Drug Monograph
Vedolizumab
Entyvio (Takeda)
Pharmacokinetic Profile
Half-Life
25.5 days (linear phase)
Metabolism
Proteolytic degradation (no CYP involvement)
Protein Binding
Not characterised (humanised IgG1)
Bioavailability
IV: 100%; SC: not formally reported
Volume of Distribution
Vc 3.19 L; Vp 1.66 L
Clinical Information
Drug Class
Anti-α4β7 integrin monoclonal antibody
Available Doses
300 mg IV vial; 108 mg SC pen/syringe
Route
IV infusion + SC injection
Renal Adjustment
No data; not studied
Hepatic Adjustment
No data; not studied
Pregnancy
Registry data: no increased risk observed
Lactation
Detected in animal milk; caution advised
Schedule / Legal Status
Prescription only (biologic)
Biosimilars Available
No (as of current labelling)
Gut Selectivity
Yes — selective for GI mucosal trafficking
Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Ulcerative colitis | Adults with moderately to severely active disease | Induction and maintenance; mono or with immunomodulators | FDA Approved |
| Crohn’s disease | Adults with moderately to severely active disease | Induction and maintenance; mono or with immunomodulators | FDA Approved |
Vedolizumab is a gut-selective biologic that occupies a distinct therapeutic niche among IBD treatments. Unlike systemically acting TNF inhibitors, vedolizumab selectively targets lymphocyte trafficking to the gastrointestinal mucosa, which theoretically confers a more favourable systemic safety profile. Both IV and SC formulations are approved for maintenance, although induction must begin with at least two IV doses. The drug is not approved for paediatric use; safety and efficacy in patients under 18 years have not been established.
Off-Label Uses
Immune checkpoint inhibitor-related colitis — steroid-refractory GI toxicity from anti-PD-1/CTLA-4 agents. Evidence quality: Moderate (retrospective series, NCCN recommendation).
Graft-versus-host disease (GI tract) — steroid-refractory acute GI GVHD. Evidence quality: Moderate (prospective cohorts, NCCN recommendation).
Pouchitis — chronic antibiotic-refractory pouchitis after ileal pouch-anal anastomosis. Evidence quality: Low (case series, retrospective data).
Dosing
Standard Dosing by Clinical Scenario (Adults)
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| UC or CD — IV induction | 300 mg IV at Week 0 | 300 mg IV at Week 2 | 300 mg per infusion | Infuse over approximately 30 minutes; do not administer as IV push All patients begin with IV induction regardless of planned maintenance route |
| UC or CD — IV maintenance | 300 mg IV at Week 6 | 300 mg IV every 8 weeks | 300 mg every 8 weeks | Reassess by Week 14; discontinue if no therapeutic benefit Q4-week dosing did not show additional benefit over Q8-week (FDA PI) |
| UC or CD — SC maintenance (after IV induction) | 108 mg SC at Week 6 | 108 mg SC every 2 weeks | 108 mg every 2 weeks | Switch to SC after completing at least 2 IV doses (Weeks 0 and 2) Patients on stable IV maintenance may also switch to SC at any time |
| UC or CD — transition from established IV to SC | 108 mg SC in place of next scheduled IV dose | 108 mg SC every 2 weeks | 108 mg every 2 weeks | For patients already responding on IV Q8W who wish to transition to self-injection |
Clinical Pearl — Dosing Nuances
Vedolizumab has a slower onset than TNF inhibitors, particularly in Crohn’s disease. Assess response at Week 14 before discontinuing; some patients, especially in CD, may not show clinical benefit until Week 14 or beyond. If a SC dose is missed, inject as soon as possible and resume every 2 weeks. The 300 mg IV dose is fixed (not weight-based), simplifying administration. Concomitant aminosalicylates, corticosteroids, and immunomodulators may be continued during treatment and tapered when clinical remission is achieved.
