Pertuza IV Infusion

Pertuzumab is a recombinant humanized monoclonal antibody that targets the extracellular dimerization domain (Subdomain II) of the human epidermal growth factor receptor 2 protein (HER2). Pertuzumab targets the extracellular dimerization domain (Subdomain II) of the human epidermal growth factor receptor 2 protein (HER2) and, thereby, blocks ligand-dependent heterodimerization of HER2 with other HER family members, including EGFR, HER3, and HER4. As a result, Pertuzumab inhibits ligand-initiated intracellular signaling through two major signal pathways, mitogen-activated protein (MAP) kinase, and phosphoinositide 3-kinase (PI3K). Inhibition of these signaling pathways can result in cell growth arrest and apoptosis, respectively. In addition, Pertuzumab mediates antibody-dependent cell-mediated cytotoxicity.

For intravenous infusion only. It should not be administered as an intravenous push or bolus. The initial Pertuzumab 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

Metastatic breast cancer: Pertuzumab should be administered with Trastuzumab and Docetaxel by intravenous infusion every 3 weeks

Neoadjuvant: Pertuzumab should be administered with Trastuzumab and Docetaxel by intravenous infusion preoperatively every 3 weeks for 3 to 6 cycles.

Pediatric Use: Safety and effectiveness of Pertuzumab have not been established in pediatric patients.

Pertuzumab should be administered as an intravenous infusion only. It should not be administered as an intravenous push or bolus. Pertuzumab should not be used with other drugs.

Patients who receive anthracycline after stopping Pertuza may be at increased risk of cardiac dysfunction because of Pertuza’s long wash out period. If possible, physicians should avoid anthracycline-based therapy for up to 7 months after stopping Pertuza. If anthracyclines are used, the patient’s cardiac function should be monitored carefully.

Pertuzumab is contraindicated in patients with known hypersensitivity to pertuzumab or to any of its excipients

Left Ventricular Dysfunction: Pertuza can result in subclinical and clinical cardiac failure manifesting as CHF, and decreased LVEF. Evaluate cardiac function prior to and during treatment. Discontinue Pertuza treatment for a confirmed clinically significant decrease in left ventricular function.

Embryo-fetal Toxicity: Exposure to Pertuza can result in embryo-fetal death and birth defects. Studies in animals have resulted in oligohydramnios, delayed renal development, and death. Patients should be advised of these risks and the need for effective contraception.

Metastatic Breast Cancer: The most common adverse reactions (> 30%) with Pertuza in combination with Trastuzumab and Docetaxel were diarrhea, alopecia, neutropenia, nausea, fatigue, rash, and peripheral neuropathy.

Neoadjuvant Treatment of Breast Cancer:

• The most common adverse reactions (>30%) with Pertuza in combination with Trastuzumab and Docetaxel were alopecia, diarrhea, nausea, and neutropenia.
• The most common adverse reactions (>30%) with Pertuza in combination with Trastuzumab and Docetaxel when given for 3 cycles following 3 cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) were fatigue, alopecia, diarrhea, nausea, vomiting, and neutropenia.
• The most common adverse reactions (>30%) with Pertuza in combination with Docetaxel, Carboplatin, and Trastuzumab (TCH) were fatigue, alopecia, diarrhea, nausea, vomiting, neutropenia, thrombocytopenia, and anemia.

Pregnancy Category D. There are no adequate and well-controlled studies of Pertuzumab in pregnant women. If Pertuzumab is administered during pregnancy or if a patient becomes pregnant while receiving Pertuzumab or within 7 months following the last dose of Pertuzumab in combination with Trastuzumab, the patient should be apprised of the potential hazard to the fetus.

Lactation: It is not known whether Pertuzumab is excreted in human milk, but human IgG is excreted in human
milk. Because many drugs are secreted in human milk and because of the potential for serious adverse actions in nursing infants from Pertuzumab a decision should be made whether to discontinue nursing, or discontinue drug, taking into account the elimination half-life of Pertuzumab and the importance of the drug to the mother.

Left Ventricular Dysfunction: LVEF should be monitored and dosing should be withheld as appropriate.

Embryo-fetal toxicity: Fetal harm can occur when administered to a pregnant woman.

Infusion-Related Reactions: Should be monitored for signs and symptoms. If a significant infusion-associated reaction occurs, the infusion should be slowed or interrupted and appropriate medical therapies should be administered.

Hypersensitivity Reactions/Anaphylaxis: Should be monitored for signs and symptoms. If a severe hypersensitivity reaction/anaphylaxis occurs, the infusion should be discontinued immediately and appropriate medical therapies should be administered.

Targeted Cancer Therapy

The solution for infusion should be prepared using aseptic technique, as follows:

• Parenteral drug products should be inspected visually for particulates and discoloration prior to administration
• The appropriate volume of Pertuza solution should be withdrawn from the vial(s)
• Pertizumab should be diluted into a 250 mL 0.9% sodium chloride PVC or non-PVC polyolefin infusion bag
• Diluted solution should be mixed by gentle inversion. It should not be shaken
• Pertuza should be administered immediately once prepared
• If the diluted infusion solution is not used immediately, it can be stored at 2˚C to 8˚C for up to 24 hours.
• Dilution should be done with 0.9% Sodium Chloride injection only. Dextrose (5%) solution should not be use.

Store vials in a refrigerator at 2°C to 8°C until time of use. Keep vial in the outer carton in order to protect from light.