Vedolizumab is a monoclonal antibody that is a specific integrin receptor antagonist. It is used for the treatment of moderately to severely active ulcerative colitis and Crohn's disease in adult patients. Treatment with vedolizumab is appropriate for patients who have failed to fully respond to tumor necrosis factor (TNF) blocker, immunomodulator, or corticosteroid therapy or who are intolerant to or demonstrated dependence on corticosteroids. Vedolizumab binds to and blocks the interaction between integrin alpha-4-beta-7 and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in the gut which inhibits the migration of specific memory T-lymphocytes across the endothelium into inflamed gastrointestinal parenchymal tissue. The action reduces the chronic inflammatory process present in both ulcerative colitis and Crohn's disease. In clinical evaluation, treatment with vedolizumab was associated with an improvement in the endoscopic appearance of the gut mucosa as well as a greater percentage of patients achieving clinical remission relative to placebo. Vedolizumab is administered via intravenous infusion for ulcerative colitis and Crohn's disease, or by subcutaneous injection following first 2 IV infusions for ulcerative colitis. Adverse reactions to vedolizumab are consistent with similar drugs and include headache, arthralgia, nausea fever, and rash; hypersensitivity and infusion reactions have occurred and use of the drug may increase the risk of infections and progressive multifocal leukoencephalopathy (PML). Guidelines strongly recommend the use of vedolizumab as an option for the induction and maintenance of remission in patients with moderately- to severely-active ulcerative colitis (UC) and for induction of remission for patients with moderately- to severely-active Crohn's disease. Appropriate selections of agents used in Crohn's disease and UC continue to be driven by treat-to-target strategies, response for induction and remission, the severity of disease, and medication tolerance.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
NOTE: Have medications for the treatment of hypersensitivity reactions available for immediate use. Discontinue vedolizumab if a severe hypersensitivity reaction occurs. A severe hypersensitivity reaction contraindicates future vedolizumab receipt.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Reconstituted solution should be clear or opalescent, colorless to light brownish yellow and free of visible particulates. Solution in prefilled syringes and pens should be clear to moderately opalescent, colorless to sightly yellow and free of visible particulates. Discard if discoloration or particulate matter are observed.
Intravenous Administration
-Administer as an intravenous (IV) infusion only, after dilution as instructed. Do not administer as an IV push or bolus.
-Prior to initial treatment, ensure patient is current on all vaccinations according to immunization guidelines.
Reconstitution and Dilution of IV infusion:
-Reconstitute vial containing lyophilized powder with 4.8 mL of Sterile Water for Injection, 0.9% Sodium Chloride Injection, or Lactated Ringer's Injection at room temperature, using a syringe with a 21 to 25 gauge needle.
-Insert the syringe needle into the vial and direct the stream of Sterile Water for Injection, 0.9% Sodium Chloride Injection, or Lactated Ringer's Injection to the glass wall of the vial to avoid excessive foaming.
-Gently swirl the vial for 15 seconds to dissolve the lyophilized powder. Do not shake or invert.
-Allow the solution to stand for up to 20 minutes at room temperature to allow for reconstitution and for any foam to settle; the vial can be swirled and inspected for dissolution during this time. If not fully dissolved after 20 minutes, allow another 10 minutes for dissolution. Discard if product has not dissolved within 30 minutes.
-Following dissolution, gently invert vial 3 times.
-Immediately withdraw 5 mL (300 mg) of reconstructed product using a 21 to 25 gauge needle. Discard remaining product.
-Add the 5 mL (300 mg) of reconstituted product to 250 mL of 0.9% Sodium Chloride Injection or Lactated Ringer's Injection and gently mix the infusion bag. Do not mix with other medications. Administer solution as soon as possible.
-Storage: Do not freeze the reconstituted solution in the vial or the diluted solution in the infusion bag. Storage time periods for the infusion bags assume the reconstituted solution was immediately diluted. If the reconstituted solution is not immediately diluted, subtract the time in the vial from the time the diluted solution is stored in the infusion bag.-Reconstituted solution in Sterile Water for Injection, 0.9% Sodium Chloride Injection, or Lactated Ringer's Injection inside vial: Use immediately after reconstitution if stored at room temperature (20 to 25 degrees C [68 to 77 degrees F]) or within 8 hours if stored under refrigeration at 2 to 8 degrees C (36 to 46 degrees F).
