Dosage guidance:
Safety: Prior to initiating treatment, all patients should be brought up to date with all immunizations according to current immunization guidelines.
Colitis, immune checkpoint inhibitor-induced (off-label use):
Note: For grade 2, 3, or 4 colitis with either high-risk endoscopic features on initial endoscopy examination or with persistent symptoms despite 3 days of corticosteroid therapy, consider adding vedolizumab to the treatment regimen (Ref).
IV: 300 mg at 0, 2, and 6 weeks and then (if needed) once every 8 weeks thereafter; use in combination with a corticosteroid (Ref).
Crohn disease:
IV: 300 mg at 0, 2, and 6 weeks and then every 8 weeks thereafter. Discontinue therapy in patients who show no evidence of therapeutic benefit by week 14.
SUBQ: Maintenance: 108 mg once every 2 weeks beginning after at least 2 IV infusions; administer in place of next scheduled IV dose and then every 2 weeks thereafter.
Missed dose: Administer next dose as soon as possible and then every 2 weeks thereafter. In the case of incomplete dose administration (eg, uncertain if full dose administered), notify health care provider.
Ulcerative colitis:
IV: 300 mg at 0, 2, and 6 weeks and then every 8 weeks thereafter. Discontinue therapy in patients who show no evidence of therapeutic benefit by week 14.
SUBQ: Maintenance: 108 mg once every 2 weeks beginning after at least 2 IV infusions; administer in place of next scheduled IV dose and then every 2 weeks thereafter.
Missed dose: Administer next dose as soon as possible and then every 2 weeks thereafter. In the case of incomplete dose administration (eg, uncertain if full dose administered), notify health care provider.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). Discontinue use with jaundice or signs/symptoms of hepatic injury.
Refer to adult dosing.
Infusion-related reactions have been reported, including symptoms resembling anaphylaxis. Symptoms include flushing, skin rash, urticaria, arthralgia, myalgias, and fever (Ref). Acute noncardiac chest pain has also been reported. Other cutaneous manifestations (eg, IgA-mediated leukocytoclastic vasculitis or Henoch-Schönlein purpura, nodular vasculitis, pyoderma gangrenosum) have been reported and may be delayed, occurring weeks to months after initiation therapy (Ref).
Mechanism:
Immediate: Vedolizumab also contains polysorbate 80, which is a known excipient that can induce immediate hypersensitivity reactions (Ref).
Delayed reactions: Unknown; dermatological-associated events may be triggered by the impact of vedolizumab on peripheral skin inflammatory cascades (Ref); other infusion-related reactions may result from development of anti-vedolizumab antibodies, which have been detected in severe reactions including noncardiac chest pain during the infusion (Ref).
Onset: Varied; most infusion-related reactions have occurred within 2 hours of the completion of the infusion but can occur within minutes of the start of the infusion (Ref). In general, cutaneous vasculitis and other cutaneous reactions typically occur within 7 to 10 days of the inducing factor but have been identified after several vedolizumab infusions were previously tolerated and can occur after weeks or months (Ref).
Risk factors:
• Some studies suggest the presence of anti-vedolizumab antibodies in patients with infusion reactions in the absence of detectable vedolizumab trough levels (Ref).
Increased serum alanine aminotransferase and increased serum aspartate aminotransferase (≥3 times the upper limit of normal) have been reported with vedolizumab (Ref). Increased serum transaminases are commonly encountered in patients with inflammatory bowel disease (Ref), while the incidence of vedolizumab-induced hepatic injury is rare (Ref). Reported cases of vedolizumab-induced hepatic injury may present as mixed or cholestatic, and liver biochemistries tend to improve upon discontinuation (Ref). Underlying liver diseases (eg, primary biliary sclerosis) must also be excluded if vedolizumab-induced hepatic injury is suspected (Ref).
