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Trastuzumab and hyaluronidase (subcutaneous): Drug information

Trastuzumab and hyaluronidase (subcutaneous): Drug information
(For additional information see "Trastuzumab and hyaluronidase (subcutaneous): Patient drug information")

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

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

Pulmonary toxicity:

Trastuzumab and hyaluronidase administration can result in serious and fatal pulmonary toxicity. Symptoms usually occur during or within 24 hours of trastuzumab and hyaluronidase administration. Discontinue trastuzumab and hyaluronidase for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome. Monitor patients until symptoms completely resolve.

Embryo-fetal toxicity:

Exposure to trastuzumab and hyaluronidase during pregnancy can result in oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Advise patients of these risks and the need for effective contraception.

Brand Names: US
  • Herceptin Hylecta
Brand Names: Canada
  • Herceptin SC
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 (ASCO [Armenian 2017]). Do not substitute trastuzumab/hyaluronidase with IV trastuzumab products (eg, conventional trastuzumab, ado-trastuzumab emtansine, fam-trastuzumab deruxtecan, or pertuzumab/trastuzumab/hyaluronidase). No loading dose is required for trastuzumab/hyaluronidase.

Breast cancer, adjuvant treatment, HER2+

Breast cancer, adjuvant treatment, HER2+: SubQ: Trastuzumab 600 mg/hyaluronidase 10,000 units once every 3 weeks for 52 weeks or until disease progression or unacceptable toxicity, whichever occurs first. Administer in combination with doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel; or in combination with docetaxel and carboplatin; or as a single agent following multi-modality anthracycline based therapy.

Breast cancer, metastatic, HER2+

Breast cancer, metastatic, HER2+: SubQ: Trastuzumab 600 mg/hyaluronidase 10,000 units once every 3 weeks (in combination with paclitaxel or as a single agent following one or more chemotherapy regimens for metastatic disease) until disease progression or unacceptable toxicity.

Breast cancer, metastatic, HER2+, relapsed/refractory disease ± brain metastases

Breast cancer, metastatic, HER2+, relapsed/refractory disease ± brain metastases (off-label combination): SubQ: Trastuzumab 600 mg/hyaluronidase 10,000 units once every 3 weeks (in combination with capecitabine and tucatinib) until disease progression or unacceptable toxicity (Murthy 2020).

Missed doses: If 1 dose is missed, administer the missed dose as soon as possible. The interval between subsequent trastuzumab/hyaluronidase doses should not be <3 weeks.

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

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

Dosing: Hepatic Impairment: Adult

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

Dosing: Adjustment for Toxicity: Adult

Cardiomyopathy:

≥16% absolute left ventricular ejection fraction (LVEF) decrease from pretreatment values or LVEF below institutional limits of normal and ≥10% absolute decrease in LVEF from pretreatment values: Withhold trastuzumab/hyaluronidase dosing for at least 4 weeks. If LVEF returns to normal limits and the absolute decrease from baseline is ≤15% within 4 to 8 weeks, may resume trastuzumab/hyaluronidase.

Persistent (>8 weeks) LVEF decline or if trastuzumab/hyaluronidase dosing is withheld on >3 occasions for cardiomyopathy: Permanently discontinue trastuzumab/hyaluronidase.

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]).

Mild cardiac dysfunction: Continue treatment with close cardiovascular monitoring (ESC [Lyon 2022]).

Moderate cardiac dysfunction: Consider continuing treatment with close cardiovascular monitoring. Initiation of heart failure medications is recommended (ESC [Lyon 2022]).

Severe cardiac 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 (ESC [Lyon 2022]).

Mild cardiac dysfunction: Consider a multidisciplinary approach for decisions regarding treatment interruption versus continuation (ESC [Lyon 2022]).

Moderate or severe cardiac dysfunction: Interrupt treatment; consider a multidisciplinary approach for decisions regarding treatment reinitiation (ESC [Lyon 2022]).

Hypersensitivity:

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

Anaphylaxis or severe hypersensitivity reactions: Permanently discontinue 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. Incidences reported may be with concomitant chemotherapy.

>10%:

Cardiovascular: Edema (12% to 14%), flushing (12% to 14%)

Central nervous system: Fatigue (21% to 46%), peripheral neuropathy (14% to 20%; grade ≥3: <1%), headache (13% to 17%), peripheral sensory neuropathy (11%)

Dermatologic: Alopecia (9% to 63%), skin rash (10% to 26%), nail disease (10% to 14%)

Gastrointestinal: Nausea (15% to 49%), diarrhea (21% to 34%), vomiting (7% to 23%), stomatitis (6% to 21%; grade ≥3: <1%), decreased appetite (20%), abdominal pain (10% to 14%), constipation (9% to 14%), dyspepsia (11%)

Hematologic & oncologic: Neutropenia (6% to 44%; grade ≥3: 4% to 30%), anemia (8% to 12%; grade ≥3: <1%), leukopenia (1% to 11%; grade ≥3: 1% to 5%)

Immunologic: Antibody development (16% to 21%; neutralizing: 6%)

Local: Injection site reaction (10% to 20%), incisional pain (11%)

Neuromuscular & skeletal: Asthenia (12% to 25%), arthralgia (18% to 21%), myalgia (14% to 21%), limb pain (10% to 11%), back pain (8% to 11%)

Respiratory: Upper respiratory tract infection (10% to 24%), cough (11% to 12%), dyspnea (7% to 11%)

Miscellaneous: Radiation injury (skin: 14%), fever (11% to 13%)

1% to 10%:

Cardiovascular: Hypertension (2% to 8%), cardiac arrhythmia (5%), reduced ejection fraction (5%), left ventricular dysfunction (3%), palpitations (2%), tachycardia (2%), cardiac failure (1%)

Central nervous system: Dizziness (6% to 10%), pain (5% to 8%), insomnia (7%), paresthesia (6%)

Dermatologic: Skin discoloration (9%), erythema of skin (7% to 9%), pruritus (6% to 9%), cellulitis (grade ≥3: 1%)

Endocrine & metabolic: Hot flash (10%), menstrual disease (grade ≥3%: 2%), amenorrhea (grade ≥3: 1%)

Gastrointestinal: Dysgeusia (10%)

Genitourinary: Urinary tract infection (6% to 4%)

Hematologic & oncologic: Febrile neutropenia (2% to 6%; grade ≥3: 2% to 6%), granulocytopenia (grade ≥3: 1%)

Hepatic: Abnormal hepatic function tests (6%)

Hypersensitivity: Hypersensitivity reaction (7% to 9%), anaphylaxis (4%)

Infection: Viral infection (5%)

Local: Erythema at injection site (7%), pain at injection site (6%)

Neuromuscular & skeletal: Musculoskeletal pain (7% to 8%), ostealgia (6%)

Respiratory: Epistaxis (6%), nasal discomfort (≤6%), rhinitis (≤6%)

<1%, postmarketing, and/or case reports: Acute respiratory distress syndrome, cardiomyopathy, decreased left ventricular ejection fraction, discomfort at injection site, drug-induced hypersensitivity reaction, hypoxia, interstitial pneumonitis, noncardiogenic pulmonary edema, pleural effusion, pulmonary fibrosis, pulmonary infiltrates, pulmonary toxicity, respiratory insufficiency

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Warnings/Precautions

Concerns related to adverse effects:

• Cardiomyopathy: [US Boxed Warning]: Trastuzumab/hyaluronidase administration can result in subclinical and clinical cardiac failure. The incidence and severity was highest in patients receiving trastuzumab/hyaluronidase with anthracycline-containing chemotherapy regimens. Evaluate left ventricular function in all patients prior to and during treatment with trastuzumab/hyaluronidase. Discontinue trastuzumab/hyaluronidase treatment in patients receiving adjuvant therapy and withhold trastuzumab/hyaluronidase in patients with metastatic disease for clinically significant decrease in left ventricular function. Trastuzumab/hyaluronidase may cause left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death. Trastuzumab/hyaluronidase may also result in an asymptomatic decline in left ventricular ejection fraction (LVEF). Other cardiac adverse effects associated with trastuzumab/hyaluronidase include tachycardia, palpitations, and heart failure. Among patients receiving trastuzumab (as a single agent or in combination with chemotherapy), 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. The incidence of symptomatic myocardial dysfunction for trastuzumab/hyaluronidase and IV trastuzumab was similar in clinical trials. Withhold trastuzumab/hyaluronidase for ≥16% absolute decrease in LVEF from pretreatment values or an LVEF value below institutional limits of normal and ≥10% absolute decrease in LVEF (from pretreatment values). The safety of continuing or resuming trastuzumab/hyaluronidase with trastuzumab-induced left ventricular cardiac dysfunction has not been studied. Patients who receive anthracycline after stopping trastuzumab/hyaluronidase may also be at increased risk of cardiac dysfunction. Conduct thorough cardiac assessment, including history, physical examination, and LVEF assessment (by echocardiogram or MUGA scan). LVEF should be assessed at baseline (immediately prior to trastuzumab/hyaluronidase initiation), every 3 months during and upon completion of trastuzumab/hyaluronidase therapy, every 4 weeks if trastuzumab/hyaluronidase is withheld for significant left ventricular cardiac dysfunction, and every 6 months for at least 2 years following completion of trastuzumab/hyaluronidase treatment when used as a component of adjuvant therapy.

