ENTYVIO (vedolizumab)

ENTYVIO (vedolizumab) for injection

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ENTYVIO (vedolizumab) for injection

Vedolizumab, an integrin receptor antagonist, is a humanized IgG1 monoclonal antibody produced in Chinese hamster ovary cells that binds to the human α4β7 integrin. ENTYVIO has an approximate molecular weight of 147 kilodaltons.

ENTYVIO (vedolizumab) for injection is supplied as a sterile, white to off-white, preservativefree, lyophilized cake for intravenous infusion. After reconstitution with 4.8 mL Sterile Water for Injection, USP, the final concentration is 60 mg/mL with a deliverable volume of 5 mL (300 mg) and the resulting pH is approximately 6.3.

Each single-dose vial contains 300 mg vedolizumab, L-arginine hydrochloride (131.7 mg), L-histidine (23 mg), L-histidine monohydrochloride (21.4 mg), polysorbate 80 (3 mg), and sucrose (500 mg).

Indications and usage

ENTYVIO is indicated in adults for the treatment of:

  • moderately to severely active ulcerative colitis.
  • moderately to severely active Crohn’s disease.

Mechanism of Action

Vedolizumab is a humanized monoclonal antibody that specifically binds to the α4β7 integrin and blocks the interaction of α4β7 integrin with mucosal addressin cell adhesion molecule-1 (MAdCAM-1) and inhibits the migration of memory T-lymphocytes across the endothelium into inflamed gastrointestinal parenchymal tissue. Vedolizumab does not bind to or inhibit function of the α4β1 and αEβ7 integrins and does not antagonize the interaction of α4 integrins with vascular cell adhesion molecule-1 (VCAM-1).

The α4β7 integrin is expressed on the surface of a discrete subset of memory T-lymphocytes that preferentially migrate into the gastrointestinal tract. MAdCAM-1 is mainly expressed on gut endothelial cells and plays a critical role in the homing of T-lymphocytes to gut lymph tissue. The interaction of the α4β7 integrin with MAdCAM-1 has been implicated as an important contributor to the chronic inflammation that is a hallmark of ulcerative colitis and Crohn’s disease.

Dosage and administration

  • Administer ENTYVIO as an intravenous infusion over 30 minutes. Do not administer as an intravenous push or bolus.
  • Reconstitute ENTYVIO lyophilized powder with Sterile Water for Injection and dilute in 250 mL of sterile 0.9% Sodium Chloride Injection or sterile Lactated Ringer’s Injection prior to administration
  • After the infusion is complete, flush with 30 mL of sterile 0.9% Sodium Chloride Injection or sterile Lactated Ringer’s Injection.
  • ENTYVIO should be administered by a healthcare professional prepared to manage hypersensitivity reactions including anaphylaxis, if they occur.

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

Dosage in Adults with Ulcerative Colitis or Crohn’s Disease: The recommended dosage of ENTYVIO in adults with ulcerative colitis or Crohn’s disease is 300 mg administered by intravenous infusion at zero, two and six weeks and then every eight weeks thereafter.

Discontinue therapy in patients who show no evidence of therapeutic benefit by Week 14.

Contraindications

ENTYVIO is contraindicated in patients who have had a known serious or severe hypersensitivity reaction to ENTYVIO or any of its excipients (such as dyspnea, bronchospasm, urticaria, flushing, rash and increased heart rate)

Warnings and precautions

Infusion-Related Reactions and Hypersensitivity Reactions: Infusion-related reactions and hypersensitivity reactions have been reported, including anaphylaxis, dyspnea, bronchospasm, urticaria, flushing, rash, and increased blood pressure and heart rate. These re actions may occur with the first or subsequent infusions of ENTYVIO and may vary in their time of onset from during infusion or up to several hours post-infusion.

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Infections: Patients treated with ENTYVIO are at increased risk for developing infections. The most commonly reported infections in clinical trials occurring at a rate greater on ENTYVIO than placebo involved the upper respiratory and nasal mucosa (e.g., nasopharyngitis, upper respiratory tract infection). Serious infections have also been reported in patients treated with ENTYVIO, including anal abscess, sepsis (some fatal), tuberculosis, salmonella sepsis, Listeria meningitis, giardiasis and cytomegaloviral colitis.

Progressive Multifocal Leukoencephalopathy: PML, a rare and often fatal opportunistic infection of the central nervous system (CNS), has been reported with systemic immunosuppressants, including another integrin receptor antagonist. PML is caused by the John Cunningham (JC) virus and typically only occurs in patients who are immunocompromised. One case of PML in an ENTYVIO-treated patient with multiple contributory factors has been reported in the postmarketing setting (e.g., human immunodeficiency virus [HIV] infection with a CD4 count of 300 cells/mm3 and prior and concomitant immunosuppression). Although unlikely, a risk of PML cannot be ruled out.

Liver Injury: There have been reports of elevations of transaminase and/or bilirubin in patients receiving ENTYVIO. In general, the combination of transaminase elevations and elevated bilirubin without evidence of obstruction is generally recognized as an important predictor of severe liver injury that may lead to death or the need for a liver transplant in some patients. ENTYVIO should be discontinued in patients with jaundice or other evidence of significant liver injury

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. Patients receiving ENTYVIO may receive non-live vaccines (e.g., influenza vaccine injection) and may receive live vaccines if the benefits outweigh the risks.

Adverse reactions

Most common adverse reactions (incidence ≥3% and ≥1% higher than placebo) are: nasopharyngitis, headache, arthralgia, nausea, pyrexia, upper respiratory tract infection, fatigue, cough, bronchitis, influenza, back pain, rash, pruritus, sinusitis, oropharyngeal pain, and pain in extremities.

Drug interactions

Natalizumab: Because of the potential for increased risk of PML and other infections, avoid the concomitant use of ENTYVIO with natalizumab.

TNF Blockers: Because of the potential for increased risk of infections, avoid the concomitant use of ENTYVIO with TNF blockers.

Live Vaccines: Live vaccines may be administered concurrently with ENTYVIO only if the benefits outweigh the risks

Use in specific populations

Pregnancy: Available pharmacovigilance data, data from the ongoing pregnancy registry, and data from published case reports and cohort studies in pregnant women have not identified an ENTYVIO associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.

Published data suggest that the risk of adverse pregnancy outcomes in women with inflammatory bowel disease (IBD) is associated with increased disease activity. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2,500 g) infants, and small for gestational age at birth.

Lactation: Data from a clinical lactation study show the presence of vedolizumab in human milk. The mean calculated daily infant dosage was 0.02 mg/kg/day orally. Systemic exposure in a breastfed infant is expected to be low because monoclonal antibodies are largely degraded in the gastrointestinal tract. There are no data on the effects of vedolizumab on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ENTYVIO and any potential adverse effects on the breastfed infant from ENTYVIO or from the underlying maternal condition.

Pediatric Use: Safety and effectiveness of ENTYVIO in pediatric patients have not been established.

Geriatric Use: Clinical trials of ENTYVIO did not include sufficient numbers of subjects aged 65 and over (46 Crohn’s and ulcerative colitis patients aged 65 and over were treated with ENTYVIO during controlled Phase 3 trials) to determine whether they respond differently from younger subjects. However, no overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients.

Storage and handling

Refrigerate unopened vials at 2° to 8°C (36° to 46°F). Retain in original package to protect from light.

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