INN monograph
Hyaluronidase
HER2/neu Receptor Antagonist [EPC], Endoglycosidase [EPC] · POM
Verified · Updated 01 Aug 2026 · Source: FDA drug label via OpenFDA/DailyMed; Local active-ingredient clinical extract; Professional class pharmacology (Therapeutic agent (verify pharmacological class))
Kenya market
Wholesale / list prices where loaded
Risk first
Contraindications
- 4 CONTRAINDICATIONS PHESGO is contraindicated in patients with known hypersensitivity to pertuzumab, or trastuzumab, or hyaluronidase, or to any of its excipients.
- PHESGO is contraindicated in patients with known hypersensitivity to pertuzumab, or trastuzumab, or hyaluronidase, or to any of its excipients.
Precautions
- 5 WARNINGS AND PRECAUTIONS Exacerbation of Chemotherapy-Induced Neutropenia.
- ( 5.4 ) Hypersensitivity and Administration-Related Reactions (ARRs): Monitor patients for systemic hypersensitivity reactions.
- Permanently discontinue PHESGO in patients who experience anaphylaxis or severe hypersensitivity reactions.
- ( 5.5 ) 5.1 Cardiomyopathy PHESGO can cause hypertension, arrhythmias, left ventricular cardiac dysfunction, disabling cardiac failure, cardiomyopathy, and cardiac death [see Boxed Warning: Cardiomyopathy ].
- PHESGO can cause asymptomatic decline in LVEF.
- An increased incidence of LVEF decline has been observed in patients treated with intravenous pertuzumab, intravenous trastuzumab, and docetaxel.
- A 4-6 fold increase in the incidence of symptomatic myocardial dysfunction has been reported among patients receiving trastuzumab, with the highest absolute incidence occurring when trastuzumab was administered with an anthracycline.
- Patients who receive anthracycline after stopping PHESGO may also be at increased risk of cardiac dysfunction [see Drug Interactions (7) and Clinical Pharmacology (12.2) ].
- Cardiac Monitoring Prior to initiation of PHESGO, conduct a thorough cardiac assessment, including history, physical examination, and determination of LVEF by echocardiogram or MUGA scan.
- During treatment with PHESGO, assess LVEF at regular intervals [see Dosage and Administration (2.4) ].
- If after a repeat assessment within approximately 3 weeks, the LVEF has not improved, has declined further, and/or the patient is symptomatic, permanently discontinue PHESGO.
- Following completion of PHESGO, continue to monitor for cardiomyopathy and assess LVEF measurements every 6 months for at least 2 years as a component of adjuvant therapy.
Point of care
Dosing
Adult
only. ( 2.2 ) PHESGO has different dosage and administration instructions than intravenous pertuzumab and trastuzumab products. ( 2.2 ) Do not administer intravenously. ( 2.2 ) Perform HER2 testing using FDA-authorized tests by laboratories with demonstrated proficiency. ( 1 , 2.1 ) The initial dose of PHESGO is 1,200 mg pertuzumab, 600 mg trastuzumab, and 30,000 units hyaluronidase administered subcutaneously over approximately 8 minutes, followed every 3 weeks by a dose of 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase administered subcutaneously over approximately 5 minutes. ( 2.2 ) Neoadjuvant: administer PHESGO by subcutaneous injection every 3 weeks and chemotherapy by intravenous infusion preoperatively for 3 to 6 cycles. ( 2.2 ) Adjuvant: administer PHESGO by subcutaneous injection every 3 weeks and chemotherapy by intravenous infusion postoperatively for a total of 1 year (up to 18 cycles). ( 2.2 ) MBC: administer PHESGO by subcutaneous injection and docetaxel by intravenous infusion every 3 weeks. ( 2.2 ) 2.1 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-authorized tests specific for breast cancer by laboratories with demonstrated proficiency. Information on the FDA-authorized 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. 2.2 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 (5.5) ]. 