ENTYVIO Pen (vedolizumab): Uses, Dosage, Side Effects & Warnings

Q: Who makes ENTYVIO Pen?

ENTYVIO Pen is listed by 1 labeler in the FDA NDC directory, including Takeda Pharmaceuticals America, Inc..

Uses

1 INDICATIONS AND USAGE ENTYVIO is indicated in adults for the treatment of: moderately to severely active ulcerative colitis (UC). moderately to severely active Crohn's disease (CD). ENTYVIO is an integrin receptor antagonist indicated in adults for the treatment of: moderately to severely active ulcerative colitis (UC). ( 1 ) moderately to severely active Crohn's disease (CD). ( 1 )

Dosage and administration

Important Administration Information Before Initiating ENTYVIO Consider evaluating patients for tuberculosis (TB) infection. ( 2.1 , 5.2 ) Update immunizations according to current immunization guidelines. ( 2.1 , 5.5 ) Intravenous Administration : ENTYVIO should be administered intravenously by a healthcare provider. ( 2.1 ) Subcutaneous Injection : ENTYVIO prefilled syringe and ENTYVIO PEN are intended for subcutaneous use. A patient may self-inject or caregiver may inject after proper training on correct subcutaneous injection technique. ( 2.1 ) Recommended Dosage ( 2.2 ) Week 0 : 300 mg infused intravenously over approximately 30 minutes. Week 2 : 300 mg infused intravenously over approximately 30 minutes. Week 6 : Patients may remain on ENTYVIO intravenous therapy or switch to subcutaneous injection after receiving two ENTYVIO intravenous doses administered at Week 0 and Week 2. Intravenous Infusion : 300 mg infused over approximately 30 minutes and then every eight weeks thereafter. Subcutaneous Injection : 108 mg subcutaneously once every two weeks. Discontinue ENTYVIO in patients who do not show evidence of therapeutic benefit by Week 14. Patients currently receiving and responding to ENTYVIO intravenous therapy after Week 6 may also be switched to subcutaneous injection. Administer the first subcutaneous dose in place of the next scheduled intravenous infusion and every two weeks thereafter. Preparation and Administration Instructions: See full prescribing information for complete information on reconstitution, dilution, administration, and storage. ( 2.3 , 2.4 ) 2.1 Important Administration Information Before Initiating ENTYVIO Consider evaluating patients for tuberculosis (TB) infection prior to initiating treatment with ENTYVIO [see Warnings and Precautions (5.2) ]. Update immunizations according to current immunization guidelines [see Warnings and Precautions (5.5) ]. Intravenous Administration ENTYVIO should be administered by a healthcare provider prepared to manage hypersensitivity reactions including anaphylaxis, if they occur [see Warnings and Precautions (5.1) ] . Appropriate monitoring and medical support measures should be available for immediate use. Observe patients during infusion and until the infusion is complete. Reconstitute and dilute ENTYVIO lyophilized powder prior to administration as a 30-minute intravenous infusion [see Dosage and Administration (2.3) ]. Subcutaneous Injection ENTYVIO prefilled syringe and ENTYVIO PEN are intended for subcutaneous use under the guidance and supervision of a healthcare professional. Patients may self-inject or caregivers may inject subcutaneous ENTYVIO using either the ENTYVIO prefilled syringe or ENTYVIO PEN after training in subcutaneous injection technique. Provide proper training to patients and/or caregivers on the subcutaneous injection technique of ENTYVIO. 2.2 Recommended Dosage in Adults with Ulcerative Colitis and Crohn’s Disease Week 0: Administer ENTYVIO 300 mg by intravenous infusion over approximately 30 minutes [ see Dosage and Administration (2.3) ]. Week 2: Administer ENTYVIO 300 mg by intravenous infusion over approximately 30 minutes. Week 6: Patients may remain on ENTYVIO intravenous therapy or switch to subcutaneous injection after receiving two ENTYVIO intravenous doses administered at Week 0 and Week 2. Intravenous Infusion : Administer ENTYVIO 300 mg by intravenous infusion over approximately 30 minutes and then every eight weeks thereafter. Subcutaneous Injection : Administer ENTYVIO 108 mg subcutaneously once every 2 weeks. Discontinue therapy in patients who show no evidence of therapeutic benefit by Week 14. Patients currently receiving and responding to ENTYVIO intravenous therapy after Week 6 may also be switched to subcutaneous injection. Administer the first subcutaneous dose in place of the next scheduled intravenous infusion and every two weeks thereafter. 2.3 Preparation and Administration Instructions for Intravenous Infusion Reconstitution Instructions Remove the flip-off cap from the single-dose vial and wipe with alcohol swab. Reconstitute ENTYVIO 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 (20°C to 25°C [68ºF to 77ºF]), using a syringe with a 21- to 25-gauge needle. Insert the syringe needle into the vial through the center of the stopper 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 at least 15 seconds to dissolve the lyophilized powder. Do not vigorously shake or invert. Allow the solution to sit 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. Do not use the vial if the drug product is not dissolved within 30 minutes. Visually inspect the reconstituted ENTYVIO solution for particulate matter and discoloration prior to dilution. Solution should be clear or opalescent, colorless to light brownish yellow and free of visible particulates. Do not administer reconstituted solution showing uncharacteristic color or containing particulates. Once dissolved, gently invert vial three times. Immediately, withdraw 5 mL (300 mg) of reconstituted ENTYVIO solution using a syringe with a 21- to 25-gauge needle. Discard any remaining portion of the reconstituted solution in the vial. Dilution Instructions Add the 5 mL (300 mg) of reconstituted ENTYVIO solution to 250 mL of 0.9% Sodium Chloride Injection, or Lactated Ringer's Injection, and gently mix the infusion bag. Do not add other medicinal products to the prepared infusion solution or intravenous infusion set.