Mechanism: Not clearly established; vedolizumab inhibits α4β7 integrin, selectively preventing gut specific signaling of T-lymphocytes and eosinophil migration and adhesion, which may increase peripheral eosinophilia commonly seen in allergic reactions such as immune-mediated hepatic injury (Ref).
Onset: Varied; range reported is 14 to 275 days after exposure (Ref).
Risk factors:
• Previous injury (Ref)
• Current alcohol use (Ref)
• Older age (≥55 years) (Ref)
Progressive multifocal leukoencephalopathy (PML) is a neurological disorder characterized by severe disability that can be fatal and is caused by John Cunningham virus (JCV) in the setting of significant immunosuppression (Ref). Natalizumab has been linked to an increased risk of PML and has a similar mechanism of action to vedolizumab, therefore prompting concerns for evaluation and monitoring of PML in patients receiving therapy. Unlike natalizumab, vedolizumab targets a different subunit of integrin expressed on gut-homing T-lymphocytes and does not impact immune surveillance within the central nervous system (Ref). Cases of vedolizumab-associated PML have yet to be identified, and the risk remains theoretical and based on data from natalizumab exposure (Ref).
Mechanism: Time related (delayed); related to the pharmacologic action (ie, monoclonal antibody targeting α4β7 integrin, a cell surface glycoprotein on B and T lymphocytes that binds to mucosal addressin cell adhesion molecule-1 on the intestinal vasculature) (Ref).
Onset: Delayed; occurs after 30 days of drug therapy (based on data from natalizumab) (Ref).
Risk factors:
• Duration of therapy >2 years (Ref)
• Prior or concurrent immunosuppression during therapy (Ref)
• Positive JCV antibody identified prior to or during therapy (Ref)
• History of blood cancers (Ref)
Although the immunosuppressive activity of vedolizumab is focused on gut specific pathways, use may be associated with an increased risk for developing infection; most reported infections included upper respiratory tract infections and nasopharyngitis (Ref). The risk of serious infections, requiring hospitalization, is like other anti-TNF agents based on recent pooled analyses (Ref) and have resolved with treatment discontinuation (Ref).
Mechanism: Related to the pharmacologic action (ie, monoclonal antibody targeting α4β7 integrin, a cell surface glycoprotein on B and T lymphocytes that binds to mucosal addressin cell adhesion molecule-1 on the intestinal vasculature) (Ref).
Risk factors:
• Prior anti-TNF use (Ref)
• Concurrent narcotic use (Ref)
• Older age (Ref)
• Concurrent corticosteroid use (Ref)
• Cirrhosis (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Nervous system: Headache (12%)
Neuromuscular & skeletal: Arthralgia (12%)
Respiratory: Nasopharyngitis (13%)
1% to 10%:
Dermatologic: Pruritus (3%), skin rash (3%)
Gastrointestinal: Nausea (9%)
Hepatic: Increased serum alanine aminotransferase (≥3 × ULN: <2%), increased serum aspartate aminotransferase (≥3 × ULN: <2%)
Hypersensitivity: Infusion-related reaction (4%) (table 1)
Drug (Vedolizumab) |
Placebo |
Indication |
Number of Patients (Vedolizumab) |
Number of Patients (Placebo) |
---|---|---|---|---|
4% |
3% |
Crohn disease or ulcerative colitis |
1,434 |
297 |
Immunologic: Antibody development (6%; neutralizing: 3% to 4%)
Infection: Influenza (4%)
Local: Injection-site reaction (3% to 10%; including bruising at injection site, erythema at injection site, hematoma at injection site, injection-site pruritus, pain at injection site, rash at injection site, swelling at injection site, urticaria at injection site)
Nervous system: Fatigue (6%)
Neuromuscular & skeletal: Back pain (4%), limb pain (3%)
Respiratory: Bronchitis (4%), cough (5%), oropharyngeal pain (3%), sinusitis (3%), upper respiratory tract infection (7%)
Miscellaneous: Fever (9%)
Frequency not defined: Hematologic & oncologic: Malignant neoplasm (excluding dysplasia, basal cell carcinoma)
