Entyvio

Entyvio (vedolizumab) is used to treat moderately to severely active ulcerative colitis (UC) and moderately to severely active Crohn's disease (CD) in adults.

Entyvio is an integrin receptor antagonist. It targets white blood cells that move into the gut, which helps reduce the inflammation that causes UC and CD symptoms.

Entyvio can be given as an intravenous (IV) infusion by a healthcare provider, or as a subcutaneous injection (under the skin) using a prefilled syringe or prefilled pen (Entyvio Pen). After training, you or a caregiver can give the subcutaneous injections at home. Treatment always starts with at least 2 IV infusions.

Entyvio IV infusion was first approved by the FDA on May 20, 2014, for UC and CD. Subcutaneous Entyvio was approved for maintenance treatment of UC in September 2023 and of CD in April 2024.

It is not known if Entyvio is safe and effective in children under 18 years of age.

Entyvio is a humanized monoclonal antibody. It binds to a protein called α4β7 integrin, which is found on the surface of certain memory T-lymphocytes (a type of white blood cell) that tend to travel to the gastrointestinal (GI) tract.

Normally, α4β7 integrin attaches to a partner protein called MAdCAM-1, which is found mainly on the lining of blood vessels in the gut. This interaction helps T-lymphocytes leave the bloodstream and enter gut tissue, and it is thought to be an important contributor to the chronic inflammation of UC and CD. By blocking this interaction, Entyvio stops these T-lymphocytes from moving into inflamed gut tissue.

Entyvio does not bind to α4β1 or αEβ7 integrins, which is why its action is focused on the gut. However, Entyvio can still increase the risk of infections (see Serious side effects below).

Entyvio was studied in 6 randomized, double-blind, placebo-controlled trials in adults with moderately to severely active UC or CD. Most people in these trials had not responded well to, or could not tolerate, corticosteroids, immunomodulators (such as azathioprine), or a TNF blocker.

Induction trials looked at results after the first 2 IV doses. Maintenance trials included only people who had responded to IV Entyvio by week 6. They were then randomly assigned to keep receiving Entyvio or switch to placebo, and were followed to week 52.

In the IV maintenance trials, more people who were taking corticosteroids at the start were able to stop them and stay in remission at week 52 with Entyvio than with placebo (31% vs 14% in UC and 32% vs 16% in CD). In UC, Entyvio also improved the appearance of the bowel lining on endoscopy.

A second CD induction trial, in which most patients had previously failed a TNF blocker, did not show a statistically significant difference in remission at week 6 (15% with Entyvio vs 12% with placebo).

Giving IV Entyvio every 4 weeks did not work better than every 8 weeks.

Entyvio is given into a vein (intravenously) by a healthcare provider, or under the skin (subcutaneously) by a healthcare provider, a caregiver, or yourself.

Entyvio infusion

• You may receive Entyvio through a needle placed in a vein (intravenous infusion) in your arm.
• Entyvio is given over about 30 minutes.
• Your healthcare provider will monitor you during and after the infusion for side effects to see if you have a reaction to the treatment.

Entyvio subcutaneous injection

• You may receive your first subcutaneous injection after at least 2 IV infusions, in place of your next scheduled infusion. After that, Entyvio is injected under the skin 1 time every 2 weeks.
• Entyvio is available as a single-dose prefilled syringe or a single-dose prefilled pen (Entyvio Pen). Your healthcare provider will prescribe the type that is best for you.
• If your healthcare provider decides that you or your caregiver can give injections at home, you or your caregiver should be shown the right way to prepare and inject Entyvio. Do not inject Entyvio until you have been shown how.
• Always check the label of your prefilled syringe or pen to make sure you have the correct medicine before each injection.
• Do not shake Entyvio.
• Inject Entyvio into your upper legs (thighs) or stomach area (abdomen). The upper arms may also be used if a caregiver gives the injection.
• Use a different injection site each time. Do not inject into moles, scars, bruises, or skin that is tender, hard, red, or damaged.

See the detailed Instructions for Use that come with Entyvio for how to prepare and give an injection.

What happens if I miss a dose?

