Drug Safety-related Labeling Changes (SrLC)

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ENTYVIO (BLA-125476)

(VEDOLIZUMAB)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

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02/25/2026 (SUPPL-66)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Infections

Additions and/or revisions underlined:

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.

5.5 Immunizations

Section title revised

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

Additions and/or revisions underlined:

What is the most important information I should know about ENTYVIO? ENTYVIO may cause serious side effects, including:

…

• Infections. ENTYVIO may increase your risk of getting a serious infection. Before receiving ENTYVIO and during treatment with ENTYVIO, tell your healthcare provider if you think you have an infection or have symptoms of an infection such as fever, chills, muscle aches, cough, shortness of breath, runny nose, sore throat, red or painful skin or sores on your body, tiredness, or pain during urination. If your healthcare provider feels that you are at risk for tuberculosis (TB), you may be treated with medicine for TB before you begin treatment with ENTYVIO.

…

03/14/2024 (SUPPL-58)

Approved Drug Label (PDF)

7 Drug Interactions

7.3 CYP450 Substrates

Newly added subsection:

The formation of CYP450 enzymes may be suppressed by increased levels of certain cytokines (e.g., IL-6, IL-10, TNF?, 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.

02/23/2024 (SUPPL-54)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Infusion-Related Reactions and Hypersensitivity Reactions

(Additions and/or revisions underlined)

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.

5.5 Live and Oral Vaccines

(Additions and/or revisions underlined)

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)].

6 Adverse Reactions

6.1 Clinical Trials Experience

(Additions and/or revisions underlined)

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 greater than or equal to 3% of patients treated with intravenous ENTYVIO in the UC Trials I and II and CD Trials I and III combined group and greater than or equal to 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).

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 Crohn’s 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 IRR 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. Less than 1% of patients treated with intravenous ENTYVIO had IRRs assessed by the investigator as severe, and IRRs requiring discontinuation of study treatment occurred in <1%.

In clinical trials, for patients with mild IRRs or hypersensitivity reactions, physicians were allowed to pretreat with standard medical treatment (e.g., antihistamine, hydrocortisone and/or acetaminophen) prior to next infusion.

Infections

In UC Trials I and II and CD Trials I and III, the rate of infections was 0.85 per patient-year in the patients treated with intravenous ENTYVIO and 0.7 per patient-year in the patients treated with placebo [see Warnings and Precautions (5.2)]. The infections consisted primarily of nasopharyngitis, upper respiratory tract infection, sinusitis, and urinary tract infection. Two percent of patients discontinued intravenous ENTYVIO due to infections.

In UC Trials I and II and CD Trials I and III, the rate of serious infections was 0.07 per patient- year in patients treated with intravenous ENTYVIO and 0.06 per patient-year in patients treated with placebo. Serious infections were more common in Crohn’s disease patients than ulcerative colitis patients, and anal abscesses were the most frequently reported serious adverse reaction in Crohn’s disease patients. Over 48 months, there was no increase in the rate of serious infections.

In controlled- and open-label long-term extension trials in adults treated with intravenous ENTYVIO, serious infections have been reported, including anal abscess, sepsis (some fatal), tuberculosis, salmonella sepsis, Listeria meningitis, giardiasis and cytomegaloviral colitis.

In UC Trials I and II and CD Trials I and III, sepsis, including bacterial sepsis and septic shock,was reported in four of 1,434 (0.3%) patients treated with intravenous ENTYVIO and in two of 297 patients treated with placebo (0.7%). During these trials, two Crohn’s disease patients treated with intravenous ENTYVIO died due to reported sepsis or septic shock; both patients had significant comorbidities and a complicated hospital course that contributed to the deaths. In an open label, long-term extension trial, additional cases of sepsis (some fatal), including bacterial sepsis and septic shock, were reported. The rate of sepsis in patients with ulcerative colitis or Crohn’s disease receiving intravenous ENTYVIO was two per 1,000 patient-years.

In clinical trials, all patients were screened for tuberculosis. One case of latent, pulmonary tuberculosis was diagnosed during the controlled trials with intravenous ENTYVIO. Additional cases of pulmonary tuberculosis were diagnosed during the open-label trial. All of these observed cases occurred outside the United States (U.S.), and none of the patients had extrapulmonary manifestations.

