Vedolizumab (Monograph)

Brand name: Entyvio
Drug class: Disease-modifying Antirheumatic Drugs, Miscellaneous

Medically reviewed by Drugs.com on Nov 10, 2024. Written by ASHP.

Introduction

Recombinant humanized anti-α4β7-integrin monoclonal antibody; integrin receptor antagonist.

Uses for Vedolizumab

Ulcerative Colitis

Treatment of moderately to severely active ulcerative colitis; used to induce and maintain clinical response and clinical remission, improve endoscopic appearance of mucosa, and achieve corticosteroid-free remission in adults with moderately to severely active disease.

Guidelines recommend the use of vedolizumab as a first or second-line treatment for moderate to severe ulcerative colitis for induction and maintenance of remission.

Crohn Disease

Treatment of moderately to severely active Crohn disease; used to achieve clinical response, clinical remission, and corticosteroid-free remission in adults with moderately to severely active disease.

Guidelines generally recommend use of other biologic agents including TNF inhibitors and ustekinumab over vedolizumab in patients with moderate to severe active Crohn disease.

Vedolizumab Dosage and Administration

General

Pretreatment Screening

Ensure patient is up to date with all immunizations according to current immunization guidelines prior to initiating therapy.
Treat underlying active, severe infections prior to initiating therapy.
Perform a pregnancy test prior to initiating therapy in females of reproductive potential.

Patient Monitoring

Monitor patients for signs and symptoms of infusion-related and hypersensitivity reactions (including anaphylaxis) during and after infusions.
Monitor patients for progressive muscle weakness, vision disturbances, changes in memory and orientation, confusion, or personality changes.

Other General Considerations

Aminosalicylates, corticosteroids, and immunosuppressive agents (azathioprine, mercaptopurine) were continued in clinical studies evaluating vedolizumab in patients with ulcerative colitis or Crohn disease.

Administration

Administer by IV infusion. May be administered by sub-Q therapy after initial IV therapy.

IV Administration

Administer by IV infusion over approximately 30 minutes.

Do not mix with or administer through the same administration set with other drugs.

Flush IV line with 30 mL of 0.9% sodium chloride injection or Lactated Ringer's injection after the infusion is complete.

Lyophilized powder must be reconstituted at room temperature and diluted prior to administration.

Reconstitution

Reconstitute vedolizumab lyophilized powder by adding 4.8 mL of sterile water for injection, 0.9% sodium chloride injection, or Lactated Ringers injection (using a syringe with a 21- to 25-gauge needle) to a 300-mg vial to provide a solution containing 60 mg/mL. Direct diluent toward wall of vial to avoid excessive foaming.

Gently swirl vial for at least 15 seconds to dissolve powder. Do not shake vigorously or invert. Allow solution to stand for up to 20 minutes at room temperature to allow for reconstitution and for any foam to settle. Vial can be swirled and inspected for dissolution during this time. If not fully dissolved within 20 minutes, allow an additional 10 minutes. Do not use vial if drug is not dissolved within 30 minutes.

May refrigerate reconstituted solution in vial for up to 8 hours prior to further dilution; however, maximum storage time for reconstituted solution in vial may be limited by diluent selected to prepare the final infusion solution.

Dilution

Gently invert vial 3 times, then immediately withdraw 5 mL (300 mg) of reconstituted solution (using a syringe with a 21- to 25-gauge needle). Add the reconstituted solution to an infusion bag containing 250 mL of 0.9% sodium chloride injection or Lactated Ringer's injection and mix gently.

Storage time for diluted solution depends on storage conditions and diluent.

Discard any unused portions of reconstituted or diluted solutions.

Rate of Administration

Administer by IV infusion over approximately 30 minutes.

Sub-Q Administration

May switch patients from IV to sub-Q therapy at week 6 after the first 2 IV doses have been administered at week 0 and week 2; also may switch from IV to sub-Q therapy in patients who receive and respond to IV therapy beyond week 6.

To switch to sub-Q therapy, administer the first sub-Q dose in place of the next scheduled IV infusion and then every 2 weeks thereafter.

Available in single-use prefilled syringes and single-use prefilled pens.

Patients or caregivers may administer sub-Q injections using either the prefilled syringe or pen after appropriate training is provided.

Administer each sub-Q injection at a different anatomic location (such as thighs, any quadrant of abdomen, or upper arms. Do not inject into moles, scars, bruises, or areas where the skin is tender, erythematous, or indurated.

If treatment is interrupted or if a scheduled dose(s) is missed, inject the next sub-Q 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 the pen, however it is uncertain if a full dose was administered), instruct patient to call their pharmacy or healthcare provider.

