HERZUMA® 150MG POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION

CELLTRION HEALTHCARE SINGAPORE PRIVATE LIMITED

CELLTRION HEALTHCARE SINGAPORE PRIVATE LIMITED

Therapeutic

Prescription Only

INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION

**2.2 Dosage and Administration** HER2 testing is mandatory prior to initiation of Herzuma® therapy. Herzuma is a biosimilar product. Substitution by any other biological medicinal product requires the consent of the prescribing physician. Physician to assess and monitor response upon switching of product. Herzuma® 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 Herzuma® (trastuzumab) and not Kadcyla (trastuzumab emtansine). _**Herzuma® (see section 4. Pharmaceutical Particulars**_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_) _:_ Herzuma® 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 Herzuma® administered as a 90-minute intravenous infusion. Patients should be observed for fever and chills or other infusion-associated symptoms (see 2.6 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 Herzuma® 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 2.6 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 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 Herzuma® 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 Herzuma® is 8 mg/kg body weight. The recommended maintenance dose of Herzuma® 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:_ Herzuma® 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 3.1 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. Patients with early breast cancer should be treated for 1 year or until disease recurrence, whichever occurs first. Extending treatment in EBC beyond one year is not recommended (see section 3.1.2 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 Section 4.2 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_. **Dose reduction** If the patient develops an infusion-related reaction (IRR), the infusion rate of Herzuma IV may be slowed or interrupted. No reductions in the dose of trastuzumab were made during clinical trials. Patients may continue Herzuma® 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 Herzuma® 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 Herzuma® 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 Herzuma® by more than one week, a re-loading dose of Herzuma® should be administered over approximately 90 minutes (weekly regimen: 4 mg/kg; 3- weekly regimen: 8 mg/kg) as soon as possible. Subsequent Herzuma® 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. **Duration of treatment** In clinical studies, patients with metastatic breast cancer were treated with trastuzumab until progression of disease. Patients with early breast cancer should be treated for 1 year or until disease recurrence, whichever occurs first. Extending treatment in EBC beyond one year is not recommended (see section 3.1.2 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 Section 4.2 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_. **Dose reduction** If the patient develops an infusion-related reaction (IRR), the infusion rate of Herzuma IV may be slowed or interrupted. No reductions in the dose of trastuzumab were made during clinical trials. Patients may continue Herzuma® 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. **2.2.1 Special Dosage Instructions** _Elderly_ Data suggest that the disposition of trastuzumab is not altered based on age or serum creatinine (see Pharmacokinetics in special populations). In clinical trials, elderly patients 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. _Children_ The safety and efficacy of trastuzumab in pediatric patients have not been established.