Postmarketing:
Dermatologic: Acne fulminans (Blankenship 2022), acneiform eruption (Magdaleno-Tapial 2018), dermatitis (reactive granulomatous, interstitial type) (Beuerlein 2022)
Gastrointestinal: Acute pancreatitis (Picardo 2018), cholestasis (Honap 2021), stomatitis (sereve erosive gingivostomatitis) (Semeria 2020)
Hematologic & oncologic: Peripheral eosinophilia (De Marco 2022)
Hepatic: Hepatic injury (De Marco 2022), hepatitis (including toxic hepatitis) (Mascarenhas Saraiva 2020), increased serum bilirubin, increased serum transaminases (including increased gamma-glutamyl transferase, increased serum alkaline phosphatase) (De Marco 2022)
Hypersensitivity: Hypersensitivity angiitis (de Freitas 2021), hypersensitivity reaction (including anaphylaxis)
Infection: Infection (including anal abscess, sepsis, tuberculosis, salmonella sepsis, meningitis due to Listeria monocytogenes, giardiasis, cytomegalovirus disease [colitis])
Nervous system: Progressive multifocal leukoencephalopathy (in a patient with multiple risk factors [ie, HIV, CD4 count 300 cells/mm3, prolonged prior and concurrent immunosuppression]) (Loftus 2020)
Renal: Acute interstitial nephritis (Subhaharan 2022)
Respiratory: Interstitial lung disease (Rizos 2021), pneumonitis (including eosinophilic pneumonitis) (Faria 2023)
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.
Disease-related concerns:
• Infection: Therapy is not recommended in patients with uncontrolled, active, severe infections. If a patient develops a serious infection, consider discontinuing therapy. Use with caution in patients with a history of recurring severe infections.
Other warnings/precautions:
• Immunizations: Patients should be brought up to date with all immunizations according to immunization guidelines before initiating therapy. Live vaccines should not be given concurrently unless the benefits outweigh the risks; there are no data on the secondary transmission of infection by live vaccines with vedolizumab. Non-live vaccines may be given concurrently.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Pen-injector, Subcutaneous:
Entyvio: 108 mg/0.68 mL (0.68 mL) [contains polysorbate 80]
Solution Reconstituted, Intravenous [preservative free]:
Entyvio: 300 mg (1 ea) [contains polysorbate 80]
No
Solution (reconstituted) (Entyvio Intravenous)
300 mg (per each): $10,399.90
Solution Pen-injector (Entyvio Subcutaneous)
108MG/0.68ML (per 0.68 mL): $3,743.96
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Pen-injector, Subcutaneous:
Entyvio: 108 mg/0.68 mL (0.68 mL) [contains polysorbate 80]
Solution Prefilled Syringe, Subcutaneous:
Entyvio: 108 mg/0.68 mL (0.68 mL) [contains polysorbate 80]
Solution Reconstituted, Intravenous:
Entyvio: 300 mg (1 ea) [contains mouse (murine) and/or hamster protein, polysorbate 80]
IV: Infuse over 30 minutes. Do not administer by IV push or bolus. Following infusion, flush with 30 mL of sterile 0.9% sodium chloride injection or LR. Observe patients during infusion (until complete) and monitor for hypersensitivity reactions; discontinue if a reaction occurs.
SUBQ: Allow pen to reach room temperature (30 minutes) after removing from refrigerator; do not warm in other ways or let sit in direct sunlight. Do not shake. Administer by SUBQ injection into front of thighs, abdomen (avoid area 2 inches around navel), or back of the upper arm (if administered by health care provider or caregiver); rotate injection sites. Do not inject into bruises, moles, scars, or damaged, hard, red, or tender skin. Initial use is recommended under supervision of physician; self injection may occur after proper training. Do not reuse prefilled pens; single use only.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Entyvio: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/125476s054,761133s003lbl.pdf#page=25
Crohn disease: Treatment of Crohn disease in adults.