-Diluted solution in 0.9% Sodium Chloride Injection: Use within 12 hours if stored at room temperature or 24 hours if stored under refrigeration (refrigerated time may include up to 12 hours at room temperature).
-Diluted solution in Lactated Ringer's Injection: Use immediately after dilution if stored at room temperature or within 6 hours if stored under refrigeration.
IV Infusion administration
-Only health care providers prepared to manage hypersensitivity reactions, including anaphylaxis and infusion-related reaction, should administer vedolizumab.
-Do not infuse concomitantly in the same intravenous line with other agents.
-Infuse over 30 minutes. After infusion, flush line with 30 mL of 0.9% Sodium Chloride Injection or Lactated Ringer's Injection. Discard any unused infusion solution.
Subcutaneous Administration
-Patients and/or caregivers may self inject the prefilled syringe or pen after proper instruction on subcutaneous injection technique has been given.
-Administer injection subcutaneously into thigh, any quadrant of the abdomen, or upper arms. Subsequent injections must be in different anatomic location than previous injection. Do not inject into moles, scars, bruises, or areas where skin is tender, erythematous, or indurated.
-Missed Dose: If treatment with vedolizumab is interrupted or if a scheduled dose is missed, inject the next subcutaneous dose as soon as possible and then every 2 weeks thereafter. In the event of incomplete dose administration (ie.e, patient attempts administration of dose with pen, however it is uncertain if a full dose was administered), instruct the patient to call their pharmacy or healthcare provider.
-Storage: Keep unopened product refrigerated; DO NOT freeze. If needed, the prefilled syringes or prefilled pens can be stored at room temperature up to 25 degrees C (77 degrees F) for up to 7 days. Do not use product if left out of the refrigerator for more than 7 days. Do not shake. Keep in original package and protect from light.
The safety of vedolizumab for the treatment of ulcerative colitis and Crohn's disease was studied in several trial settings, including 4 placebo-controlled trials as well as 1 open-label treatment arm. Study patients received 300 mg of vedolizumab (n = 1,434) or placebo (n = 297) for up to 52 weeks; mean duration of exposure ranged from 247 to 259 days, depending on the study. The most common adverse reactions reported, occurring in 3% or more of vedolizumab treated patients and occurring at least 1% higher than in placebo-treated patients included headache (12%), arthralgia (12%), nausea (9%), fatigue (6%), back pain (4%), and musculoskeletal pain in extremities (3%).
Infusion-related reactions and hypersensitivity reactions have been reported with vedolizumab therapy, including anaphylaxis (anaphylactoid reactions), dyspnea, bronchospasm, urticaria, flushing, rash, increased blood pressure, and increased heart rate. The safety of vedolizumab for the treatment of ulcerative colitis and Crohn's disease was studied in several trial settings, including 4 placebo-controlled trials as well as 1 open-label treatment arm. Study patients received 300 mg of vedolizumab (n = 1,434) or placebo (n = 297) for up to 52 weeks; mean duration of exposure ranged from 247 to 259 days, depending on the study. The most common hypersensitivity related adverse reactions reported, occurring in 3% or more of vedolizumab treated patients and 1% or higher than in placebo, included rash (3%) and pruritus (3%). Infusion-related reactions were also reported in 4% of vedolizumab treated patients. Associated symptoms typically occurring within the first two hours after an infusion included nausea, headache, pruritus, dizziness, pyrexia, urticaria and vomiting; in this context, each of these symptoms were reported in less than 1% of patients. In these cases, the reactions generally resolved with no treatment or following antihistamine and intravenous hydrocortisone treatment. Serious infusion-related reactions and hypersensitivity reactions including anaphylactoid reactions have also been reported following vedolizumab administration. During clinical trials, one patient with Crohn's disease (0.07%) experienced anaphylaxis. Reported symptoms were dyspnea, bronchospasm, flushing, rash, increased blood pressure, and heart rate. In this case, vedolizumab was discontinued and the individual was treated with an antihistamine and intravenous hydrocortisone. Clinicians should note that infusion reaction-related or allergic symptoms may occur at any time during infusion, immediately following infusion, or up to several hours post-infusion. Vedolizumab should be administered in a facility prepared to immediately administer medications for the treatment of hypersensitivity reactions in the event of a reaction. If anaphylaxis or other serious infusion-related or hypersensitivity reaction occurs, immediately discontinue vedolizumab and initiate appropriate therapy.
