people)
 common cold
 joint pain
 headache

Common side effects (may affect up to 1 in 10 people)
 fever 
 chest infection 
 tiredness
 cough
 flu (influenza)
 back pain
 throat pain
 sinus infection
 itching / itchiness
 rash and redness
 pain in the limb
 muscle cramps
 muscle weakness
 throat infection
 stomach flu
 anal infection
 anal sore
 hard faeces
 bloated stomach
 passing gas
 high blood pressure
 prickling or tingling
 heart burn
 haemorrhoids
 blocked nose
 eczema
 night sweats
 acne (pimples)

Uncommon side effects (may affect up to 1 in 100 people)
 redness and tenderness of hair follicle
 throat and mouth yeast infection
 vaginal infection
 shingles (herpes zoster)

Very rare side effects (may affect up to 1 in 10,000 people)
 pneumonia
 blurred vision (loss of sharpness of eyesight)
 sudden, severe allergic reaction which can cause breathing difficulty, swelling, fast heartbeat, 

sweating, drop in blood pressure, light-headedness, loss of consciousness and collapse 
(anaphylactic reaction and anaphylactic shock)

Reporting of side effects
If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not 
listed in this leaflet. You can also report side effects directly via the national reporting system listed in



69

Appendix V. By reporting side effects you can help provide more information on the safety of this 
medicine.

5. How to store Entyvio

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton after “EXP”. The expiry 
date refers to the last day of that month.

Entyvio is given by a doctor or nurse and patients should not need to store or handle Entyvio.

Entyvio is for single use only.

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

Reconstituted and diluted solutions: Use immediately. If this is not possible, reconstituted solution 
in the vial can be stored for up to 8 hours at 2 °C-8 °C. Diluted solution in sodium chloride 9 mg/mL 
(0.9%) solution for injection can be stored up to 12 hours at a room temperature of not above 25 °C, or 
up to 24 hours in a refrigerator (2 °C-8 °C), or for up to 12 hours at room temperature and in a 
refrigerator (2 °C-8 °C), up to a combined total of 24 hours. 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 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.

Do not freeze.

Do not use this medicine if you notice any particles in the liquid or discolouration (solution should be 
clear or opalescent, colourless to light yellow) prior to administration.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Entyvio contains
 The active substance is vedolizumab. Each vial contains 300 mg of vedolizumab.
 The other ingredients are L-histidine, L-histidine monohydrochloride, L-arginine 

hydrochloride, sucrose, and polysorbate 80.

What Entyvio looks like and contents of the pack
 Entyvio is a white to off-white powder for concentrate for solution for infusion provided in a 

glass vial with a rubber stopper and a plastic cap.
 Each pack of Entyvio consists of one vial. 

Marketing Authorisation Holder

Takeda Pharma A/S
Delta Park 45
2665 Vallensbaek Strand
Denmark



70

Manufacturer

Delpharm Novara S.r.l.
Via Crosa, 86
28065 Cerano (NO)
Italy

Takeda Austria GmbH
St. Peter-Straße 25
4020 Linz
Austria

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder:

België/Belgique/Belgien
Takeda Belgium
Tél./Tel.: +32 2 464 06 11
takeda-belgium@takeda.com

Lietuva
Takeda, UAB
Tel.: +370 521 09 070

България 
Такеда България
Тел.: +359 2 958 27 36

Luxembourg/Luxemburg
Takeda Belgium
Tél/Tel: +32 2 464 06 11
takeda-belgium@takeda.com

Česká republika
Takeda Pharmaceuticals Czech Republic s.r.o.
Tel: +420 234 722 722

Magyarország 
Takeda Pharma Kft.
Tel.: +361 2707030 

Danmark 
Takeda Pharma A/S
Tlf./Tel.: +45 46 77 11 11

Malta
Takeda Italia S.p.A. 
Tel.: +39 06 502601

Deutschland
Takeda GmbH
Tel.: +49 (0) 800 825 3325
medinfoEMEA@takeda.com

Nederland
Takeda Nederland bv
Tel.: +31 20 203 5492
medinfoEMEA@takeda.com

Eesti
Takeda Pharma AS
Tel.: +372 6177 669
info@takeda.ee

Norge
Takeda AS
Tlf.: +47 6676 3030
infonorge@takeda.com

Ελλάδα 
TAKEDA ΕΛΛΑΣ Α.Ε.
Τηλ.: +30 210 6387800
gr.info@takeda.com

Österreich
Takeda Pharma Ges.m.b.H. 
Tel.: +43 (0) 800 20 80 50 

España
Takeda Farmacéutica España S.A.
Tel.: +34 917 90 42 22
spain@takeda.com

Polska
Takeda Pharma sp. z o.o.
Tel.: +48 22 608 13 00 



71

France
Takeda France SAS
Tel.: +33 1 40 67 33 00
medinfoEMEA@takeda.com

Portugal
Takeda Farmacêuticos Portugal, Lda.
Tel.: +351 21 120 1457

Hrvatska
Takeda Pharmaceuticals Croatia d.o.o.
Tel: +385 1 377 88 96

România 
Takeda Pharmaceuticals SRL
Tel.: +40 21 335 03 91 

Ireland
Takeda Products Ireland Ltd.
Tel.: +353 (0) 1 6420021

Slovenija
Takeda GmbH, Podružnica Slovenija
Tel.: +386 (0) 59 082 480 

Ísland
Vistor hf.
Tel.: +354 535 7000
vistor@vistor.is

Slovenská republika
Takeda Pharmaceuticals Slovakia s.r.o.
Tel.: +421 (2) 20 602 600 