Dosage

Adults

Ulcerative Colitis

IV

300 mg at 0, 2, and 6 weeks and then every 8 weeks thereafter.

Discontinue if no therapeutic benefit is evident by week 14 of therapy.

Sub-Q

Following administration of the first 2 IV doses at week 0 and week 2, may administer by sub-Q injection at a dose of 108 mg at week 6 and then once every 2 weeks thereafter.

Discontinue therapy if no therapeutic benefit is evident by week 14 of therapy.

Crohn Disease

IV

300 mg at 0, 2, and 6 weeks and then every 8 weeks thereafter.

Discontinue if no therapeutic benefit is evident by week 14 of therapy.

Sub-Q

Following administration of the first 2 IV doses at week 0 and week 2, may administer by sub-Q injection at a dose of 108 mg at week 6 and then once every 2 weeks thereafter.

Discontinue therapy if no therapeutic benefit is evident by week 14 of therapy.

Special Populations

Hepatic Impairment

Manufacturer makes no specific dosage recommendations.

Renal Impairment

Manufacturer makes no specific dosage recommendations.

Geriatric Patients

Manufacturer makes no specific dosage recommendations.

Cautions for Vedolizumab

Contraindications

Known history of serious or severe hypersensitivity reaction (e.g., dyspnea, bronchospasm, urticaria, flushing, rash, increased heart rate) to the drug or any ingredient in the formulation.

Warnings/Precautions

Infusion-related and Hypersensitivity Reactions

Infusion-related and hypersensitivity reactions, including anaphylaxis, dyspnea, bronchospasm, urticaria, flushing, rash, and increased BP and heart rate, reported. Infusion-related reactions also may include nausea, headache, pruritus, dizziness, fatigue, pyrexia, and vomiting.

Reactions may occur with the first infusion or with subsequent infusions; time of onset may be variable (during or up to several hours after an infusion).

Clinicians should be prepared to treat hypersensitivity and infusion-related reactions. Ensure appropriate equipment and agents for treating such reactions are available for immediate use, and monitor patient until infusion is completed. If anaphylaxis or other serious infusion-related or hypersensitivity reactions occur, immediately discontinue the infusion and initiate appropriate treatment.

In clinical trials, patients who experienced a mild infusion-related or hypersensitivity reaction to the drug could receive premedication (e.g., antihistamine, hydrocortisone, and/or acetaminophen) prior to subsequent infusions.

Infections

Increased risk of infections. Most common infections are nasopharyngeal and upper respiratory tract infections. However, serious infections (e.g., anal abscess, sepsis [sometimes fatal], tuberculosis, Salmonella sepsis, Listeria meningitis, giardiasis, cytomegaloviral colitis) also reported, more commonly in patients with Crohn disease than in those with ulcerative colitis.

Delay initiation of vedolizumab until any active severe infection has been controlled. If severe infection develops during therapy, consider interrupting vedolizumab therapy.

Exercise caution when considering use in patients with a history of recurring severe infections.

Consider screening for active or latent tuberculosis infection.

Progressive Multifocal Leukoencephalopathy (PML)

PML, an opportunistic infection of the brain caused by the JC virus, reported in patients receiving systemic immunosuppressive agents, including natalizumab, an anti-α4-integrin monoclonal antibody. PML generally occurs only in immunocompromised patients and usually progresses to death or severe disability. Also reported during postmarketing experience in a vedolizumab-treated patient with multiple contributory factors (e.g., HIV infection with CD4⁺ T-cell count of 300 cells/mm³ and prior and concomitant immunosuppression). Although considered unlikely, risk of PML in vedolizumab-treated patients cannot be ruled out.

Monitor for any new or worsening neurologic manifestations. If PML is suspected, withhold drug and refer patient to a neurologist. Permanently discontinue if PML is confirmed.

Liver Injury

Increases in serum ALT and AST concentrations and/or bilirubin concentrations, including several cases of hepatitis, reported following 2–5 doses of the drug; unclear whether reactions were drug induced or autoimmune. All patients recovered following drug discontinuance, although some patients also required corticosteroid treatment.

Discontinue vedolizumab in patients with jaundice or other evidence of clinically significant hepatic injury.

Live and Oral Vaccines

Administer all appropriate vaccines as recommended by current immunization guidelines prior to initiation of vedolizumab.

Patients receiving vedolizumab may receive inactive vaccines (e.g., parenteral influenza virus vaccine inactivated) and may receive live vaccines if potential benefits justify possible risks.