The safety of vedolizumab for the treatment of ulcerative colitis and Crohn's disease was studied in several trial settings, including 4 placebo-controlled trials as well as 1 open-label treatment arm. Study patients received 300 mg of vedolizumab (n = 1,434) or placebo (n = 297) for up to 52 weeks; mean duration of exposure ranged from 247 to 259 days, depending on the study. The most common infectious related adverse reactions reported, occurring in 3% or more of vedolizumab treated patients and at least 1% higher incidence than in placebo, included pharyngitis (13%), fever (9%), upper respiratory tract infection (7%), cough (5%), bronchitis (4%), influenza (4%), sinusitis (3%), and oropharyngeal pain (3%). In addition, cases of serious infections have been reported during vedolizumab trials including anal abscess, sepsis (some fatal), tuberculosis, salmonella sepsis, Listeria meningitis, giardiasis and cytomegaloviral colitis.
Progressive multifocal leukoencephalopathy (PML) is a rare and sometimes fatal opportunistic infection of the central nervous system (CNS) caused by the John Cunningham virus. PML typically only effects immunocompromised individuals. During clinical evaluation, patients receiving vedolizumab were carefully monitored for unexplained CNS changes. Although no cases of PML were identified during studies, the risk of PML exists in patients receiving vedolizumab. Therefore, monitor patients for any new or worsening neurological signs and symptoms. Signs and symptoms associated with PML vary, are progressive over days to weeks, and include: increased weakness on one side of the body or clumsiness of limbs, visual disturbance, and changes in thinking, memory, and orientation leading to confusion and personality changes. Severe disability or death can come over weeks or months. Interrupt vedolizumab therapy if PML is suspected and refer patient to a neurologist; if confirmed, discontinue therapy without rechallange.
Reports of elevated hepatic enzymes including elevated transaminase and/or bilirubin in patients receiving vedolizumab have been reported. Elevated transaminase and bilirubin, without evidence of obstruction, is predictive of severe liver injury that may be fatal or hepatic failure that may require a liver transplant in some patients. Hepatitis, manifested as elevated transaminases with or without elevated bilirubin and symptoms consistent with hepatitis (e.g., malaise, nausea, vomiting, abdominal pain, and anorexia) was also reported. All symptomatic patients recovered following discontinuation of therapy with some requiring corticosteroid therapy. In addition, the reported incidence of ALT and AST elevations at least 3 times the upper limit of normal was less than 2%. Monitor patients closely for evidence of liver dysfunction including symptoms of fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. If hepatic dysfunction is suspected, discontinue vedolizumab therapy immediately.
Similar to other therapeutic proteins, patients treated with vedolizumab may experience antibody formation. In clinical evaluation, antibody formation against vedolizumab occurred in 6% of patients (86 patients out of 1,427) who received continuous intravenous treatment for 52 weeks. Among the 86 individuals who tested positive for anti-vedolizumab antibodies, 20 were persistently positive at 2 or more study visits and 56 developed neutralizing antibodies. Of the 20 patients with persistently positive anti-vedolizumab antibody status, 14 had undetectable or reduced vedolizumab serum concentrations and 5 achieved clinical remission at week 52. In patients who received subcutaneous vedolizumab, antibody formation occurred in 6% of patients (6 patients out of 106). Of the 6 patients who tested positive for anti-vedolizumab antibodies, 4 patients were persistently positive (at 2 or more study visits), and 3 patients developed neutralizing antibodies to vedolizumab. None of the 6 antibody-positive patients achieved clinical remission in week 52 with subcutaneous injections. Overall, no apparent correlation between the development of anti-vedolizumab antibodies and incidence of adverse reactions has been identified. Vedolizumab appears to be associated with less immunogenicity than the tumor necrosis factor (TNF) blockers in patients with inflammatory bowel disease.