Liver Injury

There have been reports of elevations of transaminase and/or bilirubin in patients receiving intravenous ENTYVIO [see Warnings and Precautions (5.4)]. In UC Trials I and II and CD Trials I and III, three patients reported serious adverse reactions of hepatitis, manifested as elevated transaminases with or without elevated bilirubin and symptoms consistent with hepatitis (e.g., malaise, nausea, vomiting, abdominal pain, anorexia). These adverse reactions occurred following two to five intravenous ENTYVIO doses; however, based on case report information it is unclear if the reactions indicated drug-induced or autoimmune etiology. All patients recovered following discontinuation of therapy with some requiring corticosteroid treatment. In controlled trials, the incidence of ALT and AST elevations ?3x ULN was <2% in patients treated with intravenous ENTYVIO and in patients treated with placebo. In the open- label trial, one additional case of serious hepatitis was observed.

Malignancies

In UC Trials I and II and CD Trials I and III, malignancies (excluding dysplasia and basal cell carcinoma) were reported in six of 1,434 (0.4%) patients treated with intravenous ENTYVIO, 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). Malignancy was reported in one of 297 (0.3%) 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. Overall, the number of malignancies in the clinical trials was small; however, long-term exposure was limited.

Subcutaneous Injection for UC after Two Intravenous Doses of ENTYVIO

ENTYVIO was administered as a subcutaneous injection in adult patients with ulcerative colitis in a double-blind, placebo-controlled clinical trial. Patients who achieved clinical response following two doses of ENTYVIO administered as an intravenous infusion at Week 0 and Week 2 were randomized 2:1 at Week 6 to ENTYVIO as a subcutaneous injection (N=106) or placebo (N=56) (SC UC Trial) [see Clinical Studies (14.1)].

The safety profile was similar between patients who were switched to ENTYVIO as a subcutaneous injection in SC UC Trial and patients in UC and CD clinical trials who received ENTYVIO as an intravenous infusion (Table 2) except for injection site reactions, which were reported with subcutaneous ENTYVIO. Injection site reactions with subcutaneous ENTYVIO in SC UC Trial were reported in 9% (10/106) of patients, including injection site erythema, rash, swelling, bruising, and hematoma.

Live and Oral Vaccines

There are no data on the secondary transmission of infection by live vaccines in patients receiving ENTYVIO.

In a placebo-controlled study of healthy volunteers, 61 subjects were given a single intravenous ENTYVIO 750 mg dose (2.5 times the recommended dose), and 62 subjects received placebo followed by intramuscular vaccination with Hepatitis B surface antigen and oral cholera vaccine. After intramuscular vaccination with three doses of recombinant Hepatitis B surface antigen, those treated with intravenous ENTYVIO did not have lower rates of protective immunity to Hepatitis B virus.

However, those exposed to intravenous ENTYVIO did have lower seroconversion rates and anti-cholera titers relative to placebo after receiving the two doses of a killed, oral cholera vaccine. The impact on other oral vaccines and on nasal vaccines in patients is unknown.

8 Use in Specific Populations

8.1 Pregnancy

(Additions and/or revisions underlined)

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…

…

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.

8.4 Geriatric Use

(Additions and/or revisions underlined)

Clinical trials of ENTYVIO did not include sufficient numbers of subjects aged 65 and over (56 Crohn’s and ulcerative colitis patients aged 65 and over were treated with ENTYVIO during controlled Phase 3 trials) to determine whether they respond differently from younger subjects. However, no overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

17 PATIENT COUNSELING INFORMATION

(Additions and/or revisions underlined)

Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

…

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].

MEDICATION GUIDE

(Extensive changes; please refer to label for complete information)

09/28/2023 (SUPPL-57)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

Extensive changes; please refer to label for complete information

7 Drug Interactions

7.1 Natalizumab Products

Additions and/or revisions underlined:

Because of the potential for increased risk of PML and other infections, avoid the concomitant use of ENTYVIO with natalizumab products.

8 Use in Specific Populations

8.5 Geriatric Use

Additions and/or revisions underlined:

Clinical trials of ENTYVIO did not include sufficient numbers of subjects aged 65 and over (56 Crohn’s and ulcerative colitis patients aged 65 and over were treated with ENTYVIO during controlled Phase 3 trials) to determine whether they respond differently from younger subjects. However, no overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

…

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].