Malignancies

Malignancies (excluding dysplasia and basal cell carcinoma) reported during clinical trials in ulcerative colitis or Crohn disease. Malignancies also reported during extension phases of the trials; however, data regarding effects of long-term exposure to the drug are limited.

Immunogenicity

Formation of antibodies, including neutralizing antibodies, to vedolizumab reported. Presence of persistently positive anti-vedolizumab antibodies associated with undetectable or negligible serum concentrations of the drug and failure to achieve clinical remission.

Specific Populations

Pregnancy

Available data in pregnant women have not reliably identified a vedolizumab-associated risk of major birth defects, spontaneous abortion, or adverse maternal or fetal outcomes.

Increased disease activity in women with inflammatory bowel disease may increase the risk of adverse pregnancy outcomes (e.g., preterm delivery, low birth weight, small size for gestational age at birth).

Use during pregnancy could affect immune responses in neonates and infants exposed to the drug in utero. Clinical importance of low concentrations of the drug in infants exposed in utero is unknown. Safety of administering live vaccines to infants exposed to the drug in utero also is unknown.

Lactation

Vedolizumab distributes into human milk in low concentrations. Effects on nursing infants, including potential effects of local GI exposure or systemic exposure (expected to be low), are unknown; effects on milk production also unknown.

Consider developmental and health benefits of breast-feeding along with the mother's clinical need for vedolizumab and any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

Pediatric Use

Safety and efficacy not established in pediatric patients.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults; however, no overall differences in efficacy and safety observed.

Hepatic Impairment

No specific information available from the manufacturer.

Renal Impairment

No specific information available from the manufacturer.

Common Adverse Effects

Most common adverse reactions (≥3%): Nasopharyngitis, headache, arthralgia, nausea, pyrexia, upper respiratory tract infection, fatigue, cough, bronchitis, influenza, back pain, rash, pruritus, sinusitis, oropharyngeal pain, pain in extremities.

Adverse effects with sub-Q vedolizumab are similar to those reported with IV vedolizumab with the exception of injection site reactions with sub-Q vedolizumab.

Drug Interactions

CYP450 Substrates

Formation of CYP450 enzymes may be suppressed by increased levels of certain cytokines during chronic inflammation. Upon initiation or discontinuation of vedolizumab in patients treated with CYP450 substrates, monitor drug concentrations or other therapeutic parameters, and adjust dosage of the substrate as needed.

Vaccines

Inactivated vaccines: Effect of vedolizumab on immune responses to oral or intranasal vaccines other than IM hepatitis B vaccine and oral inactivated cholera vaccine is not known. Manufacturer states patients receiving vedolizumab may receive inactivated vaccines.

Live vaccines: No data on secondary transmission of infection by live vaccines in patients receiving vedolizumab. Manufacturer states patients receiving vedolizumab may receive live vaccines if potential benefits justify possible risks.

Specific Drugs

Drug	Interaction	Comments
Cholera vaccine, oral inactivated	Single vedolizumab dose given 4 days before initiation of immunization series reduced seroconversion rate and titers of antibody to cholera toxin	May be used concomitantly
Hepatitis B vaccine	Single vedolizumab dose given 4 days before initiation of IM immunization series did not affect seroconversion rate	May be used concomitantly
Influenza virus vaccine inactivated		May be used concomitantly
Natalizumab	Increased risk of PML and other infections	Avoid concomitant use
Tumor necrosis factor (TNF) blocking agents	Increased risk of infections	Avoid concomitant use

Vedolizumab Pharmacokinetics

Absorption

Bioavailability

108 mg single-dose sub-Q injection compared to a 300 mg single-dose IV infusion in healthy subjects approximately 75%.

Distribution

Extent

Not known whether vedolizumab distributes into human milk.

Not detected in CSF at 5 weeks after single IV dose (450 mg).

Elimination

Half-life

Approximately 25 days at 300-mg dose.

Clearance dependent on linear and nonlinear pathways; nonlinear clearance decreases with increasing concentrations.

Special Populations

Pharmacokinetics similar in patients with ulcerative colitis and those with Crohn disease.

Pharmacokinetics not formally studied in patients with renal or hepatic impairment.

Disease severity, body weight, prior treatment with TNF blocking agents, age (within range of 18–78 years), serum albumin concentration, and concomitant therapy (azathioprine, mercaptopurine, methotrexate, aminosalicylates) did not have a clinically meaningful effect on pharmacokinetics.

Presence of persistently positive anti-vedolizumab antibodies may reduce serum vedolizumab concentrations to undetectable or negligible levels.