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 myocardial infarction, 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 hypersensitivity reactions, including anaphylaxis, have been reported with 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. Grades 3 or 4 reactions have occurred (rare); permanent discontinuation due to hypersensitivity or anaphylaxis was required in a small number of patients. Serious and fatal reactions have been reported following treatment with IV trastuzumab products. Monitor for systemic hypersensitivity reactions, particularly with the initial dose. Permanently discontinue trastuzumab/hyaluronidase in patients who experience anaphylaxis or severe hypersensitivity 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 trastuzumab/hyaluronidase doses in patients who experienced a reversible grade 1 or 2 hypersensitivity reaction.

• Pulmonary toxicity: [US Boxed Warning]: Trastuzumab/hyaluronidase administration can result in serious and fatal pulmonary toxicity. Symptoms usually occur during or within 24 hours of trastuzumab/hyaluronidase administration. Discontinue trastuzumab/hyaluronidase for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome. Monitor patients until symptoms completely resolve. Pulmonary toxicity includes dyspnea, interstitial pneumonitis, pulmonary infiltrates, pleural effusions, noncardiogenic pulmonary edema, pulmonary insufficiency and hypoxia, acute respiratory distress syndrome, 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: 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 trastuzumab (compared to those who received chemotherapy alone).

Special populations:

• Pregnancy: [US Boxed Warning]: Exposure to trastuzumab/hyaluronidase during pregnancy can result in oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Advise patients of these risks and the need for effective contraception.

Dosage form specific issues:

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

Other warnings/precautions:

• HER2 expression: Establish human epidermal growth receptor 2 (HER2) status prior to treatment with an approved test, either HER2 protein overexpression by validated immunohistochemistry assay or gene amplification by fluorescence in situ hybridization assay. 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 or 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]:

Herceptin Hylecta: Trastuzumab 600 mg and hyaluronidase-oysk 10,000 units per 5 mL (5 mL)

Generic Equivalent Available: US

No

Pricing: US

Solution (Herceptin Hylecta Subcutaneous)

600-10000 mg-unit/5 ml (per mL): $1,122.06

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:

Herceptin SC: 600 mg/5 mL (5 mL)

Administration: Adult

SubQ: Administer subcutaneously over 2 to 5 minutes. For subcutaneous use only. 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 administer other subcutaneous medications at the same sites as trastuzumab/hyaluronidase. To avoid clogging the needle, attach the injection needle to the syringe immediately prior to administration followed by volume adjustment to 5 mL.

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

Use: Labeled Indications

Breast cancer, adjuvant treatment: Adjuvant treatment of HER2 overexpressing node positive or node negative (ER/PR negative or with one high risk feature) in adults with breast cancer, as part of a treatment regimen consisting of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel; as part of a treatment regimen with docetaxel and carboplatin; as a single agent following multi-modality anthracycline-based therapy.

Breast cancer, metastatic: First-line treatment of HER2-overexpressing metastatic breast cancer (in combination with paclitaxel) in adults; single agent treatment of HER2-overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease.

Limitations of use: Select patients for trastuzumab treatment based on an approved companion diagnostic test for tumor specimen for HER2 overexpression or HER2 gene amplification.

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

Herceptin Hylecta may be confused with Herceptin, Rituxan Hycela.

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

High alert medication:

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

Administration issues:

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

Other safety concerns:

Trastuzumab/hyaluronidase (Hylecta) may be confused with conventional trastuzumab (Herceptin or trastuzumab biosimilars), ado-trastuzumab emtansine (Kadcyla), fam-trastuzumab deruxtecan (Enhertu), or pertuzumab/trastuzumab/hyaluronidase (Phesgo); 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

[US Boxed Warning]: Advise patients of the risks of exposure to trastuzumab/hyaluronidase during pregnancy and the need for effective contraception.

Evaluate pregnancy status of females of reproductive potential prior to the initiation of therapy. Females of reproductive potential should use effective contraception during treatment and for at least 7 months after the last trastuzumab/hyaluronidase dose.

Pregnancy Considerations

[US Boxed Warning]: Exposure to trastuzumab/hyaluronidase during pregnancy can result in oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Advise patients of these risks. Adverse fetal events may occur with exposure during pregnancy or if exposure occurs within 7 months prior to conception.

Also refer to individual monographs for additional information.

If exposure to trastuzumab/hyaluronidase occurs during pregnancy, or if a patient becomes pregnant during or within 7 months after treatment, report exposure to Genentech Adverse Events at 1-888-835-2555.

Breastfeeding Considerations

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

Trastuzumab is a humanized immunoglobulin. Because many immunoglobulins are secreted in milk, the manufacturer recommends the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. The 7-month wash out period for trastuzumab should be considered for decisions regarding breastfeeding after treatment is completed.

Also refer to individual 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 (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, every 3 months during treatment, and upon therapy completion, and if treatment is withheld for significant LVEF dysfunction, monitor LVEF at 4-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 closely for signs/symptoms of hypersensitivity (particularly during the first dose) and/or pulmonary toxicity.

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 virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends 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

Trastuzumab is a monoclonal antibody which binds to the extracellular domain of the human epidermal growth factor receptor 2 protein (HER-2); it mediates antibody-dependent cellular cytotoxicity by inhibiting proliferation of cells which overexpress HER-2 protein.

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

Pharmacokinetics (Adult Data Unless Noted)

Distribution: Trastuzumab: SubQ: 2.9 L

Bioavailability: Absolute: Trastuzumab: SubQ: 0.77

Time to peak: Trastuzumab: SubQ: ~3 days (Jackisch 2015)

Excretion: Trastuzumab: SubQ: In most patients, trastuzumab is estimated to reach concentrations of <1 mcg/mL by 7 months following the last trastuzumab/hyaluronidase dose.

Clearance: Linear: Trastuzumab: SubQ: 0.11 L/day

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Body weight: While not clinically relevant, body weight demonstrated a statistically significant influence on pharmacokinetics. The mean steady state AUC of trastuzumab was ~80% higher after trastuzumab/hyaluronidase (compared to IV trastuzumab) in patients <51 kg. The AUC was 20% lower after trastuzumab/hyaluronidase (compared to IV trastuzumab) in patients >90 kg.

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

  • (PR) Puerto Rico: Herceptin hylecta;
  • (QA) Qatar: Herceptin SC
  1. 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]
  2. Gligorov J, Ataseven B, Verrill M, et al. Safety and tolerability of subcutaneous trastuzumab for the adjuvant treatment of human epidermal growth factor receptor 2-positive early breast cancer: SafeHer phase III study's primary analysis of 2573 patients. Eur J Cancer. 2017;82:237-246. [PubMed 28625777]
  3. Herceptin Hylecta (trastuzumab and hyaluronidase) [prescribing information]. South San Francisco, CA: Genentech, Inc; February 2019.
  4. 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. Published online July 27, 2020. doi:10.1200/JCO.20.01757 [PubMed 32716741]
  5. Ismael G, Hegg R, Muehlbauer S, et al. Subcutaneous versus intravenous administration of (neo)adjuvant trastuzumab in patients With HER2-positive, clinical stage I–III breast cancer (HannaH Study): a phase 3, open-label, multicentre, randomised trial. Lancet Oncol. 2012;13(9):869-878. doi: 10.1016/S1470-2045(12)70329-7. [PubMed 22884505]
  6. Jackisch C, Kim SB, Semiglazov V, et al. Subcutaneous versus intravenous formulation of trastuzumab for HER2-positive early breast cancer: updated results from the phase III HannaH study. Ann Oncol. 2015;26(2):320-325. [PubMed 25403587]
  7. 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]
  8. Murthy RK, Loi S, Okines A, et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med. 2020;382(7):597‐609. doi:10.1056/NEJMoa1914609 [PubMed 31825569]
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