Entyvio

Selective Adhesion Molecule Inhibitors

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.
 

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. Discard if discoloration or particulate matter are observed.

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.

new primary malignancy / Delayed / 0-1.0
anaphylactoid reactions / Rapid / Incidence not known
bronchospasm / Rapid / Incidence not known
progressive multifocal leukoencephalopathy / Delayed / Incidence not known
hepatic failure / Delayed / Incidence not known
pancreatitis / Delayed / Incidence not known

antibody formation / Delayed / 6.0-6.0
dyspnea / Early / Incidence not known
infusion-related reactions / Rapid / Incidence not known
jaundice / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known

pharyngitis / Delayed / 13.0-13.0
arthralgia / Delayed / 12.0-12.0
headache / Early / 12.0-12.0
nausea / Early / 9.0-9.0
fever / Early / 9.0-9.0
fatigue / Early / 6.0-6.0
cough / Delayed / 5.0-5.0
back pain / Delayed / 4.0-4.0
influenza / Delayed / 4.0-4.0
musculoskeletal pain / Early / 3.0-3.0
pruritus / Rapid / 3.0-3.0
rash / Early / 3.0-3.0
sinusitis / Delayed / 3.0-3.0
flushing / Rapid / Incidence not known
urticaria / Rapid / Incidence not known
infection / Delayed / Incidence not known

Entyvio

Rx

Monoclonal antibody that is a specific integrin receptor antagonist; given via IV infusion, dosed every 8 weeks for maintenance
Used for the treatment of moderately to severely active ulcerative colitis and Crohn's disease in adults
Monitor for infusion and hypersensitivity reactions and increased risk for infection

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.

300 mg IV infusion at weeks 0, 2, and 6, then 300 mg IV infusion 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.

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.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

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.
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.
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.
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.
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.
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.
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.
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.

Entyvio Intravenous Inj Pwd F/Sol: 300mg

300 mg/dose IV.

300 mg/dose IV.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

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. Vedolizumab displays both linear and non-linear pharmacokinetics. Population pharmacokinetic analyses indicated that the linear clearance was approximately 0.157 L/day, the serum half-life was approximately 25 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.

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 negligible levels at weeks 6 and 52 (n = 8).

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.[57235] 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.[64164]