Ulcerative colitis: Treatment of ulcerative colitis in adults.
Colitis, immune checkpoint inhibitor-induced
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Antithymocyte Globulin (Equine): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Anti-TNF Agents: May enhance the adverse/toxic effect of Vedolizumab. Risk X: Avoid combination
Baricitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG Products: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Chikungunya Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Cladribine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Coccidioides immitis Skin Test: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing therapeutic immunosuppressants several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
CYP Substrates (Narrow Therapeutic Index/Sensitive with Inducers): Vedolizumab may decrease the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor therapy
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Denosumab. Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate 2 to 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Natalizumab: Vedolizumab may enhance the adverse/toxic effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Pidotimod: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Pimecrolimus. Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Rabies Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Ritlecitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Rozanolixizumab: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Ruxolitinib (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tofacitinib. Management: Coadministration of tofacitinib with potent immunosuppressants is not recommended. Use with non-biologic disease-modifying antirheumatic drugs (DMARDs) was permitted in psoriatic arthritis clinical trials. Risk X: Avoid combination
Travelers' Diarrhea and Cholera Vaccine: Vedolizumab may diminish the therapeutic effect of Travelers' Diarrhea and Cholera Vaccine. Management: Administer travelers' diarrhea and cholera vaccine prior to initiation of therapy with vedolizumab. Risk D: Consider therapy modification
Typhoid Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to starting immunosuppressants when possible. Patients vaccinated less than 14 days before or during therapy should be revaccinated at least 2 to 3 months after therapy is complete. Risk D: Consider therapy modification
Yellow Fever Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Biologics, such as vedolizumab, may be continued in patients with inflammatory bowel disease planning to become pregnant (Mahadevan 2019). Treatment algorithms are available for use of biologics in patients with Crohn disease who are planning a pregnancy (Weizman 2019). When treatment for inflammatory bowel disease is needed, serum levels of biologic therapy should be optimized prior to conception (Mahadevan 2019).
Vedolizumab crosses the placenta (Flanagan 2020; Julsgaard 2021; Mahadevan 2021; Mitrova 2021).
Vedolizumab is a humanized monoclonal antibody (IgG1). Human IgG crosses the placenta. Fetal exposure is dependent upon the IgG subclass, maternal serum concentrations, placental integrity, newborn birth weight, and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis and the highest during the third trimester (Clements 2020; Palmeira 2012; Pentsuk 2009). Vedolizumab concentrations in cord blood and newborn serum are generally lower than those in the maternal serum at delivery (Flanagan 2020; Julsgaard 2021; Mahadevan 2021). In a study of 17 mother-infant pairs, vedolizumab serum concentrations were available in a subset of infants at 6 to 8 weeks of age (last intrapartum dose given at a median 30 weeks). Vedolizumab was measurable in the serum of 6 infants and not detected in the serum of 4 infants. Vedolizumab remained measurable in 1 infant at 12 weeks of age (Flanagan 2020). In a study of 43 mother-infant pairs, there were no infants exposed to vedolizumab in utero that had detectable serum concentrations at 6 months of age (Julsgaard 2021).
Data related to the use of vedolizumab in pregnancy are available (Bar-Gil Shitrit 2019; Chambers 2021; Chugh 2023; Cohen 2020; Ghalandari 2022; Gorodensky 2023; Julsgaard 2017; Mahadevan 2017; Meyer 2024; Mitrova 2022; Moens 2019; Moens 2020; Sheridan 2017; Wils 2021). Based on data from the Organization of Teratology Information Specialists/MotherToBaby ENTYVIO Pregnancy Registry, product labeling notes an increased risk for major structural birth defects has not been observed following maternal use during pregnancy.
Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of vedolizumab may be altered. Maternal serum levels may decrease as pregnancy progresses due increased clearance; however, the changes are not clinically significant (Flanagan 2020).