Italia
Takeda Italia S.p.A
Tel.: +39 06 502601

Suomi/Finland
Takeda Oy
Puh./Tel.: +358 20 746 5000
infoposti@takeda.com

Κύπρος
A.Potamitis Medicare Ltd
Tηλ: +357 22583333
info@potamitismedicare.com

Sverige
Takeda Pharma AB
Tel.: +46 8 731 28 00
infosweden@takeda.com

Latvija
Takeda Latvia SIA
Tel.: +371 67840082

United Kingdom
Takeda UK Ltd
Tel.: +44 (0)1628 537 900

This leaflet was last revised in 

Other sources of information

This leaflet is available in formats suitable for the blind or partially sighted patient and can be 
requested from respective local representative of the Marketing Authorisation Holder.

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.
-----------------------------------------------------------------------------------------------------------------------



72

The following information is intended for healthcare professionals only:

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

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 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.

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

Storage Condition
Refrigerator (2 °C-8 °C) 20 °C-25 °C

Reconstituted solution in the vial 8 hours Do not hold1

Diluted solution in sodium chloride 9 mg/mL 
(0.9%) solution for injection

24 hours2, 3 12 hours2

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.

Do not freeze. Do not store any unused portion of the reconstituted solution or infusion solution for 
reuse.
Each vial is for single use only.



73

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



74

Package leaflet: Information for the patient

Entyvio 108 mg solution for injection in pre-filled syringe
vedolizumab

Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you.
 Keep this leaflet. You may need to read it again.
 If you have any further questions, ask your doctor, pharmacist or nurse.
 This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.
 If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Entyvio is and what it is used for
2. What you need to know before you use Entyvio
3. How to use Entyvio
4. Possible side effects
5. How to store Entyvio
6. Contents of the pack and other information

1. What Entyvio is and what it is used for

What Entyvio is
Entyvio contains the active substance ‘vedolizumab’. Vedolizumab belongs to a group of biological
medicines called monoclonal antibodies (MAbs).

How Entyvio works
Entyvio works by blocking a protein on the surface of white blood cells that cause the inflammation in 
ulcerative colitis and Crohn’s disease. This reduces the amount of inflammation.

What Entyvio is used for
Entyvio is used to treat the signs and symptoms in adults of:
 moderately to severely active ulcerative colitis
 moderately to severely active Crohn’s disease.

Ulcerative colitis
Ulcerative colitis is a disease that causes inflammation of the large bowel. If you have ulcerative 
colitis, you will first be given other medicines. If you do not respond well enough or cannot tolerate
these medicines, your doctor may give you Entyvio to reduce the signs and symptoms of your disease. 

Crohn’s disease
Crohn’s disease is a disease that causes inflammation of the digestive system. If you have Crohn’s 
disease you will first be given other medicines. If you do not respond well enough or cannot tolerate
these medicines, your doctor may give you Entyvio to reduce the signs and symptoms of your disease. 



75

2. What you need to know before you use Entyvio

Do not use Entyvio
 if you are allergic to vedolizumab or any of the other ingredients of this medicine (listed in 

section 6).
 if you have an active severe infection - such as TB (tuberculosis), blood poisoning, severe 

diarrhoea and vomiting (gastroenteritis), nervous system infection.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using Entyvio.

Tell your doctor, pharmacist or nurse immediately when you first use this medicine, during 
treatment, and between doses: 

 if you experience blurred, loss of or double vision, difficulty speaking, weakness in an arm or a 
leg, a change in the way you walk or problems with your balance, persistent numbness, 
decreased sensation or loss of sensation, memory loss or confusion. These may all be symptoms 
of a serious and potentially fatal brain condition known as progressive multifocal 
leukoencephalopathy (PML).

 if you have an infection, or think you have an infection -signs include chills, shivering, 
persistent cough or a high fever. Some infections may become serious and possibly even 
life-threatening if left untreated.

 if you experience signs of an allergic reaction such as wheezing, difficulty breathing, hives, 
itching, swelling or dizziness. For more detailed information, see allergic reactions in section 4.

 if you are going to receive any vaccination or have recently had a vaccination. Entyvio may 
affect the way you respond to a vaccination.

 if you have cancer, tell your doctor. Your doctor will have to decide if you can still be given 
Entyvio.

 if you are not feeling any better as vedolizumab may take up to 14 weeks to work in some 
patients with very active Crohn’s disease.

