ENT wasdiscontinued if the elevation exceeded a 3-fold increase and the patient showed symptoms related to hepatic dysfunction.
Patients who develop symptoms suggestive of hepatic dysfunction, such as unexplained nausea, vomiting, abdominalpain, fatigue, anorexia, rash with eosinophilia, or jaundice and/or dark urine during treatment, should have liver enzymeschecked. MAYZENT should be discontinued if significant liver injury is confirmed.
Although there are no data to establish that patients with preexisting liver disease are at increased risk to develop elevatedliver function test values when taking MAYZENT, caution should be exercised when using MAYZENT in patients with ahistory of significant liver disease.
5.6 Increased Blood Pressure
In Study 1, MAYZENT-treated patients had an average increase over placebo of approximately 3 mmHg in systolicpressure and 1.2 mmHg in diastolic pressure, which was first detected after approximately 1 month of treatment initiationand persisted with continued treatment. Hypertension was reported as an adverse reaction in 12.5% of MAYZENT-treatedpatients and in 9.2% of patients receiving placebo. Blood pressure should be monitored during treatment with MAYZENTand managed appropriately.
5.7 Fetal Risk
Based on animal studies, MAYZENT may cause fetal harm [see Use in Specific Populations (8.1)]. Because it takesapproximately 10 days to eliminate MAYZENT from the body, women of childbearing potential should use effectivecontraception to avoid pregnancy during and for 10 days after stopping MAYZENT treatment.
5.8 Posterior Reversible Encephalopathy Syndrome
Rare cases of posterior reversible encephalopathy syndrome (PRES) have been reported in patients receiving asphingosine 1-phosphate (S1P) receptor modulator. Such events have not been reported for MAYZENT-treated patients inthe development program. However, should a MAYZENT-treated patient develop any unexpected neurological or
psychiatric symptoms/signs (e.g., cognitive deficits, behavioral changes, cortical visual disturbances, or any otherneurological cortical symptoms/signs), any symptom/sign suggestive of an increase of intracranial pressure, or acceleratedneurological deterioration, the physician should promptly schedule a complete physical and neurological examination andshould consider a MRI. Symptoms of PRES are usually reversible but may evolve into ischemic stroke or cerebralhemorrhage.
Delay in diagnosis and treatment may lead to permanent neurological sequelae. If PRES is suspected,MAYZENT should be discontinued.
5.9 Unintended Additive Immunosuppressive Effects From Prior Treatment With Immunosuppressive orImmune-Modulating TherapiesWhen switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must beconsidered to avoid unintended additive immunosuppressive effects while at the same time minimizing risk of diseasereactivation, when initiating MAYZENT.
Initiating treatment with MAYZENT after treatment with alemtuzumab is not recommended [see Drug Interactions(7.1)].
5.10 Severe Increase in Disability After Stopping MAYZENTSevere exacerbation of disease, including disease rebound, has been rarely reported after discontinuation of a S1P receptormodulator. The possibility of severe exacerbation of disease should be considered after stopping MAYZENT treatment.
Patients should be observed for a severe increas |