Dosage forms and strengths

Intravenous infusion For injection: 300 mg vedolizumab in a single-dose vial. ( 3 ) Subcutaneous injection Injection: 108 mg/0.68 mL solution in a single-dose prefilled syringe with needle safety device. ( 3 ) Injection: 108 mg/0.68 mL solution in a single-dose prefilled pen (ENTYVIO PEN). ( 3 ) Intravenous Infusion For injection: 300 mg of vedolizumab as a white to off-white lyophilized cake in a single-dose vial for reconstitution. Subcutaneous Injection Injection: 108 mg/0.68 mL vedolizumab as a clear to moderately opalescent, colorless to slightly yellow solution in a single-dose prefilled syringe with needle safety device. Injection: 108 mg/0.68 mL vedolizumab as a clear to moderately opalescent, colorless to slightly yellow solution in a single-dose prefilled pen (ENTYVIO PEN).

Contraindications

4 CONTRAINDICATIONS ENTYVIO is contraindicated in patients who have had a known serious or severe hypersensitivity reaction to ENTYVIO or any of its excipients (such as dyspnea, bronchospasm, urticaria, flushing, rash and increased heart rate) [see Warnings and Precautions (5.1) ] . Patients who have had a known serious or severe hypersensitivity reaction to ENTYVIO or any of its excipients. ( 4 )