Treatment with vedolizumab may cause a new primary malignancy. In clinical evaluation, malignancies (excluding dysplasia and basal cell carcinoma) were reported in 0.4% of patients treated with vedolizumab, including colon cancer (n = 2), transitional cell carcinoma (n = 1), breast cancer (n = 1), carcinoid tumor of the appendix (n = 1) and squamous cell carcinoma (n = 1). In contrast, malignancy was reported in 0.3% of patients treated with placebo (squamous cell carcinoma). Malignancies (excluding dysplasia and basal cell carcinoma) observed during the ongoing open-label long-term extension trial included B-cell lymphoma, breast cancer, colon cancer, malignant hepatic neoplasm, malignant lung neoplasm, malignant melanoma, lung cancer of primary neuroendocrine carcinoma, renal cancer and squamous cell carcinoma. Long-term exposure was limited in these trials and a causal relationship to vedolizumab therapy is unknown.
Acute pancreatitis has been reported with postmarketing use of vedolizumab.
During clinical trials, injection site reaction was reported in 9% of patients receiving vedolizumab subcutaneous injection for ulcerative colitis. Reactions included injection site erythema, rash, swelling, bruising, and hematoma.
Use vedolizumab with caution in patients with a history of hepatic disease. Monitor vedolizumab patients closely for evidence of liver disfunction, including elevated hepatic enzymes, jaundice, malaise, nausea, vomiting, abdominal pain, and anorexia. Reports of elevated transaminase and/or bilirubin in patients receiving vedolizumab have occured. Elevated transaminase and bilirubin, without evidence of obstruction, is predictive of severe liver injury that may be fatal or may require a liver transplant in some patients. If hepatic dysfunction is suspected, discontinue vedolizumab therapy immediately.
Patients treated with vedolizumab are at an increased risk of developing infections due to immunosuppression. Cases of serious infections have been reported during vedolizumab trials including anal abscess, sepsis (some fatal), tuberculosis, salmonella sepsis, Listeria meningitis, giardiasis and cytomegaloviral colitis. Patients need to be evaluated for tuberculosis risk factors and for latent or active tuberculosis infection with a tuberculin skin test both before and during treatment. Do not administer vedolizumab to patients with a clinically important active infection like influenza or sepsis. Educate patients about the symptoms of infection, and closely monitor patients for signs and symptoms of an infection during and after vedolizumab treatment. Patients who develop a new infection during treatment should be closely monitored and evaluated for appropriate antimicrobial therapy. If a patient develops a serious infection or sepsis, discontinue vedolizumab.
Progressive multifocal leukoencephalopathy (PML), a rare and often fatal opportunistic infection of the central nervous system (CNS), has been reported with systemic immunosuppressants, including another integrin receptor antagonist. PML is caused by the John Cunningham virus and typically only effects immunocompromised individuals. One case of PML has been reported with postmarketing use of vedolizumab. The individual had multiple contributory factors, such as human immunodeficiency virus (HIV) infection with a CD4 count of 300 cells/mm3 and both prior and concomitant immunosuppression. Although unlikely, a risk of PML cannot be ruled out. Therefore, monitor patients for any new or worsening neurological signs and symptoms. Signs and symptoms associated with PML vary, are progressive over days to weeks, and include: increased weakness on one side of the body or clumsiness of limbs, visual disturbance, and changes in thinking, memory, and orientation leading to confusion and personality changes. Severe disability or death can come over weeks or months. Interrupt vedolizumab therapy if PML is suspected and refer patient to a neurologist; if confirmed, permanently discontinue therapy without rechallange.