Children and adolescents
Entyvio is not recommended for use in children or adolescents (under 18 years of age) due to the lack 
of information regarding the use of this medicine in this age group.

Other medicines and Entyvio
Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other
medicines.

 Entyvio should not be given with other biologic medicines that suppress your immune system as 
the effect of this is not known.

Tell your doctor if you have previously taken:
 natalizumab (a medicine for multiple sclerosis) or 
 rituximab (a medicine for certain types of cancer and rheumatoid arthritis).
Your doctor will decide if you can be given Entyvio. 

Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor for advice before taking this medicine.



76

Pregnancy
The effects of Entyvio in pregnant women are not known. Therefore, this medicine is not
recommended for use during pregnancy. You and your doctor should decide if the benefit to you 
clearly outweighs the potential risk to yourself and your baby.

If you are a woman of childbearing potential, you are advised to avoid becoming pregnant while using 
Entyvio. You should use adequate contraception during treatment and for at least 4.5 months after the 
last treatment.

Breast-feeding
Tell your doctor if you are breast-feeding or planning to breast-feed. Entyvio passes into breast milk. 
There is not enough information on what effect this may have on your baby. A decision must be made 
whether to stop breast-feeding or to stop using Entyvio therapy taking into account the benefit of 
breast-feeding for your child and the benefit of therapy for you.

Driving and using machines
This medicine has a minor effect on your ability to drive or use tools or machines. A small number of 
patients have felt dizzy after receiving Entyvio. If you feel dizzy, do not drive or use tools or 
machines. 

Entyvio 108 mg solution for injection contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially 
‘sodium-free’.

3. How to use Entyvio

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure.

You or your caregiver will be given training on how to use Entyvio injections under the skin 
(subcutaneous injections).

How much Entyvio you will receive
Treatment with Entyvio is the same for ulcerative colitis and Crohn’s disease.

The recommended dose is 108 mg of Entyvio administered by subcutaneous injection once every
2 weeks.
 At the start of treatment, the doctor will give initial doses of Entyvio through a drip into a vein 

in your arm (intravenous infusion) over about 30 minutes. 
 After at least 2 intravenous infusions, you can start receiving Entyvio by a subcutaneous 

injection. The first subcutaneous injection is given at the time of the next scheduled intravenous 
infusion, and every 2 weeks thereafter.

Injecting Entyvio
The subcutaneous injections can be given by yourself or a caregiver, after training on how to do it. 
Instructions are provided at the end of this leaflet.

If you forget to take or miss your Entyvio injection
If you forget or miss a dose, inject the next dose as soon as possible and then every 2 weeks thereafter.

If you stop using Entyvio
Do not stop using Entyvio without talking with your doctor first. 

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.



77

4. Possible side effects

Like all medicines, this medicine can cause side effects although not everybody gets them.

Serious side effects
Tell your doctor immediately if you notice any of the following:
 allergic reactions (may affect up to 1 in 100 people) - the signs may include: wheezing or 

difficulty breathing, hives, itching of the skin, swelling, feeling sick, redness of skin
 infections (may affect up to 1 in 10 people) - the signs may include: chills or shivering, high 

fever or rash

Other side effects
Tell your doctor as soon as possible if you notice any of the following:

Very common side effects (may affect more than 1 in 10 people)
 common cold
 joint pain
 headache 

Common side effects (may affect up to 1 in 10 people)
 fever
 chest infection
 tiredness
 cough
 flu (influenza)
 back pain
 throat pain
 sinus infection
 itching / itchiness
 rash and redness
 pain in the limb
 muscle cramps
 muscle weakness
 throat infection
 stomach flu
 anal infection
 anal sore
 hard faeces
 bloated stomach
 passing gas
 high blood pressure
 prickling or tingling
 heart burn
 haemorrhoids
 blocked nose
 eczema
 night sweats
 acne (pimples)
 injection site reactions (including pain, swelling, redness or itching)



78

Uncommon side effects (may affect up to 1 in 100 people)
 redness and tenderness of hair follicle
 throat and mouth yeast infection
 vaginal infection
 shingles (herpes zoster)

Very rare side effects (may affect up to 1 in 10,000 people)
 pneumonia
 blurred vision (loss of sharpness of eyesight)
 sudden, severe allergic reaction which can cause breathing difficulty, swelling, fast heartbeat, 

sweating, drop in blood pressure, light-headedness, loss of consciousness and collapse 
(anaphylactic reaction and anaphylactic shock)

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine.

5. How to store Entyvio

 Keep this medicine out of the sight and reach of children.
 Do not use this medicine after the expiry date which is stated on the carton after “EXP”. The 

expiry date refers to the last day of that month.
 Entyvio is for single use only.
 Store in a refrigerator (2 °C-8 °C). Keep the pre-filled syringe in the original carton in order to 

protect from light. If needed, the pre-filled syringe can be left out of the refrigerator in its 
original carton at room temperature (up to 25 °C) for up to 7 days. Do not use if left out of the 
refrigerator for more than 7 days.

