Note: Prior to initiating treatment, all patients should be brought up to date with all immunizations according to current immunization guidelines.
Crohn disease (alternative agent) (AGA [Feuerstein 2021]):
Note: Combination with an immunomodulator is generally preferred (Al Hashash 2021).
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 [Canadian product]: 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.
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 [Canadian product]: 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.
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [preservative free]:
Entyvio: 300 mg (1 ea) [contains polysorbate 80]
No
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]
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/2021/125476s038s039lbl.pdf#page=20
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 [Canadian product]: Allow pen to reach room temperature (30 minutes) after removing from refrigerator; do not warm in other ways or let sit in direct sunlight. Administer by SubQ injection into front of thighs, abdomen (avoid area 2 inches around navel), or back of the upper arm; rotate injection sites. Do not inject into bruises, moles, scars, or damaged, hard, red, or tender skin. Administer first injection under health care provider supervision and observe for signs of severe injection-site reactions or anaphylaxis. Do not reuse prefilled pens; single use only.
Crohn disease: Treatment of Crohn disease in adults.
Guideline Recommendations: The American Gastroenterological Association guidelines on the medical management of moderate to severe luminal and perianal fistulizing Crohn disease suggest the use of vedolizumab with or without an immunomodulator for treatment-naïve patients, or in patients with primary or secondary nonresponse to tumor necrosis factor-alpha inhibitors. In addition, vedolizumab may be used in combination with an antibiotic in patients with fistulizing disease for induction or maintenance of fistula remission (AGA [Feuerstein 2021]).
Ulcerative colitis: Treatment of ulcerative colitis in adults.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Immunologic: Antibody development (4% to 13%; neutralizing: 2%)
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 x ULN: <2%), increased serum aspartate aminotransferase (≥3 x ULN: <2%)
Infection: Influenza (4%)
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%), infusion related reaction (4%)
Frequency not defined: Hematologic & oncologic: Malignant neoplasm (excluding dysplasia and basal cell carcinoma)
Postmarketing:
Hepatic: Hepatitis, increased serum bilirubin, increased serum transaminases
Hypersensitivity: Anaphylaxis, bronchospasm, hypersensitivity reaction
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)
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.
Concerns related to adverse effects:
• Hypersensitivity/infusion-related reactions: Hypersensitivity and infusion-related reactions have been reported including anaphylaxis, dyspnea, bronchospasm, urticaria, flushing, rash, and increased BP and heart rate. Reactions may occur with the first or subsequent infusions; onset may vary from during the infusion or up to several hours post-infusion. If anaphylaxis or other serious infusion-related or hypersensitivity reactions occur, discontinue administration immediately and initiate appropriate treatment.
• Infections: Use may be associated with an increased risk for developing infections; most commonly reported infections included upper respiratory and nasal mucosa. Serious infections have also been reported in patients treated, including anal abscess, sepsis (some fatal), tuberculosis, salmonella sepsis, Listeria meningitis, giardiasis, and cytomegaloviral colitis. 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. Screening for tuberculosis should be considered.
• Liver injury: Elevations of transaminase and/or bilirubin have been reported in patients receiving vedolizumab. Discontinue therapy in patients with jaundice or other evidence of significant liver injury such as fatigue, anorexia, right upper abdominal discomfort, or dark urine.
• Progressive multifocal leukoencephalopathy: Progressive multifocal leukoencephalopathy (PML), a rare and often fatal opportunistic infection of the CNS caused by the John Cunningham virus, has been reported with integrin receptor antagonists, including vedolizumab. The case with vedolizumab occurred in a patient with multiple risk factors for PML (ie, HIV, CD4 count 300 cells/mm3, prolonged prior and concurrent immunosuppression) (Lotus 2020). Monitor patients for any new onset or worsening of neurological signs and symptoms including 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. Symptoms may progress over days to weeks and can lead to death or severe disability in weeks to months. If PML is suspected, withhold therapy and refer to a neurologist; if confirmed, discontinue therapy permanently.
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.
None known.
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
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
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: In the US, after receipt of the single dose COVID-19 adenovirus vector vaccine (Janssen), administer an additional 2nd dose using an mRNA COVID-19 vaccine, at least 28 days after the primary vaccine dose, in patients taking immunosuppressive therapies. 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: Consider administration of a 3rd dose of COVID-19 vaccine, at least 28 days after completion of the primary 2-dose series, in patients 5 years of age and older taking immunosuppressive therapies. 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
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
Echinacea: May diminish the therapeutic effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Management: Consider avoiding echinacea in patients receiving therapeutic immunosuppressants. If coadministered, monitor for reduced efficacy of the immunosuppressant during concomitant use. Risk D: Consider therapy modification
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
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
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 post-exposure rabies vaccination is required during immunosuppressant therapy, administer a 5th dose of vaccine and check for rabies antibodies. Risk D: Consider therapy modification
Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of 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 Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
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
Upadacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Vaccines (Inactivated). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 2 to 3 months after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): May enhance the adverse/toxic effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
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 females with inflammatory bowel disease planning a pregnancy (Mahadevan 2019). Treatment algorithms are available for use of biologics in female 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; Mahadevan 2016).
Vedolizumab is a humanized monoclonal antibody (IgG1). Placental transfer of human IgG is dependent upon the IgG subclass, maternal serum concentrations, birth weight, and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009). Vedolizumab concentrations in cord blood and newborn serum are lower than those in the maternal serum at delivery (Flanagan 2020; Mahadevan 2016). Newborn clearance of vedolizumab is variable. 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).
Information related to the use of vedolizumab in pregnancy is available (Bar-Gil Shitrit 2019; Julsgaard 2017; Mahadevan 2017; Moens 2019; Moens 2020; Sheridan 2017). Based on available data, an increased risk of adverse maternal or fetal effects has not been observed following vedolizumab exposure in pregnancy (Nielsen 2020; Terjung 2020).
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, this may not be 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 women, 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).
Data collection to monitor pregnancy and infant outcomes following exposure to vedolizumab is ongoing. Health care providers are encouraged to enroll women exposed to vedolizumab during pregnancy in a pregnancy exposure registry. Information about the registry can be obtained by calling 1-877-825-3327.
Vedolizumab is present 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 a maternal dose. 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 third study of 11 women also observed peak breast milk concentrations of vedolizumab to occur on days 3 to 4 following the maternal dose then decrease exponentially. Vedolizumab could be detected in breast milk in low levels up to 57 days after the infusion (Sun 2020).
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 2020). 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; 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.
Bioavailability: SubQ (Canadian product): ~75%.
Distribution: Vd: 5 L.
Half-life elimination: IV: 25 days (serum, at 300 mg dosage); SubQ (Canadian product): 23 days.
Time to peak: SubQ (Canadian product): 7 days (range: 3 to 14 days).
Solution (reconstituted) (Entyvio Intravenous)
300 mg (per each): $9,255.88
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