Warnings and precautions

Infusion-Related Reactions and Hypersensitivity Reactions : Discontinue ENTYVIO and initiate appropriate treatment if serious reactions occur. ( 5.1 ) Infections : Treatment with ENTYVIO should not be initiated in patients with a clinically important active infection until the infection resolves or is adequately treated. If a serious infection develops, ENTYVIO should not be administered until the infection resolves. ( 5.2 ) Progressive Multifocal Leukoencephalopathy (PML) : Although unlikely, a risk of PML cannot be ruled out. Monitor patients for any new or worsening neurological signs or symptoms. ( 5.3 ) 5.1 Infusion-Related Reactions and Hypersensitivity Reactions Infusion-related reactions and hypersensitivity reactions have been reported, including anaphylaxis, dyspnea, bronchospasm, urticaria, flushing, rash, and increased blood pressure and heart rate [see Adverse Reactions (6.1 , 6.2) ]. These reactions may occur with the first or subsequent infusions of ENTYVIO and may vary in their time of onset from during infusion or up to several hours post-infusion. If anaphylaxis or other serious infusion-related or hypersensitivity reactions occur, discontinue administration of ENTYVIO immediately and initiate appropriate treatment. 5.2 Infections Patients treated with ENTYVIO are at increased risk for developing infections [see Adverse Reactions (6.1) ]. Serious infections reported in clinical trials include anal abscess, sepsis (some fatal), tuberculosis (TB), salmonella sepsis, Listeria meningitis, giardiasis, and cytomegaloviral colitis. Postmarketing cases of systemic bacterial, fungal, viral, and parasitic opportunistic infections have been reported. Treatment with ENTYVIO should not be initiated in patients with a clinically important active infection until the infection resolves or is adequately treated. In patients with a chronic infection or a history of recurrent infection, consider the risks and benefits prior to prescribing ENTYVIO. During treatment with ENTYVIO, instruct patients to seek medical advice if signs or symptoms of clinically important acute or chronic infection occur. If a serious infection develops or an infection is not responding to standard therapy, monitor the patient closely. ENTYVIO should not be administered until the infection resolves. Tuberculosis Consider evaluating patients for TB infection prior to initiating treatment with ENTYVIO. Treatment with Entyvio should not be administered to patients with active TB infection. Initiate treatment of latent TB prior to administering ENTYVIO. Consider anti-TB therapy prior to initiation of ENTYVIO in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Monitor patients for signs and symptoms of active TB during and after ENTYVIO treatment. 5.3 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 (JC) virus and typically only occurs in patients who are immunocompromised. One case of PML in an ENTYVIO-treated patient with multiple contributory factors has been reported in the postmarketing setting (e.g., human immunodeficiency virus [HIV] infection with a CD4 count of 300 cells/mm 3 and prior and concomitant immunosuppression). Although unlikely, a risk of PML cannot be ruled out. Monitor patients on ENTYVIO for any new onset, or worsening, of neurological signs and symptoms. Typical signs and symptoms associated with PML are diverse, progress over days to weeks, and include 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. The progression of deficits usually leads to death or severe disability over weeks or months. If PML is suspected, withhold dosing with ENTYVIO and refer to a neurologist; if confirmed, discontinue dosing permanently. 5.4 Liver Injury There have been reports of elevations of transaminase and/or bilirubin in patients receiving ENTYVIO. In general, the combination of transaminase elevations and elevated bilirubin without evidence of obstruction is generally recognized as an important predictor of severe liver injury that may lead to death or the need for a liver transplant in some patients. ENTYVIO should be discontinued in patients with jaundice or other evidence of significant liver injury [see Adverse Reactions (6.1) ] . 5.5 Immunizations Prior to initiating treatment with ENTYVIO, all patients should be brought up to date with all immunizations according to current immunization guidelines [see Dosage and Administration (2.1) ] . Patients receiving ENTYVIO may receive non-live vaccines (e.g., influenza vaccine injection) and may receive live vaccines if the benefits outweigh the risks. There are no data on the secondary transmission of infection by live vaccines in patients receiving ENTYVIO [see Adverse Reactions (6.1) ] .

