40 mg vial of Herceptin with 20 mL of Bacteriostatic Water for Injection (BWFI), USP, containing 1.1% benzyl alcohol as a preservative to yield a multi‑dose solution containing 21 mg/mL trastuzumab. In patients with known hypersensitivity to benzyl alcohol, reconstitute with 20 mL of Sterile Water for Injection (SWFI) without preservative to yield a single use solution.
Use appropriate aseptic technique when performing the following reconstitution steps:
Dilution
440 mg lyophilized powder per multi‑use vial.
None.
Herceptin can cause left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death [see Boxed Warning: Cardiomyopathy ]. Herceptin can also cause asymptomatic decline in left ventricular ejection fraction (LVEF).
There is a 4–6 fold increase in the incidence of symptomatic myocardial dysfunction among patients receiving Herceptin as a single agent or in combination therapy compared with those not receiving Herceptin. The highest absolute incidence occurs when Herceptin is administered with an anthracycline.
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:
In Study 1, 16% (136/844) of patients discontinued Herceptin due to clinical evidence of myocardial dysfunction or significant decline in LVEF. In Study 3, the number of patients who discontinued Herceptin due to cardiac toxicity was 2.6% (44/1678). In Study 4, 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 32 patients receiving adjuvant chemotherapy (Studies 1 and 2) who developed congestive heart failure, one patient 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 Table 1. The safety of continuation or resumption of Herceptin in patients with Herceptin‑induced left ventricular cardiac dysfunction has not been studied.
In Study 4, the incidence of NCI‑CTC Grade 3/4 cardiac ischemia/infarction was higher in the Herceptin containing regimens: (AC‑TH: 0.3% (3/1068) and TCH 0.2% (: 2/1056)) as compared to none in AC‑T.
Table 1: Incidence of Congestive Heart Failure in Adjuvant Breast Cancer Studies
|
|
Incidence of CHF |
|
Study |
Regimen |
Herceptin |
Control |
|
1 & 2Includes 1 patient with fatal cardiomyop |