Vedolizumab recipients may receive vaccinations except for live or live attenuated vaccines. No data are available on the response to live vaccination or the secondary transmission of infection by live vaccines in patients receiving vedolizumab. According to the manufacturer, live vaccines may be administered concurrently with vedolizumab only if the benefits outweigh the risks.
Available pharmacovigilance data, data from the pregnancy registry, and data from published case reports and cohort studies in pregnant women have not identified a vedolizumab associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Data from the vedolizumab pregnancy exposure registry showed the proportion of major birth defects among live-born infants in patients with UC or CD treated with vedolizumab and patients with UC or CD treated with other biological products was 7.4% (7/94) and 5.6% (4/71), respectively. Overall, there was no evidence of increased risk for major structural birth defects (adjusted RR 1.07, 95% CI: 0.33, 3.52). The methodological limitations of the registry, including small sample size and the nonrandomized design, resulted in a limited ability to estimate the risk of major birth defects and other maternal and infant outcomes. The conclusions from the pregnancy registry were consistent with the published literature and pharmacovigilance. Although not always predictive of human response, animal reproduction studies revealed no fetal harm with IV administration of vedolizumab to rabbits and monkeys at dose levels 20 times the recommended human dosage. Vedolizumab administered during pregnancy could affect immune responses in the in utero exposed neonates and infants. The clinical significance of low levels of vedolizumab in the exposed infants and the safety of administering live or live-attenuated vaccines to exposed infants are unknown. Guidelines generally recommend that the pregnant patient continue their biologic treatment as prescribed. For vedolizumab, experts recommend that practitioners plan the administration of the final pregnancy dose 6 to 10 weeks before the estimated delivery date, then resume treatment postpartum. Experts also recommend the avoidance of live vaccines for 6 months following birth for in utero exposed infants.
There are no data on the effects of vedolizumab on the breastfed infant, or the effects on milk production. Available published literature suggests the presence of vedolizumab in human milk. A milk-only lactation study was performed in 9 lactating individuals treated for either ulcerative colitis or Crohn's disease with intravenous vedolizumab every 8 weeks after reaching steady-state and completing the induction phase. Mean vedolizumab concentrations in human milk ranged from 0.03 to 0.26 mcg/mL. The mean calculated daily infant dose of vedolizumab was 0.2 mg/kg/day. Since monoclonal antibodies are largely degraded in the gastrointestinal tract, systemic exposure in a breast-fed infant is expected to be low. However, the effects of local gastrointestinal exposure and expected low systemic exposure to vedolizumab on the breastfed infant are unknown. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. Experts generally recommend the continuation of biologics such as vedolizumab during lactation and do not discourage breast-feeding; breastfed infants exposed to biologic or immunomodulating treatments did not appear to have differences in infection rates or developmental milestones compared to non-exposed infants according to available data from the Pregnancy in Inflammatory bowel disease and Neonatal Outcomes (PIANO) registry. Fewer data were available for vedolizumab vs. other agents at the time of review.
Similar to other therapeutic proteins, patients treated with vedolizumab may develop human anti-chimeric antibody (HACA). In clinical evaluation, antibody formation against vedolizumab occurred in 6% of patients (86 patients out of 1,427) who received continuous intravenous treatment for 52 weeks. Of the 20 patients with persistently positive anti-vedolizumab antibody status, 14 had undetectable or reduced vedolizumab serum concentrations and 5 achieved clinical remission at week 52. In patients who received subcutaneous vedolizumab, antibody formation occurred in 6% of patients (6 patients out of 106). Of the 6 patients who tested positive for anti-vedolizumab antibodies, 4 patients were persistently positive (at 2 or more study visits), and 3 patients developed neutralizing antibodies to vedolizumab. None of the 6 antibody-positive patients achieved clinical remission in week 52. Overall, no apparent correlation between the development of anti-vedolizumab antibodies and incidence of adverse reactions has been identified.
