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

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Some side effects may occur during the injection. Tell your caregiver right away if you feel warm or tingly, or if you have a severe headache, fast heart rate, pounding in your neck or ears, chest tightness, or trouble breathing.

Some people using a medicine similar to vedolizumab have developed a serious viral infection of the brain that can lead to disability or death. Call your doctor right away if you have any change in your mental state, decreased vision, or problems with speech or walking. These symptoms may start gradually and get worse quickly.

Stop using vedolizumab and call your doctor at once if you have:

• fever, chills, body aches, cold or flu symptoms, mouth and throat ulcers, skin sores;
• pain, warmth, swelling, or oozing around your anal area;
• nausea, vomiting, severe diarrhea, diarrhea that is watery or bloody, stomach cramps, weight loss;
• cough, pain when swallowing; or
• liver problems--nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Common side effects may include:

• fever, sore throat, flu symptoms;
• cold symptoms such as stuffy nose, sinus pain, sneezing, cough;
• pain in your arms or legs;
• tired feeling;
• headache, joint pain, back pain;
• rash, itching; or
• nausea.

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 FDA at 1-800-FDA-1088.

Vedolizumab is a prescription medication used to in patients with moderate to severe active ulcerative colitis when certain other ulcerative colitis medicines have not worked well enough or cannot be tolerated.

Vedolizumab is also used in patients with moderate to severe active Crohn’s disease when certain other Crohn’s disease medicines have not worked well enough or cannot be tolerated.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

If vedolizumab is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention

Call your doctor for instructions if you miss an appointment for your vedolizumab injection.

Usual Adult Dose for Crohn's Disease -- Maintenance:

Ulcerative colitis and Crohn's disease: 300 mg IV at zero, two and six weeks and then every eight weeks thereafter.

Comments: Discontinue if no evidence of therapeutic benefit by Week 14.

Uses:
Adult Ulcerative Colitis (UC):
Adults with moderately to severely active UC who have had an inadequate response with, lost response to, or were intolerant to a tumor necrosis factor (TNF) blocker or immunomodulator; or had an inadequate response with, were intolerant to, or demonstrated dependence on corticosteroids. This drug is used for inducing and maintaining clinical response or remission, improving endoscopic appearance of the mucosa, or achieving corticosteroid-free remission.

Adult Crohn's Disease(CD):
Adults with moderately to severely active CD who have had an inadequate response with, lost response to, or were intolerant to a TNF blocker or immunomodulator; or had an inadequate response with, were intolerant to, or demonstrated dependence on corticosteroids. This drug is used for achieving clinical response or remission, or achieving corticosteroid-free remission.

Usual Adult Dose for Ulcerative Colitis:

Ulcerative colitis and Crohn's disease: 300 mg IV at zero, two and six weeks and then every eight weeks thereafter.

Comments: Discontinue if no evidence of therapeutic benefit by Week 14.

Uses:
Adult Ulcerative Colitis (UC):
Adults with moderately to severely active UC who have had an inadequate response with, lost response to, or were intolerant to a tumor necrosis factor (TNF) blocker or immunomodulator; or had an inadequate response with, were intolerant to, or demonstrated dependence on corticosteroids. This drug is used for inducing and maintaining clinical response or remission, improving endoscopic appearance of the mucosa, or achieving corticosteroid-free remission.

Adult Crohn's Disease(CD):
Adults with moderately to severely active CD who have had an inadequate response with, lost response to, or were intolerant to a TNF blocker or immunomodulator; or had an inadequate response with, were intolerant to, or demonstrated dependence on corticosteroids. This drug is used for achieving clinical response or remission, or achieving corticosteroid-free remission.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Back pain.
• Signs of a common cold.
• Headache.
• Joint pain.
• Upset stomach.
• Nose and throat irritation.
• Pain in arms or legs.
• Feeling tired or weak.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

• Entyvio

Serious or severe hypersensitivity to vedolizumab or any component of the formulation

Canadian labeling: Additional contraindications (not in US labeling): Patients with active severe infections or opportunistic infections.

>10%:

Central nervous system: Headache (12%)

Immunologic: Antibody development (4% to 13%; neutralizing: 2%)

Neuromuscular & skeletal: Arthralgia (12%)

Respiratory: Nasopharyngitis (13%)

1% to 10%:

Central nervous system: Fatigue (6%)

Dermatologic: Pruritus (3%), skin rash (3%)

Gastrointestinal: Nausea (9%)

Hepatic: Increased serum ALT (≥3 x ULN: <2%), increased serum AST (≥3 x ULN: <2%)

Infection: Influenza (4%)

Neuromuscular & skeletal: Back pain (4%), limb pain (3%)

Respiratory: Upper respiratory tract infection (7%), cough (5%), bronchitis (4%), oropharyngeal pain (3%), sinusitis (3%)

Miscellaneous: Fever (9%), infusion related reaction (4%)

<1% (Limited to important or life-threatening): Hepatitis, hypersensitivity reaction, infection (including anal abscess, sepsis, tuberculosis, salmonella sepsis, listeria meningitis, giardiasis, cytomegaloviral colitis), malignant neoplasm (excluding dysplasia and basal cell carcinoma)