 Do not freeze. Do not leave in direct sunlight.
 Do not use this medicine if you notice any particles in the liquid or discolouration (should be 

colourless to yellow) prior to administration.
 Do not throw away any medicines via wastewater or household waste. Ask your pharmacist 

how to throw away medicines you no longer use. These measures will help protect the 
environment.

6. Contents of the pack and other information

What Entyvio contains
 The active substance is vedolizumab. Each pre-filled syringe contains 108 mg of vedolizumab.
 The other ingredients are citric acid monohydrate, sodium citrate dihydrate, L-histidine, 

L-histidine monohydrochloride, L-arginine hydrochloride, polysorbate 80 and water for 
injections. 

What Entyvio looks like and contents of the pack
 Entyvio is a colourless to yellow solution for injection provided in a glass pre-filled syringe 

with a needle safety device that activates to extend and lock a guard over the needle once the 
injection is completed. The syringe has a rubber needle cover encased in a plastic shell and 
rubber stopper.

 Entyvio is available in a carton containing 1 pre-filled syringe and multipacks containing 
2 (2x1 pre-filled syringes), or 6 (6x1 pre-filled syringes). Not all pack sizes may be marketed.



79

Marketing Authorisation Holder

Takeda Pharma A/S
Delta Park 45
2665 Vallensbaek Strand
Denmark

Manufacturer

Takeda Austria GmbH
St. Peter-Straße 25
4020 Linz
Austria

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder:

België/Belgique/Belgien
Takeda Belgium
Tél./Tel.: +32 2 464 06 11
takeda-belgium@takeda.com

Lietuva
Takeda, UAB
Tel.: +370 521 09 070

България 
Такеда България
Тел.: +359 2 958 27 36

Luxembourg/Luxemburg
Takeda Belgium
Tél/Tel: +32 2 464 06 11
takeda-belgium@takeda.com

Česká republika
Takeda Pharmaceuticals Czech Republic s.r.o.
Tel: +420 234 722 722

Magyarország 
Takeda Pharma Kft.
Tel.: +361 2707030 

Danmark 
Takeda Pharma A/S
Tlf./Tel.: +45 46 77 11 11

Malta
Takeda Italia S.p.A. 
Tel.: +39 06 502601

Deutschland
Takeda GmbH
Tel.: +49 (0) 800 825 3325
medinfoEMEA@takeda.com

Nederland
Takeda Nederland bv
Tel.: +31 20 203 5492
medinfoEMEA@takeda.com

Eesti
Takeda Pharma AS
Tel.: +372 6177 669
info@takeda.ee

Norge
Takeda AS
Tlf.: +47 6676 3030
infonorge@takeda.com

Ελλάδα 
TAKEDA ΕΛΛΑΣ Α.Ε.
Τηλ.: +30 210 6387800
gr.info@takeda.com

Österreich
Takeda Pharma Ges.m.b.H.
Tel.: +43 (0) 800 20 80 50 

España
Takeda Farmacéutica España S.A.
Tel.: +34 917 90 42 22
spain@takeda.com

Polska
Takeda Pharma sp. z o.o.
Tel.: +48 22 608 13 00 



80

France
Takeda France SAS
Tel.: +33 1 40 67 33 00
medinfoEMEA@takeda.com

Portugal
Takeda Farmacêuticos Portugal, Lda.
Tel.: +351 21 120 1457

Hrvatska
Takeda Pharmaceuticals Croatia d.o.o.
Tel: +385 1 377 88 96

România 
Takeda Pharmaceuticals SRL
Tel.: +40 21 335 03 91 

Ireland
Takeda Products Ireland Ltd.
Tel.: +353 (0) 1 6420021

Slovenija
Takeda GmbH, Podružnica Slovenija
Tel.: +386 (0) 59 082 480 

Ísland
Vistor hf.
Tel.: +354 535 7000
vistor@vistor.is

Slovenská republika
Takeda Pharmaceuticals Slovakia s.r.o.
Tel.: +421 (2) 20 602 600

Italia
Takeda Italia S.p.A
Tel.: +39 06 502601

Suomi/Finland
Takeda Oy
Puh./Tel.: +358 20 746 5000
infoposti@takeda.com

Κύπρος
A.Potamitis Medicare Ltd
Tηλ: +357 22583333
info@potamitismedicare.com

Sverige
Takeda Pharma AB
Tel.: +46 8 731 28 00
infosweden@takeda.com

Latvija
Takeda Latvia SIA
Tel.: +371 67840082

United Kingdom
Takeda UK Ltd
Tel.: +44 (0)1628 537 900

This leaflet was last revised in 

Other sources of information

This leaflet is available in formats suitable for the blind or partially sighted patient and can be 
requested from respective local representative of the Marketing Authorisation Holder.

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.
-----------------------------------------------------------------------------------------------------------------------

The following information is intended for healthcare professionals only:

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



81

Instructions for use:

Read and follow these instructions before you inject. Your doctor, nurse or pharmacist should show 
you how to use the Entyvio pre-filled syringe before you use it for the first time.