2.3 Recommended Doses and Schedules The recommended dosage and administration schedule for PHESGO are shown in Table 1 . Table 1: Recommended Dosage and Administration Schedule Dose Strength Administration Instructions Initial dose 1,200 mg pertuzumab, 600 mg trastuzumab, and 30,000 units hyaluronidase in 15 mL Administer subcutaneously over approximately 8 minutes (1,200 mg, 600 mg, and 30,000 units/15 mL) Maintenance dose (administer every 3 weeks) 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase in 10 mL (600 mg, 600 mg, and 20,000 units/10 mL) Administer subcutaneously over approximately 5 minutes every 3 weeks 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 (14.2) ] . 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 (14.2) ] . 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. 2.4 Dose Modification Dose Modification for Delayed or Missed Doses For delayed or missed doses of PHESGO, if the time between two sequential injections is less than 6 weeks, administer the maintenance dose of 600 mg, 600 mg, and 20,000 units/10 mL. Do not wait until the next planned dose. If the time between two sequential injections is 6 weeks or more, re-administer the initial dose of 1,200 mg, 600 mg, and 30,000 units/15 mL, followed every 3 weeks thereafter by a maintenance dose of 600 mg, 600 mg, and 20,000 units/10 mL. For chemotherapy dose modifications, see relevant prescribing information. Cardiomyopathy [see Boxed Warning , Warnings and Precautions (5.1) ] Assess left ventricular ejection fraction (LVEF) prior to initiation of PHESGO and at regular intervals during treatment as indicated in Table 2 . The recommendations on dose modifications in the event of LVEF dysfunction are indicated in Table 2 [see Warnings and Precautions (5.1) ]. Table 2: Dose Modifications for Left Ventricular Dysfunction Pre-treatment LVEF: Monitor LVEF every: Withhold PHESGO for at least 3 weeks for an LVEF decrease to: Resume PHESGO after 3 weeks if LVEF has recovered to: Early Breast Cancer ≥ 55% For patients receiving anthracycline-based chemotherapy, a LVEF of ≥ 50% is required after completion of anthracyclines, before starting PHESGO ~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 Metastatic Breast Cancer ≥ 50% ~12 weeks Either Either <40% 40%-45% with a fall of ≥10%-points below pre-treatment value >45% 40%-45% with a fall of <10%-points below pre-treatment value If after a repeat assessment within approximately 3 weeks, the LVEF has not improved, has declined further, and/or the patient is symptomatic, permanently discontinue PHESGO [see Warnings and Precautions (5.1) ] . Hypersensitivity and Administration-Related Reactions Discontinue the injection immediately if the patient experiences a serious hypersensitivity reaction (e.g. anaphylaxis) [see Warnings and Precautions (5.5) ] . 2.5 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.
Paediatric
8.4 Pediatric Use The safety and effectiveness of PHESGO in pediatric patients have not been established.
Renal
Review renal impairment dosing; many agents need CrCl/eGFR adjustment.
- CrCl 0–120: Confirm renal dosing in product SmPC / primary label.
Hepatic
Review hepatic impairment dosing; monitor LFTs if agent is hepatically cleared or hepatotoxic.
Safety
Drug interactions
- Professional use: confirm indication, dose, duration, monitoring and patient counselling points against current Kenya STG / EML and the product SmPC.
- Document allergy status and key interactions.
Safety
Adverse effects
- 6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the label: Cardiomyopathy [see Warnings and Precautions (5.1) ] Embryo-Fetal Toxicity [see Warnings and Precautions (5.2) ] Pulmonary Toxicity [see Warnings and Precautions (5.3) ] Exacerbation of Chemotherapy-Induced Neutropenia [see Warnings and Precautions (5.4) ] Hypersensitivity and Administration-Related Reactions [see Warnings and Precautions (5.5) ] Neoadjuvant and Adjuvant Treatment of Breast Cancer The most common adverse reactions (>30%) with PHESGO were alopecia, nausea, diarrhea, anemia, and asthenia.
- ( 6.1 ) Metastatic Breast Cancer (based on intravenous pertuzumab ) The most common adverse reactions (> 30%) with pertuzumab in combination with trastuzumab and docetaxel were diarrhea, alopecia, neutropenia, nausea, fatigue, rash, and peripheral neuropathy.
- ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
- Neoadjuvant and Adjuvant Treatment of Breast Cancer The safety of PHESGO was evaluated in an open-label, multicenter, randomized trial (FeDeriCa) conducted in 500 patients with HER2 overexpressing early breast cancer [see Clinical Studies (14.2) ] .
- Patients were randomized to receive either PHESGO (1,200 mg pertuzumab, 600 mg trastuzumab, and 30,000 units hyaluronidase/15 mL) followed every 3 weeks by a maintenance dose of 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase/10 mL or the recommended dosages for intravenous pertuzumab and intravenous trastuzumab.
- Patients were randomized to receive 8 cycles of neoadjuvant chemotherapy with concurrent administration of 4 cycles of either PHESGO or intravenous pertuzumab and trastuzumab during cycles 5-8, followed by surgery.
- Following surgery, patients continued therapy with PHESGO alone or intravenous pertuzumab and trastuzumab (intravenous or subcutaneously administered) as treated prior to surgery, for an additional 14 cycles, to complete 18 cycles.
- The median duration of treatment for PHESGO was 24 weeks (range: 0-42 weeks).
- Serious adverse reactions occurred in 16% of patients who received PHESGO.
- Serious adverse reactions in > 1% of patients included febrile neutropenia (4%), neutropenic sepsis (1%), and neutrophil count decreased (1%).
- One fatal adverse reaction occurred in 1/248 (0.4%) of patients, which was due to acute myocardial infarction, and occurred prior to the start of HER2 targeted treatment with PHESGO.
- Adverse reactions resulting in permanent discontinuation of any study drug occurred in 8% of patients on the PHESGO arm.
- Adverse reactions which resulted in permanent discontinuation of PHESGO were ejection fraction decreased (1.2%), cardiac failure (0.8%), and pneumonitis/pulmonary fibrosis (0.8%).
- Dosage interruptions due to an adverse reaction occurred in 40% of patients who received PHESGO.
Use
Indications
- 1 INDICATIONS AND USAGE PHESGO is a combination of pertuzumab and trastuzumab, HER2/neu receptor antagonists, and hyaluronidase, an endoglycosidase, indicated for: Use in combination with chemotherapy as: neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer.
- ( 1.1 ) adjuvant treatment of patients with HER2-positive early breast cancer at high risk of recurrence ( 1.1 ) Use in combination with docetaxel for treatment of patients with HER2-positive metastatic breast cancer (MBC) who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease.
- ( 1.2 ) 1.1 Early Breast Cancer (EBC) PHESGO is indicated for use in combination with chemotherapy for the neoadjuvant treatment of adult patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer [see Dosage and Administration (2.2) and Clinical Studies (14.2) ] . the adjuvant treatment of adult patients with HER2-positive early breast cancer at high risk of recurrence [see Dosage and Administration (2.2) and Clinical Studies (14.2) ] .
- Select patients for therapy based on an FDA-authorized companion diagnostic test [see Dosage and Administration (2.1) ]. 1.2 Metastatic Breast Cancer (MBC) PHESGO is indicated for use in combination with docetaxel for the treatment of adult patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease [see Dosage and Administration (2.2) and Clinical Studies (14.1) ] .
- Select patients for therapy based on an FDA-authorized companion diagnostic test [see Dosage and Administration (2.1) ].
Pharmacology
Mode of action
12.
Full mechanism text
12.1 Mechanism of Action Pertuzumab targets the extracellular dimerization domain (subdomain II) of 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 signaling 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. Trastuzumab binds to subdomain IV of the extracellular domain of the HER2 protein to inhibit the ligand-independent, HER2 mediated cell proliferation and PI3K signaling pathway in human tumor cells that overexpress HER2. Both pertuzumab and trastuzumab-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) have been shown to be preferentially exerted on HER2 overexpressing cancer cells compared with cancer cells that do not overexpress HER2. While pertuzumab alone inhibited the proliferation of human tumor cells, the combination of pertuzumab and trastuzumab augmented anti-tumor activity in HER2-overexpressing xenograft models. Hyaluronan is a polysaccharide found in the extracellular matrix of the subcutaneous tissue. It is depolymerized by the naturally occurring enzyme hyaluronidase. Unlike the stable structural components of the interstitial matrix, hyaluronan has a half-life of approximately 0.5 days. Hyaluronidase increases permeability of the subcutaneous tissue by depolymerizing hyaluronan. In the doses administered, hyaluronidase in PHESGO acts transiently and locally. The effects of hyaluronidase are reversible and permeability of the subcutaneous tissue is restored within 24 to 48 hours. Hyaluronidase has been shown to increase the absorption rate of a trastuzumab product into the systemic circulation when given in the subcutis of Göttingen Minipigs.
