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Pertuzumab, trastuzumab, and hyaluronidase: Drug information

Pertuzumab, trastuzumab, and hyaluronidase: Drug information
(For additional information see "Pertuzumab, trastuzumab, and hyaluronidase: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Cardiomyopathy

Pertuzumab/trastuzumab/hyaluronidase administration can result in subclinical and clinical cardiac failure. The incidence and severity was highest in patients receiving pertuzumab/trastuzumab/hyaluronidase with anthracycline-containing chemotherapy regimens. Evaluate cardiac function prior to and during treatment with pertuzumab/trastuzumab/hyaluronidase. Discontinue pertuzumab/trastuzumab/hyaluronidase treatment in patients receiving adjuvant therapy and withhold pertuzumab/trastuzumab/hyaluronidase in patients with metastatic disease for clinically significant decrease in left ventricular function.

Embryo-fetal toxicity

Exposure to pertuzumab/trastuzumab/hyaluronidase 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.

Pulmonary toxicity

Pertuzumab/trastuzumab/hyaluronidase administration can result in serious and fatal pulmonary toxicity. Discontinue pertuzumab/trastuzumab/hyaluronidase for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome. Monitor patients until symptoms completely resolve.

Brand Names: US
  • Phesgo
Brand Names: Canada
  • Phesgo
Pharmacologic Category
  • Antineoplastic Agent, Anti-HER2;
  • Antineoplastic Agent, Monoclonal Antibody
Dosing: Adult

Note: Actively manage modifiable cardiac risk factors (smoking, hypertension, diabetes, dyslipidemia, obesity) before initiating treatment (Ref). Do not substitute pertuzumab/trastuzumab/hyaluronidase with conventional trastuzumab products, trastuzumab/hyaluronidase, ado-trastuzumab emtansine, fam-trastuzumab deruxtecan, or pertuzumab.

Breast cancer, early, neoadjuvant treatment, HER2+

Breast cancer, early, neoadjuvant treatment, HER2+:

SubQ: Note: Administer 3 to 6 cycles of pertuzumab/trastuzumab/hyaluronidase as part of a neoadjuvant treatment regimen for early breast cancer.

Initial loading dose: Pertuzumab 1,200 mg/trastuzumab 600 mg/hyaluronidase 30,000 units initially, followed 3 weeks later by maintenance dosing.

Maintenance dosing: Pertuzumab 600 mg/trastuzumab 600 mg/hyaluronidase 20,000 units once every 3 weeks. Following surgery, continue pertuzumab/trastuzumab/hyaluronidase to complete 1 year of treatment (up to 18 cycles) or until disease progression or unacceptable toxicity, whichever occurs first.

Breast cancer, early, adjuvant treatment, HER2+

Breast cancer, early, adjuvant treatment, HER2+:

SubQ: Note: Administer as part of a complete regimen for early breast cancer, including anthracycline- and/or taxane-based chemotherapy. If part of anthracycline-based therapy, administer pertuzumab/trastuzumab/hyaluronidase following completion of anthracycline therapy. Initiate pertuzumab/trastuzumab/hyaluronidase on day 1 of the first taxane-containing cycle.

Initial loading dose: Pertuzumab 1,200 mg/trastuzumab 600 mg/hyaluronidase 30,000 units initially, followed 3 weeks later by maintenance dosing.

Maintenance dosing: Pertuzumab 600 mg/trastuzumab 600 mg/hyaluronidase 20,000 units once every 3 weeks for a total of 1 year (up to 18 cycles) or until disease progression or unacceptable toxicity, whichever occurs first.

Breast cancer, metastatic, HER2+

Breast cancer, metastatic, HER2+:

SubQ: Note: Administer in combination with docetaxel.

Initial loading dose: Pertuzumab 1,200 mg/trastuzumab 600 mg/hyaluronidase 30,000 units initially, followed 3 weeks later by maintenance dosing.

