Entyvio Special Precautions

Infusion concentrate: Vedolizumab should be administered by a healthcare professional prepared to manage hypersensitivity reactions including anaphylaxis, if they occur. Appropriate monitoring and medical support measures should be available for immediate use when administering Vedolizumab. Observe patients during infusion and until the infusion is complete.
Traceability: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Infusion-related reactions/Hypersensitivity reactions: In clinical studies, infusion-related reactions (IRR) and hypersensitivity reactions have been reported, with the majority being mild to moderate in severity (see Adverse Reactions).
If a severe IRR, anaphylactic reaction, or other severe reaction occurs, administration of Vedolizumab must be discontinued immediately and appropriate treatment initiated (e.g., epinephrine and antihistamines) (see Contraindications).
Infusion concentrate: If a mild to moderate IRR occurs, the infusion rate can be slowed or interrupted and appropriate treatment initiated (e.g., epinephrine and antihistamines). Once the mild or moderate IRR subsides, continue the infusion. Physicians should consider pre-treatment (e.g., with antihistamine, hydrocortisone and/or paracetamol) prior to the next infusion for patients with a history of mild to moderate IRR to Vedolizumab, in order to minimize their risks.
Infections: Vedolizumab is a gut-selective integrin antagonist with no identified systemic immunosuppressive activity. Physicians should be aware of the potential increased risk of opportunistic infections or infections for which the gut is a defensive barrier. Vedolizumab treatment is not to be initiated in patients with active, severe infections such as tuberculosis, sepsis, cytomegalovirus, listeriosis, and opportunistic infections until the infections are controlled, and physicians should consider withholding treatment in patients who develop a severe infection while on chronic treatment with Vedolizumab.
Caution should be exercised when considering the use of Vedolizumab in patients with a controlled chronic severe infection or a history of recurring severe infections. Patients should be monitored closely for infections before, during and after treatment.
Some integrin antagonists and some systemic immunosuppressive agents have been associated with progressive multifocal leukoencephalopathy (PML), which is a rare and often fatal opportunistic infection caused by the John Cunningham (JC) virus. By binding to the α4β7 integrin expressed on gut-homing lymphocytes, Vedolizumab exerts an immunosuppressive effect specific to the gut. No systemic immunosuppressive effect was noted in healthy subjects. Healthcare professionals should monitor patients on Vedolizumab for any new onset or worsening of neurological signs and symptoms, and consider neurological referral if they occur. If PML is suspected, treatment with Vedolizumab must be withheld; if confirmed, treatment must be permanently discontinued.
Infusion concentrate: Typical signs and symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body, 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.
Solution for injection: Vedolizumab is contraindicated in patients with active tuberculosis (see Contraindications). Before starting treatment with vedolizumab, patients must be screened for tuberculosis according to the local practice. If latent tuberculosis is diagnosed, appropriate treatment must be started with anti-tuberculosis treatment in accordance with local recommendations, before beginning vedolizumab. In patients diagnosed with TB whilst receiving vedolizumab therapy, then vedolizumab therapy should be discontinued until the TB infection has been resolved.
Although no systemic immunosuppressive effect was noted in healthy subjects the effects on systemic immune system function in patients with inflammatory bowel disease is not known.
Malignancies: The risk of malignancy is increased in patients with ulcerative colitis and Crohn's disease.
Immunomodulatory medicinal products may increase the risk of malignancy (see Adverse Reactions).
Prior and concurrent use of biological products: No Vedolizumab clinical trial data are available for patients previously treated with natalizumab or rituximab (solution for injection). No clinical trial data for concomitant use of Vedolizumab with biologic immunosuppressants are available.
Therefore, the use of Vedolizumab in such patients is not recommended.
Solution for injection: Caution should be exercised when considering the use of vedolizumab in these patients.
Patients previously exposed to natalizumab should normally wait a minimum of 12 weeks prior to initiating therapy with vedolizumab, unless otherwise indicated by the patient's clinical condition.
Vaccinations: Infusion concentrate: Prior to initiating treatment with Vedolizumab all patients should be brought up to date with all recommended immunizations. Patients receiving Vedolizumab receive non-live vaccines (e.g., subunit or inactivated vaccines) and may receive live vaccines only if the benefits outweigh the risks. In a placebo-controlled study of healthy volunteers, a single 750 mg dose of Vedolizumab did not lower rates of protective immunity to hepatitis B virus in subjects who were vaccinated intramuscularly with three doses of recombinant hepatitis B surface antigen. Vedolizumab-exposed subjects had lower seroconversion rates after receiving a killed, oral cholera vaccine. The impact on other injectable, oral and nasal vaccines is unknown.
Live and oral vaccines: In a placebo-controlled study of healthy volunteers, a single 750 mg dose of vedolizumab did not lower rates of protective immunity to hepatitis B virus in subjects who were vaccinated intramuscularly with three doses of recombinant hepatitis B surface antigen. Vedolizumab-exposed subjects had lower seroconversion rates after receiving a killed, oral cholera vaccine. The impact on other injectable (infusion concentrate), oral and nasal vaccines is unknown.
Solution for injection: It is recommended that all patients be brought up to date with all immunisations in agreement with current immunisation guidelines prior to initiating vedolizumab therapy. Patients receiving vedolizumab treatment may continue to receive non-live vaccines. There are no data on the secondary transmission of infection by live vaccines in patients receiving vedolizumab. Administration of the influenza vaccine should be by injection in line with routine clinical practice. Other live vaccines may be administered concurrently with vedolizumab only if the benefits clearly outweigh the risks.
Induction of remission in Crohn's disease: Solution for injection: Induction of remission in Crohn's disease may take up to 14 weeks in some patients. The reasons for this are not fully known and are possibly related to the mechanism of action. This should be taken into consideration, particularly in patients with severe active disease at baseline not previously treated with TNFα antagonists (see also Pharmacology: Pharmacodynamics under Actions).
Exploratory subgroup analyses from the clinical studies in Crohn's disease suggested that vedolizumab administered in patients without concomitant corticosteroid treatment may be less effective for induction of remission in Crohn's disease than in those patients already receiving concomitant corticosteroids (regardless of use of concomitant immunomodulators; see Pharmacology: Pharmacodynamics under Actions).
Sodium content: Solution for injection: This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially 'sodium-free'.
Effects on Ability to Drive and Use Machines: Vedolizumab may have a minor influence on the ability to drive or operate machines, as dizziness has been reported in a small percentage of patients.