Withhold Herceptin for ≥ 16% absolute decrease in LVEF from pre‑treatment values or an LVEF value below institutional limits of normal and ≥ 10% absolute decrease in LVEF from pretreatment values [see Dosage and Administration (2.2)]. The safety of continuation or resumption of Herceptin in patients with Herceptin‑induced left ventricular cardiac dysfunction has not been studied.

Cardiac Monitoring

Conduct thorough cardiac assessment, including history, physical examination, and determination of LVEF by echocardiogram or MUGA scan. The following schedule is recommended:

• Baseline LVEF measurement immediately prior to initiation of Herceptin
• LVEF measurements every 3months during and upon completion of Herceptin
• Repeat LVEF measurement at 4week intervals if Herceptin is withheld for significant left ventricular cardiac dysfunction [ see Dosage and Administration (2.2)]
• LVEF measurements every 6 months for at least 2 years following completion of Herceptin as a component of adjuvant therapy.

In Study1, 16% (136/844) of patients discontinued Herceptin due to clinical evidence of myocardial dysfunction or significant decline in LVEF. In Study3, the number of patients who discontinued Herceptin due to cardiac toxicity was 2.6% (44/1678). In Study4, a total of 2.9% (31/1056) patients in the TCH arm (1.5% during the chemotherapy phase and 1.4% during the monotherapy phase) and 5.7% (61/1068) patients in the AC‑TH arm (1.5% during the chemotherapy phase and 4.2% during the monotherapy phase) discontinued Herceptin due to cardiac toxicity.

Among 32patients receiving adjuvant chemotherapy (Studies1 and 2) who developed congestive heart failure, onepatient died of cardiomyopathy and all other patients were receiving cardiac medication at last follow‑up. Approximately half of the surviving patients had recovery to a normal LVEF (defined as ≥50%) on continuing medical management at the time of last follow‑up. Incidence of congestive heart failure is presented in Table1. The safety of continuation or resumption of Herceptin in patients with Herceptin‑induced left ventricular cardiac dysfunction has not been studied.