Prescribing Entyvio

The administration of Entyvio (vedolizumab) should be initiated and supervised by specialist healthcare professionals experienced in the diagnosis and treatment of ulcerative colitis (UC) or Crohn’s disease (CD).1

Please refer to the Entyvio Summary of Product Characteristics for full dosing and administration guidance in UC and CD.

Patients should be given the package leaflet and the patient alert card.1

Select from the options below for further information:

The recommended dose of Entyvio for both UC and CD is 300 mg administered by intravenous infusion at Weeks 0, 2 and 6 and then every 8 weeks thereafter.1

Therapy for patients with ulcerative colitis should be discontinued if no evidence of therapeutic benefit is observed by week 10.1

Some patients with UC who have experienced a decrease in their response may benefit from an increase in dosing frequency to every 4 weeks.1

In patients who have responded to treatment with Entyvio, steroids may be reduced and/or discontinued in accordance with standard of care.1

Maintenance chart

* Patients should be monitored during the infusion and for 2 hours after their first 2 infusions. This can be reduced to 1 hour for subsequent infusions.1
Patients with CD who have not shown a response may benefit from an additional dose of Entyvio at Week 10. Continue therapy every 8 weeks from week 14 in responding patients.

The recommended dose of Entyvio for both UC and CD is 300 mg administered by intravenous infusion at Weeks 0, 2 and 6 and then every 8 weeks thereafter.1

Patients with CD who have not shown a response may benefit from an additional dose of Entyvio at Week 10. Continue therapy every 8 weeks from Week 14 in responding CD patients. Therapy for patients with CD should not be continued if no evidence of therapeutic benefit is seen by Week 14.1

In patients who have responded to treatment with Entyvio, steroids may be reduced and/or discontinued in accordance with standard of care.1

Maintenance chart

* Patients should be monitored during the infusion and for 2 hours after their first 2 infusions. This can be reduced to 1 hour for subsequent infusions.1
Patients with CD who have not shown a response may benefit from an additional dose of Entyvio at Week 10. Continue therapy every 8 weeks from week 14 in responding patients.

Entyvio is administered as an intravenous infusion over 30 minutes. It requires reconstitution and further dilution prior to intravenous administration. Patients should be monitored during and after infusion.1

Vedolizumab should be administered in a healthcare setting equipped to allow management of acute hypersensitivity reactions including anaphylaxis, if they occur. Appropriate monitoring and medical support measures should be available for immediate use when administering vedolizumab. All patients should be observed continuously during each infusion. For the first two 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 one hour following completion of the infusion.

Instructions for reconstitution and infusion


1

Use aseptic technique when preparing Entyvio solution for intravenous infusion. Remove flip-off cap from the vial and wipe with alcohol swab. Reconstitute vedolizumab with 4.8 ml of sterile water for injection at room temperature (20–25°C), using a syringe with a 21–25 gauge needle.

2

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.

3

Gently swirl the vial for at least 15 seconds. Do not vigorously shake or invert.

4

Let the vial sit for up to 20 minutes to room temperature (20–25°C) 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.

5

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.

6

Once dissolved, gently invert vial 3 times.

7

Immediately withdraw 5 ml (300 mg) of reconstituted Entyvio using a syringe with a 21–25 gauge needle.

8

Add the 5 ml (300 mg) of reconstituted Entyvio to 250 ml of sterile 0.9% sodium chloride solution, and gently mix the infusion bag (5 ml of 0.9% sodium chloride solution 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. Do not store any unused portion of the infusion solution for reuse. Each vial is for single-use only. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Instructions for Storage and shelf life

Entyvio has a shelf life of 3 years.

In-use stability of the reconstituted solution in the vial has been demonstrated for 8 hours at 2–8°C.

In-use stability of the diluted solution in 0.9% sodium chloride solution in infusion bag has been demonstrated for 12 hours at 20–25°C or 24 hours at 2–8°C.

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

Storage condition
Refridgerator (2-8°C) 20-25°C
Reconstituted solution in the vial 8 hours Do not hold*
Diluted solution in 0.9% sodium chloride solution 24 hours†‡ 12 hours

* Up to 30 minutes are allowed for reconstitution.

This time assumes the reconstituted solution is immediately diluted in the 0.9% sodium chloride solution 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.

This period may include up to 12 hours at 20–25°C.