If you are not able to inject Entyvio at your regular time, or you miss a dose, inject the dose as soon as possible. Then inject your next dose every 2 weeks after that. If you are not sure when to inject Entyvio, call your healthcare provider.

What happens if I use too much?

If you inject more Entyvio than you were told to, call your healthcare provider.

Do not receive Entyvio if you have had an allergic reaction to Entyvio or any of the ingredients in Entyvio.

Before receiving Entyvio, tell your healthcare provider about all of your medical conditions, including if you:

• Have an infection, think you may have an infection, or have infections that keep coming back
• Have liver problems
• Have TB or have been in close contact with someone with TB
• Have recently received or are scheduled to receive a vaccine. Talk to your healthcare provider about bringing your vaccines up to date before starting treatment with Entyvio
• Are pregnant or plan to become pregnant
• Are breastfeeding or plan to breastfeed.

Your healthcare provider may check you for TB before you start Entyvio.

Pregnancy

It is not known if Entyvio will harm your unborn baby. Tell your healthcare provider right away if you become pregnant while receiving Entyvio.

Data from a pregnancy registry, published studies, and safety reports have not reliably identified a risk of major birth defects, miscarriage, or other problems for the mother or baby with Entyvio. Active inflammatory bowel disease during pregnancy is linked to a higher risk of preterm delivery and low birth weight.

Entyvio received during pregnancy could affect the immune response of a newborn baby. It is not known if live vaccines are safe for babies who were exposed to Entyvio in the womb, so make sure any doctor caring for your baby knows you received Entyvio during pregnancy.

Breastfeeding

Entyvio can pass into breast milk in small amounts. The effects on a breastfed baby are not known. Talk to your healthcare provider about the best way to feed your baby if you receive Entyvio.

Common side effects

In clinical trials, side effects were reported in 52% of people receiving IV Entyvio and 45% of people receiving placebo. Serious side effects occurred in 7% of people receiving Entyvio and 4% receiving placebo.

The most common side effects of Entyvio, reported in at least 3% of people and more often than with placebo, were:

Side effects with subcutaneous Entyvio were similar to those with IV Entyvio, except for injection site reactions. These occurred in 10% of people with UC and 3% of people with CD, and included pain, swelling, itching, hives, bruising, rash, or redness at the injection site.

Infusion-related reactions occurred in 4% of people receiving IV Entyvio and 3% receiving placebo. These usually happened within 2 hours after the infusion.

Serious side effects

Entyvio may cause serious side effects, including:

• Infusion-related and serious allergic reactions. These reactions can happen while you are receiving Entyvio or several hours after treatment, and with the first or later infusions. You may need treatment if you have an allergic reaction. Tell your healthcare provider or get medical help right away if you get any of these symptoms during or after an infusion of Entyvio: Rash Itching Swelling of your lips, tongue, throat, or face Shortness of breath or trouble breathing Wheezing Dizziness Feeling hot Palpitations (feel like your heart is racing).
• Infections. Entyvio may increase your risk of getting a serious infection. Serious infections reported in clinical trials include anal abscess, sepsis (some fatal), tuberculosis (TB), salmonella sepsis, Listeria meningitis, giardiasis, and cytomegalovirus colitis. Bacterial, fungal, viral, and parasitic opportunistic infections have also been reported since Entyvio was approved. Before receiving Entyvio and during treatment, tell your healthcare provider if you think you have an infection or have symptoms of an infection, such as: Fever Chills Muscle aches Cough Shortness of breath Runny nose Sore throat Red or painful skin or sores on your body Tiredness Pain during urination. If you have an infection, Entyvio should not be started, or given again, until the infection has cleared or been treated. Your healthcare provider may test you for TB before you start Entyvio, and if you are at risk for TB, you may be treated with medicine for TB before you begin treatment.
• Progressive multifocal leukoencephalopathy (PML). People with weakened immune systems can get PML, a rare, serious brain infection caused by a virus. PML has been reported with another integrin receptor antagonist. One case has been reported in a person receiving Entyvio who had other risk factors, including HIV infection and past and current immunosuppressant treatment. Although unlikely while receiving Entyvio, a risk of PML cannot be ruled out. PML can result in death or severe disability. There is no known treatment, prevention, or cure for PML. Tell your healthcare provider right away if you have any of the following symptoms: Confusion or problems thinking Loss of balance Change in the way you walk or talk Decreased strength or weakness on one side of the body Blurred vision or loss of vision.
• Liver problems. Liver problems, including raised liver enzymes and bilirubin, can happen in people who receive Entyvio. Entyvio should be stopped if you develop jaundice or other signs of significant liver injury. Tell your healthcare provider right away if you have any of the following symptoms: Tiredness Loss of appetite Pain on the right side of your stomach (abdomen) Dark urine Yellowing of the skin and eyes (jaundice).

