Entyvio

ENTYVIO is indicated in adults for the treatment of:

• moderately to severely active ulcerative colitis (UC).
• moderately to severely active Crohn's disease (CD).

• Before initiating ENTYVIO, update immunizations according to current immunization guidelines. (
  2.1 Important Administration Information

  Before initiating ENTYVIO, update immunizations according to current immunization guidelines

  [see Warnings and Precautions (5.5)].

  Intravenous Administration

  • ENTYVIO should be administered by a healthcare provider prepared to manage hypersensitivity reactions including anaphylaxis, if they occur
    [see Warnings and Precautions (5.1)]
    . Appropriate monitoring and medical support measures should be available for immediate use. Observe patients during infusion and until the infusion is complete.
  • Reconstitute and dilute ENTYVIO lyophilized powder prior to administration as a 30-minute intravenous infusion
    [see Dosage and Administration (2.3)].

  Subcutaneous Injection

  • ENTYVIO prefilled syringe and ENTYVIO PEN are intended for subcutaneous use under the guidance and supervision of a healthcare professional.
  • Patients may self-inject or caregivers may inject subcutaneous ENTYVIO using either the ENTYVIO prefilled syringe or ENTYVIO PEN after training in subcutaneous injection technique. Provide proper training to patients and/or caregivers on the subcutaneous injection technique of ENTYVIO.
  ,
  5.5 Live and Oral Vaccines

  Prior to initiating treatment with ENTYVIO, all patients should be brought up to date with all immunizations according to current immunization guidelines

  [see Dosage and Administration (2.1)]

  .

  Patients receiving ENTYVIO may receive non-live vaccines (e.g., influenza vaccine injection) and may receive live vaccines if the benefits outweigh the risks. There are no data on the secondary transmission of infection by live vaccines in patients receiving ENTYVIO

  [see Adverse Reactions (6.1)]

  .
  )
• Intravenous Administration
  : ENTYVIO should be administered intravenously by a healthcare provider. (
  2.1 Important Administration Information

  Before initiating ENTYVIO, update immunizations according to current immunization guidelines

  [see Warnings and Precautions (5.5)].

  Intravenous Administration

  • ENTYVIO should be administered by a healthcare provider prepared to manage hypersensitivity reactions including anaphylaxis, if they occur
    [see Warnings and Precautions (5.1)]
    . Appropriate monitoring and medical support measures should be available for immediate use. Observe patients during infusion and until the infusion is complete.
  • Reconstitute and dilute ENTYVIO lyophilized powder prior to administration as a 30-minute intravenous infusion
    [see Dosage and Administration (2.3)].

  Subcutaneous Injection

  • ENTYVIO prefilled syringe and ENTYVIO PEN are intended for subcutaneous use under the guidance and supervision of a healthcare professional.
  • Patients may self-inject or caregivers may inject subcutaneous ENTYVIO using either the ENTYVIO prefilled syringe or ENTYVIO PEN after training in subcutaneous injection technique. Provide proper training to patients and/or caregivers on the subcutaneous injection technique of ENTYVIO.
  )
• Subcutaneous Injection
  : ENTYVIO prefilled syringe and ENTYVIO PEN are intended for subcutaneous use. A patient may self-inject or caregiver may inject after proper training on correct subcutaneous injection technique. (
  2.1 Important Administration Information

  Before initiating ENTYVIO, update immunizations according to current immunization guidelines

  [see Warnings and Precautions (5.5)].

  Intravenous Administration

  • ENTYVIO should be administered by a healthcare provider prepared to manage hypersensitivity reactions including anaphylaxis, if they occur
    [see Warnings and Precautions (5.1)]
    . Appropriate monitoring and medical support measures should be available for immediate use. Observe patients during infusion and until the infusion is complete.
  • Reconstitute and dilute ENTYVIO lyophilized powder prior to administration as a 30-minute intravenous infusion
    [see Dosage and Administration (2.3)].

  Subcutaneous Injection

  • ENTYVIO prefilled syringe and ENTYVIO PEN are intended for subcutaneous use under the guidance and supervision of a healthcare professional.
  • Patients may self-inject or caregivers may inject subcutaneous ENTYVIO using either the ENTYVIO prefilled syringe or ENTYVIO PEN after training in subcutaneous injection technique. Provide proper training to patients and/or caregivers on the subcutaneous injection technique of ENTYVIO.
  )

• Week 0
  : 300 mg infused intravenously over approximately 30 minutes.
• Week 2
  : 300 mg infused intravenously over approximately 30 minutes.
• Week 6
  : Patients may remain on ENTYVIO intravenous therapy or switch to subcutaneous injection after receiving two ENTYVIO intravenous doses administered at Week 0 and Week 2.
  