Stability

Storage

Parenteral

Powder for IV Infusion

2–8°C. Keep in original package to protect from light.

Reconstituted solution

Reconstituted solution in vial: 2–8°C for up to 8 hours (but may be limited by diluent selected to prepare the final infusion solution). Do not freeze.

Diluted solution

Infusion solution (in 0.9% sodium chloride): 2–8°C for up to 24 hours (may include up to 12 hours at room temperature) or 20–25°C for up to 12 hours; these storage times include any time that the reconstituted solution was refrigerated prior to dilution.

Infusion solution (in Lactated Ringer's injection): 2–8°C for up to 6 hours (including any time that the reconstituted solution was refrigerated prior to dilution); if not refrigerated, use immediately after dilution. Do not freeze.

Prefilled syringe or pen for sub-Q injection

2–8°C. Keep in original carton to protect from light.

May store in the original package at room temperature up to 25°C for up to 7 days (for example, when traveling). Do not use if left out of refrigerator for more than 7 days.

Actions

Binds specifically to α4β7 integrin, a protein expressed on the surface of a small subset of memory T-lymphocytes that preferentially migrate into the GI tract. Binding of vedolizumab to α4β7 integrin blocks interaction of α4β7 integrin with mucosal addressin cell adhesion molecule-1 (MAdCAM-1), which is expressed mainly on vascular endothelial cells in the GI tract, and inhibits migration of memory T-lymphocytes across the endothelium into inflamed GI parenchymal tissue.
Interaction of α4β7 integrin with MAdCAM-1 implicated as an important contributor to the chronic inflammation of ulcerative colitis and Crohn disease.
Does not bind to or inhibit the function of α4β1 and αEβ7 integrins; does not antagonize the interaction of α4 integrins with vascular cell adhesion molecule-1 (VCAM-1).
Appears to exert a more selective effect on the GI tract than does natalizumab, which binds to α4 subunits of α4β1 and α4β7 integrins expressed on the surface of all leukocytes except neutrophils.

Advice to Patients

Provide patients with a copy of the manufacturer's patient information (medication guide).
Risk of hypersensitivity reaction. Instruct patients to immediately report symptoms consistent with a hypersensitivity reaction (e.g., rash, pruritus, shortness of breath or difficulty breathing, wheezing, dizziness, flushing, palpitations, swelling of the lips, tongue, throat, or face) that occur during or following an infusion of vedolizumab.
Risk of infection. Advise patients that they may be more likely to develop infections while receiving vedolizumab. Instruct patients to inform a clinician if they develop any signs or symptoms of infection (e.g., fever, chills, cough, dyspnea, fatigue, red or painful skin or sores, myalgia, rhinorrhea, sore throat, pain on urination) while receiving vedolizumab.
Risk of progressive multifocal leukoencephalopathy. Inform patients that progressive multifocal leukoencephalopathy (PML) has occurred in patients receiving some integrin receptor antagonist and systemic immunosuppressive agents. Instruct patients to report any new or worsening neurologic manifestations (e.g., progressive weakness on one side of the body or clumsiness of limbs; changes in speech or walking; vision changes; changes in thinking, memory, and orientation leading to confusion and personality changes) immediately to their clinician.
Risk of liver injury. Inform patients that increased serum aminotransferase (ALT and AST) concentrations with or without elevated bilirubin concentrations have occurred in patients who received vedolizumab. Advise patients to promptly report any symptoms suggestive of hepatic injury (e.g., fatigue, anorexia, right upper abdominal discomfort, dark urine, jaundice) while receiving vedolizumab.
Advise patients to review their vaccination status with their clinician and receive all appropriate vaccines prior to initiation of vedolizumab therapy.
Instruct patients and caregivers on proper sub-Q administration technique, and on the correct use of the vedolizumab single-dose prefilled syringe or single-dose prefilled pen.
Advise patients to inform clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses (e.g., hepatic disease, tuberculosis or other infection) or any history of recurrent infections.
Advise females to inform their clinician if they are or plan to become pregnant or plan to breast-feed.
Advise patients to inform their clinician of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Vedolizumab can only be obtained through designated specialty pharmacies. Contact the manufacturer or consult the Entyvio website ([Web]) for specific information.

Vedolizumab
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	For injection, for IV infusion	300 mg	Entyvio (available as single-dose vials)	Takeda
	Injection, for subcutaneous use	108 mg/0.68 mL	Entyvio (available as a single-dose prefilled syringe and single-dose prefilled pen)	Takeda