TRAZIMERA POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION 440MG/VIAL [SIN16038P]

Product Info

TRAZIMERA POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION 440MG/VIAL

[SIN16038P]

4.1. Therapeutic indications

Metastatic breast cancer (MBC)

TRAZIMERA is indicated for the treatment of patients with metastatic breast cancer who have tumours that overexpress human epidermal growth factor receptor 2 (HER2):

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

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

• in combination with an aromatase inhibitor for the treatment of postmenopausal patients with hormone-receptor positive metastatic breast cancer, not previously treated with trastuzumab. This indication is based on data from one Phase III trial which studied the use of trastuzumab in combination with anastrozole (see section 5.1 – 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)

TRAZIMERA is indicated for the treatment of patients with HER2 positive early breast cancer.

• following surgery, chemotherapy (neoadjuvant or adjuvant) and radiotherapy (if applicable) (see section 5.1 – 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 TRAZIMERA therapy, for locally advanced (including inflammatory) disease or tumours >2 cm in diameter (see sections 4.4 and 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

TRAZIMERA should only be used in patients whose tumours have either HER2 overexpression or HER2 gene amplification as determined by an accurate and validated assay (see sections 4.4 and 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Metastatic gastric cancer (MGC)

TRAZIMERA 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.

TRAZIMERA 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 (see sections 4.4 and 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

4.2. Posology and method of administration

General

HER2 testing is mandatory prior to initiation of therapy (see sections 4.4 and 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

TRAZIMERA treatment should only be initiated by a physician experienced in the administration of cytotoxic chemotherapy (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information), and should be administered by a healthcare professional only.

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

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

TRAZIMERA intravenous formulation is not intended for subcutaneous administration and should be administered via an intravenous infusion only.

Do not administer as an intravenous push or bolus.

In order to prevent medication errors it is important to check the vial labels to ensure that the drug being prepared and administered is TRAZIMERA (trastuzumab) and not Kadcyla (trastuzumab emtansine).

Metastatic breast cancer

Weekly schedule

Loading dose: The recommended initial loading dose is 4 mg/kg body weight TRAZIMERA administered as a 90-minute intravenous infusion. Patients should be observed for fever and chills or other infusion-associated symptoms (see section 4.8 – 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 TRAZIMERA 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 section 4.8 – 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 (BO16216) trastuzumab and anastrozole were administered from day 1. There were no restrictions on the relative timing of trastuzumab 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 TRAZIMERA 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 TRAZIMERA is 8 mg/kg body weight. The recommended maintenance dose of TRAZIMERA 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.

See section 5.1 for chemotherapy combination dosing – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

Metastatic gastric cancer

3-weekly schedule

TRAZIMERA 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 section 5.1 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 section 5.1 – 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 section 6.6 – 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 TRAZIMERA may be slowed or interrupted (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

No reductions in the dose of trastuzumab were made during clinical trials. Patients may continue trastuzumab 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 TRAZIMERA 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 TRAZIMERA maintenance doses should 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 TRAZIMERA by more than one week, a re-loading dose of TRAZIMERA should be administered over approximately 90 minutes (weekly regimen: 4 mg/kg; three-weekly regimen: 8 mg/kg) as soon as possible. Subsequent TRAZIMERA 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 trastuzumab is not altered based on age or serum creatinine. In clinical trials, patients ≥65 years of age did not receive reduced doses of trastuzumab. 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 trastuzumab disposition.

Paediatric use

The safety and efficacy of TRAZIMERA in paediatric patients <18 years of age have not been established.

4.3. Contraindications

• Hypersensitivity to trastuzumab, murine proteins, or to any of the excipients.

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