 

MEDICATION GUIDE

Extensive changes; please refer to label for complete information

08/17/2021 (SUPPL-39)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Immunogenicity

(Additions and/or revisions underlined)

The incidence of anti-vedolizumab antibodies to intravenous ENTYVIO using a drug-tolerant electrochemiluminescence (ECL) method for patients in UC Trials I and II and CD Trials I and III who had continuous treatment for 52 weeks was 6% (86 out of 1,427). Of the 86 patients who tested positive for anti-vedolizumab antibodies, 20 patients were persistently positive (at two or more study visits) and 56 developed neutralizing antibodies to vedolizumab. Among the 20 patients with persistently positive anti-vedolizumab antibody status, 14 had undetectable or reduced vedolizumab serum concentrations [see Clinical Pharmacology (12.3)]. Five of the 20 patients with persistently positive anti-vedolizumab antibody achieved clinical remission at Week 52 in the controlled trials. Overall, there was no apparent correlation of anti-vedolizumab antibody development to adverse reactions following intravenous administration of ENTYVIO.

6.3 Postmarketing Experience

(Newly added information)

Gastrointestinal system disorders: Acute Pancreatitis

8 Use in Specific Populations

8.2 Lactation

(Additions and/or revisions underlined)

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.

03/31/2020 (SUPPL-25)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1          Infusion-Related Reactions and Hypersensitivity Reactions

(Additions and/or revisions underlined)

Infusion-related reactions and hypersensitivity reactions have been reported, including anaphylaxis, dyspnea, bronchospasm, urticaria, flushing, rash, and increased blood pressure and heart rate 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.

5.3           Progressive Multifocal Leukoencephalopathy

(Additions and/or revisions underlined)

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/mm3 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.

6 Adverse Reactions

6.3          Postmarketing Experience

(Newly added subsection)

The following adverse reactions have been identified during post-approval use of ENTYVIO. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Immune system disorders: Anaphylaxis

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

17.         PATIENT COUNSELING INFORMATION

(Additions and/or revisions underlined)

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

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.

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 signs or symptoms of an infection.

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.

03/31/2020 (SUPPL-30)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1         Infusion-Related Reactions and Hypersensitivity Reactions

(Additions and/or revisions underlined)

Infusion-related reactions and hypersensitivity reactions have been reported, including anaphylaxis, dyspnea, bronchospasm, urticaria, flushing, rash, and increased blood pressure and heart rate 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.

5.3           Progressive Multifocal Leukoencephalopathy

(Additions and/or revisions underlined)

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/mm3 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.

6 Adverse Reactions

6.3          Postmarketing Experience

(Newly added subsection)

The following adverse reactions have been identified during post-approval use of ENTYVIO. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Immune system disorders: Anaphylaxis

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

17.         PATIENT COUNSELING INFORMATION

(Additions and/or revisions underlined)

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

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.

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 signs or symptoms of an infection.

Progressive Multifocal Leukoencephalopathy

Inform patients that progressive multifocal leukoencephalopathy (PML) has occurred in patients who received some integrin receptor antagonist and systemic immunosuppressant products.

05/07/2019 (SUPPL-24)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.1 Pregnancy

(Pregnancy and Lactation Labeling Rule (PLLR) Conversion; Extensive additions and/or revisions - please refer to labeling)

8.2 Lactation

(Pregnancy and Lactation Labeling Rule (PLLR) Conversion; Additions and/or revisions are underlined)

Risk Summary

Available published literature suggests the presence of vedolizumab in human milk. The effects of local gastrointestinal exposure and expected low systemic exposure to vedolizumab on the breastfed infant are unknown. 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.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

17 PATIENT COUNSELING INFORMATION

(Additions and/or revisions are underlined)

Pregnancy

Inform patients that there is a pregnancy registry to monitor pregnancy outcomes of women who are pregnant or become pregnant while exposed to ENTYVIO.

MEDICATION GUIDE ENTYVIO (en ti’ vee oh) (vedolizumab) for injection, for intravenous use

(Extensive changes; please refer to labeling)