Infusion-related reactions and hypersensitivity reactions have been reported with vedolizumab, including anaphylaxis, dyspnea, bronchospasm, urticaria, flushing, rash, increased blood pressure, and increased heart rate. These reactions may occur with the first or subsequent vedolizumab infusions and time of onset may occur during infusion or up to several hours post-infusion. Vedolizumab should be administered in a facility prepared to immediately administer medications for the treatment of hypersensitivity reactions in the event of a reaction. Observe patients during infusion and instruct patients to report any hypersensitivity or infusion reaction related symptoms during and following vedolizumab administration. If anaphylaxis or other serious infusion-related or hypersensitivity reactions occur, immediately discontinue vedolizumab and initiate appropriate treatment.
For the treatment of moderately to severely active ulcerative colitis:
Intravenous dosage:
Adults: 300 mg IV infusion at weeks 0, 2, and 6, then 300 mg IV infusion every 8 weeks. Discontinue therapy if inadequate response by week 14. Guidelines strongly recommend the use of vedolizumab for the induction and maintenance of remission in persons with moderately to severely active ulcerative colitis.
Subcutaneous dosage:
Adults: Prior to initiating subcutaneous vedolizumab, a 300 mg IV infusion is administered at week 0 and week 2. Then at week 6 and thereafter, administer 108 mg subcutaneously once every 2 weeks. Discontinue therapy if no evidence of therapeutic benefit by week 14. Guidelines strongly recommend the use of vedolizumab for the induction and maintenance of remission in persons with moderately to severely active ulcerative colitis.
For moderate to severe active Crohn's disease:
Intravenous dosage:
Adults: 300 mg IV at weeks 0, 2, and 6, then 300 mg IV every 8 weeks. Full response is usually observed by 6 weeks; persons who do not respond by week 14 are unlikely to respond with continued treatment and consideration should be given to discontinuing therapy. Guidelines state that vedolizumab with or without an immunomodulator is more effective than placebo and should be considered for induction of symptomatic remission in persons with moderately to severely active Crohn's disease.
Therapeutic Drug Monitoring:
Target concentrations of vedolizumab in patients with Inflammatory Bowel Disease per guidelines
-Week 6: at least 33 to 37 mcg/mL
-Week 14: at least 15 to 20 mcg/mL
-Maintenance therapy: at least 10 to 15 mcg/mL
Maximum Dosage Limits:
-Adults
300 mg/dose IV for Crohn's disease or ulcerative colitis.
108 mg/dose subcutaneously for ulcerative colitis.
-Geriatric
300 mg/dose IV for Crohn's disease or ulcerative colitis.
108 mg/dose subcutaneously for ulcerative colitis.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; use with caution. There have been reports of elevations of transaminase and/or bilirubin as well as serious adverse reactions of hepatitis in patients receiving vedolizumab. Evaluate patients with signs or symptoms of hepatic dysfunction and discontinue vedolizumab therapy if these occur.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Adalimumab: (Major) Vedolizumab should not be used in combination with tumor necrosis factor (TNF) modifiers because of the potential for increased risk of progressive multifocal leukoencephalopathy and other infections. Ordinarily, patients receiving chronic immunosuppressant or immunomodulatory therapy should not be treated with vedolizumab.
Bacillus Calmette-Guerin Vaccine, BCG: (Major) Avoid administering live vaccines to vedolizumab recipients unless the benefits outweigh the risks; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving vedolizumab. Before initiation of vedolizumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Vedolizumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Certolizumab pegol: (Major) Vedolizumab should not be used in combination with tumor necrosis factor (TNF) modifiers because of the potential for increased risk of progressive multifocal leukoencephalopathy and other infections. Ordinarily, patients receiving chronic immunosuppressant or immunomodulatory therapy should not be treated with vedolizumab.
Chikungunya Vaccine, Live: (Major) Avoid administering live vaccines to vedolizumab recipients unless the benefits outweigh the risks; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving vedolizumab. Before initiation of vedolizumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Vedolizumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Etanercept: (Major) Vedolizumab should not be used in combination with tumor necrosis factor (TNF) modifiers because of the potential for increased risk of progressive multifocal leukoencephalopathy and other infections. Ordinarily, patients receiving chronic immunosuppressant or immunomodulatory therapy should not be treated with vedolizumab.