Your Entyvio single-dose pre-filled syringe

Before Use
Needle guard Medicine Needle

Purple plunger Finger Grip Spring Needle cap

After Use
Needle guard

Covered needle

Each pre-filled syringe has a needle guard. It will automatically cover the needle after the plunger is 
pushed down as far as it will go and then released.

1) Place what you need for the injection on a clean a flat surface

 Take 1 pre-filled syringe carton out of the refrigerator.
 Do not use the pre-filled syringe if any of the seals on the 

carton are broken or missing.
 Check the expiry date (EXP) on the carton. Do not use if the 

expiry date on the carton has passed.

 Wait 30 minutes to let the pre-filled syringe come to room 
temperature. 
 Do not warm the pre-filled syringe in any other way.
 Do not let it sit in direct sunlight. 
 Do not take the pre-filled syringe out of its tray until you are 

ready to inject.

 You will also need:
 Alcohol pad 
 Cotton ball or gauze 
 Sharps disposal container

Wait 30 minutes



82

2) Open and check the pre-filled syringe

 Wash your hands 

 Peel back the paper on the tray and lift the pre-filled syringe out by 
the body.
 Do not touch or lift from the purple plunger.
 Do not remove the needle cap until ready to inject.

 Inspect the pre-filled syringe for damage.
 Do not use the pre-filled syringe if any part of it is damaged.

 Check the expiry date on the pre-filled syringe. 
 Do not use if the expiry date on the pre-filled syringe has 

passed.

 Check the medicine. It should be colourless to yellow. 
 Do not use the pre-filled syringe if the medicine is cloudy or 

has particles floating in it.

 You may see air bubbles in the syringe. This is normal.
 Do not attempt to remove air bubbles from the pre-filled 

syringe.
 Do not shake

3) Prepare the injection site

 Choose an injection site on your bare skin from 1 of the 
following. 
 Front of the thighs, or
 Stomach area (abdomen) except for the area 5 cm around the 

belly button (navel), or
 Back of the upper arm (only if a caregiver gives the injection).

 Use a new injection site or a different area within the same 
injection site for each injection.
 Do not inject into moles, scars, bruises, or skin that is tender, 

hard, red, or damaged.

 Wipe the chosen site with an alcohol pad. Let your skin dry.
 Do not touch this area again before you inject.



83

4) Inject Entyvio

 Pull the needle cap straight off.
 Do not touch or pull back the purple plunger.
 You may see a drop of liquid at the end of the needle. 

This is normal.
 Do not touch or re-cap the needle.
 Do not use a dropped pre-filled syringe.
 Do not use a pre-filled syringe with a bent or broken needle.

 Throw away the cap.

 Hold the pre-filled syringe with 1 hand and pinch the skin around 
the injection site with your other hand.
 Hold the pinch until the injection is completed.

 Insert the needle at about a 45-degree angle all the way into the 
pinched skin.

 Push down on the plunger as far as it will go to inject all the 
medicine.
 Keep pressure on the plunger and take the needle out of the 

skin.

 Take your thumb off the plunger to allow the needle guard to 
cover the needle.

 You may see a small amount of blood at the injection site. If you 
do, press on your skin with a cotton ball or gauze.

5) Throw away used material

 Put the used pre-filled syringe in a puncture-resistant container, 
like a sharps container, immediately after use.
 Dispose of your sharps container according to your local 

regulations.

 The rest of the material can be thrown in your household rubbish.



84

Package leaflet: Information for the patient

Entyvio 108 mg solution for injection in pre-filled pen
vedolizumab

Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you.
 Keep this leaflet. You may need to read it again.
 If you have any further questions, ask your doctor, pharmacist or nurse.
 This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.
 If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Entyvio is and what it is used for
2. What you need to know before you use Entyvio
3. How to use Entyvio
4. Possible side effects
5. How to store Entyvio
6. Contents of the pack and other information

1. What Entyvio is and what it is used for

What Entyvio is
Entyvio contains the active substance ‘vedolizumab’. Vedolizumab belongs to a group of biological 
medicines called monoclonal antibodies (MAbs).

How Entyvio works
Entyvio works by blocking a protein on the surface of white blood cells that cause the inflammation in 
ulcerative colitis and Crohn’s disease. This reduces the amount of inflammation.

What Entyvio is used for
Entyvio is used to treat the signs and symptoms in adults of:
 moderately to severely active ulcerative colitis
 moderately to severely active Crohn’s disease.

Ulcerative colitis
Ulcerative colitis is a disease that causes inflammation of the large bowel. If you have ulcerative 
colitis, you will first be given other medicines. If you do not respond well enough or cannot tolerate 
these medicines, your doctor may give you Entyvio to reduce the signs and symptoms of your disease.

Crohn’s disease
Crohn’s disease is a disease that causes inflammation of the digestive system. If you have Crohn’s 
disease you will first be given other medicines. If you do not respond well enough or cannot tolerate 
these medicines, your doctor may give you Entyvio to reduce the signs and symptoms of your disease.