Side effects

The following topics are also discussed in detail in the Warnings and Precautions section: Infusion-Related Reactions and Hypersensitivity Reactions [see Warnings and Precautions (5.1) ] Infections [see Warnings and Precautions (5.2) ] Progressive Multifocal Leukoencephalopathy [see Warnings and Precautions (5.3) ] Liver Injury [see Warnings and Precautions (5.4) ] Most common adverse reactions (incidence ≥3% and ≥1% higher than placebo) are: nasopharyngitis, headache, arthralgia, nausea, pyrexia, upper respiratory tract infection, fatigue, cough, bronchitis, influenza, back pain, rash, pruritus, sinusitis, oropharyngeal pain, and pain in extremities. ( 6.1 ) Adverse reactions with subcutaneous ENTYVIO are similar to those reported with intravenous ENTYVIO with the exception of injection site reactions reported with subcutaneous ENTYVIO. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals U.S.A., Inc. at 1-877-TAKEDA-7 (1-877-825-3327) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below reflect exposure to intravenous ENTYVIO in 3,326 patients and healthy volunteers in clinical trials, including 1,396 exposed for greater than one year, and 835 exposed for greater than two years. Intravenous Infusion The safety data described in Table 2 are derived from four controlled Phase 3 trials (UC Trials I and II and CD Trials I and III); data from adult patients receiving open-label intravenous ENTYVIO treatment at Weeks 0 and 2 (prior to entry into UC Trial II and CD Trial III) and from Weeks 6 to 52 (non-responders at Week 6 of UC Trial I and CD Trial I) are included [see Clinical Studies (14.1 , 14.2) ] . In these trials, 1,434 patients received ENTYVIO 300 mg intravenously for up to 52 weeks, and 297 patients received placebo for up to 52 weeks. Of these, 769 patients had ulcerative colitis and 962 patients had Crohn's disease. Patients were exposed for a mean duration of 259 days (UC Trials I and II) and 247 days (CD Trials I and III). Adverse reactions were reported in 52% of patients treated with intravenous ENTYVIO and 45% of patients treated with placebo (UC Trials I and II: 49% with ENTYVIO and 37% with placebo; CD Trials I and III: 55% with ENTYVIO and 47% with placebo). Serious adverse reactions were reported in 7% of patients treated with intravenous ENTYVIO compared to 4% of patients treated with placebo (UC Trials I and II: 8% with ENTYVIO and 7% with placebo; CD Trials I and III: 12% with ENTYVIO and 9% with placebo). The most common adverse reactions (reported by ≥3% of patients treated with intravenous ENTYVIO in the UC Trials I and II and CD Trials I and III combined group and ≥1% higher than in combined placebo group) were nasopharyngitis, headache, arthralgia, nausea, pyrexia, upper respiratory tract infection, fatigue, cough, bronchitis, influenza, back pain, rash, pruritus, sinusitis, oropharyngeal pain, and pain in extremities (Table 2) . Table 2. Adverse Reactions in ≥3% of Intravenous ENTYVIO-Treated Adult Patients and ≥1% Higher than in Placebo (UC Trials I and II Data from patients receiving open-label intravenous ENTYVIO treatment at Weeks 0 and 2 (prior to entry into UC Trial II and CD Trial III) and from Weeks 6 to 52 (non-responders at Week 6 of UC Trial I and CD Trial I) are included. and CD Trials I and III ) Adverse Reaction ENTYVIO IV Patients who received ENTYVIO for up to 52 weeks. (N=1434) Placebo Patients who received placebo for up to 52 weeks. (N=297) Nasopharyngitis 13% 7% Headache 12% 11% Arthralgia 12% 10% Nausea 9% 8% Pyrexia 9% 7% Upper respiratory tract infection 7% 6% Fatigue 6% 3% Cough 5% 3% Bronchitis 4% 3% Influenza 4% 2% Back pain 4% 3% Rash 3% 2% Pruritus 3% 1% Sinusitis 3% 1% Oropharyngeal pain 3% 1% Pain in extremities 3% 1% Safety data for patients (n=279) in UC Trials I and II and CD Trials I and III who received intravenous ENTYVIO at Weeks 0 and 2 and were then randomized to placebo at Week 6 for up to 52 weeks, and for patients (n=416) in CD Trial II, a 10-week Crohn's disease trial, are similar to those listed in Table 2 . Infusion-Related Reactions and Hypersensitivity Reactions Serious infusion-related reactions and hypersensitivity reactions including anaphylaxis have been reported following intravenous ENTYVIO administration in clinical trials [see Warnings and Precautions (5.1) ] . In UC Trials I and II and CD Trials I and III, one case of anaphylaxis [one out of 1,434 patients treated with intravenous ENTYVIO (0.07%)] was reported by a Crohn's disease patient during the second infusion (symptoms reported were dyspnea, bronchospasm, urticaria, flushing, rash, and increased blood pressure and heart rate) and was managed with discontinuation of infusion and treatment with antihistamine and intravenous hydrocortisone. In UC Trials I and II and CD Trials I and III, 4% of patients treated with intravenous ENTYVIO and 3% of patients treated with placebo experienced an infusion-related reaction (IRR). The most frequently observed IRRs in the patients treated with intravenous ENTYVIO (reported more than twice) were nausea, headache, pruritus, dizziness, fatigue, infusion-related reaction, pyrexia, urticaria, and vomiting (each of these adverse reactions occurred in <1% in all patients treated with intravenous ENTYVIO) and no individual adverse reaction reported occurred at a rate above 1%. These reactions generally occurred within the first two hours after the infusion and resolved with no treatment or following antihistamine and/or IV hydrocortisone treatment.

