[Herceptin Drug Name]

Trade Name: Herceptin

Generic Name: Trastuzumab for Injection

English Name: Trastuzumab Injection

Pinyin: Zhusheyong Qutuozhudankang

[Herceptin Composition] The main active ingredient of Herceptin is trastuzumab.

[Herceptin Description] Each vial of this medication contains 440 mg of concentrated trastuzumab powder; it is a white to pale yellow lyophilized powder.

[Herceptin Indications]

Herceptin is indicated for the treatment of metastatic breast cancer with HER2 overexpression.

a) As a single agent for the treatment of metastatic breast cancer in patients who have received one or more chemotherapy regimens.

b) In combination with taxanes for the treatment of metastatic breast cancer in patients who have not received chemotherapy.

[Herceptin Dosage and Administration]

Initial Loading Dose: The recommended initial loading dose of Herceptin is 4 mg/kg. It should be administered via intravenous infusion over 90 minutes. Maintenance Dose: The recommended weekly maintenance dose of Herceptin is 2 mg/kg. If the initial loading dose was well-tolerated, this dose may be infused over 30 minutes. Herceptin treatment may be continued until disease progression occurs. According to data from international market surveys, patients receiving treatment typically use the medication continuously for approximately 24 to 26 weeks.

[Herceptin Pharmacology]

Herceptin is a recombinant DNA-derived humanized monoclonal antibody that selectively targets the extracellular domain of the human epidermal growth factor receptor-2 (HER2). HER2 overexpression has been observed in 25% to 30% of patients with primary breast cancer. Studies have shown that patients with HER2-overexpressing tumors have a shorter disease-free survival period compared to those without overexpression. In both in vitro and animal studies, Herceptin has demonstrated the ability to inhibit the proliferation of tumor cells that overexpress HER2. Additionally, Herceptin acts as a potential mediator of antibody-dependent cell-mediated cytotoxicity (ADCC). In *in vitro* studies, Herceptin-mediated ADCC was demonstrated to occur preferentially in cancer cells that overexpress HER2 compared to those that do not overexpress HER2.

[Herceptin Pharmacokinetics]

Drug Clearance: Studies in patients with metastatic breast cancer indicate that the pharmacokinetics of trastuzumab, administered as a short-duration intravenous infusion at doses of 10, 50, 100, 250, and 500 mg once weekly, are dose-dependent. As the dose level increases, the mean half-life increases, and the clearance rate decreases. In clinical trials utilizing an initial loading dose of 4 mg/kg followed by a weekly maintenance dose of 2 mg/kg, the observed mean half-life was 5.8 days (ranging from 1 to 32 days); steady-state plasma concentrations of trastuzumab were achieved between 16 and 32 weeks, with a mean trough concentration of approximately 75 µg/mL. Pharmacokinetics in special clinical situations—specifically, the influence of patient characteristics (such as age and plasma creatinine concentration) on the distribution of trastuzumab—were also evaluated. The data indicate that the *in vivo* distribution of trastuzumab remains unchanged across various patient subgroups.

[Herceptin Adverse Reactions]

All adverse event data were derived from clinical trials in which the drug was administered at recommended doses, either as monotherapy or in combination with chemotherapy agents (anthracyclines [doxorubicin or epirubicin] plus cyclophosphamide, or paclitaxel). Herceptin monotherapy was administered to patients with HER2-overexpressing metastatic cancer who had previously failed one or more chemotherapy regimens. In a cohort of 213 patients, the following adverse reactions occurred with an incidence of ≥ 5%: General: Abdominal pain, accidental injury, asthenia, back pain, chest pain, chills, fever, flu-like symptoms, headache, infection, neck pain, and pain. Cardiovascular: Vasodilation. Digestive: Anorexia, constipation, diarrhea, dyspepsia, flatulence, vomiting, and nausea. Metabolic: Peripheral edema, edema. Musculoskeletal: Arthralgia, myalgia. Nervous System: Anxiety, depression, dizziness, insomnia, paresthesia, somnolence. Respiratory System: Asthma, increased cough, dyspnea, epistaxis, pulmonary disorders, pleural effusion, pharyngitis, rhinitis, sinusitis. Skin: Pruritus, rash.

[Herceptin Contraindications] Use is contraindicated in patients with known hypersensitivity to trastuzumab or to any of the other components of the product.