85

2. What you need to know before you use Entyvio

Do not use Entyvio
 if you are allergic to vedolizumab or any of the other ingredients of this medicine (listed in 

section 6).
 if you have an active severe infection - such as TB (tuberculosis), blood poisoning, severe 

diarrhoea and vomiting (gastroenteritis), nervous system infection.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using Entyvio.

Tell your doctor, pharmacist or nurse immediately when you first use this medicine, during 
treatment, and between doses:

 if you experience blurred, loss of or double vision, difficulty speaking, weakness in an arm or a 
leg, a change in the way you walk or problems with your balance, persistent numbness, 
decreased sensation or loss of sensation, memory loss or confusion. These may all be symptoms 
of a serious and potentially fatal brain condition known as progressive multifocal 
leukoencephalopathy (PML).

 if you have an infection, or think you have an infection – signs include chills, shivering, 
persistent cough or a high fever. Some infections may become serious and possibly even 
life-threatening if left untreated.

 if you experience signs of an allergic reaction such as wheezing, difficulty breathing, hives, 
itching, swelling or dizziness. For more detailed information, see allergic reactions in section 4.

 if you are going to receive any vaccination or have recently had a vaccination. Entyvio may 
affect the way you respond to a vaccination.

 if you have cancer, tell your doctor. Your doctor will have to decide if you can still be given 
Entyvio.

 if you are not feeling any better as vedolizumab may take up to 14 weeks to work in some 
patients with very active Crohn’s disease.

Children and adolescents
Entyvio is not recommended for use in children or adolescents (under 18 years of age) due to the lack 
of information regarding the use of this medicine in this age group.

Other medicines and Entyvio
Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other 
medicines.

 Entyvio should not be given with other biologic medicines that suppress your immune system as 
the effect of this is not known.

Tell your doctor if you have previously taken:
 natalizumab (a medicine for multiple sclerosis) or
 rituximab (a medicine for certain types of cancer and rheumatoid arthritis).
Your doctor will decide if you can be given Entyvio.

Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor for advice before taking this medicine.



86

Pregnancy
The effects of Entyvio in pregnant women are not known. Therefore, this medicine is not 
recommended for use during pregnancy. You and your doctor should decide if the benefit to you 
clearly outweighs the potential risk to yourself and your baby.

If you are a woman of childbearing potential, you are advised to avoid becoming pregnant while using 
Entyvio. You should use adequate contraception during treatment and for at least 4.5 months after the 
last treatment.

Breast-feeding
Tell your doctor if you are breast-feeding or planning to breast-feed. Entyvio passes into breast milk. 
There is not enough information on what effect this may have on your baby. A decision must be made 
whether to stop breast-feeding or to stop using Entyvio therapy taking into account the benefit of 
breast-feeding for your child and the benefit of therapy for you.

Driving and using machines
This medicine has a minor effect on your ability to drive or use tools or machines. A small number of 
patients have felt dizzy after receiving Entyvio. If you feel dizzy, do not drive or use tools or 
machines.

Entyvio 108 mg solution for injection contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially 
‘sodium-free’.

3. How to use Entyvio

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure.

You or your caregiver will be given training on how to use Entyvio injections under the skin 
(subcutaneous injections).

How much Entyvio you will receive
Treatment with Entyvio is the same for ulcerative colitis and Crohn’s disease. 

The recommended dose is 108 mg of Entyvio administered by subcutaneous injection once every 
2 weeks.

 At the start of treatment, the doctor will give initial doses of Entyvio through a drip into a vein 
in your arm (intravenous infusion) over about 30 minutes.

 After at least 2 intravenous infusions, you can start receiving Entyvio by a subcutaneous 
injection. The first subcutaneous injection is given at the time of the next scheduled intravenous 
infusion, and every 2 weeks thereafter.

Injecting Entyvio
The subcutaneous injections can be given by yourself or a caregiver, after training on how to do it. 
Instructions are provided at the end of this leaflet.

If you forget to take or miss your Entyvio injection
If you forget or miss a dose, inject the next dose as soon as possible and then every 2 weeks thereafter.

If you stop using Entyvio
Do not stop using Entyvio without talking with your doctor first. 

If you have any further questions on the use of this medicine, ask your doctor pharmacist or nurse.



87

4. Possible side effects

Like all medicines, this medicine can cause side effects although not everybody gets them.