Drug interactions

7.1 Natalizumab Products Because of the potential for increased risk of PML and other infections, avoid the concomitant use of ENTYVIO with natalizumab products. 7.2 TNF Blockers Because of the potential for increased risk of infections, avoid the concomitant use of ENTYVIO with TNF blockers. 7.3 CYP450 Substrates The formation of CYP450 enzymes may be suppressed by increased levels of certain cytokines (e.g., IL-6, IL-10, TNFα, IFN) during chronic inflammation. Therefore, use of ENTYVIO may normalize the formation of CYP450 enzymes by modulating the underlying disease. Upon initiation or discontinuation of ENTYVIO in patients treated with CYP450 substrates, monitor drug concentrations or other therapeutic parameters, and adjust the dosage of the CYP substrate as needed. See the prescribing information of specific CYP substrates.

Use in specific populations

8.1 Pregnancy Risk Summary Available data from the Organization of Teratology Information Specialists (OTIS)/MotherToBaby ENTYVIO Pregnancy Registry, published literature and pharmacovigilance in pregnant women have not reliably identified an ENTYVIO-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes (see Data ) . There are risks to the mother and the fetus associated with inflammatory bowel disease in pregnancy (see Clinical Considerations ) . No fetal harm was observed in animal reproduction studies with intravenous administration of vedolizumab to rabbits and monkeys at dose levels 20 times the recommended human dosage (see Data ) . The background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and miscarriage is 15 to 20%, respectively. Clinical Considerations Disease-Associated Maternal and Embryo/Fetal Risk Published data suggest that the risk of adverse pregnancy outcomes in women with inflammatory bowel disease (IBD) is associated with increased disease activity. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2,500 g) infants, and small for gestational age at birth. Fetal/Neonatal Adverse Reactions ENTYVIO administered during pregnancy could affect immune responses in the in utero-exposed newborn and infant. The clinical significance of low levels of ENTYVIO in utero-exposed infants is unknown. The safety of administering live or live-attenuated vaccines in exposed infants is unknown. Data Human Data The vedolizumab pregnancy exposure registry conducted by OTIS/MotherToBaby study in the United States and Canada collected prospective observational data between 2015 and 2022 to assess the risk of major birth defects in live-born infants of women with ulcerative colitis (UC) or Crohn’s disease (CD) treated with vedolizumab during pregnancy. The study compared pregnant patients with UC or CD exposed to vedolizumab with pregnant patients with UC or CD treated with other biological products. The registry included 99 women (58 with UC, 41 with CD) treated with vedolizumab during pregnancy, and 76 women (27 with UC, 49 with CD) exposed to other biological products during pregnancy. 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 non-randomized 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. Animal Data A reproduction study has been performed in pregnant rabbits at single intravenous doses up to 100 mg/kg administered on gestation Day 7 (about 20 times the recommended human dosage) and has revealed no evidence of impaired fertility or harm to the fetus due to vedolizumab. A pre- and post-natal development study in monkeys showed no evidence of any adverse effect on pre- and post-natal development at intravenous doses up to 100 mg/kg (about 20 times the recommended human dosage). 8.2 Lactation Risk Summary Data from a clinical lactation study show the presence of vedolizumab in human milk. The mean calculated daily infant dosage was 0.02 mg/kg/day orally ( see Data ) . Systemic exposure in a breastfed infant is expected to be low because monoclonal antibodies are largely degraded in the gastrointestinal tract. There are no data on the effects of vedolizumab on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for ENTYVIO and any potential adverse effects on the breastfed infant from ENTYVIO or from the underlying maternal condition. Data A milk-only lactation study was conducted in 9 adult lactating women being treated for active ulcerative colitis or Crohn's disease with intravenous ENTYVIO every 8 weeks after reaching steady state and completing the induction phase (ENTYVIO administration at 0, 2, and 6 weeks). Mean concentrations of ENTYVIO in human milk ranged from 0.03 to 0.26 mcg/mL. The mean calculated daily infant oral dosage was 0.02 mg/kg/day calculated as a product of the average concentration over the 8-week dosing interval and the standardized milk consumption of 150 mL/kg/day. 8.4 Pediatric Use Safety and effectiveness of ENTYVIO in pediatric patients have not been established. 8.5 Geriatric Use Clinical trials of ENTYVIO did not include sufficient numbers of patients aged 65 and over (72 patients with Crohn's disease or ulcerative colitis aged 65 and over were treated with ENTYVIO during controlled Phase 3 trials) to determine whether they respond differently from younger adult patients. However, no overall differences in safety or effectiveness were observed between these patients and younger adult patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients.