Maintenance dosing: Pertuzumab 600 mg/trastuzumab 600 mg/hyaluronidase 20,000 units once every 3 weeks; continue pertuzumab/trastuzumab/hyaluronidase until disease progression or unacceptable toxicity, whichever occurs first.

Conversion to pertuzumab/trastuzumab/hyaluronidase (SubQ) from IV pertuzumab and trastuzumab:

If <6 weeks since the last IV pertuzumab and trastuzumab dose: SubQ: Administer maintenance dose of pertuzumab 600 mg/trastuzumab 600 mg/hyaluronidase 20,000 units and then every 3 weeks.

If ≥6 weeks since the last IV pertuzumab and trastuzumab dose: SubQ: Administer initial dose of pertuzumab 1,200 mg/trastuzumab 600 mg/hyaluronidase 30,000 units, followed 3 weeks later by maintenance dosing of pertuzumab 600 mg/trastuzumab 600 mg/hyaluronidase 20,000 units once every 3 weeks.

Missed doses: For delayed or missed doses, if the time between 2 sequential SubQ doses is <6 weeks, administer the maintenance dose of pertuzumab 600 mg/trastuzumab 600 mg/hyaluronidase 20,000 units; do not wait until the next scheduled dose. If the time between 2 sequential SubQ doses is ≥6 weeks, administer the initial dose of pertuzumab 1,200 mg/trastuzumab 600 mg/hyaluronidase 30,000 units, followed every 3 weeks thereafter by the maintenance dosing of pertuzumab 600 mg/trastuzumab 600 mg/hyaluronidase 20,000 units.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically significant differences in pertuzumab and trastuzumab pharmacokinetics were observed.

CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Obesity: Adult

American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2 : The dosing in the FDA-approved prescribing information should be followed in all patients, regardless of obesity status. If a patient with a BMI ≥30 kg/m2 experiences high-grade toxicity from systemic anticancer therapy, the same dosage modification recommendations should be followed for all patients, regardless of obesity status (Ref). Note: According to the prescribing information, no dosage adjustments are necessary based on patient body weight.

Dosing: Adjustment for Toxicity: Adult

Refer to specific drug monographs for information on dosage adjustment for individual concomitant chemotherapy agents.

Cardiotoxicity:

Pertuzumab/Trastuzumab/Hyaluronidase Dose Modifications for Left Ventricular Dysfunctiona

Pretreatment LVEFb

Monitor LVEF every:

Withhold for at least 3 weeks for an LVEF decrease to:

Resume after 3 weeksc if LVEF has recovered to:

a Asymptomatic heart disease: Consider initiating heart failure medications (eg, angiotensin-converting enzyme inhibitors or an angiotensin receptor blocker, and/or beta-blockers) in patients with asymptomatic (stage B) heart disease (ASCO [Armenian 2017], ESC (Lyon 2022]). For mild cardiac dysfunction, continue treatment with close cardiovascular monitoring; for moderate dysfunction, consider continuing treatment with close cardiovascular monitoring - initiation of heart failure medications is recommended; for severe dysfunction, interrupt treatment and utilize a multidisciplinary approach when deciding if/when to restart - initiation of heart failure medications is recommended (ESC [Lyon 2022]). Symptomatic heart disease: Initiate heart failure medications; for mild cardiac dysfunction, consider a multidisciplinary approach for decisions regarding treatment interruption versus continuation; for moderate or severe cardiac dysfunction, interrupt treatment and consider a multidisciplinary approach for decisions regarding treatment reinitiation (ESC [Lyon 2022]).

b LVEF = left ventricular ejection fraction.

c If LVEF has not improved after 3 weeks, has declined further, and/or the patient is symptomatic, permanently discontinue pertuzumab/trastuzumab/hyaluronidase.

Early breast cancer

≥55% (if receiving anthracycline-based chemotherapy, a LVEF of ≥50% is required after anthracycline completion)

~12 weeks (once during neoadjuvant therapy)

<50% with a fall of ≥10 percentage points below pretreatment value

Either

≥50%

<10 percentage points below pretreatment value

Metastatic breast cancer

≥50%

~12 weeks

Either

Either

<40%

40% to 45% with a fall of ≥10 percentage points below pretreatment value

>45%

40% to 45% with a fall of <10 percentage points below pretreatment value

Hypersensitivity: If a significant injection-related reaction occurs, slow down or interrupt the injection and administer appropriate medical management. Evaluate and monitor until complete resolutions of signs/symptoms.

Grade 1 or 2 hypersensitivity (reversible): Consider premedication with an analgesic, antipyretic, or an antihistamine prior to subsequent pertuzumab/trastuzumab/hyaluronidase doses.

Serious hypersensitivity reaction, anaphylaxis, or severe injection-related reactions: Permanently discontinue pertuzumab/trastuzumab/hyaluronidase.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions include neoadjuvant chemotherapy. Also see individual agents.

>10%:

Dermatologic: Alopecia (77%), skin rash (16%), xeroderma (15%)

Endocrine & metabolic: Decreased serum albumin (16%), decreased serum sodium (13%), hot flash (12%), increased serum potassium (13%), weight loss (11%)

Gastrointestinal: Constipation (22%), decreased appetite (17%), diarrhea (60%), dysgeusia (17%), dyspepsia (14%), nausea (60%), stomatitis (15% to 25%; grades 3/4: ≤1%), vomiting (20%)

Hematologic & oncologic: Anemia (36% to 90%; grades 3/4: 2% to 3%), decreased absolute lymphocyte count (89%; grade 3/4: 37%), neutropenia (22%; grades 3/4: 14%), thrombocytopenia (27%)

Hepatic: Increased serum alanine aminotransferase (58%), increased serum aspartate aminotransferase (50%)

Local: Injection site reaction (15%)

Nervous system: Dizziness (13%), fatigue (29%), headache (17%), insomnia (17%), peripheral neuropathy (12%; grades 3/4: ≤1%), peripheral sensory neuropathy (16%), procedural pain (13%)

Neuromuscular & skeletal: Arthralgia (24%), asthenia (31%), myalgia (25%)

Renal: Increased serum creatinine (84%)

Respiratory: Cough (15%), epistaxis (12%), upper respiratory tract infection (11%)

Miscellaneous: Fever (13%), radiation injury (19%, skin)

1% to 10%:

Cardiovascular: Cardiac failure (≤1%), peripheral edema (8%), reduced ejection fraction (4%)

Dermatologic: Dermatitis (7%), erythema of skin (9%), nail discoloration (9%), nail disease (7%), palmar-plantar erythrodysesthesia (6%), paronychia (7%), pruritus (3%)

Endocrine & metabolic: Decreased serum glucose (9%), hypokalemia (7%), increased serum sodium (7%)

Gastrointestinal: Abdominal pain (9%), hemorrhoids (9%), upper abdominal pain (8%)

Genitourinary: Urinary tract infection (7%)

Hematologic & oncologic: Febrile neutropenia (7%; grades 3/4: 7%; serious febrile neutropenia: 4%), leukopenia (9%; grades 3/4: 2%)

Hepatic: Increased serum bilirubin (9%)

Hypersensitivity: Hypersensitivity reaction (1%)

Immunologic: Antibody development (1% to 5%)

Infection: Neutropenic sepsis (1%)

Local: Pain at injection site (2%)

Nervous system: Malaise (7%), paresthesia (10%)

Neuromuscular & skeletal: Back pain (10%), limb pain (6%), muscle spasm (6%), musculoskeletal pain (6%), ostealgia (7%)

Ophthalmic: Dry eye syndrome (5%), increased lacrimation (5%)

Respiratory: Dyspnea (10%), flu-like symptoms (5%), nasopharyngitis (9%), rhinorrhea (7%)

Miscellaneous: Infusion related reaction (4%)

Frequency not defined:

Cardiovascular: Cardiac arrhythmia, cardiomyopathy, hypertension, left ventricular dysfunction

Respiratory: Pulmonary toxicity

Contraindications

Known hypersensitivity to pertuzumab, trastuzumab, or hyaluronidase, or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Cardiomyopathy: [US Boxed Warning]: Pertuzumab/trastuzumab/hyaluronidase administration can result in subclinical and clinical cardiac failure. The incidence and severity was highest in patients receiving pertuzumab/trastuzumab/hyaluronidase with anthracycline-containing chemotherapy regimens. Evaluate cardiac function prior to and during pertuzumab/trastuzumab/hyaluronidase treatment. Discontinue pertuzumab/trastuzumab/hyaluronidase in patients receiving adjuvant therapy, and withhold pertuzumab/trastuzumab/hyaluronidase in patients with metastatic disease for clinically significant decrease in left ventricular function. Pertuzumab/trastuzumab/hyaluronidase may cause left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death. Pertuzumab/trastuzumab/hyaluronidase may also result in an asymptomatic left ventricular ejection fraction (LVEF) decline. Patients who received IV pertuzumab, IV trastuzumab, and docetaxel experienced an increased incidence of LVEF decline. Among patients receiving trastuzumab, there is a 4- to 6-fold increase in the incidence of symptomatic myocardial dysfunction compared to patients not receiving trastuzumab. The highest absolute incidence occurs when trastuzumab is administered with an anthracycline. If an anthracycline-based regimen is indicated, pertuzumab/trastuzumab/hyaluronidase should not begin until after anthracycline therapy is completed. Patients who receive anthracycline after stopping pertuzumab/trastuzumab/hyaluronidase may also be at increased risk of cardiac dysfunction. Pertuzumab/trastuzumab/hyaluronidase and/or IV pertuzumab and trastuzumab have not been studied in patients with a pretreatment LVEF of <55% (in early breast cancer) or <50% (in metastatic breast cancer), a prior history of heart failure, conditions that could impair LVEF such as uncontrolled hypertension, recent myocardial infarction (MI), serious cardiac arrhythmia requiring treatment, or a cumulative prior anthracycline exposure of >360 mg/m2 of doxorubicin (or equivalent). Conduct a thorough cardiac assessment, including history, physical examination, and LVEF assessment (by ECG or MUGA scan) prior to treatment initiation. Assess LVEF immediately prior to pertuzumab/trastuzumab/hyaluronidase initiation, every 3 months during pertuzumab/trastuzumab/hyaluronidase therapy, every 3 weeks if pertuzumab/trastuzumab/hyaluronidase is withheld for significant left ventricular cardiac dysfunction, and every 6 months for at least 2 years following completion of adjuvant pertuzumab/trastuzumab/hyaluronidase therapy. Cardiotoxicity may require therapy interruption and/or permanent discontinuation.

According to American Society of Clinical Oncology (ASCO) guidelines for prevention and monitoring of cardiac dysfunction in adult survivors of cancer (ASCO [Armenian 2017]), the risk of cardiac dysfunction related to trastuzumab is increased with the following:

- Trastuzumab alone AND any of the following risk factors: multiple cardiovascular risk factors (≥2 risk factors), including smoking, hypertension, diabetes, dyslipidemia, and obesity (during or after completion of therapy), or older age (≥60 years of age) at cancer treatment, or compromised cardiac function (eg, borderline low LVEF [50% to 55%], history of MI, moderate or higher valvular heart disease) before or during treatment.

- Treatment with lower-dose anthracycline (eg, doxorubicin <250 mg/m2, epirubicin <600 mg/m2) followed by trastuzumab (sequential therapy).

• Hypersensitivity: Severe administration-related reactions, including hypersensitivity, anaphylaxis, and fatal outcomes, have been reported with pertuzumab/trastuzumab/hyaluronidase. Patients with dyspnea at rest due to complications of advanced malignancy and/or comorbidities may be at increased risk of a severe or fatal adverse reaction. The most common administration-related reactions with pertuzumab/trastuzumab/hyaluronidase were injection-site reactions and injection-site pain. Serious and fatal reactions have been reported with IV trastuzumab products. Closely monitor for systemic hypersensitivity reactions, particularly with the initial dose (monitor for at least 30 minutes after initial dose and 15 minutes after maintenance doses). If a significant administration-related reaction occurs, slow down or pause the injection and initiate appropriate medical management. Permanently discontinue pertuzumab/trastuzumab/hyaluronidase in patients who experience anaphylaxis or severe administration-related reactions. Medications to treat anaphylaxis or hypersensitivity and emergency equipment should be available for immediate use. Consider premedication with an analgesic, antipyretic, or an antihistamine prior to subsequent pertuzumab/trastuzumab/hyaluronidase doses in patients who experienced a reversible grade 1 or 2 hypersensitivity reaction.

• Pulmonary toxicity: [US Boxed Warning]: Pertuzumab/trastuzumab/hyaluronidase can result in serious and fatal pulmonary toxicity. Discontinue pertuzumab/trastuzumab/hyaluronidase for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome (ARDS). Monitor until symptoms completely resolve. Pulmonary toxicity reported with trastuzumab includes dyspnea, interstitial pneumonitis, pulmonary infiltrates, pleural effusions, noncardiogenic pulmonary edema, pulmonary insufficiency and hypoxia, ARDS, and pulmonary fibrosis. Patients with symptomatic intrinsic lung disease or extensive pulmonary tumor involvement, resulting in dyspnea at rest, appear to have more severe pulmonary toxicity.

Concurrent drug therapy issues:

• Chemotherapy: Pertuzumab/trastuzumab/hyaluronidase may increase the incidence of neutropenia when used in combination with myelosuppressive chemotherapy. The incidences of grades 3 and 4 neutropenia and febrile neutropenia were higher in patients receiving IV trastuzumab (compared to those who received chemotherapy alone).

Special populations:

• Pregnancy: [US Boxed Warning]: Exposure to pertuzumab/trastuzumab/hyaluronidase during pregnancy can result in embryo-fetal death and birth defects. Advise patients of these risks and the need for effective contraception.

Dosage form specific issues:

• Do not interchange: Pertuzumab/trastuzumab/hyaluronidase and conventional trastuzumab products, trastuzumab/hyaluronidase, ado-trastuzumab emtansine, fam-trastuzumab deruxtecan, or pertuzumab are not interchangeable. Verify product label prior to reconstitution and administration to prevent medication errors. Dosing and treatment schedules differ between pertuzumab/trastuzumab/hyaluronidase and conventional trastuzumab (Herceptin or trastuzumab biosimilars), trastuzumab/hyaluronidase (Herceptin Hylecta), ado-trastuzumab emtansine (Kadcyla), fam-trastuzumab deruxtecan (Enhertu), or pertuzumab (Perjeta).

Other warnings/precautions:

• HER2 expression: Establish HER2 status prior to treatment with an approved test, either HER2 protein overexpression or gene amplification in tumor specimens. Tests appropriate for breast cancer should be used to assess HER2 status. Unreliable results may occur from improper assay performance, such as use of suboptimally fixed tissue, failure to utilize specified reagents, failure to include appropriate controls for assay validation, or incorrectly following specific assay instructions. Information regarding HER2 diagnostic testing may be found at http://www.fda.gov/CompanionDiagnostics.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Subcutaneous [preservative free]:

Phesgo: Pertuzumab 60 mg, trastuzumab 60 mg, and hyaluronidase-zzxf 2,000 units per mL (10 mL); Pertuzumab 80 mg, trastuzumab 40 mg, and hyaluronidase-zzxf 2,000 units per mL (15 mL)

Generic Equivalent Available: US

No

Pricing: US

Solution (Phesgo Subcutaneous)

60-60-2000MG-MG-U/ML (per mL): $1,047.02

80-40-2000MG-MG-U/ML (per mL): $1,047.06

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Subcutaneous:

Phesgo: 60-60 MG/ML (10 mL); 80-40 MG/ML (15 mL)

Administration: Adult

SubQ: Administer initial (loading) dose SubQ over ~8 minutes; administer maintenance dose over ~5 minutes. For SubQ use only; do not administer by other routes. Doses should be administered by a health care professional. Alternate the injection site between the left and right thigh. Administer new injections on healthy skin at least 2.5 cm from the previous site; do not administer into areas where the skin is red, bruised, tender, or hard, or areas where there are moles or scars. Do not split the dose between 2 syringes or between 2 sites of administration. Do not administer other SubQ medications at the same sites as pertuzumab/trastuzumab/hyaluronidase. To avoid clogging the needle, attach the injection needle to the syringe immediately prior to administration followed by the appropriate volume adjustment.

Observe patients for at least 30 minutes after the initial pertuzumab/trastuzumab/hyaluronidase dose and 15 minutes after each maintenance dose (for signs/symptoms of hypersensitivity and/or administration-related reactions).

If receiving in combination with docetaxel or paclitaxel, administer pertuzumab/trastuzumab/hyaluronidase first, followed by the taxane.

Check label to ensure appropriate product is being administered; pertuzumab/trastuzumab/hyaluronidase, trastuzumab/hyaluronidase, conventional trastuzumab products, ado-trastuzumab emtansine, fam-trastuzumab deruxtecan, and pertuzumab are different products and are NOT interchangeable.

Hazardous Drugs Handling Considerations

Pertuzumab is a hazardous agent (NIOSH 2016 [group 1]).

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).

Use: Labeled Indications

Breast cancer, early (adjuvant or neoadjuvant): Neoadjuvant treatment of HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either >2 cm in diameter or node positive), in combination with chemotherapy, as part of a complete treatment regimen for early breast cancer in adults; adjuvant treatment of HER2-positive early breast cancer, in combination with chemotherapy, in adults at high risk of recurrence.

Breast cancer, metastatic: Treatment of HER2-positive metastatic breast cancer (in combination with docetaxel) in adults who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease.

Medication Safety Issues
Sound-alike/look-alike issues:

Pertuzumab/trastuzumab/hyaluronidase may be confused with ado-trastuzumab emtansine, daratumumab/hyaluronidase, fam-trastuzumab deruxtecan, hyaluronidase, pertuzumab, rituximab/hyaluronidase, trastuzumab (conventional), trastuzumab/hyaluronidase.

High alert medication:

This medication is in a class the Institute for Safe Medication Practices includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Administration issues:

Pertuzumab/trastuzumab/hyaluronidase is for SubQ administration only. Do not substitute trastuzumab (IV), trastuzumab/hyaluronidase (SubQ), or pertuzumab (IV) for pertuzumab/trastuzumab/hyaluronidase (SubQ). Use caution during product selection, preparation, and administration.

Other safety concerns:

Pertuzumab/trastuzumab/hyaluronidase (Phesgo) may be confused with conventional trastuzumab (Herceptin or trastuzumab biosimilars), trastuzumab/hyaluronidase (Herceptin Hylecta), ado-trastuzumab emtansine (Kadcyla), fam-trastuzumab deruxtecan (Enhertu), or pertuzumab (Perjeta); products are not interchangeable.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Alpha-/Beta-Agonists: Hyaluronidase may enhance the vasoconstricting effect of Alpha-/Beta-Agonists. Management: Do not use hyaluronidase to enhance the dispersion or absorption of alpha-/beta-agonists. Use of hyaluronidase for other purposes in patients receiving alpha-/beta-agonists may be considered as clinically indicated. Risk D: Consider therapy modification