Serious side effects
Tell your doctor immediately if you notice any of the following:

 allergic reactions (may affect up to 1 in 100 people) - the signs may include: wheezing or 
difficulty breathing, hives, itching of the skin, swelling, feeling sick, redness of skin and 

 infections (may affect up to 1 in 10 people) - the signs may include: chills or shivering, high 
fever or rash

Other side effects
Tell your doctor as soon as possible if you notice any of the following:

Very common side effects (may affect more than 1 in 10 people)
 common cold
 joint pain
 headache 

Common side effects (may affect up to 1 in 10 people)
 fever 
 chest infection 
 tiredness
 cough
 flu (influenza)
 back pain
 throat pain
 sinus infection
 itching / itchiness
 rash and redness
 pain in the limb
 muscle cramps
 muscle weakness
 throat infection
 stomach flu
 anal infection
 anal sore
 hard faeces
 bloated stomach
 passing gas
 high blood pressure
 prickling or tingling
 heart burn
 haemorrhoids
 blocked nose
 eczema
 night sweats
 acne (pimples)
 injection site reactions (including pain, swelling, redness or itching)



88

Uncommon side effects (may affect up to 1 in 100 people)
 redness and tenderness of hair follicle 
 throat and mouth yeast infection
 vaginal infection
 shingles (herpes zoster)

Very rare side effects (may affect up to 1 in 10,000 people)
 pneumonia
 blurred vision (loss of sharpness of eyesight)
 sudden, severe allergic reaction which can cause breathing difficulty, swelling, fast heartbeat, 

sweating, drop in blood pressure, light-headedness, loss of consciousness and collapse 
(anaphylactic reaction and anaphylactic shock)

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine.

5. How to store Entyvio

 Keep this medicine out of the sight and reach of children.
 Do not use this medicine after the expiry date which is stated on the carton after “EXP”. The 

expiry date refers to the last day of that month.
 Entyvio is for single use only.
 Store in a refrigerator (2 °C-8 °C). Keep the pre-filled pen in the original carton in order to 

protect from light. If needed the pre-filled pen can be left out of the refrigerator in its original 
carton at room temperature (up to 25 oC) for up to 7 days. Do not use if left out of the 
refrigerator for more than 7 days.

 Do not freeze. Do not leave in direct sunlight.
 Do not use this medicine if you notice any particles in the liquid or discolouration (should be 

colourless to yellow) prior to administration.
 Do not throw away any medicines via wastewater or household waste. Ask your pharmacist 

how to throw away medicines you no longer use. These measures will help protect the 
environment.

6. Contents of the pack and other information

What Entyvio contains
 The active substance is vedolizumab. Each pre-filled pen contains 108 mg of vedolizumab. 
 The other ingredients are citric acid monohydrate, sodium citrate dihydrate, L-histidine, 

L-histidine monohydrochloride, L-arginine hydrochloride, polysorbate 80 and water for 
injections.

What Entyvio looks like and contents of the pack
 Entyvio is a colourless to yellow solution for injection provided in a glass pre-filled pen 

equipped with an automated needle shield to extend and lock over the needle once the device 
is removed from the injection site.

 Entyvio is available in a carton containing 1 pre-filled pen and multipacks containing 
2 (2x1 pre-filled pens), or 6 (6x1 pre-filled pens). Not all pack sizes may be marketed.



89

Marketing Authorisation Holder

Takeda Pharma A/S
Delta Park 45
2665 Vallensbaek Strand
Denmark

Manufacturer

Takeda Austria GmbH
St. Peter-Straße 25
4020 Linz
Austria

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder:

België/Belgique/Belgien
Takeda Belgium
Tél./Tel.: +32 2 464 06 11
takeda-belgium@takeda.com

Lietuva
Takeda, UAB
Tel.: +370 521 09 070

България 
Такеда България
Тел.: +359 2 958 27 36

Luxembourg/Luxemburg
Takeda Belgium
Tél/Tel: +32 2 464 06 11
takeda-belgium@takeda.com

Česká republika
Takeda Pharmaceuticals Czech Republic s.r.o.
Tel: +420 234 722 722

Magyarország 
Takeda Pharma Kft.
Tel.: +361 2707030

Danmark 
Takeda Pharma A/S
Tlf./Tel.: +45 46 77 11 11

Malta
Takeda Italia S.p.A. 
Tel.: +39 06 502601

Deutschland
Takeda GmbH
Tel.: +49 (0) 800 825 3325
medinfoEMEA@takeda.com

Nederland
Takeda Nederland bv
Tel.: +31 20 203 5492
medinfoEMEA@takeda.com

Eesti
Takeda Pharma AS
Tel.: +372 6177 669
info@takeda.ee

Norge
Takeda AS
Tlf.: +47 6676 3030
infonorge@takeda.com

Ελλάδα
TAKEDA ΕΛΛΑΣ Α.Ε.
Τηλ.: +30 210 6387800
gr.info@takeda.com

Österreich
Takeda Pharma Ges.m.b.H. 
Tel.: +43 (0) 800 20 80 50

España
Takeda Farmacéutica España S.A.
Tel.: +34 917 90 42 22
spain@takeda.com

Polska
Takeda Pharma sp. z o.o.
Tel.: +48 22 608 13 00



90

France
Takeda France SAS
Tel.: +33 1 40 67 33 00
medinfoEMEA@takeda.com

Portugal
Takeda Farmacêuticos Portugal, Lda.
Tel.: +351 21 120 1457

Hrvatska
Takeda Pharmaceuticals Croatia d.o.o.
Tel: +385 1 377 88 96

România 
Takeda Pharmaceuticals SRL
Tel.: +40 21 335 03 91

Ireland
Takeda Products Ireland Ltd.
Tel.: +353 (0) 1 6420021

Slovenija
Takeda GmbH, Podružnica Slovenija
Tel.: +386 (0) 59 082 480

Ísland
Vistor hf.
Tel.: +354 535 7000
vistor@vistor.is

Slovenská republika
Takeda Pharmaceuticals Slovakia s.r.o.
Tel.: +421 (2) 20 602 600