[Herceptin Precautions]

Treatment with this medication must be initiated under the supervision of a physician experienced in the management of cancer patients. Signs and symptoms of cardiac dysfunction—such as dyspnea, increased cough, paroxysmal nocturnal dyspnea, peripheral edema, S3 gallop, or reduced ejection fraction—have been observed in patients treated with this medication. Congestive heart failure associated with Herceptin therapy may be severe and has been associated with fatal heart failure, death, and mucoid emboli leading to cerebral embolism. Moderate to severe cardiac dysfunction (New York Heart Association [NYHA] Class III/IV) has been observed particularly in patients with metastatic breast cancer treated with Herceptin in combination with anthracyclines (doxorubicin or epirubicin) and cyclophosphamide. Particular caution should be exercised in patients with pre-existing cardiac dysfunction. Patients selected for treatment with this medication should undergo a comprehensive baseline cardiac assessment, including medical history, physical examination, and one or more of the following tests: EKG, echocardiogram, or MUGA scan. Currently, there are no data available to identify a suitable assessment method that can reliably predict which patients are at risk of developing cardiotoxicity. Left ventricular function should be monitored frequently during treatment with this medication. Discontinuation of Herceptin should be considered if the patient develops clinically significant left ventricular dysfunction. Monitoring may not identify all patients who will develop cardiac dysfunction. Approximately two-thirds of patients who developed cardiac dysfunction were treated for their symptoms; in the majority of cases, symptoms improved following treatment. Treatment typically included diuretics, cardiac glycosides, and/or angiotensin-converting enzyme (ACE) inhibitors. The vast majority of patients who experienced clinical benefit from this medication—despite presenting with cardiac signs and symptoms—continued to receive weekly Herceptin therapy without developing further clinical cardiac complications. When used as a preservative in Bacteriostatic Water for Injection, benzyl alcohol is toxic to neonates and children under 3 years of age. When this medication is administered to patients with a known allergy to benzyl alcohol, it should be reconstituted using Sterile Water for Injection.

【Herceptin Use in Pregnant and Lactating Women】

Transplacental transfer of trastuzumab to the fetus has been observed during both early (gestation days 20–50) and late (gestation days 120–150) stages of development. Since animal reproduction studies are not always predictive of human response, Herceptin should not be used during pregnancy unless the potential benefit to the pregnant woman outweighs the potential risk to the fetus.

Lactating Women: Studies conducted in lactating cynomolgus monkeys administered Herceptin at a dose 25 times the weekly human maintenance dose (2 mg/kg) demonstrated that trastuzumab is secreted into breast milk. The presence of trastuzumab in the serum of infant monkeys during the first 3 months of life had no adverse effects on their growth and development.

【Herceptin Use in Children】 The safety and efficacy of this medication in patients under 18 years of age have not been established.

【Herceptin Strength】 440 mg

【Herceptin Storage】 Store at 2–8°C.

【Herceptin Shelf Life】 36 months

Product Specifications

Product Name: Herceptin (Trastuzumab for Injection) 440 mg | Vivitra Trastuzumab Lyophilized Powder 440 mg

Common Name: Herceptin

Composition: The active ingredient of this product is trastuzumab.

Dosage Form: Each vial of this medication contains 440 mg of concentrated trastuzumab powder; it is a white to pale yellow lyophilized powder.

Strength: 440 mg

Manufacturer: Zydus Ingenxa

Indications: Herceptin is indicated for the treatment of metastatic breast cancer with HER2 overexpression.

a) As a single agent for the treatment of metastatic breast cancer in patients who have received one or more prior chemotherapy regimens.

b) In combination with a taxane for the treatment of metastatic breast cancer in patients who have not received prior chemotherapy. **Dosage and Administration:** **Initial Loading Dose:** The recommended initial loading dose of Herceptin is 4 mg/kg. It should be administered as an intravenous infusion over 90 minutes. **Maintenance Dose:** The recommended weekly maintenance dose of Herceptin is 2 mg/kg. If the initial loading dose was well-tolerated, this dose may be infused over 30 minutes. Herceptin treatment may be continued until disease progression occurs. According to data from international market surveys, patients undergoing treatment typically receive the medication continuously for approximately 24 to 26 weeks.