Other side effects reported since Entyvio was approved include anaphylaxis (a severe allergic reaction), acute pancreatitis, interstitial lung disease, and pneumonitis (lung inflammation).

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Usual adult dose for ulcerative colitis or Crohn's disease

Induction (IV infusion):

• Week 0: 300 mg infused intravenously over about 30 minutes
• Week 2: 300 mg infused intravenously over about 30 minutes.

Maintenance, starting at week 6 (IV or subcutaneous):

• IV infusion: 300 mg over about 30 minutes at week 6, then every 8 weeks
• Subcutaneous injection: 108 mg every 2 weeks.

People who are receiving and responding to IV Entyvio after week 6 may also switch to subcutaneous injections. The first injection is given in place of the next scheduled infusion, then every 2 weeks.

Entyvio should be stopped if there is no evidence of benefit by week 14.

Before starting Entyvio, your vaccines should be brought up to date. While receiving Entyvio, you may receive non-live vaccines, such as the flu shot. Live vaccines may be given only if your healthcare provider decides the benefits outweigh the risks. Talk to your healthcare provider before receiving any vaccine.

Entyvio may increase your risk of infections. Tell your healthcare provider right away if you develop signs of an infection.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially tell your healthcare provider if you take or have recently taken:

• Tysabri (natalizumab) or Tyruko (natalizumab-sztn)
• A TNF blocker medicine, such as adalimumab or infliximab
• A medicine that weakens your immune system (immunosuppressant)
• A corticosteroid medicine.

Entyvio should not be used with natalizumab products, because of a possible increased risk of PML and other infections. Entyvio should not be used with TNF blockers, because of a possible increased risk of infections.

Inflammation can affect how the liver breaks down some medicines. When Entyvio is started or stopped, your healthcare provider may need to check levels of, or adjust the dose of, certain other medicines that are broken down by liver (CYP450) enzymes.

This is not a complete list of interactions. Other drugs may interact with vedolizumab, including prescription and over-the-counter medicines, vitamins, and herbal products. See the Entyvio Prescribing Information for more information.

• J3380: One billable unit of this code equals 1 mg of the drug.

• For IV infusion: 300 mg single-dose vial (white to off-white powder, mixed before use)
• For subcutaneous injection: 108 mg/0.68 mL single-dose prefilled syringe with needle safety device
• For subcutaneous injection: 108 mg/0.68 mL single-dose prefilled pen (Entyvio Pen).

• Store Entyvio vials, prefilled syringes, and pens in the refrigerator at 36°F to 46°F (2°C to 8°C).
• If needed, the prefilled syringe or pen can be kept out of the refrigerator in its box at room temperature up to 77°F (25°C) for up to 7 days, for example, when traveling. Do not use it if it has been out of the refrigerator for more than 7 days or left in direct sunlight.
• Do not freeze Entyvio. Do not use Entyvio if it has been frozen.
• Keep Entyvio in the original package to protect it from light until the time of use.

Entyvio is manufactured by Takeda Pharmaceuticals U.S.A., Inc., Cambridge, MA 02142.

Active ingredient: vedolizumab

Inactive ingredients (vial for IV infusion): arginine hydrochloride, histidine, histidine monohydrochloride, polysorbate 80, and sucrose.

Inactive ingredients (prefilled syringe or pen): arginine hydrochloride, citric acid monohydrate, histidine, histidine monohydrochloride, polysorbate 80, sodium citrate dihydrate, and Sterile Water for Injection.

The Entyvio prefilled syringe and Entyvio Pen are not made with natural rubber latex.