Pharmacology
Mechanism of Action
Vedolizumab is a humanised IgG1 monoclonal antibody that selectively binds the α4β7 integrin expressed on the surface of a subset of memory T-helper lymphocytes. By blocking the interaction between α4β7 integrin and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) on gut vascular endothelium, vedolizumab prevents the migration of these pro-inflammatory lymphocytes from the bloodstream into the lamina propria of the gastrointestinal tract. This mechanism is gut-selective: vedolizumab does not inhibit α4β1 integrin-mediated trafficking to the central nervous system (unlike natalizumab), which contributes to its more favourable systemic safety profile. The drug does not deplete circulating lymphocytes and does not affect systemic immune surveillance outside the gut, which distinguishes it from broadly immunosuppressive biologics.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | IV: 100% bioavailability; SC: therapeutic levels achieved with 108 mg Q2W after IV induction | SC maintenance dosing provides comparable trough levels to IV Q8W; all patients must initiate with IV |
| Distribution | Vc 3.19 L; Vp 1.66 L; not detected in CSF at 5 weeks post-dose | Primarily confined to the vascular compartment; absence from CSF supports gut-selectivity and low PML risk relative to natalizumab |
| Metabolism | Proteolytic catabolism to peptides and amino acids; dual elimination: saturable target-mediated (non-linear) at low concentrations + linear non-specific at therapeutic concentrations | No CYP involvement; however, disease-mediated CYP suppression may normalise during treatment, potentially affecting CYP substrates |
| Elimination | Linear CL 0.157 L/day; t½ 25.5 days (range 14.6–36.0 d) | Longest half-life among current IBD biologics; supports Q8W IV or Q2W SC maintenance; clearance increases with very low albumin, very high body weight, and anti-drug antibodies |
Side Effects
≥10%
Very Common
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Nasopharyngitis | 13% (vs 7% placebo) | Most common adverse effect; self-limiting in most cases; reflects mild upper airway infections |
| Headache | 12% (vs 11% placebo) | Marginal difference from placebo; manage with simple analgesics; rule out infusion-related cause if occurs during or shortly after IV dose |
| Arthralgia | 12% (vs 10% placebo) | Differentiate from IBD-associated extraintestinal manifestations; generally mild and non-progressive |
| Injection site reactions (SC formulation only) | 10% (UC); 3% (CD) | Includes erythema, rash, pruritus, swelling, bruising; did not lead to discontinuation in trials |
1–10%
Common
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Nausea | 9% (vs 8% placebo) | Mild; can occur as part of infusion-related reaction or independently |
| Pyrexia | 9% (vs 7% placebo) | Often transient post-infusion; distinguish from infectious fever |
| Upper respiratory tract infection | 7% (vs 6% placebo) | Treat per standard guidelines; assess for secondary bacterial infection if prolonged |
| Fatigue | 6% (vs 3% placebo) | May overlap with disease activity; assess nutritional status and anaemia |
| Cough | 5% (vs 3% placebo) | Usually benign; evaluate if persistent to exclude opportunistic infection |
| Bronchitis | 4% (vs 3% placebo) | Treat appropriately; no dose adjustment required |
| Influenza | 4% (vs 2% placebo) | Annual influenza vaccination recommended (inactivated vaccine safe) |
| Back pain | 4% (vs 3% placebo) | Evaluate for associated spondyloarthropathy in IBD patients |
| Rash | 3% (vs 2% placebo) | Usually mild and non-specific; differentiate from hypersensitivity |
| Pruritus | 3% (vs 1% placebo) | May indicate hypersensitivity; evaluate in context of infusion timing |
| Sinusitis | 3% (vs 1% placebo) | Treat per standard guidelines |
| Oropharyngeal pain | 3% (vs 1% placebo) | Usually self-limiting |
| Pain in extremities | 3% (vs 1% placebo) | Differentiate from extraintestinal IBD manifestations |
Serious
Serious (Regardless of Frequency)
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Serious infections (sepsis, TB, CMV colitis, Listeria meningitis, anal abscess) | 0.07 per patient-year (vs 0.06 placebo) | Any time during treatment | Withhold vedolizumab; initiate appropriate antimicrobial therapy; do not restart until fully resolved |
| Infusion-related reactions (IV) | 4% (vs 3% placebo); severe <1% | During or within 2 hours of infusion | Discontinue infusion if serious; treat with antihistamines and/or IV hydrocortisone; premedicate before subsequent infusions if mild |
| Anaphylaxis | 0.07% (1 in 1,434) | During second or subsequent infusion | Emergency management; permanently discontinue vedolizumab |
| Progressive multifocal leukoencephalopathy (PML) | Very rare; 1 post-marketing case (with HIV and concurrent immunosuppression) | Variable; progressive over weeks | Withhold vedolizumab immediately; refer to neurology; permanently discontinue if confirmed |
| Liver injury (elevated transaminases and/or bilirubin) | Rare; 3 cases of serious hepatitis in clinical trials | Variable | Discontinue vedolizumab in patients with jaundice or evidence of significant liver injury; check LFTs |
Discontinuation
Discontinuation Rates
Adults (IV Pivotal Trials)
~2% due to infections
IRR-related: <1% discontinued due to infusion reactions
Adults (SC Trials)
0% due to injection site reactions
ISR did not lead to discontinuation in the VISIBLE 1 or SC CD trials
| Reason for Discontinuation | Incidence | Context |
|---|---|---|
| Infections | 2% | Most common reason for stopping therapy in controlled IV trials; infections were primarily upper respiratory |
| Infusion-related reactions | <1% | Severe IRRs rare; mild IRRs managed with premedication in subsequent infusions |
| Injection site reactions (SC) | 0% | No discontinuations due to ISR in VISIBLE 1 or SC CD trials |
| Hepatic adverse events | <1% | 3 serious hepatitis cases in combined trials; very low overall rate |
Gut-Selective Safety Advantage
Unlike systemically acting immunosuppressive biologics (e.g., anti-TNF agents), vedolizumab selectively targets gut mucosal lymphocyte trafficking without suppressing systemic immunity. This translates to a lower rate of serious systemic infections in clinical trials and real-world data compared with TNF inhibitors. The serious infection rate of 0.07 per patient-year is notably low for a biologic in this disease population. There is no boxed warning on the vedolizumab label.
