Phesgo pertuzumab, trastuzumab, and hyaluronidase-zzxf 600 mg/10mL; 600 mg/10mL; 20000 U/10mL Injection, Solution
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the HER2/neu Receptor Antagonist class.
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🏭 Manufacturer & labeler
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🩺 Clinical
The combination of pertuzumab, trastuzumab, and hyaluronidase-zzxf is used in combination with chemotherapy to treat certain types of early breast cancer that has spread to nearby tissues. It is also used to treat a certain type of early breast cancer to decrease the chance that a certain type of breast cancer will return. The combination of pertuzumab, trastuzumab, and hyaluronidase-zzxf is also used with docetaxel (Taxotere) to treat certain types of breast cancer that has spread to other parts of the body. Pertuzumab and trastuzumab are in a class of medications called monoclonal antibodies...
Read the full MedlinePlus article ↗- Phesgo combines two cancer-fighting antibodies — pertuzumab and trastuzumab — that work together to attack HER2, the protein driving your cancer's growth. They work at two differen...
- What exactly is Phesgo and why do I need three ingredients in one shot?
- Yes, heart effects are one of the most important things to monitor with Phesgo. It can weaken your heart's pumping strength — sometimes without any symptoms at first. Your care tea...
- Will this affect my heart? What should I watch for?
Patient education
Supplement & herbal interactions
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII 4QD397987E
An amino acid used as a buffer and stabilizer in medications. It helps maintain the pH balance and protects the active drug from breaking down during storage and use.
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UNII 1D5Q932XM6
An amino acid salt used in medicines as a buffer and pH regulator. It helps maintain the proper acidity level in liquid formulations to keep the drug stable and effective.
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UNII AE28F7PNPL
Methionine is an amino acid used as a nutrient supplement and pH buffer in medicines. It helps stabilize the formulation and supports the product's overall composition.
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UNII 7T1F30V5YH
A synthetic emulsifier derived from sorbitol and oleic acid. It helps mix oil and water-based ingredients together and keeps them from separating in liquid formulations.
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UNII C151H8M554
A natural sugar derived from sugar cane or sugar beets. It's used as a sweetener, filler, and binder to improve taste, add bulk, and help hold tablet or capsule ingredients together.
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UNII 7YIN7J07X4
A natural sugar derived from plants and microorganisms. It acts as a filler to give the medication bulk and stability, and helps preserve the active ingredient during storage and manufacturing.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
7 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Phesgo 600 mg/10mL; 600 mg/10mL; 20000 U/10mLthis 50242-0260-86 | Genentech, | 1 vial | — | — | FDA listed | — |
Where does this data come from?
⏳ Availability & biosimilar status
Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.
Why the date isn’t exact: Biosimilar timing can change because patents may be challenged, settled, licensed, added or removed, and litigation can move the real date earlier or later.
🛈 What do these terms mean?
- Biologic patent
- A patent the reference product’s maker has publicly listed. A biosimilar generally can’t launch until these expire — unless they’re invalidated or resolved in a settlement.
- Reference-product exclusivity
- A flat 12 years of FDA market protection from the biologic’s first licensure (the BPCIA). No biosimilar can be licensed before it ends, regardless of patents.
- Interchangeable exclusivity
- The first interchangeable biosimilar can earn a period as the only interchangeable version (pharmacists can substitute it without the prescriber).
- Earliest biosimilar (LOE)
- The latest of all the dates above — the soonest a biosimilar can realistically reach the market. Litigation and settlements can move it earlier.
Biologics have no small-molecule “generics” — competition comes from FDA-licensed biosimilars, tracked in the FDA Purple Book.
| Code | What it grants | Expires |
|---|---|---|
| RefProduct | Reference-product exclusivity (12-year, BPCIA) — no biosimilar can be licensed before this date | Jun 29, 2032 |
Is there a biosimilar for PHESGO 600-600 MG-20,000 UNIT?
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💊 Medicaid utilization by pack size
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 50242-0260-01 | 1 VIAL, SINGLE-DOSE in 1 CARTON (50242-260-01) / 10 mL in 1 VIAL, SINGLE-DOSE | 2020-06-29 | Active |
| 50242-0260-86 You're viewing this | 1 VIAL, SINGLE-DOSE in 1 CARTON (50242-260-86) / 10 mL in 1 VIAL, SINGLE-DOSE | 2021-05-03 | Active |
This pack shows little to no recent Medicaid volume — a different pack size carries most fills. See all packs ↓
Pack size FAQ
What quantity is in NDC 50242-0260-86?
What NDC number is used to bill for this package of Phesgo pertuzumab, trastuzumab, and hyaluronidase-zzxf 600 mg/10mL; 600 mg/10mL; 20000 U/10mL Injection, Solution?
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
Questions about this listing
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: CARDIOMYOPATHY, EMBRYO-FETAL TOXICITY, and PULMONARY TOXICITY WARNING: CARDIOMYOPATHY, EMBRYO-FETAL TOXICITY, and PULMONARY TOXICITY See full prescribing information for complete boxed warning. Cardiomyopathy: PHESGO administration can result in subclinical and clinical cardiac failure manifesting as CHF, and decreased LVEF, with greatest risk when administered concurrently with anthracyclines. Evaluate cardiac function prior to and during treatment.