The safety of administering live vaccines to infants exposed to vedolizumab in utero is not known. Vaccination with live vaccines (eg, rotavirus vaccine) should be avoided for the first 6 months of life if exposure to a biologic agent occurs during the third trimester of pregnancy (eg, >27 weeks' gestation) (Mahadevan 2019).
Inflammatory bowel disease is associated with adverse pregnancy outcomes including an increased risk of miscarriage, premature delivery, delivery of a low-birth-weight infant, and poor maternal weight gain. Management of maternal disease should be optimized prior to pregnancy. Treatment decreases disease flares, disease activity, and the incidence of adverse pregnancy outcomes (Mahadevan 2019).
When treatment for inflammatory bowel disease is needed in pregnant patients, appropriate biologic therapy can be continued without interruption. Serum levels should be evaluated prior to conception and optimized to avoid subtherapeutic concentrations or high levels which may increase placental transfer. Dosing can be adjusted so delivery occurs at the lowest serum concentration. For vedolizumab, the final injection can be given 6 to 10 weeks prior to the estimated date of delivery (4 to 5 weeks before delivery if every-4-week dosing), then continued 48 hours' postpartum (Mahadevan 2019).
Vedolizumab is present in breast milk.
Multiple reports summarize data related to the presence of vedolizumab in breast milk:
• In 2 studies, with a total of 10 lactating women, breast milk was sampled prior to and up to 14 days following administration of vedolizumab 300 mg IV. Vedolizumab was present at each time point evaluated. The highest concentrations occurred 3 to 7 days after the dose and were ≤1% of the maternal serum concentration. Breastfed infants were followed for up to 10 months and reached their developmental milestones (Julsgaard 2018; Lahat 2018); GI infections were not observed (Lahat 2018) and inactivated vaccines were administered without complication (Julsgaard 2018).
• A study evaluated breast milk concentrations of vedolizumab over 57 (±3) days in 11 women. All patients were at least 5 weeks postpartum and receiving maintenance treatment prior to the study. Dosing was vedolizumab 300 mg IV every 4 (n=1), 6 (n=1), or 8 (n=9) weeks. Peak breast milk concentrations of vedolizumab occurred on days 3 to 4 following the maternal dose then decreased exponentially. Vedolizumab could be detected in breast milk in low levels up to 57 days after the infusion. Concentrations of vedolizumab in breast milk were ~0.4% to 2.2% of the maternal plasma over the study period (Sun 2021).
Vedolizumab was not detectable in the serum of 4 infants exposed in-utero and via breast milk. Vedolizumab was present in cord blood at birth, but not detectable in their serum at 3 months of age and until sampling stopped at 12 months of age. Vedolizumab breast milk concentrations were not evaluated in this study (Julsgaard 2021).
It is expected that any vedolizumab ingested via breast milk would be degraded in the infant GI tract and have minimal impact to the breastfed infant (Julsgaard 2018; Lahat 2018; Sun 2021). According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother; however, available guidelines note maternal use of vedolizumab is considered compatible with breastfeeding (Mahadevan 2019).
Observe patients during infusion (until complete) and monitor for hypersensitivity reactions; LFTs; tuberculosis screening according to local practice; signs/symptoms of infection; signs/symptoms of progressive multifocal leukoencephalopathy, including new onset or worsening of neurological signs and symptoms (eg, progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes); any new onset or worsening of neurological signs and symptoms
Vedolizumab is a humanized monoclonal antibody that binds to the alpha4beta7 integrin and blocks the interaction of alpha4beta7 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. The interaction of the alpha4beta7 integrin with MAdCAM-1 has been implicated as an important contributor to the chronic inflammation that is a hallmark of ulcerative colitis and Crohn disease.
Distribution: Vd: ~5 L.
Bioavailability: SUBQ: ~75%.
Half-life elimination: ~26 days.
Time to peak: SUBQ: 7 days (range: 3 to 14 days).
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