Drug Interactions
Vedolizumab is a monoclonal antibody cleared by proteolysis, not by cytochrome P450 enzymes. Its gut-selective mechanism limits systemic immunosuppressive overlap with other biologics, but concomitant use with natalizumab or TNF blockers is specifically cautioned against due to additive infection risk or, in the case of natalizumab, increased PML risk.
MajorNatalizumab
MechanismBoth target integrins involved in lymphocyte trafficking; natalizumab blocks α4 broadly (including CNS trafficking)
EffectPotentially increased risk of PML and other serious infections
ManagementAvoid concomitant use; ensure adequate washout period before switching between integrin inhibitors
FDA PIMajorTNF Blockers (adalimumab, infliximab, etc.)
MechanismAdditive immunosuppression from combining gut-selective and systemic immune blockade
EffectIncreased risk of infections and PML without established additional efficacy
ManagementAvoid concomitant use; allow appropriate washout when switching
FDA PIModerateCYP450 Substrates (warfarin, cyclosporine, theophylline)
MechanismDisease-mediated suppression of CYP450 enzymes may normalise as vedolizumab controls inflammation
EffectPotential changes in serum levels of narrow-therapeutic-index CYP substrates
ManagementMonitor drug levels or therapeutic parameters (e.g., INR) upon initiation and discontinuation of vedolizumab; adjust substrate doses as needed
FDA PIMinorLive Vaccines
MechanismGut-selective immunosuppression may reduce mucosal immune response to oral live vaccines
EffectDiminished vaccine response possible; no safety data on secondary transmission
ManagementUpdate all vaccinations before initiating vedolizumab; live vaccines may be given if benefits outweigh risks (less restrictive than anti-TNF guidance); non-live vaccines are safe
FDA PIMonitoring
-
TB Screening
Baseline (per local practice)
Routine Consider screening for latent TB according to local practice before initiating vedolizumab. One case of latent pulmonary TB was detected in controlled trials. Risk is lower than with anti-TNF agents but screening is still prudent. -
Liver Function Tests
Baseline, then periodically
Routine Monitor transaminases and bilirubin. ALT elevations above 5x ULN occurred in less than 2% of vedolizumab-treated patients (similar to placebo). Discontinue if jaundice or significant liver injury develops. Three cases of serious hepatitis occurred in clinical trials. -
Signs of Infection
Every visit
Routine Assess for active infection at each infusion or clinic visit. Overall infection rate was 0.85 per patient-year (vs 0.7 placebo). Most infections involved the upper respiratory tract. Serious infections occurred at 0.07 per patient-year. -
Infusion Observation
Each IV infusion
Routine Observe patients during and after each IV infusion for infusion-related reactions and hypersensitivity. Emergency medications and equipment must be readily available. IRRs occurred in 4% of vedolizumab-treated patients. -
Therapeutic Response
Week 14
Routine Evaluate clinical response by Week 14. Discontinue vedolizumab if no evidence of therapeutic benefit. Clinical response may take longer in CD compared with UC. -
Neurological Symptoms
If symptoms develop
Trigger-based Monitor for any new or worsening neurological signs (progressive weakness, visual disturbance, cognitive changes) suggestive of PML. Though very rare with vedolizumab, the risk cannot be ruled out. Withhold dosing and refer to neurology if suspected. -
Vaccination Status
Before initiation
Routine Bring all vaccinations up to date before starting vedolizumab. Patients may receive non-live vaccines during treatment. Live vaccines may be given if benefits outweigh risks.
