vedolizumab (Entyvio)

Dosing and uses of Entyvio (vedolizumab)

• Adult
• Pediatric

 

Adult dosage forms and strengths

lyophilized powder

• 300mg/vial (300mg/5mL after reconstituted)

 

Ulcerative Colitis

Indicated for adults with moderate-to-severe active ulcerative colitis who have had an inadequate response with, lost response to, or were intolerant of a TNF blocker or immunomodulator; or had an inadequate response with, were intolerant to, or demonstrated dependence on corticosteroids

Induction: 300 mg IV at weeks 0, 2, and 6, THEn

Maintenance: 300 mg IV q8weeks

Indication includes

• inducing and maintaining clinical response
• inducing and maintaining clinical remission
• improving the endoscopic appearance of the mucosa, and
• achieving corticosteroid-free remission

 

Crohn Disease

Indicated for adults with moderate-to-severe active Crohn disease who have had an inadequate response with, lost response to, or were intolerant of a TNF blocker or immunomodulator; or had an inadequate response with, were intolerant to, or demonstrated dependence on corticosteroids

Induction: 300 mg IV at weeks 0, 2, and 6, THEn

Maintenance: 300 mg IV q8weeks

Indication includes

• achieving clinical response
• achieving clinical remission, and
• achieving corticosteroid-free remission

 

Dosing Considerations

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

Discontinue if evidence of therapeutic benefit is not shown by week 14

 

Graft vs Host Disease (Orphan)

Orphan designation for prevention of graft versus host disease (GVHD)

Sponsor

• Millennium Pharmaceuticals, Inc; 40 Landsdowne St; Cambridge, Massachusetts 02139

 

Pediatric dosage forms and strengths

Safety and efficacy not established

 

Entyvio (vedolizumab) adverse (side) effects

>10%

Nasopharyngitis (13%)

Headache (12%)

Arthralgia (12%)

 

1-10%

Nausea (9%)

Pyrexia (9%)

Upper respiratory tract infection (7%)

Fatigue (6%)

Cough (5%)

Bronchitis (4%)

Influenza (4%)

Back pain (4%)

Rash (3%)

Pruritus (3%)

Sinusitis (3%)

Oropharyngeal pain (3%)

Pain in extremities (3%)

 

<1%

Infections (0.85% per patient-year)

Infusion-related hypersensitivity (0.07%)

Serious infections (0.06% per patient-year)

 

Warnings

Contraindications

Hypersensitivity

 

Cautions

Allergic reactions including dyspnea, bronchospasm, urticaria, flushing, rash, and increased BP and HR observed

Increased risk for developing infections; serious infections have also been reported, including anal abscess, sepsis (some fatal), tuberculosis, salmonella sepsis, Listeria meningitis, giardiasis, and cytomegaloviral colitis

Elevated liver transaminases and/or bilirubin reported; discontinue if jaundice occurs or other evidence of liver injury (eg, fatigue, anorexia, right upper abdominal discomfort); the combination of elevated transaminase and 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 liver transplantation

Immunizations for each patient should be current before initiating treatment; patients may receive nonlive vaccines (eg, influenza vaccine injection) and may receive live vaccines if the benefits outweigh the risks; there are no data on secondary transmission of infection by live vaccines in patients receiving vedolizumaB

Progressive multifocal leukoencephalopathy (PML)

• Another integrin receptor antagonist (natalizumab) has been associated with PML, a rare and often fatal opportunistic infection of the CNS
• Vedolizumab inhibits α4β7 integrin; whereas, natalizumab inhibits both α4β7 (gut integrin) and α4β1 (CNS integrin)
• In vedolizumab clinical trials, patients were actively monitored for PML with frequent and regular screenings and evaluations of any new, unexplained neurological symptoms, as necessary
• While zero cases of PML were identified among patients with at least 24 months of vedolizumab exposure, a risk of PML cannot be ruled out
• No claims of comparative safety to other integrin receptor antagonists can be made based on these data

 

Pregnancy and lactation

Pregnancy category: B

No studies in pregnant women; animal studies in rabbits and monkeys using ~20 times the human dose showed no evidence of any adverse effect on prenatal and postnatal development

Any adverse pregnancy effect would likely be greater during the 2nd and 3rd trimesters of pregnancy; monoclonal antibodies are transported across the placenta in a linear fashion as pregnancy progresses, with the largest amount transferred during the 3rd trimester

Lactation: Unknown if distributed in human breast milk

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Entyvio (vedolizumab)

Mechanism of action

Recombinant humanized monoclonal antibody that binds specifically to 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

Does not bind to or inhibit function of α4β1 and αEβ7 integrins and does not antagonize α4 integrins interaction with vascular cell adhesion molecule-1 (VCAM-1)

Elicits no activity against α4β1 integrin, and therefore there has no effect on CNS inflammation

 

Absorption

Trough levels (0-6 weeks): 25.3-27.4 mcg/mL

Trough levels (6-52 weeks): 11.2-13 mcg/mL

 

Distribution

Vd: 5 L

 

Elimination

Half-life: 25 days

Clearance (linear): 0.157 L/day

 

Administration

IV Preparation

Reconstitution

• Reconstitute vial containing lyophilized powder with 4.8 mL sterile water for injection, using a syringe with a 21- to 25-gauge needle
• Insert syringe needle into the vial through the center of the stopper and direct the stream of sterile water for 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 solution for particulate matter and discoloration prior to administration; 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
• Prior to withdrawing the reconstituted solution from the vial, gently invert vial 3 times
• Withdraw 5 mL (300 mg) of reconstituted solution using a syringe with a 21- to 25-gauge needle
• Discard any remaining portion of the reconstituted solution in the vial

Further dilution

• Add the 5 mL (300 mg) of reconstituted solution to 250 mL 0.9% NaCl and gently mix the infusion bag
• Once reconstituted and diluted, use the infusion solution as soon as possible

 

IV Administration

Infuse IV over 30 minutes; do not administer as IV push or bolus

Administer by a healthcare professional prepared to manage hypersensitivity reactions including anaphylaxis, if they occur

Appropriate monitoring and medical support measures should be available for immediate use

Observe patients during infusion and until the infusion is complete

 

Storage

Unopened vials

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

Diluted infusion solution

• If necessary, may be stored for up to 4 hr at 2-8°C (36- 46ºF)
• Do not freeze
• Discard any unused portion of the infusion solution