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

PFIZER PRIVATE LIMITED

PFIZER PRIVATE LIMITED

Therapeutic

Prescription Only

INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION

**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), and should be administered by a healthcare professional only – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_. 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.