Contraindications & Cautions
Absolute Contraindications
- Known serious or severe hypersensitivity reaction to vedolizumab or any of its excipients (e.g., prior anaphylaxis, dyspnoea, bronchospasm, urticaria, flushing, rash, or increased heart rate during a previous dose).
Relative Contraindications (Specialist Input Recommended)
- Active, severe infection — treatment is not recommended until the infection is controlled. Consider withholding in patients who develop a severe infection while on therapy.
- Concomitant use with natalizumab — increased risk of PML and infections. Ensure adequate washout before switching.
- Concomitant use with TNF blockers — increased risk of infections without proven additive benefit.
Use with Caution
- History of recurring severe infections — exercise caution and monitor closely.
- Patients with known hepatic disease — monitor LFTs; discontinue if jaundice or significant liver injury develops.
- Immunocompromised patients (e.g., prior immunosuppressive therapies, HIV) — PML risk, though very low, increases with level of immunosuppression.
- Pregnancy — monoclonal antibodies cross the placenta, particularly in the third trimester. Registry data show no increased risk of adverse outcomes, but discuss risks and benefits individually.
No Boxed Warning
Unlike TNF inhibitors and JAK inhibitors, vedolizumab does not carry an FDA boxed warning. This reflects its gut-selective mechanism and the comparatively lower systemic infection and malignancy signal observed in clinical trials. However, prescribers should remain vigilant for the rare risk of PML and serious infections, and counsel patients accordingly.
Patient Counselling
Purpose of Therapy
Vedolizumab works differently from many other biologic treatments for IBD. Instead of broadly suppressing the immune system, it specifically blocks inflammatory cells from entering the lining of the gut. This targeted approach is designed to control bowel inflammation while minimising effects on the rest of the body. It does not cure ulcerative colitis or Crohn’s disease, but it can bring about and maintain remission, reduce the need for corticosteroids, and improve quality of life.
How to Take
Treatment begins with two intravenous (IV) infusions given at Weeks 0 and 2 in a clinical setting, each lasting about 30 minutes. From Week 6, you may continue with IV infusions every 8 weeks at a treatment centre, or transition to a self-administered injection under the skin (subcutaneous) using the Entyvio Pen every 2 weeks at home. Your gastroenterologist will determine which maintenance route is best for you.
Infection Risk
Tell patientAlthough vedolizumab is more targeted than many other biologics, it can still slightly increase susceptibility to infections, particularly of the nose, throat, and sinuses. Practice good hand hygiene and avoid close contact with people who are unwell.
Call prescriberIf you develop a fever that does not resolve, persistent cough, unusual tiredness, or signs of infection that worsen or do not improve within a few days, contact your prescriber promptly.
Infusion or Injection Reactions
Tell patientReactions during or shortly after IV infusions can occur but are uncommon. They usually involve mild symptoms like nausea, headache, or itching. You will be monitored during each infusion. For SC injections, mild redness, swelling, or itching at the injection site may occur and usually resolves on its own.
Call prescriberSeek immediate medical attention if you experience difficulty breathing, facial swelling, rapid heartbeat, hives, or severe dizziness during or after an infusion or injection.
Liver Health
Tell patientLiver problems have been reported rarely with vedolizumab. Your doctor will monitor liver blood tests periodically during treatment.
Call prescriberReport immediately if you notice yellowing of the skin or eyes, dark urine, right-sided abdominal pain, unusual tiredness, or loss of appetite.
Neurological Symptoms
Tell patientA very rare brain infection called PML has been associated with similar types of medication. While the risk is extremely low with vedolizumab, it is important to be aware of the signs.
Call prescriberReport any new or worsening weakness on one side of the body, changes in vision, difficulty thinking or remembering, confusion, or personality changes immediately.
SC Pen Storage & Handling
Tell patientStore the Entyvio Pen in the refrigerator at 2–8°C. Do not freeze. Remove from the refrigerator and allow to reach room temperature before use. Rotate injection sites between the abdomen and thigh. Dispose of used pens in an FDA-cleared sharps container.
Call prescriberIf the pen has been frozen, dropped, or appears damaged, do not use it. Contact your pharmacy for a replacement.
Sources
Regulatory (PI / SmPC)
- ENTYVIO (vedolizumab) for injection, for intravenous use; ENTYVIO (vedolizumab) injection, for subcutaneous use. Full prescribing information. Takeda Pharmaceuticals. Revised 4/2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/125476s060s061lbl.pdf Primary source for all dosing, indications, contraindications, and adverse reaction data (Table 2) in this monograph.