  • Intravenous Infusion
    : 300 mg infused over approximately 30 minutes and then every eight weeks thereafter.
  • Subcutaneous Injection
    : 108 mg subcutaneously once every two weeks.
• Discontinue ENTYVIO in patients who do not show evidence of therapeutic benefit by Week 14.
• Patients currently receiving and responding to ENTYVIO intravenous therapy after Week 6 may also be switched to subcutaneous injection. Administer the first subcutaneous dose in place of the next scheduled intravenous infusion and every two weeks thereafter.

• See full prescribing information for complete information on reconstitution, dilution, administration, and storage. (
  2.3 Preparation and Administration Instructions for Intravenous Infusion

  Reconstitution Instructions

  • Remove the flip-off cap from the single-dose vial and wipe with alcohol swab. Reconstitute ENTYVIO vial containing lyophilized powder with 4.8 mL of Sterile Water for injection, 0.9% Sodium Chloride Injection, or Lactated Ringer's Injection, at room temperature (20°C to 25°C [68ºF to 77ºF]), using a syringe with a 21- to 25-gauge needle.
  • Insert the syringe needle into the vial through the center of the stopper and direct the stream of Sterile Water for Injection, 0.9% Sodium Chloride Injection, or Lactated Ringer's Injection, to the glass wall of the vial to avoid excessive foaming.
  • Gently swirl the vial for at least 15 seconds to dissolve the lyophilized powder.
    Do not vigorously shake or invert.
  • Allow the solution to sit for up to 20 minutes at room temperature 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. Do not use the vial if the drug product is not dissolved within 30 minutes.
  • Visually inspect the reconstituted ENTYVIO solution for particulate matter and discoloration prior to dilution. Solution should be clear or opalescent, colorless to light brownish yellow and free of visible particulates. Do not administer reconstituted solution showing uncharacteristic color or containing particulates.
  • Once dissolved, gently invert vial three times.
  • Immediately, withdraw 5 mL (300 mg) of reconstituted ENTYVIO solution using a syringe with a 21- to 25-gauge needle. Discard any remaining portion of the reconstituted solution in the vial.

  Dilution Instructions

  Add the 5 mL (300 mg) of reconstituted ENTYVIO solution to 250 mL of 0.9% Sodium Chloride Injection, or Lactated Ringer's Injection, and gently mix the infusion bag. Do not add other medicinal products to the prepared infusion solution or intravenous infusion set. Once reconstituted and diluted, use the infusion solution as soon as possible.

  Discard any unused portion of the infusion solution

  .

  Administration Instructions

  After the infusion is complete, flush with 30 mL of 0.9% Sodium Chloride Injection, or Lactated Ringer's Injection.

  Storage and Stability

  Specific storage conditions and timing for the reconstituted solution in vial and diluted solution in the infusion bag are outlined in

  Table 1

  .

  Do not freeze the reconstituted solution in the vial or the diluted solution in the infusion bag.

  Table 1. Storage Instructions for Reconstituted Solution in Vial and Diluted Solution in Infusion Bag

  Solution	Storage Conditions
  	Refrigeration (2°C to 8°C [36°F to 46°F])	Room Temperature (20°C to 25°C [68°F to 77°F])
  Reconstituted Solution (in Sterile Water for Injection, 0.9% Sodium Chloride Injection, or Lactated Ringer's Injection, inside vial)	8 hours	Use immediately after reconstitution
  Diluted Solution (in 0.9% Sodium Chloride Injection)	24 hoursThis time assumes the reconstituted solution is immediately diluted in the 0.9% Sodium Chloride Injection, or Lactated Ringer's Injection, and held in the infusion bag only. Any time that the reconstituted solution was held in 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 room temperature (20°C to 25°C [68°F to 77°F]).	12 hours
  Diluted Solution (in Lactated Ringer's Injection)	6 hours	Use immediately after dilution

  The combined storage time of reconstituted ENTYVIO solution in the vial and the diluted solution in the infusion bag with 0.9% Sodium Chloride Injection, is a total of 12 hours at room temperature (20°C to 25°C [68°F to 77°F]) or 24 hours refrigerated (2°C to 8°C [36°F to 46°F]). This combined storage time may include up to eight hours of the reconstituted solution in the vial at 2°C to 8°C.