Pregnancy

8.1 Pregnancy Risk Summary Available data from the Organization of Teratology Information Specialists (OTIS)/MotherToBaby ENTYVIO Pregnancy Registry, published literature and pharmacovigilance in pregnant women have not reliably identified an ENTYVIO-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes (see Data ) . There are risks to the mother and the fetus associated with inflammatory bowel disease in pregnancy (see Clinical Considerations ) . No fetal harm was observed in animal reproduction studies with intravenous administration of vedolizumab to rabbits and monkeys at dose levels 20 times the recommended human dosage (see Data ) . The background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and miscarriage is 15 to 20%, respectively. Clinical Considerations Disease-Associated Maternal and Embryo/Fetal Risk Published data suggest that the risk of adverse pregnancy outcomes in women with inflammatory bowel disease (IBD) is associated with increased disease activity. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2,500 g) infants, and small for gestational age at birth. Fetal/Neonatal Adverse Reactions ENTYVIO administered during pregnancy could affect immune responses in the in utero-exposed newborn and infant. The clinical significance of low levels of ENTYVIO in utero-exposed infants is unknown. The safety of administering live or live-attenuated vaccines in exposed infants is unknown. Data Human Data The vedolizumab pregnancy exposure registry conducted by OTIS/MotherToBaby study in the United States and Canada collected prospective observational data between 2015 and 2022 to assess the risk of major birth defects in live-born infants of women with ulcerative colitis (UC) or Crohn’s disease (CD) treated with vedolizumab during pregnancy. The study compared pregnant patients with UC or CD exposed to vedolizumab with pregnant patients with UC or CD treated with other biological products. The registry included 99 women (58 with UC, 41 with CD) treated with vedolizumab during pregnancy, and 76 women (27 with UC, 49 with CD) exposed to other biological products during pregnancy. 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 non-randomized 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. Animal Data A reproduction study has been performed in pregnant rabbits at single intravenous doses up to 100 mg/kg administered on gestation Day 7 (about 20 times the recommended human dosage) and has revealed no evidence of impaired fertility or harm to the fetus due to vedolizumab. A pre- and post-natal development study in monkeys showed no evidence of any adverse effect on pre- and post-natal development at intravenous doses up to 100 mg/kg (about 20 times the recommended human dosage).