- Entyvio (vedolizumab) Summary of Product Characteristics. Takeda Pharma A/S. European Medicines Agency. https://www.ema.europa.eu/en/medicines/human/EPAR/entyvio European regulatory summary providing SmPC data including dose escalation guidance and long-term safety perspective.
Key Clinical Trials
- Feagan BG, Rutgeerts P, Sands BE, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis (GEMINI 1). N Engl J Med. 2013;369(8):699-710. doi:10.1056/NEJMoa1215734 Pivotal phase III RCT establishing vedolizumab efficacy for induction (Week 6) and maintenance (Week 52) in moderately to severely active UC.
- Sandborn WJ, Feagan BG, Rutgeerts P, et al. Vedolizumab as induction and maintenance therapy for Crohn’s disease (GEMINI 2). N Engl J Med. 2013;369(8):711-721. doi:10.1056/NEJMoa1215739 Pivotal phase III RCT establishing vedolizumab efficacy for induction and maintenance in Crohn’s disease; basis for initial FDA approval in CD.
- Sands BE, Peyrin-Biroulet L, Loftus EV Jr, et al. Vedolizumab versus adalimumab for moderate-to-severe ulcerative colitis (VARSITY). N Engl J Med. 2019;381(13):1215-1226. doi:10.1056/NEJMoa1905725 First head-to-head biologic trial in UC demonstrating vedolizumab superiority over adalimumab for clinical remission and endoscopic improvement at Week 52.
- Sandborn WJ, Baert F, Danese S, et al. Efficacy and safety of vedolizumab subcutaneous formulation in a randomized trial of patients with ulcerative colitis (VISIBLE 1). Gastroenterology. 2020;158(3):562-572.e12. doi:10.1053/j.gastro.2019.08.027 Phase III trial establishing efficacy and safety of vedolizumab 108 mg SC Q2W as maintenance therapy in UC following IV induction.
Guidelines
- Feuerstein JD, Isaacs KL, Schneider Y, et al. AGA clinical practice guidelines on the management of moderate to severe ulcerative colitis. Gastroenterology. 2020;158(5):1450-1461. doi:10.1053/j.gastro.2020.01.006 AGA guideline positioning vedolizumab among higher-efficacy options for moderate-to-severe UC in advanced therapy-naive patients.
- Lichtenstein GR, Loftus EV, Isaacs KL, et al. ACG clinical guideline: management of Crohn’s disease in adults. Am J Gastroenterol. 2018;113(4):481-517. doi:10.1038/ajg.2018.27 ACG guideline recommending vedolizumab as an option for induction and maintenance in moderate-to-severe CD.
Mechanistic / Basic Science
- Soler D, Chapman T, Yang LL, et al. The binding specificity and selective antagonism of vedolizumab, an anti-alpha4beta7 integrin therapeutic antibody in development for inflammatory bowel diseases. J Pharmacol Exp Ther. 2009;330(3):864-875. doi:10.1124/jpet.109.153973 Foundational study characterising vedolizumab’s selective binding to α4β7 integrin without cross-reactivity to α4β1 (brain trafficking).
Pharmacokinetics / Special Populations
- Rosario M, Dirks NL, Milch C, et al. A review of the clinical pharmacokinetics, pharmacodynamics, and immunogenicity of vedolizumab. Clin Pharmacokinet. 2017;56(11):1287-1301. doi:10.1007/s40262-017-0546-0 Comprehensive PK review reporting the population PK model, t½ of 25.5 days, CL of 0.159 L/day, and exposure-response relationships.
- Rosario M, French JL, Dirks NL, et al. Exposure-efficacy relationships for vedolizumab induction therapy in patients with ulcerative colitis or Crohn’s disease. J Crohns Colitis. 2017;11(8):921-929. doi:10.1093/ecco-jcc/jjx021 Exposure-response analysis supporting the fixed 300 mg IV dose and identifying trough concentration targets associated with clinical remission.
- Loftus EV Jr, Feagan BG, Panaccione R, et al. Long-term safety of vedolizumab for inflammatory bowel disease (GEMINI LTS). J Crohns Colitis. 2020;14(10):1395-1404. doi:10.1093/ecco-jcc/jjaa042 Long-term safety extension study (up to 9 years of exposure) confirming stable safety profile with no new signals for PML, malignancy, or opportunistic infections.