ADME
Pharmacokinetics & PD
| Onset | Product-specific |
|---|---|
| Duration | Product-specific |
| Route | SUBCUTANEOUS |
| Absorption | rate of a trastuzumab product into the systemic circulation when given in the subcutis of Göttingen Minipigs. 12.2 Pharmacodynamics The exposure-response relationship and time course of pharmacodynamic response for the safety and effectiveness of pertuzumab and trastuzumab in PHE... |
| Distribution | The volume of distribution of pertuzumab and trastuzumab at steady state was 2.8 L and 2.9 L, respectively. |
| Elimination | For pertuzumab, the clearance (CV%) was 0.2 L/day (24%). For trastuzumab, the linear clearance was 0.1 L/day (30%); the non-linear elimination Vmax (CV%) was 12 mg/day (20%) and Km (CV%) was 34 mg/L (39%). The terminal |
| Half-life | of approximately 0.5 days. Hyaluronidase increases permeability of the subcutaneous tissue by depolymerizing hyaluronan. In the doses administered, hyaluronidase in PHESGO acts transiently and locally. The effects of hyaluronidase are reversible and permeability of the subcutaneo... |
Full PK/PD text
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Pertuzumab targets the extracellular dimerization domain (subdomain II) of 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 signaling 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. Trastuzumab binds to subdomain IV of the extracellular domain of the HER2 protein to inhibit the ligand-independent, HER2 mediated cell proliferation and PI3K signaling pathway in human tumor cells that overexpress HER2. Both pertuzumab and trastuzumab-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) have been shown to be preferentially exerted on HER2 overexpressing cancer cells compared with cancer cells that do not overexpress HER2. While pertuzumab alone inhibited the proliferation of human tumor cells, the combination of pertuzumab and trastuzumab augmented anti-tumor activity in HER2-overexpressing xenograft models. Hyaluronan is a polysaccharide found in the extracellular matrix of the subcutaneous tissue. It is depolymerized by the naturally occurring enzyme hyaluronidase. Unlike the stable structural components of the interstitial matrix, hyaluronan has a half-life of approximately 0.5 days. Hyaluronidase increases permeability of the subcutaneous tissue by depolymerizing hyaluronan. In the doses administered, hyaluronidase in PHESGO acts transiently and locally. The effects of hyaluronidase are reversible and permeability of the subcutaneous tissue is restored within 24 to 48 hours. Hyaluronidase has been shown to increase the absorption rate of a trastuzumab product into the systemic circulation when given in the subcutis of Göttingen Minipigs. 12.2 Pharmacodynamics The exposure-response relationship and time course of pharmacodynamic response for the safety and effectiveness of pertuzumab and trastuzumab in PHESGO have not been fully characterized. Cardiac Electrophysiology The effect of intravenous pertuzumab with an initial dose of 840 mg followed by a maintenance dose of 420 mg every three weeks on QTc interval was evaluated in a subgroup of 20 patients with HER2-positive breast cancer (NCT00567190). No large changes in the mean QT interval (i.e., greater than 20 ms) from placebo based on Fridericia correction method were detected in the trial. A small increase in the mean QTc interval (i.e., less than 10 ms) cannot be excluded because of the limitations of the trial design. The effects of trastuzumab on electrocardiographic (ECG) endpoints, including QTc interval duration, were evaluated in patients with HER2 positive solid tumors. Trastuzumab had no clinically relevant effect on the QTc interval duration and there was no apparent relationship between serum trastuzumab concentrations and change in QTcF interval duration in patients with HER2 positive solid tumors. 