Pediatric use

8.4 Pediatric Use Safety and effectiveness of ENTYVIO in pediatric patients have not been established.

Geriatric use

8.5 Geriatric Use Clinical trials of ENTYVIO did not include sufficient numbers of patients aged 65 and over (72 patients with Crohn's disease or ulcerative colitis aged 65 and over were treated with ENTYVIO during controlled Phase 3 trials) to determine whether they respond differently from younger adult patients. However, no overall differences in safety or effectiveness were observed between these patients and younger adult patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients.

Description

Vedolizumab, an integrin receptor antagonist, is a humanized IgG 1 monoclonal antibody produced in Chinese hamster ovary cells that binds to the human α4β7 integrin. ENTYVIO has an approximate molecular weight of 147 kilodaltons. Intravenous ENTYVIO ENTYVIO (vedolizumab) for injection is supplied as a sterile, white to off-white, preservative-free, lyophilized cake for intravenous infusion. After reconstitution with 4.8 mL Sterile Water for Injection, USP, 0.9% Sodium Chloride Injection, USP, or Lactated Ringer's Injection, USP, the resulting concentration is 60 mg/mL with a deliverable volume of 5 mL (300 mg) and the resulting pH is approximately 6.3. Each single-dose vial contains 300 mg vedolizumab, arginine hydrochloride (131.7 mg), histidine (23 mg), histidine monohydrochloride (21.4 mg), polysorbate 80 (3 mg), and sucrose (500 mg). Subcutaneous ENTYVIO ENTYVIO (vedolizumab) injection is supplied as a sterile, clear to moderately opalescent, colorless to slightly yellow, preservative-free solution for subcutaneous administration. Each single-dose prefilled syringe or single-dose prefilled pen (ENTYVIO PEN) contains 108 mg vedolizumab, arginine hydrochloride (17.77 mg), citric acid monohydrate (0.18 mg), histidine (3.86 mg), histidine monohydrochloride (1.86 mg), polysorbate 80 (1.35 mg), sodium citrate dihydrate (4.71 mg) and Sterile Water for Injection, USP, at a pH of 6.5.

Mechanism of action

12.1 Mechanism of Action Vedolizumab is a humanized monoclonal antibody that specifically binds to the α4β7 integrin and blocks the interaction of α4β7 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. Vedolizumab does not bind to or inhibit function of the α4β1 and αEβ7 integrins and does not antagonize the interaction of α4 integrins with vascular cell adhesion molecule-1 (VCAM-1). The α4β7 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. The interaction of the α4β7 integrin with MAdCAM-1 has been implicated as an important contributor to the chronic inflammation that is a hallmark of ulcerative colitis and Crohn's disease.

How supplied

How Supplied Intravenous Infusion ENTYVIO (vedolizumab) for injection for intravenous infusion is supplied in sterile single-dose glass vials, containing 300 mg of vedolizumab as a white to off-white lyophilized cake. ENTYVIO: 300 mg single-dose vial in individual carton: NDC 64764-300-20 Subcutaneous Injection ENTYVIO (vedolizumab) injection for subcutaneous use is available in a prefilled syringe or a prefilled pen as a clear to moderately opalescent and colorless to slightly yellow solution. The single-dose, disposable ENTYVIO prefilled syringe and single-dose, disposable ENTYVIO prefilled pen (ENTYVIO PEN) are comprised of a 1 mL long glass syringe with a fixed 27 gauge thin wall, ½ inch needle. The syringe has a rubber needle cover encased in a plastic shell and rubber stopper. Not made with natural rubber latex. ENTYVIO: 108 mg/0.68 single-dose prefilled syringe in an individual carton: NDC 64764-107-11 ENTYVIO PEN : 108 mg/0.68 single-dose prefilled pen in an individual carton: NDC 64764-108-21 Storage and Handling Refrigerate ENTYVIO unopened vials, prefilled syringes, and prefilled pens at 2°C to 8°C (36° to 46°F). If needed, the ENTYVIO prefilled syringe or ENTYVIO PEN can be left out of the refrigerator in the original package at room temperature up to 25°C (77°F) for up to 7 days (for example, when traveling). Do not use ENTYVIO prefilled syringe or ENTYVIO PEN if left out of the refrigerator for more than 7 days. Do not freeze ENTYVIO vial, prefilled syringe, or prefilled pen. Do not use ENTYVIO vial, prefilled syringe, or prefilled pen if it has been frozen. Do not shake the ENTYVIO prefilled syringe or ENTYVIO PEN. Retain in original package to protect from light until the time of use.

