TRAZHER (TRASTUZUMAB) POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION 420MG/VIAL [SIN16898P]

Product Info

TRAZHER (TRASTUZUMAB) POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION 420MG/VIAL

[SIN16898P]

INDICATIONS
Trazher IV

Metastatic Breast Cancer (MBC)
Trazher is indicated for the treatment of patients with metastatic breast cancer who have tumors that overexpress HER2:

1. as monotherapy for the treatment of those patients who have received one or more chemotherapy regimens for their metastatic disease

2. in combination with paclitaxel for the treatment of those patients who have not received chemotherapy for their metastatic disease

3. in combination with an aromatase inhibitor for the treatment of postmenopausal patients with hormone-receptor positive metastatic breast cancer, not previously treated with Trazher. This indication is based on data from one Phase III trial which studied the use of Trazher in combination with anastrozole (see Clinical/ Efficacy Studies – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).
   Experience with other aromatase inhibitors is limited.

Early Breast Cancer (EBC)
Trazher is indicated for the treatment of patients with HER2 positive early breast cancer.

• following surgery, chemotherapy (neoadjuvant or adjuvant) and radiotherapy (if applicable) (see Clinical/ Efficacy Studies – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

• following adjuvant chemotherapy with doxorubicin and cyclophosphamide, in combination with paclitaxel or docetaxel.

• in combination with adjuvant chemotherapy consisting of docetaxel and carboplatin.

• in combination with neoadjuvant chemotherapy followed by adjuvant Trazher therapy, for locally advanced (including inflammatory) disease or tumours > 2 cm in diameter (see Special Warnings and Precautions for Use, and Clinical/ Efficacy Studies – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Trazher should only be used in patients whose tumours have either HER2 overexpression or HER2 gene amplification as determined by an accurate and validated assay.

Metastatic Gastric Cancer (MGC)
Trazher in combination with capecitabine or 5-fluorouracil and cisplatin is indicated for the treatment of patients with HER2 positive metastatic adenocarcinoma of the stomach or gastro-esophageal junction who have not received prior anti-cancer treatment for their metastatic disease.

Trazher should only be used in patients with metastatic gastric cancer whose tumours have HER2 overexpression as defined by IHC2+ and a confirmatory FISH+ result, or IHC 3+, as determined by an accurate and validated assay.

DOSAGE AND ADMINISTRATION

General
HER2 testing is mandatory prior to initiation of Trazher therapy.

Substitution by any other biological medicinal product requires the consent of the prescribing physician.

The safety and efficacy of alternating or switching between Herceptin and products that are biosimilar but not deemed interchangeable to Herceptin has not been established. Therefore, the benefit/risk of alternating or switching need to be carefully considered.

Trazher should be administered by a qualified health care professional.

In order to prevent medication errors it is important to check the vial labels to ensure that the drug being prepared and administered is Trazher (trastuzumab) and not another trastuzumab-containing product (eg. trastuzumab emtansine or trastuzumab deruxtecan).

Trazher IV (see Composition, Pharmaceutical Form, Presentations, and Conditions for Preservation and Storage – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information):
Trazher IV is not to be used for subcutaneous administration and should be administered as intravenous infusion.

Do not administer as an intravenous push or bolus.

Metastatic Breast Cancer
Weekly schedule:
Loading dose: The recommended initial loading dose is 4 mg/kg body weight Trazher IV administered as a 90-minute intravenous infusion. Patients should be observed for fever and chills or other infusion-associated symptoms (see Undesirable effects – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Interruption of the infusion may help control such symptoms. The infusion may be resumed when symptoms abate.

Subsequent doses: The recommended weekly dose of Trazher IV is 2 mg/kg body weight. If the prior dose was well tolerated, the dose can be administered as a 30-minute infusion. Patients should be observed for fever and chills or other infusion-associated symptoms (see Undesirable effects – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Administration in combination with an aromatase inhibitor
In the pivotal trial trastuzumab IV and anastrozole were administered from day 1. There were no restrictions on the relative timing of trastuzumab IV and anastrozole at administration (for dose, see the Product Information for anastrozole or other aromatase inhibitors).