Golimumab: (Major) Vedolizumab should not be used in combination with tumor necrosis factor (TNF) modifiers because of the potential for increased risk of progressive multifocal leukoencephalopathy and other infections. Ordinarily, patients receiving chronic immunosuppressant or immunomodulatory therapy should not be treated with vedolizumab.
Infliximab: (Major) Vedolizumab should not be used in combination with tumor necrosis factor (TNF) modifiers because of the potential for increased risk of progressive multifocal leukoencephalopathy and other infections. Ordinarily, patients receiving chronic immunosuppressant or immunomodulatory therapy should not be treated with vedolizumab.
Intranasal Influenza Vaccine: (Major) Avoid administering live vaccines to vedolizumab recipients unless the benefits outweigh the risks; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving vedolizumab. Before initiation of vedolizumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Vedolizumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Live Vaccines: (Major) Avoid administering live vaccines to vedolizumab recipients unless the benefits outweigh the risks; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving vedolizumab. Before initiation of vedolizumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Vedolizumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Major) Avoid administering live vaccines to vedolizumab recipients unless the benefits outweigh the risks; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving vedolizumab. Before initiation of vedolizumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Vedolizumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Measles/Mumps/Rubella Vaccines, MMR: (Major) Avoid administering live vaccines to vedolizumab recipients unless the benefits outweigh the risks; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving vedolizumab. Before initiation of vedolizumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Vedolizumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Natalizumab: (Major) Avoid concomitant use of vedolizumab and natalizumab. The concomitant use of vedolizumab and natalizumab may further increase the risk of serious infections, including progressive multifocal leukoencephalopathy and other opportunistic infections, over the risk observed with use of vedolizumab alone. The safety and efficacy of vedolizumab in combination with natalizumab have not been established.
Rotavirus Vaccine: (Major) Avoid administering live vaccines to vedolizumab recipients unless the benefits outweigh the risks; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving vedolizumab. Before initiation of vedolizumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Vedolizumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Major) Avoid administering live vaccines to vedolizumab recipients unless the benefits outweigh the risks; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving vedolizumab. Before initiation of vedolizumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Vedolizumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Smallpox Vaccine, Vaccinia Vaccine: (Major) Avoid administering live vaccines to vedolizumab recipients unless the benefits outweigh the risks; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving vedolizumab. Before initiation of vedolizumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Vedolizumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Tumor Necrosis Factor modifiers: (Major) Vedolizumab should not be used in combination with tumor necrosis factor (TNF) modifiers because of the potential for increased risk of progressive multifocal leukoencephalopathy and other infections. Ordinarily, patients receiving chronic immunosuppressant or immunomodulatory therapy should not be treated with vedolizumab.
Typhoid Vaccine: (Major) Avoid administering live vaccines to vedolizumab recipients unless the benefits outweigh the risks; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving vedolizumab. Before initiation of vedolizumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Vedolizumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Varicella-Zoster Virus Vaccine, Live: (Major) Avoid administering live vaccines to vedolizumab recipients unless the benefits outweigh the risks; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving vedolizumab. Before initiation of vedolizumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Vedolizumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Yellow Fever Vaccine, Live: (Major) Avoid administering live vaccines to vedolizumab recipients unless the benefits outweigh the risks; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving vedolizumab. Before initiation of vedolizumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Vedolizumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Vedolizumab is a humanized monoclonal antibody that specifically binds to alpha-4-beta-7 integrin and blocks the interaction between alpha-4-beta-7 integrin with mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in the gastrointestinal tract. Vedolizumab in turn inhibits the migration of memory T-lymphocytes across the endothelium into inflamed gastrointestinal parenchymal tissue. It does not, however, bind to or inhibit function of the alpha-4-beta-1 and alpha-E-beta-7 integrins and does not antagonize the interaction of alpha-4 integrins with vascular cell adhesion molecule-1 (VCAM-1). The alpha-4-beta-7 integrin is expressed on the surface of a discrete subset of memory T-lymphocytes that preferentially migrate into the gastrointestinal tract. MAdCAM-1 is mainly expressed on gut endothelial cells and plays a critical role in the homing of T-lymphocytes to gut lymph tissue. Blocking the interaction of the alpha-4-beta-7 integrin with MAdCAM-1 reduces the chronic inflammatory process present in both ulcerative colitis and Crohn's disease.
