n 4.4% of MAYZENT-treated patients compared to 2.9% of patients receiving placebo.
Patients who experienced bradycardia were generally asymptomatic. Few patients experienced symptoms, includingdizziness or fatigue, and these symptoms resolved within 24 hours without intervention [see Adverse Reactions (6.1)].
Heart rates below 40 bpm were rarely observed.
Atrioventricular Conduction Delays
Initiation of MAYZENT treatment has been associated with transient atrioventricular conduction delays that follow asimilar temporal pattern as the observed decrease in heart rate during dose titration. The AV conduction delays manifestedin most of the cases as first-degree AV block (prolonged PR interval on ECG), which occurred in 5.1% of MAYZENTtreatedpatients and in 1.9% of patients receiving placebo in Study 1. Second-degree AV blocks, usually Mobitz type I(Wenckebach), have been observed at the time of treatment initiation with MAYZENT in less than 1.7% of patients inclinical trials. The conduction abnormalities typically were transient, asymptomatic, resolved within 24 hours, rarelyrequired treatment with atropine, and did not require discontinuation of MAYZENT treatment.
If treatment with MAYZENT is considered, advice from a cardiologist should be sought:
In patients with significant QT prolongation (QTc greater than 500 msec)
In patients with arrhythmias requiring treatment with Class Ia or Class III anti-arrhythmic drugs [see DrugInteractions (7.2)]
In patients with ischemic heart disease, heart failure, history of cardiac arrest or myocardial infarction,cerebrovascular disease, and uncontrolled hypertension
In patients with a history of second-degree Mobitz type II or higher AV block, sick-sinus syndrome, or sino-atrialheart block [see Contraindications (4)]
Treatment-Initiation Recommendations
Obtain an ECG in all patients to determine whether preexisting conduction abnormalities are present.
In all patients, a dose titration is recommended for initiation of MAYZENT treatment to help reduce cardiac effects[see Dosage and Administration (2.2, 2.3)].
In patients with sinus bradycardia (HR less than 55 bpm), first- or second-degree [Mobitz type I] AV block, or ahistory of myocardial infarction or heart failure with onset > 6 months prior to initiation, ECG testing and first-dosemonitoring is recommended [see Dosage and Administration (2.1, 2.4)].
Since significant bradycardia may be poorly tolerated in patients with history of cardiac arrest, cerebrovasculardisease, uncontrolled hypertension, or severe untreated sleep apnea, MAYZENT is not recommended in thesepatients. If treatment is considered, advice from a cardiologist should be sought prior to initiation of treatment in orderto determine the most appropriate monitoring strategy.
Use of MAYZENT in patients with a history of recurrent syncope or symptomatic bradycardia should be based on anoverall benefit-risk assessment. If treatment isconsidered, advice from a cardiologist should be sought prior toinitiation of treatment in order to determine the most appropriate monitoring.
Experience with MAYZENT is limited in patients receiving concurrent therapy with drugs that decrease heart-rate(e.g., beta-blockers, calcium channel blockers - diltiazem and verapamil, and other drugs that may decrease heart rate,such as ivabrad |