3-weekly schedule:
Alternatively the following loading and subsequent doses are recommended for monotherapy and in combination with paclitaxel or an aromatase inhibitor.

Initial Trazher IV loading dose of 8 mg/kg body weight, followed by 6 mg/kg body weight 3 weeks later and then 6 mg/kg repeated at 3-weekly intervals administered as infusions over approximately 90 minutes. If the initial loading dose was well tolerated, the subsequent doses can be administered as a 30-minute infusion.

Early Breast Cancer
3-weekly schedule:
As a three-weekly regimen the recommended initial loading dose of Trazher IV is 8 mg/kg body weight. The recommended maintenance dose of Trazher at three-weekly intervals is 6 mg/kg body weight, beginning three weeks after the loading dose.

Alternative weekly schedule:
As a weekly regimen (initial loading dose of 4 mg/kg followed by 2 mg/kg every week) concomitantly with paclitaxel following chemotherapy with doxorubicin and cyclophosphamide.

Metastatic Gastric Cancer
3-weekly schedule:
Trazher IV is administered at an initial loading dose of 8 mg/kg body weight, followed by 6 mg/kg body weight 3 weeks later and then 6 mg/kg repeated at 3-weekly intervals administered as infusions over approximately 90 minutes. If the initial loading dose is well tolerated, the subsequent doses can be administered as a 30-minute infusion (see Clinical/ Efficacy Studies for chemotherapy combination dosing – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Duration of Treatment
In clinical studies, patients with metastatic breast cancer or metastatic gastric cancer were treated with trastuzumab until progression of disease or unmanageable toxicity. Patients with early breast cancer should be treated for 1 year or until disease recurrence or unmanageable toxicity, whichever occurs first. Extending treatment in EBC beyond one year is not recommended (see Clinical/ Efficacy Studies – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

For instructions for use and handling refer to Preparation, and Method of Administration – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

Dose Modification
If the patient develops an infusion-related reaction (IRR), the infusion rate of Trazher IV may be slowed or interrupted (see Special Warnings and Precautions for Use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).
No reductions in the dose of Trazher were made during clinical trials. Patients may continue Trazher therapy during periods of reversible, chemotherapy-induced myelosuppression, but they should be monitored carefully for complications of neutropenia during this time. The specific instructions to reduce or hold the dose of chemotherapy should be followed.

Missed Doses
If the patient has missed a dose of Trazher IV by one week or less, then the usual maintenance dose (weekly regimen: 2 mg/kg; three-weekly regimen: 6 mg/kg) should be administered as soon as possible. Do not wait until the next planned cycle. Subsequent Trazher IV maintenance doses be administered 7 days or 21 days later according to the weekly or three-weekly schedules, respectively.
If the patient has missed a dose of Trazher IV by more than one week, a re-loading dose of Trazher IV should be administered over approximately 90 minutes (weekly regimen: 4 mg/kg; 3-weekly regimen: 8 mg/kg) as soon as possible. Subsequent Trazher IV maintenance doses (weekly regimen: 2 mg/kg; three-weekly regimen 6 mg/kg respectively) should be administered 7 days or 21 days later according to the weekly or three-weekly schedules respectively.

Special Dosage Instructions
Geriatric use
Data suggest that the disposition of Trazher is not altered based on age or serum creatinine (see Pharmacokinetics in Special Populations – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). In clinical trials, patients ≥ 65 years of age did not receive reduced doses of Trazher. Dedicated pharmacokinetic studies in the elderly and those with renal or hepatic impairment have not been carried out. However in a population pharmacokinetic analysis, age and renal impairment were not shown to affect Trazher disposition.

Paediatric use
The safety and efficacy of Trazher in pediatric patients < 18 years of age have not been established.

CONTRAINDICATIONS

• Hypersensitivity to trastuzumab, murine proteins, or to any of the excipients/inactive ingredients

• Severe dyspnea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy.