Pertuzumab, trastuzumab, and hyaluronidase (human recombinant)

In post-marketing reports, use of intravenous trastuzumab during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. In an animal reproduction study, administration of intravenous pertuzumab to pregnant cynomolgus monkeys during the period of organogenesis resulted in oligohydramnios, delayed fetal kidney development, and embryo-fetal death at exposures 2.5 to 20 times the exposure in humans at the recommended dose, based on C max .

Important Dosage and Administration Information PHESGO is for subcutaneous use only in the thigh. Do not administer intravenously. PHESGO has different dosage and administration instructions than intravenous pertuzumab, intravenous trastuzumab, and subcutaneous trastuzumab when administered alone. Do not substitute PHESGO for or with pertuzumab, trastuzumab, ado-trastuzumab emtansine, or fam-trastuzumab deruxtecan.

PHESGO must always be administered by a healthcare professional. In patients receiving an anthracycline-based regimen for early breast cancer, administer PHESGO following completion of the anthracycline. In patients receiving PHESGO for early breast cancer with docetaxel or paclitaxel, administer docetaxel or paclitaxel after PHESGO.

In patients receiving PHESGO for metastatic breast cancer with docetaxel, administer docetaxel after PHESGO. Observe patients for a minimum of 30 minutes after initial dose of PHESGO and 15 minutes after each maintenance dose of PHESGO for signs or hypersensitivity symptoms or administration-related reactions. Medications to treat such reactions, as well as emergency equipment, should be available for immediate use [see Warnings and Precautions ].

Recommended Doses and Schedules The recommended dosage and administration schedule for PHESGO are shown in Table 1 . [See table below.] No dose adjustments for PHESGO are required for patient body weight or for concomitant chemotherapy regimen. Patients currently receiving intravenous pertuzumab and trastuzumab can transition to PHESGO.

In patients receiving intravenous pertuzumab and trastuzumab with < 6 weeks since their last dose, administer PHESGO as a maintenance dose of 600 mg pertuzumab/600 mg trastuzumab and every 3 weeks for subsequent administrations. In patients receiving intravenous pertuzumab and trastuzumab with ≥ 6 weeks since their last dose, administer PHESGO as an initial dose of 1,200 mg pertuzumab/600 mg trastuzumab, followed by a maintenance dose of 600 mg pertuzumab/600 mg trastuzumab every 3 weeks for subsequent administrations .

Neoadjuvant Treatment of Breast Cancer Administer PHESGO every 3 weeks for 3 to 6 cycles as part of a treatment regimen for early breast cancer [see Clinical Studies ] . Refer to the prescribing information for pertuzumab, administered in combination with trastuzumab and chemotherapy, for recommended dose and dosage modifications.

Following surgery, patients should continue to receive PHESGO to complete 1 year of treatment (up to 18 cycles) or until disease recurrence or unmanageable toxicity, whichever occurs first, as a part of a complete regimen for early breast cancer. Adjuvant Treatment of Breast Cancer Administer PHESGO every 3 weeks for a total of 1 year (up to 18 cycles) or until disease recurrence or unmanageable toxicity, whichever occurs first, as part of a complete regimen for early breast cancer, including standard anthracycline- and/or taxane-based chemotherapy.

Start PHESGO on Day 1 of the first taxane-containing cycle [see Clinical Studies ] . Metastatic Breast Cancer (MBC) When administered with PHESGO, 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.

Administer PHESGO until disease progression or unmanageable toxicity, whichever occurs first.

Preparation for Administration To prevent medication errors, it is important to check the vial labels to ensure that the drug being prepared and administered is PHESGO and not intravenous pertuzumab, or intravenous trastuzumab, or subcutaneous trastuzumab. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Do not use vial if particulates or discoloration is present. Do not shake. Discard any unused portion remaining in the vial. For both the initial and maintenance dose, each corresponding PHESGO vial is ready-to-use for one subcutaneous injection and should not be diluted. A syringe, a transfer needle, and an injection needle are needed to withdraw PHESGO solution from the vial and inject it subcutaneously.

PHESGO may be injected using 25G-27G (3/8"-5/8") hypodermic injection needles. To avoid needle clogging, attach the hypodermic injection needle to the syringe immediately prior to administration followed by volume adjustment to 15 mL (initial dose) and 10 mL (maintenance dose). If the dose is not to be administered immediately, and the solution of PHESGO has been withdrawn from the vial into the syringe, replace the transfer needle with a syringe closing cap.

Label the syringe with the peel-off sticker and store the syringe in the refrigerator [2°C to 8°C (36°F to 46°F)] for up to 24 hours and at room temperature [20°C to 25°C (68°F to 77°F)] for up to 4 hours and avoid unnecessary storage. PHESGO is compatible with stainless steel, polypropylene, polycarbonate, polyethylene, polyurethane, polyvinyl chloride and fluorinated ethylene polypropylene.

Administration Administer PHESGO 1,200 mg, 600 mg, 30,000 units/15 mL subcutaneously over approximately 8 minutes Administer PHESGO 600 mg, 600 mg, 20,000 units/10 mL subcutaneously over approximately 5 minutes The subcutaneous injection site should be alternated between the left and right thigh only. New injections should be given at least 1 inch (2.5 cm) from the previous site on healthy skin and never into areas where the skin is red, bruised, tender, or hard.

Do not split the dose between two syringes or between two sites of administration. During the treatment course with PHESGO, other medications for subcutaneous administration should preferably be injected at different sites.