12.3 Pharmacokinetics The pharmacokinetics (PK) of pertuzumab and trastuzumab were characterized in the FeDeriCa trial following subcutaneous administration of PHESGO (1200 mg pertuzumab/600 mg trastuzumab initial dose followed by 600 mg pertuzumab/600 mg trastuzumab every 3 weeks) and intravenous administration of pertuzumab and trastuzumab (840 mg pertuzumab/8 mg/kg trastuzumab initial dose followed by 420 mg pertuzumab/6 mg/kg trastuzumab every 3 weeks). Trastuzumab is estimated to reach concentrations that are <1 mcg/mL by 7 months in at least 95% patients. Pertuzumab Cycle 7 C trough was 88.7 mcg/mL for PHESGO and 72.4 mcg/mL for intravenous pertuzumab with a geometric mean ratio (GMR) of 1.22 (90% CI: 1.14–1.31). Trastuzumab Cycle 7 C trough was 57.5 mcg/mL for PHESGO and 43.2 mcg/mL for intravenous trastuzumab with a GMR of 1.33 (90% CI: 1.24–1.43) [see Clinical Studies (14.2) ] . Following subcutaneous administration of PHESGO , the pertuzumab median Cycle 7 C max was 34% lower and AUC 0-21days was 5% higher than that following intravenous administration of pertuzumab. The median trastuzumab Cycle 7 C max was 31% lower and AUC 0-21days was 10% higher, than that following intravenous administration of trastuzumab. Absorption The mean absolute bioavailability (CV%) was 0.71 (18%) for pertuzumab and 0.77 (13%) for trastuzumab after subcutaneous administration of the approved recommended dosage of PHESGO. The median time to reach Cmax was 3.8 days for both pertuzumab and trastuzumab. Distribution The volume of distribution of pertuzumab and trastuzumab at steady state was 2.8 L and 2.9 L, respectively. Elimination For pertuzumab, the clearance (CV%) was 0.2 L/day (24%). For trastuzumab, the linear clearance was 0.1 L/day (30%); the non-linear elimination Vmax (CV%) was 12 mg/day (20%) and Km (CV%) was 34 mg/L (39%). The terminal half-life of pertuzumab and trastuzumab was 24 days and 22 days, respectively. Steady state concentration was achieved at Cycle 7 for pertuzumab and at Cycle 11 for trastuzumab. Specific Populations No dose adjustments based on body weight or baseline albumin level are needed, as the exposure changes are not considered clinically relevant. In patients with a body weight <58 kg, mean Cycle 7 AUC 0-21 days of trastuzumab was about 33% higher after PHESGO than after intravenous trastuzumab treatment, whereas in the highest BW group (>77 kg) Cycle 7 AUC 0-21 days was 24% lower after PHESGO than after intravenous trastuzumab treatment. However, no body weight-based dose adjustments are needed, as the exposure changes are not considered clinically relevant. No clinically significant differences in the pharmacokinetics of pertuzumab and trastuzumab were observed based on age (25 to 80 years), race (Asian and non-Asian), and renal impairment (creatinine clearance 30 mL/min or greater determined by Cockcroft-Gault). The effects of hepatic impairment on the pharmacokinetics of pertuzumab and trastuzumab are unknown. Drug Interaction Studies There have been no formal clinical drug interaction studies performed with PHESGO. 12.6 Immunogenicity The observed incidence of anti-drug antibodies (ADA) is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of ADA in the trial described below, including those of PHESGO or of other pertuzumab or trastuzumab products. During treatment and post-treatment with subcutaneous administration of PHESGO and concurrent administration with neoadjuvant chemotherapy in the FeDeriCa trial [see Clinical Studies (14.1) ] , the incidence of anti-pertuzumab and anti-trastuzumab antibodies was 12.9% (31/241) and 2.1% (5/241), respectively. During treatment and post-treatment with intravenous pertuzumab and trastuzumab and concurrent administration with neoadjuvant chemotherapy, the incidence of anti-pertuzumab and anti-trastuzumab antibodies was 10.6 % (26/245) and 0.4% (1/245), respectively. The incidence of neutralizing antibodies (NAb) to pertuzumab and to trastuzumab was 6% (2/31) and 20% (1/5), respectively, in patients treated with PHESGO. The corresponding incidences of NAb were 11.5% (3/26) and 0% (0/1), respectively, in patients treated with intravenous pertuzumab and trastuzumab. Because of limited immunogenicity data, the effect of anti-pertuzumab and anti-trastuzumab antibodies on the pharmacokinetics and effectiveness of PHESGO is unknown. There was no identified clinically significant effect of anti-pertuzumab and anti-trastuzumab antibodies on the safety of PHESGO. In the FeDeriCa trial, the incidence of anti-rHuPH20 antibodies was 6.3% (15/238) and the incidence of NAb was 0% (0/15) in patients treated with PHESGO. Because of limited immunogenicity data, the clinical impact of anti-rHuPH20 antibodies is unknown.
Kenya
Brands & prices
| Brand | Company | Pack | KES |
|---|---|---|---|
| Hyalase | CP Pharmaceuticals Ltd | Standard Commercial Pack | — |
Special populations
Pregnancy & lactation
Pregnancy
8.1 Pregnancy If PHESGO is administered during pregnancy, or if a patient becomes pregnant while receiving PHESGO or within 7 months following the last dose of PHESGO, health care providers and patients should immediately report PHESGO exposure to Genentech at 1-888-835-2555. Risk Summary PHESGO can cause fetal harm when administered to a pregnant woman. 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 (see Data ) . In an animal reproduction study, administration of pertuzumab to pregnant cynomolgus monkeys during the period of organogenesis resulted in oligohydramnios, delayed fetal kidney development, and embryo-fetal deaths at clinically relevant exposures that were 2.5 to 20-fold greater than exposures in humans receiving the recommended dose, based on C max (see Data ) . Apprise the patient of the potential risks to a fetus. There are clinical considerations if PHESGO is used during pregnancy or within 7 months prior to conception (see Clinical Considerations ) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Monitor women who received PHESGO during pregnancy or within 7 months prior to conception for oligohydramnios. If oligohydramnios occurs, perform fetal testing that is appropriate for gestational age and consistent with community standards of care. Data Human Data In post-marketing reports, use of trastuzumab during pregnancy resulted in cases of oligohydramnios and of oligohydramnios sequence, manifesting in the fetus as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. These case reports described oligohydramnios in pregnant women who received trastuzumab either alone or in combination with chemotherapy. In some case reports, amniotic fluid index increased after trastuzumab was stopped. In one case, trastuzumab therapy resumed after amniotic index improved and oligohydramnios recurred. Animal Data PHESGO for subcutaneous injection contains pertuzumab, trastuzumab, and hyaluronidase [see Description (11) ] . Pertuzumab: Pregnant cynomolgus monkeys were treated on Gestational Day (GD) 19 with loading doses of 30 to 150 mg/kg pertuzumab, followed by bi-weekly doses of 10 to 100 mg/kg. These dose levels resulted in clinically relevant exposures of 2.5 to 20-fold greater than exposures in humans receiving the recommended dose, based on C max . Intravenous administration of pertuzumab from GD19 through GD50 (period of organogenesis) was embryotoxic, with dose-dependent increases in embryo-fetal death between GD25 to GD70. The incidences of embryo-fetal loss were 33, 50, and 85%. At Caesarean section on GD100, oligohydramnios, decreased relative lung and kidney weights, and microscopic evidence of renal hypoplasia consistent with delayed renal development were identified in all pertuzumab dose groups. Pertuzumab exposure was reported in offspring from all treated groups, at levels of 29% to 40% of maternal serum levels at GD100. Trastuzumab: In studies where intravenous trastuzumab was administered to pregnant cynomolgus monkeys during the period of organogenesis at doses up to 25 mg/kg given twice weekly (up to 25 times the recommended weekly human dose of 2 mg/kg), trastuzumab crossed the placental barrier during the early (Gestation Days 20 to 50) and late (Gestation Days 120 to 150) phases of gestation. The resulting concentrations of trastuzumab in fetal serum and amniotic fluid were approximately 33% and 25%, respectively, of those present in the maternal serum but were not associated with adverse developmental effects. Hyaluronidase: In an embryo-fetal study, mice have been dosed daily by subcutaneous injection during the period of organogenesis with hyaluronidase (recombinant human) at dose levels up to 2,200,000 U/kg, which is >2,400 and 3,600, based on loading and maintenance doses, respectively, times higher than the human dose. The study found no evidence of teratogenicity. Reduced fetal weight and increased numbers of fetal resorptions were observed, with no effects found at a daily dose of 360,000 U/kg, which is >400 and 600, based on loading and maintenance doses, respectively, times higher than the human dose. In a peri-and post-natal reproduction study, mice have been dosed daily by subcutaneous injection, with hyaluronidase (recombinant human) from implantation through lactation and weaning at dose levels up to 1,100,000 U/kg, which is >1,200 and 1,800, based on loading and maintenance doses, respectively, times higher than the human dose. The study found no adverse effects on sexual maturation, learning and memory or fertility of the offspring.