Discontinue PHESGO for cardiomyopathy. ( 2.3 , 5.1 ) Embryo-fetal Toxicity: Exposure to PHESGO can result in embryo-fetal death and birth defects. Advise patients of these risks and the need for effective contraception.
( 5.2 , 8.1 , 8.3 ) Pulmonary Toxicity: Discontinue PHESGO for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome. ( 5.3 ) Cardiomyopathy PHESGO administration can result in subclinical and clinical cardiac failure. The incidence and severity were highest in patients receiving PHESGO with anthracycline-containing chemotherapy regimens.
Evaluate cardiac function prior to and during treatment with PHESGO. Discontinue PHESGO treatment in patients receiving adjuvant therapy and withhold PHESGO in patients with metastatic disease for clinically significant decrease in left ventricular function [see Dosage and Administration (2.3) and Warnings and Precautions (5.1) ] . Embryo-fetal Toxicity Exposure to PHESGO can result in embryo-fetal death and birth defects, including oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death.
Advise patients of these risks and the need for effective contraception [see Warnings and Precautions (5.2) and Use in Specific Populations (8.1) , (8.3) ]. Pulmonary Toxicity PHESGO administration can result in serious and fatal pulmonary toxicity. Discontinue PHESGO for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome.
Monitor patients until symptoms completely resolve [see Warnings and Precautions (5.3) ].
🎯 Indications and Usage ▾
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 )
1.1Early 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) ].
1.2Metastatic 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) ].
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION For subcutaneous use in the thigh 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 )
2.1Patient 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.
2.2Important 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) ].
2.3Recommended 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 receivi…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Injection: PHESGO is a clear to opalescent, and colorless to slightly brownish solution provided as: 1,200 mg pertuzumab, 600 mg trastuzumab, and 30,000 units hyaluronidase/15 mL (80 mg, 40 mg, and 2,000 units/mL) of solution in a single-dose vial 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase/10 mL (60 mg, 60 mg, and 2,000 units/mL) of solution in a single-dose vial Injection: 1,200 mg pertuzumab, 600 mg trastuzumab, and 30,000 units hyaluronidase/15 mL (80 mg, 40 mg, and 2,000 units/mL) of solution in a single-dose vial.
( 3 ) 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase/10 mL (60 mg, 60 mg, and 2,000 units/mL) of solution in a single-dose vial. ( 3 )
⛔ 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. ( 4 )
⚠️ Warnings and Cautions ▾
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 )
5.1Cardiomyopathy 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.
PHESGO In the FeDeriCa trial, the percentage of patients with at least one cardiac disorder was 22% in the PHESGO arm. The most frequent cardiac adverse reaction in the PHESGO arm was ejection fraction decreased. The incidence of cardiac failure (NYHA Class III/IV) with a LVEF decline ≥ 10% and a drop to less than 50% was 0.8% in the PHESGO arm.
Confirmed asymptomatic or mildly symptomatic (NYHA Class II) declines in LVEF ≥ 10% and a drop to less than 50% was 1.2% in the PHESGO arm [see Adverse Reactions (6.1) ] . PHESGO and/or intravenous pertuzumab and trastuzumab have not been studied in patients with a pretreatment LVEF value of < 55% (EBC) or <50% (MBC); a prior history of CHF, conditions that could impair left ventricular function such as uncontrolled hypertension, recent myocardial infarction, serious cardiac arrhythmia requiring treatment or a cumulative prior anthracycline exposure to > 360 mg/m 2 of doxorubicin or its equivalent.
5.2Embryo-Fetal Toxicity 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. 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 .
Verify the pregnancy status of females of reproductive potential prior to the initiation of PHESGO. Advise pregnant women and females of reproductive potential that exposure to PHESGO during pregnancy or within 7 months prior to conception can result in fetal harm. 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 , 8.3) and Clinical Pharmacology (12.3) ].
5.3Pulmonary Toxicity PHESGO can cause serious and fatal pulmonary toxicity. These adverse reactions have been reported with intravenous trastuzumab. Pulmonary toxi…
🤒 Adverse Reactions ▾
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.
6.1Clinical 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. Adverse reactions which required dosage interruption in > 1% of patients who received PHESGO included neutropenia (8%), neutrophil count decreased (4%), and diarrhea (7%).
