Arrhythmia Risk With Concomitant Use of Qtc Interval Prolonging Drugs

QTc Interval Prolongation

ETCAMAH in combination with a CDK4/6 inhibitor is associated with QTc interval prolongation [see Clinical Pharmacology (12.2)].

When ETCAMAH is used in combination with ribociclib, a CDK4/6 inhibitor that causes QTc interval prolongation and is a strong CYP3A inhibitor, there is potential for an increased risk of Torsades de Pointes, other ventricular arrhythmias, and sudden death. One case of Torsades de Pointes was observed in a dose-finding trial when ETCAMAH was used with ribociclib [see Drug Interactions (7.1, 7.3) and Clinical Pharmacology (12.2)].

In SERENA-6, QTc interval prolongation occurred in 2.6% of patients treated with ETCAMAH in combination with a CDK4/6 inhibitor. QTc interval prolongation led to dose interruption of ETCAMAH in 0.6% of patients. ETCAMAH also causes bradycardia, which increases the risk of QTc interval prolongation. [see Warnings and Precautions (5.2)].

Perform an ECG prior to initiating ETCAMAH, then every week for the first 2 weeks of treatment, and periodically during treatment as clinically indicated [see Dosage and Administration (2.2)].

Obtain serum electrolytes at baseline and during treatment as clinically indicated, and correct electrolyte abnormalities.

Avoid concomitant use of ETCAMAH in combination with a CDK4/6 inhibitor with products that can cause QTc interval prolongation, are strong CYP3A inhibitors, and/or drugs known to lower heart rate [see Warnings and Precautions (5.2) and Drug Interactions (7.1, 7.3, 7.4)].

Withhold or permanently discontinue ETCAMAH based on severity [see Dosage and Administration (2.4)].

Bradycardia

ETCAMAH causes a decrease in heart rate. Bradycardia increases the risk for life-threatening arrhythmias and sudden death when concomitant QTc interval prolongation is present, such as when ETCAMAH is used in combination with ribociclib, both a QTc interval prolonging product and a strong CYP3A inhibitor [see Warnings and Precautions (5.1)and Drug Interactions (7.1, 7.3)].

In SERENA-6, bradycardia adverse events occurred in 8% of patients treated with ETCAMAH. The mean heart rate decrease from baseline was approximately 13 beats per minute (bpm) with ETCAMAH with the maximum decrease observed on Day 15. The median time to onset of adverse reaction was 17 days (range 13 to 283) after starting ETCAMAH. Bradycardia led to dose interruption of ETCAMAH in 3.9% of patients. The safety of ETCAMAH has not been established in patients with a baseline resting heart rate less than 55 bpm as these patients were excluded from SERENA-6.

Monitor heart rate more frequently during the first 30 days of treatment with ETCAMAH in patients with bradycardia (heart rate less than 60 bpm) at baseline and those on concomitant medications known to lower heart rate (e.g., beta-blockers) [see Dosage and Administration (2.2), and Drug Interactions (7.4)].

Withhold or permanently discontinue ETCAMAH based on severity [see Dosage and Administration (2.4)]