Storage

Storage and Handling Refrigerate ENTYVIO unopened vials, prefilled syringes, and prefilled pens at 2°C to 8°C (36° to 46°F). If needed, the ENTYVIO prefilled syringe or ENTYVIO PEN can be left out of the refrigerator in the original package at room temperature up to 25°C (77°F) for up to 7 days (for example, when traveling). Do not use ENTYVIO prefilled syringe or ENTYVIO PEN if left out of the refrigerator for more than 7 days. Do not freeze ENTYVIO vial, prefilled syringe, or prefilled pen. Do not use ENTYVIO vial, prefilled syringe, or prefilled pen if it has been frozen. Do not shake the ENTYVIO prefilled syringe or ENTYVIO PEN. Retain in original package to protect from light until the time of use.

Patient information

Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). Infusion-Related and Hypersensitivity Reactions Instruct patients to report immediately if they experience symptoms consistent with a hypersensitivity reaction during or following an infusion of ENTYVIO [see Warnings and Precautions (5.1) ] . Infections Inform patients that they may be more likely to develop infections when taking ENTYVIO. Instruct patients to tell their healthcare provider if they develop any symptoms of an infection [see Warnings and Precautions (5.2) ] . Progressive Multifocal Leukoencephalopathy Inform patients that progressive multifocal leukoencephalopathy (PML) has occurred in patients who received some integrin receptor antagonist and systemic immunosuppressant products. Instruct patients to report if they experience any new onset or worsening of neurological signs and symptoms immediately, as these could be indicative of PML [see Warnings and Precautions (5.3) ]. Liver Injury Inform patients that elevated transaminase levels with or without elevated bilirubin has occurred in patients who received ENTYVIO. Instruct patients to report promptly any symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice [see Warnings and Precautions (5.4) ] . Subcutaneous Dosing Technique Provide guidance to patients and caregivers on proper subcutaneous administration technique, and how to use the ENTYVIO single-dose prefilled syringe, or ENTYVIO single-dose prefilled pen correctly [see Instructions for Use] .

Active ingredients

Vedolizumab in 1 product

ENTYVIO Pen NDC products (1)

NDC	Strength & form	Labeler	Type
64764-108	Vedolizumab 108 mg/.68mL Injection, Solution	Takeda Pharmaceuticals America, Inc.	BLA

Frequently asked questions

What is ENTYVIO Pen used for?

1 INDICATIONS AND USAGE ENTYVIO is indicated in adults for the treatment of: moderately to severely active ulcerative colitis (UC). moderately to severely active Crohn's disease (CD). ENTYVIO is an integrin receptor antagonist indicated in adults for the treatment of: moderately to severely active ulcerative colitis (UC). ( 1 ) moderately to severely active Crohn's disease (CD). ( 1 )

What are the side effects of ENTYVIO Pen?

The following topics are also discussed in detail in the Warnings and Precautions section: Infusion-Related Reactions and Hypersensitivity Reactions [see Warnings and Precautions (5.1) ] Infections [see Warnings and Precautions (5.2) ] Progressive Multifocal Leukoencephalopathy [see Warnings and Precautions (5.3) ] Liver Injury [see Warnings and Precautions (5.4) ] Most common adverse reactions… See the full label for the complete list.

Who makes ENTYVIO Pen?

ENTYVIO Pen is listed by 1 labeler in the FDA NDC directory, including Takeda Pharmaceuticals America, Inc..