Table 3 summarizes the adverse reactions in FeDeriCa. Table 3: Adverse Reactions (≥5%) in Patients Who Received PHESGO in FeDeriCa Adverse Reactions PHESGO (n=248) Intravenous pertuzumab plus intravenous or subcutaneous trastuzumab (n=252) All Grades % Grades 3 – 4 % All Grades % Grades 3 – 4 % Skin and subcutaneous tissue disorders Alopecia 77 0 71
0.4Dry skin 15 0.4 13 0 Rash 16 0.4 21 0 Nail discoloration 9 0 6 0 Erythema 9 0 5 0 Dermatitis 7 0 6 0 Nail disorder 7 0 7
0.4Palmar-plantar erythrodysaesthesia syndrome 6 0.8 5
0.4 Gastrointestinal disorders Nausea 60 2 61
1.6Diarrhea 60 7 57 4.8…
🔄 Drug Interactions ▾
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.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Females and Males of Reproductive Potential: Verify the pregnancy status of females prior to initiation of PHESGO. ( 8.3 )
8.1Pregnancy 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 approximatel…
🤰 Pregnancy ▾
8.1Pregnancy 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 embr…
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of PHESGO in pediatric patients have not been established.
🧓 Geriatric Use ▾
8.5Geriatric 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.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism 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.
12.2Pharmacodynamics 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.
12.3Pharmacokinetics 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 subc…
🧬 Mechanism of Action ▾
12.1Mechanism 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.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied PHESGO (pertuzumab, trastuzumab, and hyaluronidase-zzxf) injection is a sterile, preservative-free, clear to opalescent, and colorless to slightly brownish solution in single-dose vials for subcutaneous administration supplied as each carton containing one single-dose vial: 1,200 mg pertuzumab, 600 mg trastuzumab, and 30,000 units hyaluronidase/15 mL (80 mg, 40 mg, and 2,000 units/mL) (NDC 50242-245-01). 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase/10 mL (60 mg, 60 mg, 2,000 units/mL) (NDC 50242-260-01).
Storage and Handling Store PHESGO vials in the refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze. Do not shake.
📦 Storage and Handling ▾
Storage and Handling Store PHESGO vials in the refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze. Do not shake.
📋 Description ▾
11 DESCRIPTION PHESGO is a combination of pertuzumab, trastuzumab, and hyaluronidase. 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 is produced by recombinant DNA technology in a mammalian cell (Chinese Hamster Ovary) culture.
Pertuzumab has an approximate molecular weight of 148 kDa. Trastuzumab is a humanized IgG1 kappa monoclonal antibody that selectively binds with high affinity to the extracellular domain of the human epidermal growth factor receptor 2 protein, HER2. Trastuzumab is produced by recombinant DNA technology in a mammalian cell (Chinese Hamster Ovary) culture.
Trastuzumab has a molecular weight of approximately 148 kDa. Hyaluronidase (recombinant human) is an endoglycosidase used to increase the dispersion and absorption of co-administered drugs when administered subcutaneously. It is a glycosylated single-chain protein produced by mammalian (Chinese Hamster Ovary) cells containing a DNA plasmid encoding for a soluble fragment of human hyaluronidase (PH20).
Hyaluronidase (recombinant human) has a molecular weight of approximately 61 kDa. PHESGO (pertuzumab, trastuzumab, and hyaluronidase-zzxf) injection is a sterile, preservative-free, clear to opalescent, and colorless to slightly brownish solution supplied in single-dose vials for subcutaneous administration. PHESGO injection is supplied as two different configurations: PHESGO is supplied in a 15 mL single-dose vial containing 1,200 mg of pertuzumab, 600 mg of trastuzumab, and 30,000 units of hyaluronidase, and α,α-trehalose (397 mg), L-histidine (6.75 mg), L-histidine hydrochloric monohydrate (53.7 mg), L-methionine (22.4 mg), polysorbate 20 (6 mg), and sucrose (685 mg) with a pH of 5.5.
PHESGO is supplied in a 10 mL single-dose vial containing 600 mg of pertuzumab, 600 mg of trastuzumab, and 20,000 units of hyaluronidase, and α,α-trehalose (397 mg), L-histidine (4.4 mg), L-histidine hydrochloric monohydrate (36.1 mg), L-methionine (14.9 mg), polysorbate 20 (4 mg), and sucrose (342 mg) with a pH of 5.5.
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Cardiomyopathy Advise patients to contact a health care professional immediately for any of the following: new onset or worsening shortness of breath, cough, swelling of the ankles/legs, swelling of the face, palpitations, weight gain of more than 5 pounds in 24 hours, dizziness or loss of consciousness [see Warnings and Precautions (5.1) ] . Embryo-Fetal Toxicity Advise pregnant women and females of reproductive potential that exposure to PHESGO during pregnancy or within 7 months prior to conception can result in fetal harm.
Advise female patients to contact their healthcare provider with a known or suspected pregnancy [see Use in Specific Populations (8.1) ] . Encourage women who are exposed to PHESGO during pregnancy or within 7 months prior to conception to report their pregnancy to Genentech [see Use in Specific Populations (8.1) ] . 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 (8.3) ] .
Hypersensitivity and Administration-Related Reactions Advise patients to contact their healthcare provider immediately and to report any symptoms of hypersensitivity and administration-related reactions including dizziness, nausea, chills, fever, vomiting, diarrhea, urticaria, angioedema, breathing problems, or chest pain [see Warnings and Precautions (5.5) ] .