PERJETA

2 DOSAGE AND ADMINISTRATION For intravenous infusion only. Do not administer as an intravenous push or bolus. ( 2.5 ) HER2 testing: Perform using FDA-approved tests by laboratories with demonstrated proficiency. ( 2.1 ) The initial PERJETA dose is 840 mg administered as a 60-minute intravenous infusion, followed every 3 weeks thereafter by 420 mg administered as a 30 to 60 minute intravenous infusion. ( 2.3 ) MBC: Administer PERJETA, trastuzumab or trastuzumab hyaluronidase-oysk, and docetaxel every 3 weeks. ( 2.3 ) Neoadjuvant: Administer PERJETA, trastuzumab or trastuzumab hyaluronidase-oysk, and chemotherapy preoperatively every 3 weeks for 3 to 6 cycles. ( 2.3 ) Adjuvant: Administer PERJETA, trastuzumab or trastuzumab hyaluronidase-oysk, and chemotherapy postoperatively every 3 weeks for a total of 1 year (up to 18 cycles). ( 2.3 ) 2.1 Evaluation and Testing Before Initiating Perjeta Assess left ventricular ejection fraction (LVEF) prior to initiation of PERJETA and at regular intervals during treatment [see Boxed Warning , Dosage and Administration (2.4) , Warnings and Precautions (5.1) ]. Verify the pregnancy status of females of reproductive potential prior to the initiation of PERJETA [see Warnings and Precautions (5.2) , Use in Specific Populations (8.1 , 8.3) ]. 2.2 Patient Selection Select patients based on HER2 protein overexpression or HER2 gene amplification in tumor specimens [see Indications and Usage (1) and Clinical Studies (14) ] . Assessment of HER2 protein overexpression and HER2 gene amplification should be performed using FDA-approved tests specific for breast cancer by laboratories with demonstrated proficiency. Information on the FDA-approved tests for the detection of HER2 protein overexpression and HER2 gene amplification is available at: http://www.fda.gov/CompanionDiagnostics. 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. 2.3 Recommended Dosage and Administration The initial dose of PERJETA is 840 mg administered as a 60-minute intravenous infusion, followed every 3 weeks by a dose of 420 mg administered as an intravenous infusion over 30 to 60 minutes. When administered with PERJETA, the recommended initial dose of trastuzumab is 8 mg/kg administered as a 90-minute intravenous infusion, followed every 3 weeks by a dose of 6 mg/kg administered as an intravenous infusion over 30 to 90 minutes. When administered with PERJETA, the recommended initial dose of trastuzumab hyaluronidase-oysk is 600 mg/10,000 units (600 mg trastuzumab and 10,000 units hyaluronidase) administered subcutaneously over approximately 2 to 5 minutes once every three weeks irrespective of the patient's body weight. Administer PERJETA, trastuzumab or trastuzumab hyaluronidase-oysk, and taxane sequentially. PERJETA and trastuzumab or trastuzumab hyaluronidase-oysk can be given in any order. Administer taxane after PERJETA and trastuzumab or trastuzumab hyaluronidase-oysk. An observation period of 30 to 60 minutes is recommended after each PERJETA infusion and before commencement of any subsequent administration of trastuzumab or trastuzumab hyaluronidase-oysk, or taxane [see Warnings and Precautions (5.3) ]. In patients receiving an anthracycline-based regimen, administer PERJETA and trastuzumab or trastuzumab hyaluronidase-oysk after completion of the anthracycline. Metastatic Breast Cancer (MBC) When administered with PERJETA, the recommended initial dose of docetaxel is 75 mg/m 2 administered as an intravenous infusion. The dose may be escalated to 100 mg/m 2 administered every 3 weeks if the initial dose is well tolerated. Neoadjuvant Treatment of Breast Cancer Administer PERJETA every 3 weeks for 3 to 6 cycles as part of one of the following treatment regimens [see Clinical Studies (14.2 , 14.3) ] : Four preoperative cycles of PERJETA in combination with trastuzumab or trastuzumab hyaluronidase-oysk and docetaxel followed by 3 postoperative cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) Three or four preoperative cycles of FEC alone followed by 3 or 4 preoperative cycles of PERJETA in combination with docetaxel and trastuzumab or trastuzumab hyaluronidase-oysk Six preoperative cycles of PERJETA in combination with docetaxel, carboplatin, and trastuzumab (TCH) or trastuzumab hyaluronidase-oysk (escalation of docetaxel above 75 mg/m 2 is not recommended) Four preoperative cycles of dose-dense doxorubicin and cyclophosphamide (ddAC) alone followed by 4 preoperative cycles of PERJETA in combination with paclitaxel and trastuzumab or trastuzumab hyaluronidase-oysk Following surgery, administer PERJETA and trastuzumab or trastuzumab hyaluronidase-oysk to complete 1 year of treatment (up to 18 cycles) or until disease recurrence or unmanageable toxicity, whichever occurs first. Adjuvant Treatment of Breast Cancer As part of a regimen including standard anthracycline- and/or taxane-based chemotherapy, administer PERJETA in combination with trastuzumab or trastuzumab hyaluronidase-oysk every 3 weeks for a total of 1 year (up to 18 cycles) or until disease recurrence or unmanageable toxicity, whichever occurs first. Administer PERJETA on Day 1 of the first taxane-containing cycle [see Clinical Studies (14.3) ] . 2.4 Important Dosing Considerations Missed Dose The recommended dosage modifications for delayed or missed doses are listed in Table 1 . Table 1: Recommendations for Delayed or Missed Doses Time between two sequential doses PERJETA Trastuzumab (intravenous) Trastuzumab hyaluronidase-oysk 45% 40%-45% with a fall of <10%-points below pre-treatment value Early Breast Cancer ≥ 55% For patients receiving anthracycline-based chemotherapy, a LVEF of ≥ 50% is required after completion of anthracyclines, before starting PERJETA and trastuzumab or trastuzumab hyaluronidase-oysk. ~12 weeks (once during neoadjuvant therapy) <50% with a fall of ≥10%-points below pre-treatment value Either ≥50% <10% points below pre-treatment value Infusion-Related Reactions The infusion rate of PERJETA may be slowed or interrupted if the patient develops an infusion-related reaction [see Warnings and Precautions (5.3) ] . Hypersensitivity Reactions/Anaphylaxis The infusion should be discontinued immediately if the patient experiences a serious hypersensitivity reaction [see Warnings and Precautions (5.4) ] . 2.6 Preparation for Administration Administer as an intravenous infusion only. Do not administer as an intravenous push or bolus. Do not mix PERJETA with other drugs. Preparation Prepare the solution for infusion, using aseptic technique, as follows: Parenteral drug products should be inspected visually for particulates and discoloration prior to administration, whenever solution and container permit. Withdraw the appropriate volume of PERJETA solution from the vial(s) using a sterile needle and syringe. Dilute into a 250 mL 0.45% Sodium Chloride Injection or 0.9% Sodium Chloride Injection infusion bag. Mix diluted solution by gentle inversion. Do not shake. Administer immediately once prepared. If the diluted infusion solution is not used immediately, it can be stored refrigerated at 2°C to 8°C (36 °F to 46 °F) for up to 24 hours. Dilute with 0.45% Sodium Chloride Injection or 0.9% Sodium Chloride Injection only. Do not use 5% Dextrose Injection.

See official label

1 INDICATIONS AND USAGE PERJETA is a HER2/neu receptor antagonist indicated for: Use in combination with trastuzumab and docetaxel for treatment of adults with HER2-positive metastatic breast cancer (MBC) who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease.