live attenuated vaccines should be avoided while patients are taking MAYZENT and for 4 weeks afterstopping treatment [see Drug Interactions (7.1)].
Vaccinations may be less effective if administered during MAYZENT treatment. MAYZENT treatment discontinuation 1week prior to and until 4 weeks after a planned vaccination is recommended.
5.2 Macular Edema
Macular edema was reported in 1.8% of MAYZENT-treated patients compared to 0.2% of patients receiving placebo. Themajority of cases occurred within the first four months of therapy.
An ophthalmic eva luation of the fundus, including the macula, is recommended in all patients before starting treatmentand at any time if there is any change in vision while taking MAYZENT.
Continuation of MAYZENT therapy in patients with macular edema has not been eva luated. A decision on whether or notMAYZENT should be discontinued needs to take into account the potential benefits and risks for the individual patient.
Macular Edema in Patients with a History of Uveitis or Diabetes MellitusPatients with a history of uveitis and patients with diabetes mellitus are at increased risk of macular edema duringMAYZENT therapy. The incidence of macular edema is also increased in MS patients with a history of uveitis. In theclinical trial experience in adult patients with all doses of MAYZENT, the rate of macular edema was approximately 10%in MS patients with a history of uveitis or diabetes mellitus versus 2% in those without a history of these diseases. Inaddition to the examination of the fundus, including the macula, prior to treatment, MS patients with diabetes mellitus or ahistory of uveitis should have regular follow-up examinations.
5.3 Bradyarrhythmia and Atrioventricular Conduction Delays
Since initiation of MAYZENT treatment results in a transient decrease in heart rate and atrioventricular conductiondelays, an up-titration scheme should be used to reach the maintenance dosage of MAYZENT [see Dosage andAdministration (2.2, 2.3) and Clinical Pharmacology (12.2)].
MAYZENT was not studied in patients who had:
In the last 6 months experienced myocardial infarction, unstable angina, stroke, TIA, or decompensated heart failure
requiring hospitalization
New York Heart Association Class II-IV heart failure Cardiac conduction or rhythm disorders, including complete left bundle branch block, sinus arrest or sino-atrial block,symptomatic bradycardia, sick sinus syndrome, Mobitz type II second degree AV-block or higher grade AV-block(either history or observed at screening), unless patient has a functioning pacemaker Significant QT prolongation (QTc greater than 500 msec)
Arrhythmias requiring treatment with Class Ia or Class III anti-arrhythmic drugs [see Drug Interactions (7.2)]
Reduction in Heart Rate
After the first titration dose of MAYZENT, the heart rate decrease starts within an hour, and the Day 1 decline is maximalat approximately 3-4 hours. With continued up-titration, further heart rate decreases are seen on subsequent days, withmaximal decrease from Day 1-baseline reached on Day 5-6. The highest daily post-dose decrease in absolute hourly meanheart rate is observed on Day 1, with the pulse declining on average 5-6 bpm. Post-dose declines on the following days areless pronounced. With continued dosing, heart rate starts increasing after Day 6 and reaches placebo levels within 10 daysafter treatment initiation.
In Study 1, bradycardia occurred i |
