Overview
11 DESCRIPTION Trastuzumab is a humanized IgG1 kappa monoclonal antibody that selectively binds with high affinity to the extracellular domain of the human epidermal growth factor receptor 2 protein, HER2. Trastuzumab is produced by recombinant DNA technology in a mammalian cell (Chinese Hamster Ovary) culture.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The HER2 (or c-erbB2) proto-oncogene encodes a transmembrane receptor protein of 185 kDa, 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 Pharmacodynamics Herceptin exposure-response relationships and the time course of pharmacodynamic responses are not fully characterized.
Indications
- 1 INDICATIONS AND USAGE Herceptin is a HER2/neu receptor antagonist indicated in adults for: The treatment of HER2-overexpressing breast cancer. ( 1.1 , 1.2 ) The treatment of HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma. ( 1.3 ) Select patients for therapy based on an FDA-approved companion diagnostic for Herceptin ( 1 , 2.2 ). 1.1 Adjuvant Breast Cancer Herceptin is indicated in adults for adjuvant treatment of HER2 overexpressing node positive or node negative (ER/PR negative or with one high risk feature [see Clinical Studies (14.
Common Doses
- 4 mg
- 2 mg
- 6 mg
- 8 mg
Dosage
2 DOSAGE AND ADMINISTRATION For intravenous (IV) infusion only. Do not administer as an IV push or bolus. Herceptin has different dosage and administration instructions than subcutaneous trastuzumab products. ( 2.3 ) Do not substitute Herceptin (trastuzumab) for or with ado-trastuzumab emtansine or fam-trastuzumab deruxtecan. ( 2.3 ) Perform HER2 testing using FDA-approved tests by laboratories with demonstrated proficiency. ( 1 , 2.2 ) Adjuvant Treatment of HER2-Overexpressing Breast Cancer ( 2.
Black Box Warning
WARNING: CARDIOMYOPATHY, INFUSION REACTIONS, EMBRYO-FETAL TOXICITY, and PULMONARY TOXICITY WARNING: CARDIOMYOPATHY, INFUSION REACTIONS, EMBRYO-FETAL TOXICITY, and PULMONARY TOXICITY See full prescribing information for complete boxed warning Cardiomyopathy: Herceptin can result in subclinical and clinical cardiac failure manifesting as CHF, and decreased LVEF, with greatest risk when administered concurrently with anthracyclines. Evaluate cardiac function prior to and during treatment. Discontinue Herceptin for cardiomyopathy. ( 2.5 , 5.
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the label: Cardiomyopathy [see Warnings and Precautions (5.1) ] Infusion Reactions [see Warnings and Precautions (5.2) ] Embryo-Fetal Toxicity [see Warnings and Precautions (5.3) ] Pulmonary Toxicity [see Warnings and Precautions (5.4) ] Exacerbation of Chemotherapy-Induced Neutropenia [see Warnings and Precautions (5.5) ] Adjuvant Breast Cancer Most common adverse reactions (≥ 5%) are headache, diarrhea, nausea, and chills. ( 6.
Interactions
- 7 DRUG INTERACTIONS Anthracyclines Patients who receive anthracycline after stopping Herceptin may be at increased risk of cardiac dysfunction because of trastuzumab's estimated long washout period [see Clinical Pharmacology (12.3) ] . If possible, avoid anthracycline-based therapy for up to 7 months after stopping Herceptin. If anthracyclines are used, closely monitor the patient's cardiac function.