  The combined storage time of reconstituted ENTYVIO solution in the vial and the diluted solution in the infusion bag with Lactated Ringer's Injection, is a total of six hours refrigerated (2°C to 8°C [36°F to 46°F]).
  ,
  2.4 Preparation and Administration Instructions for Subcutaneous Injection

  • Inspect the solution visually for particulate matter and discoloration prior to administration. ENTYVIO in prefilled syringe or ENTYVIO PEN should be a clear to moderately opalescent, colorless to slightly yellow solution. Do not use ENTYVIO prefilled syringes or ENTYVIO PENs with visible particulate matter or discoloration.
  • Administer each subcutaneous injection at a different anatomic location (such as thighs, any quadrant of abdomen, or upper arms) than the previous injection. Administration of ENTYVIO in the back of upper arm may only be performed by a healthcare professional or caregiver. Do not inject into moles, scars, bruises, or areas where the skin is tender, erythematous, or indurated.

  Missed Subcutaneous Dose

  If treatment with subcutaneous ENTYVIO is interrupted or if a scheduled dose(s) of subcutaneous ENTYVIO is missed, inject the next subcutaneous dose as soon as possible and then every 2 weeks thereafter.

  In the event of incomplete dose administration (i.e., patient attempts administration of dose with ENTYVIO PEN, however it is uncertain if a full dose was administered), instruct the patient to call their pharmacy or healthcare provider.
  )

• For injection: 300 mg vedolizumab in a single-dose vial. (
  3 DOSAGE FORMS AND STRENGTHS

  Intravenous infusion

  • For injection: 300 mg vedolizumab in a single-dose vial.

  Subcutaneous injection

  • Injection: 108 mg/0.68 mL solution in a single-dose prefilled syringe with needle safety device.
  • Injection: 108 mg/0.68 mL solution in a single-dose prefilled pen (ENTYVIO PEN).

  Intravenous Infusion

  • For injection: 300 mg of vedolizumab as a white to off-white lyophilized cake in a single-dose vial for reconstitution.

  Subcutaneous Injection

  • Injection: 108 mg/0.68 mL vedolizumab as a clear to moderately opalescent, colorless to slightly yellow solution in a single-dose prefilled syringe with needle safety device.
  • Injection: 108 mg/0.68 mL vedolizumab as a clear to moderately opalescent, colorless to slightly yellow solution in a single-dose prefilled pen (ENTYVIO PEN).
  )

• Injection: 108 mg/0.68 mL solution in a single-dose prefilled syringe with needle safety device. (
  3 DOSAGE FORMS AND STRENGTHS

  Intravenous infusion

  • For injection: 300 mg vedolizumab in a single-dose vial.

  Subcutaneous injection

  • Injection: 108 mg/0.68 mL solution in a single-dose prefilled syringe with needle safety device.
  • Injection: 108 mg/0.68 mL solution in a single-dose prefilled pen (ENTYVIO PEN).

  Intravenous Infusion

  • For injection: 300 mg of vedolizumab as a white to off-white lyophilized cake in a single-dose vial for reconstitution.

  Subcutaneous Injection

  • Injection: 108 mg/0.68 mL vedolizumab as a clear to moderately opalescent, colorless to slightly yellow solution in a single-dose prefilled syringe with needle safety device.
  • Injection: 108 mg/0.68 mL vedolizumab as a clear to moderately opalescent, colorless to slightly yellow solution in a single-dose prefilled pen (ENTYVIO PEN).
  )
• Injection: 108 mg/0.68 mL solution in a single-dose prefilled pen (ENTYVIO PEN). (
  3 DOSAGE FORMS AND STRENGTHS

  Intravenous infusion

  • For injection: 300 mg vedolizumab in a single-dose vial.

  Subcutaneous injection

  • Injection: 108 mg/0.68 mL solution in a single-dose prefilled syringe with needle safety device.
  • Injection: 108 mg/0.68 mL solution in a single-dose prefilled pen (ENTYVIO PEN).

  Intravenous Infusion

  • For injection: 300 mg of vedolizumab as a white to off-white lyophilized cake in a single-dose vial for reconstitution.

  Subcutaneous Injection

  • Injection: 108 mg/0.68 mL vedolizumab as a clear to moderately opalescent, colorless to slightly yellow solution in a single-dose prefilled syringe with needle safety device.
  • Injection: 108 mg/0.68 mL vedolizumab as a clear to moderately opalescent, colorless to slightly yellow solution in a single-dose prefilled pen (ENTYVIO PEN).
  )

Available data from the Organization of Teratology Information Specialists (OTIS)/MotherToBaby ENTYVIO Pregnancy Registry, published literature and pharmacovigilance in pregnant women have not reliably identified an ENTYVIO-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes

No fetal harm was observed in animal reproduction studies with intravenous administration of vedolizumab to rabbits and monkeys at dose levels 20 times the recommended human dosage

The background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and miscarriage is 15 to 20%, respectively.