Lactation
Potential: Verify the pregnancy status of females prior to initiation of PHESGO. ( 8.3 ) 8.1 Pregnancy If PHESGO is administered during pregnancy, or if a patient becomes pregnant while receiving PHESGO or within 7 months following the last dose of PHESGO, health care providers and patients should immediately report PHESGO exposure to Genentech at 1-888-835-2555. Risk Summary PHESGO can cause fetal harm when administered to a pregnant woman. 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 (see Data ) . In an animal reproduction study, administration of pertuzumab to pregnant cynomolgus monkeys during the period of organogenesis resulted in oligohydramnios, delayed fetal kidney development, and embryo-fetal deaths at clinically relevant exposures that were 2.5 to 20-fold greater than exposures in humans receiving the recommended dose, based on C max (see Data ) . Apprise the patient of the potential risks to a fetus. There are clinical considerations if PHESGO is used during pregnancy or within 7 months prior to conception (see Clinical Considerations ) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Monitor women who received PHESGO during pregnancy or within 7 months prior to conception for oligohydramnios. If oligohydramnios occurs, perform fetal testing that is appropriate for gestational age and consistent with community standards of care. Data Human Data In post-marketing reports, use of trastuzumab during pregnancy resulted in cases of oligohydramnios and of oligohydramnios sequence, manifesting in the fetus as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. These case reports described oligohydramnios in pregnant women who received trastuzumab either alone or in combination with chemotherapy. In some case reports, amniotic fluid index increased after trastuzumab was stopped. In one case, trastuzumab therapy resumed after amniotic index improved and oligohydramnios recurred. Animal Data PHESGO for subcutaneous injection contains pertuzumab, trastuzumab, and hyaluronidase [see Description (11) ] . Pertuzumab: Pregnant cynomolgus monkeys were treated on Gestational Day (GD) 19 with loading doses of 30 to 150 mg/kg pertuzumab, followed by bi-weekly doses of 10 to 100 mg/kg. These dose levels resulted in clinically relevant exposures of 2.5 to 20-fold greater than exposures in humans receiving the recommended dose, based on C max . Intravenous administration of pertuzumab from GD19 through GD50 (period of organogenesis) was embryotoxic, with dose-dependent increases in embryo-fetal death between GD25 to GD70. The incidences of embryo-fetal loss were 33, 50, and 85%. At Caesarean section on GD100, oligohydramnios, decreased relative lung and kidney weights, and microscopic evidence of renal hypoplasia consistent with delayed renal development were identified in all pertuzumab dose groups. Pertuzumab exposure was reported in offspring from all treated groups, at levels of 29% to 40% of maternal serum levels at GD100. Trastuzumab: In studies where intravenous trastuzumab was administered to pregnant cynomolgus monkeys during the period of organogenesis at doses up to 25 mg/kg given twice weekly (up to 25 times the recommended weekly human dose of 2 mg/kg), trastuzumab crossed the placental barrier during the early (Gestation Days 20 to 50) and late (Gestation Days 120 to 150) phases of gestation. The resulting concentrations of trastuzumab in fetal serum and amniotic fluid were approximately 33% and 25%, respectively, of those present in the maternal serum but were not associated with adverse developmental effects. Hyaluronidase: In an embryo-fetal study, mice have been dosed daily by subcutaneous injection during the period of organogenesis with hyaluronidase (recombinant human) at dose levels up to 2,200,000 U/kg, which is >2,400 and 3,600, based on loading and maintenance doses, respectively, times higher than the human dose. The study found no evidence of teratogenicity. Reduced fetal weight and increased numbers of fetal resorptions were observed, with no effects found at a daily dose of 360,000 U/kg, which is >400 and 600, based on loading and maintenance doses, respectively, times higher than the human dose. In a peri-and post-natal reproduction study, mice have been dosed daily by subcutaneous injection, with hyaluronidase (recombinant human) from implantation through lactation and weaning at dose levels up to 1,100,000 U/kg, which is >1,200 and 1,800, based on loading and maintenance doses, respectively, times higher than the human dose. The study found no adverse effects on sexual maturation, learning and memory or fertility of the offspring. 