Anthracyclines: Trastuzumab may enhance the cardiotoxic effect of Anthracyclines. Management: When possible, patients treated with trastuzumab should avoid anthracycline-based therapy for up to 7 months after stopping trastuzumab. Monitor closely for cardiac dysfunction in patients receiving anthracyclines with trastuzumab. Risk D: Consider therapy modification

Antihistamines: May diminish the therapeutic effect of Hyaluronidase. Risk C: Monitor therapy

Corticosteroids (Systemic): May diminish the therapeutic effect of Hyaluronidase. Management: Patients receiving corticosteroids (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Risk D: Consider therapy modification

Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy

Estrogen Derivatives: May diminish the therapeutic effect of Hyaluronidase. Risk C: Monitor therapy

Local Anesthetics: Hyaluronidase may enhance the adverse/toxic effect of Local Anesthetics. Risk C: Monitor therapy

Phenylephrine (Systemic): Hyaluronidase may enhance the vasoconstricting effect of Phenylephrine (Systemic). Management: Do not use hyaluronidase to enhance the dispersion or absorption of phenylephrine. Use of hyaluronidase for other purposes in patients receiving phenylephrine may be considered as clinically indicated. Risk D: Consider therapy modification

Rozanolixizumab: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy

Salicylates: May diminish the therapeutic effect of Hyaluronidase. Risk C: Monitor therapy

Reproductive Considerations

Evaluate pregnancy status prior to use in females of reproductive potential.

[US Boxed Warning]: Exposure to pertuzumab/trastuzumab/hyaluronidase can result in embryo-fetal death and birth defects. Advise patients of these risks and the need for effective contraception. Exposure within 7 months prior to pregnancy can cause fetal harm.

Females of reproductive potential should use effective contraception during therapy and for 7 months after the last pertuzumab/trastuzumab/hyaluronidase dose.

Refer to the Pertuzumab, Trastuzumab, and Hyaluronidase monographs for additional information.

Pregnancy Considerations

[US Boxed Warning]: Exposure to pertuzumab/trastuzumab/hyaluronidase can result in embryo-fetal death and birth defects. Exposure during therapy or within 7 months prior to pregnancy can cause fetal harm. Monitor for oligohydramnios and conduct gestational age-appropriate fetal testing if exposure occurs.

Refer to the Pertuzumab, Trastuzumab, and Hyaluronidase monographs for additional information.

Data collection to monitor pregnancy and infant outcomes following exposure to pertuzumab/trastuzumab/hyaluronidase is ongoing. Healthcare providers are encouraged to enroll females exposed during pregnancy or within 7 months after the last pertuzumab/trastuzumab/hyaluronidase dose in the Pregnancy Registry (1-888-835-2555).

Breastfeeding Considerations

It is not known if pertuzumab, trastuzumab, or hyaluronidase are present in breast milk.

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. The long elimination half-life of pertuzumab and washout period of trastuzumab (7 months) should also be considered.

Refer to the Pertuzumab, Trastuzumab, and Hyaluronidase monographs for additional information.

Monitoring Parameters

Assess for HER2 overexpression and HER2 gene amplification by validated immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) methodology (pretherapy) specific for breast cancer. Evaluate pregnancy status prior to treatment initiation (in females of reproductive potential). Conduct a comprehensive cardiovascular assessment prior to treatment initiation, including a history and physical examination. Assess left ventricular ejection fraction (LVEF) at baseline and at regular intervals during therapy; if treatment is withheld for significant LVEF dysfunction, monitor LVEF at 3-week intervals. When used for adjuvant therapy, continue to monitor for cardiomyopathy and assess LVEF every 6 months for at least 2 years following completion of treatment. Monitor for signs/symptoms of cardiomyopathy and/or pulmonary toxicity. Monitor closely for at least 30 minutes after initial dose and 15 minutes after maintenance doses for signs/symptoms of hypersensitivity and/or administration-related reactions; if a reaction occurs, monitor carefully until symptoms resolve completely.

Additional cardiovascular monitoring (guideline recommendations): Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (ASCO [Armenian 2017], ESC [Lyon 2022]). Obtain a baseline echocardiography (transthoracic preferred) and repeat every 3 months during treatment (may reduce to every 4 to 6 months if normal and asymptomatic), assess more frequently if clinically indicated and obtain echocardiography within 12 months after completion; in high- and very high-risk patients, assess troponin and natriuretic peptide at baseline and consider assessing every 2 to 3 cycles, and at 3 and 12 months after completion of therapy; in low- and moderate-risk patients, consider troponin and natriuretic peptide at baseline (post-anthracycline), every 3 months and 12 months after completion of therapy (ESC [Lyon 2022]).

The American Society of Clinical Oncology hepatitis B screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends hepatitis B virus (HBV) screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Mechanism of Action

Pertuzumab is a recombinant humanized monoclonal antibody that targets the extracellular HER2 protein dimerization domain. It inhibits HER2 dimerization and blocks HER downstream, signaling halting cell growth and initiating apoptosis. Pertuzumab binds to a different HER2 epitope than trastuzumab so that when pertuzumab is combined with trastuzumab, a more complete inhibition of HER2 signaling occurs (Baselga 2012).

Trastuzumab is a monoclonal antibody that binds to the extracellular domain of HER2; it mediates antibody-dependent cellular cytotoxicity by inhibiting proliferation of cells that overexpress HER2 protein.

Hyaluronidase increases the dispersion and absorption rate of SubQ trastuzumab-containing products by increasing permeability of SubQ tissue through temporary depolymerization of hyaluronan; at the recommended doses, hyaluronidase acts transiently and locally; permeability of the SubQ tissue is restored within 24 to 48 hours.

Pharmacokinetics (Adult Data Unless Noted)

Distribution: SubQ: Pertuzumab: 2.8 L; Trastuzumab: 2.9 L.

Bioavailability: Absolute: SubQ: Pertuzumab: (0.7); Trastuzumab (0.8).

Time to peak: SubQ: Pertuzumab and Trastuzumab: 4 days.

Excretion: Clearance: Linear: SubQ: Pertuzumab: 0.2 L/day; Trastuzumab: 0.1 L/day.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (PR) Puerto Rico: Phesgo;
  • (QA) Qatar: Phesgo
  1. <800> Hazardous Drugs—Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 43-NF 38). Rockville, MD: United States Pharmacopeia Convention; 2020:74-92.
  2. Armenian SH, Lacchetti C, Barac A, et al. Prevention and monitoring of cardiac dysfunction in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2017;35(8):893-911. doi:10.1200/JCO.2016.70.5400 [PubMed 27918725]
  3. Baselga J, Cortés J, Kim SB, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012;366(2):109-119. doi:10.1056/NEJMoa1113216 [PubMed 22149875]
  4. Griggs JJ, Bohlke K, Balaban EP, et al. Appropriate systemic therapy dosing for obese adult patients with cancer: ASCO guideline update. J Clin Oncol. 2021;39(18):2037-2048. doi:10.1200/JCO.21.00471 [PubMed 33939491]
  5. Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]
  6. Lyon AR, López-Fernández T, Couch LS, et al; ESC Scientific Document Group. 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022;43(41):4229-4361. doi:10.1093/eurheartj/ehac244 [PubMed 36017568]
  7. Phesgo (pertuzumab/trastuzumab/hyaluronidase) [prescribing information]. South San Francisco, CA: Genentech Inc; June 2020.
  8. US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. https://www.cdc.gov/niosh/docs/2016-161/. Updated September 2016. Accessed July 2, 2020.
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