Italia
Takeda Italia S.p.A
Tel.: +39 06 502601

Suomi/Finland
Takeda Oy
Puh./Tel.: +358 20 746 5000
infoposti@takeda.com

Κύπρος
A.Potamitis Medicare Ltd
Tηλ: +357 22583333
info@potamitismedicare.com

Sverige
Takeda Pharma AB
Tel.: +46 8 731 28 00
infosweden@takeda.com

Latvija
Takeda Latvia SIA
Tel.: +371 67840082

United Kingdom
Takeda UK Ltd
Tel.: +44 (0)1628 537 900

This leaflet was last revised in 

Other sources of information

This leaflet is available in formats suitable for the blind or partially sighted patient and can be 
requested from respective local representative of the Marketing Authorisation Holder.

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.
-----------------------------------------------------------------------------------------------------------------------
The following information is intended for healthcare professionals only:

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



91

Instructions for use:

Read and follow these instructions before you inject. Your doctor, nurse or pharmacist should show 
you how to use the Entyvio pre-filled pen before you use it for the first time.

Your Entyvio single-dose pre-filled pen

Before Use

Purple Cap Viewing window

After Use

Yellow needle shield
Viewing window 
(Completed Injection)

1) Place what you need for the injection on a clean a flat surface 

 Take 1 pre-filled pen carton out of the refrigerator.
 Do not use the pre-filled pen if any of the seals on the carton

are broken or missing.
 Check the expiry date (EXP) on the carton. Do not use if the 

expiry date on the carton has passed.

 Wait 30 minutes to let the pre-filled pen come to room 
temperature. 
 Do not warm the pre-filled pen in any other way.
 Do not let it sit in direct sunlight. 
 Do not take the pre-filled pen out of its tray until you are ready 

to inject.

 You will also need:
 Alcohol pad 
 Cotton ball or gauze 
 Sharps disposal container

Wait 30 minutes



92

2) Open and check the pre-filled pen

 Wash your hands. 

 Peel back the paper on the tray and lift the pre-filled pen out.

 Inspect the pre-filled pen for damage.
 Do not use the pre-filled pen if any part of it is damaged.

 Check the expiry date on the pre-filled pen. 
 Do not use if the expiry date on the pre-filled pen has passed.

 Check the medicine. It should be colourless to yellow. 
 Do not use the pre-filled pen if the medicine is cloudy or has 

particles floating in it.

 You may see air bubbles in the pre-filled pen. This is normal.
 Do not shake

3) Prepare the injection site

 Choose an injection site on your bare skin from 1 of 
the following. 

 Front of the thighs, or
 Stomach area (abdomen) except for the area 5 cm around the 

belly button (navel), or
 Back of the upper arm (only if a caregiver gives the injection).

 Use a new injection site or a different area within the same
injection site for each injection.
 Do not inject into moles, scars, bruises, or skin that is tender, 

hard, red, or damaged.

 Wipe the chosen site with an alcohol pad. Let your skin dry.
 Do not touch this area again before you inject.

 Pull the purple cap straight off and throw it away.
 Do not put or press thumb, fingers or hand over the yellow 

needle shield. 
 Do not re-cap the pre-filled pen.
 Do not use a dropped pre-filled pen.



93

4) Inject Entyvio

 Hold the pre-filled pen so you can see the viewing window.

 Place the pre-filled pen at 90 degrees to the injection site.
 Be sure the yellow end is toward the injection site.
 Do not push down until you are ready to inject.

 Push down on the pre-filled pen as far as it will go to begin the 
injection.

 Hold and count to 10 while pushing down with constant pressure. 
This will allow all of the medicine to be injected.
 You may hear 2 clicks, one at the start and one near the end of 

the injection.

 Confirm that the viewing window is filled with purple before 
you stop pushing.
 You will see a small amount of grey in the window. This is 

normal.

 Lift the pre-filled pen from the injection site.
 The yellow needle shield will drop down and lock over the 

needle.
 If the viewing window did not fill completely, call your doctor, 

nurse or pharmacist. You may not have received your full dose 
of medicine.

 You may see a small amount of blood at the injection site. 
If you do, press on your skin with a cotton ball or gauze.

PUSH

HOLD
(Count to 10)

CONFIRM

5) Throw away used material

 Put the used pre-filled pen in a puncture-resistant container, like a 
sharps container, immediately after use.
 Dispose of your sharps container according to your local 

regulations.

 The rest of the material can be thrown away in your household 
rubbish.


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET