VEDOLIZUMAB Drug Interactions: What You Need to Know

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.

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 )

AND PRECAUTIONS Infusion-Related Reactions and Hypersensitivity Reactions : Discontinue ENTYVIO and initiate appropriate treatment if serious reactions occur. ( 5.1 ) Infections : Treatment with ENTYVIO is not recommended in patients with active, severe infections until the infections are controlled. Consider withholding ENTYVIO in patients who develop a severe infection while on treatment with ENTYVIO. ( 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 <span class="opacity-50 text-xs">[see Adverse Reactions (6.1 , 6.2) ]</span>. 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 <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span>. The most commonly reported infections in clinical trials occurring at a rate greater on ENTYVIO than placebo involved the upper respiratory and nasal mucosa (e.g., nasopharyngitis, upper respiratory tract infection). Serious infections have also been reported in patients treated with ENTYVIO, including anal abscess, sepsis (some fatal), tuberculosis, salmonella sepsis, Listeria meningitis, giardiasis and cytomegaloviral colitis. ENTYVIO is not recommended in patients with active, severe infections until the infections are controlled. Consider withholding treatment in patients who develop a severe infection while on treatment with ENTYVIO. Exercise caution when considering the use of ENTYVIO in patients with a history of recurring severe infections. Consider screening for tuberculosis (TB) according to the local practice. For progressive multifocal leukoencephalopathy (PML), <span class="opacity-50 text-xs">[see Warnings and Precautions (5.3) ]</span> .

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 <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> .

5.5 Live and Oral Vaccines Prior to initiating treatment with ENTYVIO, all patients should be brought up to date with all immunizations according to current immunization guidelines <span class="opacity-50 text-xs">[see Dosage and Administration (2.1) ]</span> . 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 <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> .