Vedolizumab is administered via intravenous infusion or subcutaneous injection. Vedolizumab displays both linear and non-linear pharmacokinetics. Population pharmacokinetic analyses indicated that the linear clearance was approximately 0.169 L/day, the serum half-life was approximately 24 days at 300 mg dosage, and the distribution volume was approximately 5 L. The non-linear clearance decreases with increasing concentrations. Vedolizumab was not detected in the cerebrospinal fluid of 14 healthy subjects at five weeks after a single 450 mg intravenous administration.
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: None known
The formation of CYP450 enzymes can be altered by increased levels of certain cytokines (e.g., IL-1, IL-6, IL-10, TNFalpha, IFN) during chronic inflammation. Treatment with vedolizumab may modulate serum levels of some cytokines. Therefore, use of vedolizumab may, in theory, normalize the formation of CYP450 enzymes by modulating the underlying disease. Upon initiation or discontinuation of vedolizumab in patients treated with CYP450 substrates, monitor and adjust the dosage of the CYP substrate as needed.
-Route-Specific Pharmacokinetics
Intravenous Route
Similar pharmacokinetics were observed in ulcerative colitis and Crohn's disease patients. Vedolizumab, when administered as a 300 mg IV infusion (over 30 minutes) on weeks 0 and 2 and then starting at week 6 every 8 weeks, had trough serum concentrations for ulcerative colitis patients as follows: 26.3 +/- 12.9 mcg/ml (n = 210, week 6) and 11.2 +/- 7.2 mcg/ml (n = 77, week 46); similarly, through concentrations for Crohn's disease patients were as follows: 27.4 +/- 19.2mcg/ml (n = 198, week 6) and 13.0 +/- 9.1 mcg/ml (n = 72, week 46). Persistent anti-vedolizumab antibody were associated with reduced serum concentrations of vedolizumab, either to undetectable or reduced levels at week 52 in 14 of 20 patients who developed persistently positive antibodies to vedolizumab..
Subcutaneous Route
For patients with ulcerative colitis, the bioavailability of vedolizumab 108 mg subcutaneous injection relative to a 300 mg single dose IV infusion was approximately 75%. After 300 mg IV infusion (over 30 minutes) of vedolizumab on week 0 and week 2 and then 108 mg subcutaneous injection of vedolizumab every 2 weeks starting week 6, the mean steady state serum trough concentrations were 35.8 mcg/mL (SD +/- 15.2). After a single dose of 108 mg subcutaneous vedolizumab injection, the median Tmax was 7 days with a range of 3 to 14 days, and Cmax was 15.4 mcg/mL (SD+/- 3.2). During clinical trials in patients treated with subcutaneous injections of vedolizumab, anti-vedolizumab antibodies were persistently positive in 4 patients and vedolizumab neutralizing antibodies developed in 3 patients. Reduced or undetectable serum vedolizumab trough concentrations were associated with patients treated with intravenous vedolizumab who developed persistently positive antibodies. There is insufficient data to determine the pharmacokinetic effect of anti-vedolizumab antibodies in patients with subcutaneous treatment.
-Special Populations
Geriatric
Population pharmacokinetic analysis showed that age (18 to 78 years) did not have a clinically meaningful effect on the pharmacokinetics of vedolizumab.
Obesity
Population pharmacokinetic analysis showed that body weight did not have a clinically meaningful effect on the pharmacokinetics of vedolizumab.
Other
Population pharmacokinetic analysis showed that the severity of disease state, prior treatment with TNF blocker therapy, serum albumin, coadministered immunomodulators (including azathioprine, 6-mercaptopurine, methotrexate), and co-administered aminosalicylates did not have a clinically meaningful effect on the pharmacokinetics of vedolizumab.