Because many drugs are secreted in human milk and because of the potential for serious adverse reactions in nursing infants from Herceptin, a decision should be made whether to discontinue nursing, or discontinue drug, taking into account the elimination half‑life of trastuzumab and the importance of the drug to the mother.
8.4 Pediatric Use

The safety and effectiveness of Herceptin in pediatric patients has not been established.
8.5 Geriatric Use

Herceptin has been administered to 386patients who were 65years of age or over (253in the adjuvant treatment and 133 in metastatic breast cancer treatment settings). The risk of cardiac dysfunction was increased in geriatric patients as compared to younger patients in both those receiving treatment for metastatic disease in Studies 5 and 6, or adjuvant therapy in Studies 1 and 2. Limitations in data collection and differences in study design of the 4studies of Herceptin in adjuvant treatment of breast cancer preclude a determination of whether the toxicity profile of Herceptin in older patients is different from younger patients. The reported clinical experience is not adequate to determine whether the efficacy improvements (ORR, TTP, OS, DFS) of Herceptin treatment in older patients is different from that observed in patients <65years of age for metastatic disease and adjuvant treatment.

In Study 7 (metastatic gastric cancer), of the 294 patients treated with Herceptin 108 (37%) were 65 years of age or older, while 13 (4.4%) were 75 and over. No overall differences in safety or effectiveness were observed.
10 OVERDOSAGE

There is no experience with overdosage in human clinical trials. Single doses higher than 8mg/kg have not been tested.
11 DESCRIPTION

Herceptin (trastuzumab) is a humanized IgG1 kappa monoclonal antibody that selectively binds with high affinity to the extracellular domain of the human epidermal growth factor receptor2 protein, HER2. Trastuzumab is produced by recombinant DNA technology in a mammalian cell (Chinese Hamster Ovary) culture containing the antibiotic gentamicin. Gentamicin is not detectable in the final product.

Herceptin is a sterile, white to pale yellow, preservative‑free lyophilized powder for intravenous administration. Each multi‑use vial of Herceptin contains 440mg trastuzumab, 400mg α,α‑trehalose dihydrate, 9.9mg L‑histidine HCl, 6.4mg L‑histidine, and 1.8mg polysorbate 20, USP. Reconstitution with 20mL of the appropriate diluent (BWFI or SWFI) yields a solution containing 21mg/mL trastuzumab, at a pH of approximately 6.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action

The HER2 (or c‑erbB2) proto‑oncogene encodes a transmembrane receptor protein of 185kDa, which is structurally related to the epidermal growth factor receptor. Herceptin has been shown, in both in vitro assays and in animals, to inhibit the proliferation of human tumor cells that overexpress HER2.

Herceptin is a mediator of antibody‑dependent cellular cytotoxicity (ADCC). In vitro, Herceptin‑mediated ADCC has been shown to be preferentially exerted on HER2 overexpressing cancer cells compared with cancer cells that do not overexpress HER2.
12.2 Pharmacokinetics