OGIVRI™ LYOPHILIZED POWDER FOR INJECTION 440MG PER VIAL

MYLAN PHARMACEUTICALS PTE. LTD.

ZUELLIG PHARMA PTE. LTD.

Therapeutic

Prescription Only

INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION

**Posology and Method of Administration** **Patient Selection** Select patients based on HER2 protein overexpression or HER2 gene amplification in tumor specimens \[ _see Indications and Usage and Clinical Studies_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_\]. Assessment of HER2 protein overexpression and HER2 gene amplification should be performed using tests specific for breast or gastric cancers by laboratories with demonstrated proficiency. Assessment of HER2 protein overexpression and HER2 gene amplification in metastatic gastric cancer should be performed using tests specifically for gastric cancers due to differences in gastric vs. breast histopathology, including incomplete membrane staining and more frequent heterogeneous expression of HER2 seen in gastric cancers. Improper assay performance, including use of suboptimally fixed tissue, failure to utilize specified reagents, deviation from specific assay instructions, and failure to include appropriate controls for assay validation, can lead to unreliable results. **Recommended Doses and Schedules** - **Do not administer as an intravenous push or bolus. Do not mix Ogivri™ with other drugs.** - **Do not substitute Ogivri™ (trastuzumab) for or with trastuzumab emtansine.** _Adjuvant Treatment, Early Breast Cancer_ _Three-weekly and weekly schedule_ _As a three-weekly regimen the recommended initial loading dose of trastuzumab is 8 mg/kg body weight. The recommended maintenance dose of trastuzumab at three-weekly intervals is 6 mg/kg body weight, beginning three weeks after the loading dose._ _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 Treatment, Breast Cancer:_ _Three-weekly schedule_ _The recommended initial loading dose is 8 mg/kg body weight. The recommended maintenance dose at three-weekly intervals is 6 mg/kg body weight, beginning three weeks after the loading dose._ _Weekly schedule_ _The recommended initial loading dose of trastuzumab is 4 mg/kg body weight 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._ _The recommended weekly maintenance dose of trastuzumab is 2 mg/kg body weight, beginning one week after the loading dose. 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 paclitaxel._ _As per published literature, paclitaxel was administered the day following the first dose of trastuzumab and immediately after the subsequent doses of trastuzumab if the preceding dose of trastuzumab was well tolerated._ _Administration in combination with an aromatase inhibitor._ _As per published literature, 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._ _Metastatic Gastric Cancer:_ _Three-weekly schedule_ _The recommended initial loading dose is 8 mg/kg body weight. The recommended maintenance dose at three-weekly intervals is 6 mg/kg body weight, beginning three weeks after the loading dose._ **Important Dosing Considerations** If the patient has missed a dose of Ogivri® by one week or less, then the usual maintenance dose (weekly schedule: 2 mg/kg; three-weekly schedule: 6 mg/kg) should be administered as soon as possible. Do not wait until the next planned cycle. Subsequent Ogivri® 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 Ogivri® by more than one week, a re-loading dose of Ogivri® should be administered over approximately 90 minutes (weekly schedule: 4 mg/kg; three-weekly schedule: 8 mg/kg) as soon as possible. Subsequent Ogivri® maintenance doses (weekly schedule: 2 mg/kg; three-weekly schedule 6 mg/kg) should be administered 7 days or 21 days later according to the weekly or three-weekly schedules, respectively. _**Infusion Reactions**_ \[ _see Boxed Warning, Warnings and Precautions_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_\] - Decrease the rate of infusion for mild or moderate infusion reactions - Interrupt the infusion in patients with dyspnea or clinically significant hypotension - Discontinue Ogivri® for severe or life-threatening infusion reactions. **Cardiomyopathy** \[ _see Boxed Warning, Warnings and Precautions_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_\] Assess left ventricular ejection fraction (LVEF) prior to initiation of Ogivri® and at regular intervals during treatment. Withhold Ogivri® dosing for at least 4 weeks for either of the following: - ≥16% absolute decrease in LVEF from pre-treatment values - LVEF below institutional limits of normal and ≥10% absolute decrease in LVEF from pretreatment values. Ogivri® may be resumed if, within 4 to 8 weeks, the LVEF returns to normal limits and the absolute decrease from baseline is ≤15%. Permanently discontinue Ogivri™ for a persistent (>8 weeks) LVEF decline or for suspension of Ogivri® dosing on more than 3 occasions for cardiomyopathy.