8.2 Lactation Risk Summary There is no information regarding the presence of pertuzumab, trastuzumab or hyaluronidase in human milk, the effects on the breastfed infant, or the effects on milk production. Published data suggest that human IgG is present in human milk but does not enter the neonatal and infant circulation in substantial amounts. Trastuzumab was present in the milk of lactating cynomolgus monkeys but not associated with neonatal toxicity (see Data ) . Consider the developmental and health benefits of breast feeding along with the mother's clinical need for PHESGO treatment and any potential adverse effects on the breastfed child from PHESGO or from the underlying maternal condition. This consideration should also take into account the elimination half-life of pertuzumab and the trastuzumab wash out period of 7 months [see Clinical Pharmacology (12.3) ] . Data In lactating cynomolgus monkeys, trastuzumab was present in breast milk at about 0.3% of maternal serum concentrations after pre- (beginning Gestation Day 120) and post-partum (through Post-partum Day 28) doses of 25 mg/kg administered twice weekly (25 times the recommended weekly human dose of 2 mg/kg of intravenous trastuzumab). Infant monkeys with detectable serum levels of trastuzumab did not exhibit any adverse effects on growth or development from birth to 1 month of age. 8.3 Females and Males of Reproductive Potential PHESGO can cause embryo-fetal harm when administered during pregnancy. Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to the initiation of PHESGO. Contraception Females Advise females of reproductive potential to use effective contraception during treatment and for 7 months following the last dose of PHESGO [see Use in Specific Populations (8.1) and Clinical Pharmacology (12.3) ] . 8.4 Pediatric Use The safety and effectiveness of PHESGO in pediatric patients have not been established. 8.5 Geriatric Use Of the total number of patients in the FeDeriCa trial (n=500) treated with PHESGO, 11% were 65 and over, while 1.6% were 75 and over. Clinical studies of PHESGO did not include sufficient numbers of patients age 65 years and older to determine whether they respond differently from younger patients. In the intravenous trastuzumab trials, the risk of cardiac dysfunction was increased in geriatric patients as compared to younger patients, in both those receiving treatment for adjuvant therapy or metastatic disease. Other differences in safety or effectiveness were not observed between elderly patients and younger patients. In the intravenous pertuzumab in combination with trastuzumab trials, the risk of decreased appetite, anemia, weight decreased, asthenia, dysgeusia, neuropathy peripheral and hypomagnesemia was increased in patients 65 years of age and older compared to patients less than 65 years of age.
Diet
Food & alcohol
- Drug & food interactions (label) 7 DRUG INTERACTIONS Patients who receive anthracycline after stopping PHESGO may be at increased risk of cardiac dysfunction because of PHESGO's long washout period [see Clinical Pharmacology (12.3) ] . If possible, avoid anthracycline-based therapy for up to 7 months after stopping PHESGO. If anthracyclines are used, carefully monitor the patient's cardiac function.
Trust
Sources & disclaimer
Source: FDA drug label via OpenFDA/DailyMed; Local active-ingredient clinical extract; Professional class pharmacology (Therapeutic agent (verify pharmacological class))
Last reviewed: 01 Aug 2026
Decision support only — not a substitute for clinical judgment, product SmPC, or Kenya STG/EML.