Generic Name: Trastuzumab for Injection

Brand Name: Herceptin

English Name: Trastuzumab Injection

Pinyin: Zhusheyong Qutuozhudankang

Composition

The main active ingredient of Herceptin is trastuzumab.

Description

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

Pharmacological Actions

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

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 of trastuzumab 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—have also been evaluated. Data indicate that the in vivo distribution of trastuzumab remains unchanged across different patient subgroups.

Indications

Herceptin is indicated for the treatment of HER2-overexpressing metastatic breast cancer.

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 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 is well tolerated, subsequent doses 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.

Adverse Reactions

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

Contraindications

Herceptin is contraindicated in patients with known hypersensitivity to trastuzumab or to any of its excipients. Precautions

Treatment with this medication must be initiated under the supervision of a physician experienced in the management of cancer. 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 mural thrombus-related 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 evaluation, including medical history, physical examination, and one or more of the following tests: EKG, echocardiogram, or MUGA scan. Currently, no data are available to identify a suitable evaluation method capable of predicting 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 most 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 cardiac symptoms and signs while receiving clinically effective treatment with this medication continued to receive weekly Herceptin doses without developing further clinical cardiac complications. The supplied Bacteriostatic Water for Injection contains benzyl alcohol as a preservative; benzyl alcohol is toxic to neonates and children under 3 years of age. When this medication is administered to patients with a known hypersensitivity to benzyl alcohol, it should be reconstituted using Sterile Water for Injection.

Use in Pregnancy and Lactation

Transplacental transfer of trastuzumab to the fetus has been observed during both early (gestational days 20–50) and late (gestational days 120–150) stages of gestation. Given that animal reproductive studies do not necessarily predict human responses, Herceptin should not be used during pregnancy unless the potential benefit to the pregnant woman outweighs the potential risk to the fetus.

Nursing Mothers: 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.

Pediatric Use

The safety and efficacy of this product in patients under 18 years of age have not been established.

Storage

Store at 2–8°C.

Product Specifications

Product Name: Herceptin (Canmab) Trastuzumab 440 mg (Trastuzumab Injection)

Common Name: Herceptin

Composition: Trastuzumab

Dosage Form: Injection

Specification: 440 mg

Manufacturer: Biocon (India)

Indications: Metastatic Breast Cancer:

This product is indicated for HER2-positive metastatic breast cancer: as monotherapy for metastatic breast cancer patients who have received one or more prior chemotherapy regimens; or in combination with paclitaxel or docetaxel for metastatic breast cancer patients who have not received prior chemotherapy.

Early Breast Cancer:

This product is indicated for HER2-positive early breast cancer:

As monotherapy adjuvant treatment following surgery, anthracycline-based adjuvant chemotherapy, and radiation therapy (if applicable).

As combination adjuvant treatment, administered sequentially following doxorubicin and cyclophosphamide chemotherapy, in combination with paclitaxel or docetaxel.

As combination adjuvant treatment with docetaxel and carboplatin.

As neoadjuvant treatment in combination with chemotherapy, followed by adjuvant treatment, for locally advanced (including inflammatory) breast cancer or breast cancer with a tumor diameter > 2 cm.

Metastatic Gastric Cancer:

This product, in combination with capecitabine or 5-fluorouracil and cisplatin, is indicated for patients with HER2-positive metastatic gastric adenocarcinoma or gastroesophageal junction adenocarcinoma who have not received prior treatment for their metastatic disease. Trastuzumab is indicated only for patients with HER2-positive metastatic gastric cancer; HER2-positivity is defined as an IHC 3+ result, or an IHC 2+/FISH+ result, obtained using a validated testing method.

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. Provided 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.