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

If therapy is interrupted and there is a need to restart treatment with Entyvio, dosing at every 4 weeks may be considered.1

The treatment interruption period in clinical trials extended up to 1 year. Efficacy was regained with no evident increase in adverse events or infusion-related reactions during retreatment with vedolizumab.1

Please refer to the Entyvio Summary of Product Characteristics for full safety information.

Contraindications

Entyvio is contraindicated in patients with hypersensitivity to the active substance vedolizumab or to any of the following excipients: L-histidine, L-histidine monohydroxychloride, L-arginine hydroxycholoride, sucrose, and polysorbate 80.1

Entyvio should not be used in patients with:

  • Active severe infections, such as tuberculosis (TB), sepsis, cytomegalovirus, listeriosis
  • Opportunistic infections, such as progressive multifocal leukoencephalopathy (PML)

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Special Warnings and Precautions for Use

Vedolizumab should be administered in a healthcare setting equipped to allow management of acute hypersensitivity reactions including anaphylaxis, if they occur. Appropriate monitoring and medical support measures should be available for immediate use when administering vedolizumab.

All patients should be observed continuously during each infusion. For the first two 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.

Infusion-related Reactions

Infusion-related reactions (IRR) and hypersensitivity reactions have been reported in clinical studies, with the majority being mild to moderate in severity.1

If a severe IRR, anaphylactic reaction, or other severe reaction occurs, administration of Entyvio must be discontinued immediately and appropriate treatment initiated (e.g., adrenaline and antihistamines).1

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.1

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.1

Infections

Vedolizumab is a gut-selective integrin antagonist with no identified systemic immunosuppressive activity.

Physicians should be aware of the potential increased risk of opportunistic infections or infections for which the gut is a defensive barrier. Entyvio 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 Entyvio. 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. Entyvio is contraindicated in patients with active tuberculosis (TB). Before starting treatment with vedolizumab, patients must be screened for TB according to the local practice. If latent TB is diagnosed, appropriate treatment must be started with anti-TB 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 virus. By binding to the α4β7 integrin expressed on gut-homing lymphocytes, vedolizumab exerts an immunosuppressive effect on 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 patients 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 UC and CD. Immunomodulatory medicinal products may increase of malignancy.

Prior and Concurrent Use of Biologic 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 Entyvio in these patients.

Patients previously exposed to natalizumab should normally wait a minimum of 12 weeks prior to initiating therapy with Entyvio, 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 Entyvio 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 three 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 Entyvio 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 CD 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.1

Exploratory subgroup analyses from the clinical trials in CD suggested that vedolizumab administered in patients without concomitant steroid treatment may be less effective for induction of remission in CD than in those patients already receiving concomitant steroids (regardless of use of concomitant immunomodulators).1

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Adverse Events

1 in 10 People or More

Very Common

  • Arthralgia
  • Headache
  • Nasopharyngitis

1 in 10 People
or Less

Common

  • Abdominal distension
  • Acne
  • Anal abscess
  • Anal fissure
  • Back pain
  • Bronchitis
  • Constipation
  • Cough
  • Eczema
  • Erythema
  • Dyspepsia
  • Fatigue
  • Flatulence
  • Gastroenteritis
  • Haemorrhoids
  • Hypertension
  • Influenza
  • Muscle spasms
  • Muscular weakness
  • Nasal congestion
  • Nausea
  • Night sweats
  • Oropharyngeal pain
  • Pain in the extremity
  • Paraesthesia
  • Pharyngitis
  • Pruritus
  • Pyrexia
  • Rash
  • Sinusitis
  • Upper respiratory tract infection

1 in 100 People
or Less

Uncommon

  • Chills
  • Feeling cold
  • Infusion related reaction
  • Infusion site reaction (including infusion site pain and infusion site irritation)
  • Oral candidiasis
  • Redness and tenderness of hair follicle
  • Respiratory tract infection
  • Throat and mouth yeast infection
  • Vaginal infection
  • Vulvovaginal candidiasis
  • Shingles (herpes zoster)

1 in 10,000 People or Less

Very rare

  • Pneumonia
  • Blurred vision
  • 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)
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Adverse events should be reported. In the United Kingdom, reporting forms and information can be found at www.mhra.gov.uk/yellowcard.

Adverse events should also be reported to Takeda on 01628 537900 or e-mail DSO-UK@takeda.com