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Trastuzumab (intravenous) including biosimilars: Drug information

Trastuzumab (intravenous) including biosimilars: Drug information
(For additional information see "Trastuzumab (intravenous) including biosimilars: Patient drug information")

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

Trastuzumab product administration can result in subclinical and clinical cardiac failure. The incidence and severity was highest in patients receiving trastuzumab with anthracycline-containing chemotherapy regimens.

Evaluate left ventricular function in all patients prior to and during treatment with trastuzumab products. Discontinue trastuzumab treatment in patients receiving adjuvant therapy, and withhold trastuzumab in patients with metastatic disease for clinically significant decrease in left ventricular function.

Infusion reactions and pulmonary toxicity:

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

Pregnancy:

Exposure to trastuzumab products 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;
  • Herzuma;
  • Kanjinti;
  • Ogivri;
  • Ontruzant;
  • Trazimera
Brand Names: Canada
  • Herceptin;
  • Herzuma;
  • Kanjinti;
  • Ogivri;
  • Ontruzant;
  • Trazimera
Pharmacologic Category
  • Antineoplastic Agent, Anti-HER2;
  • Antineoplastic Agent, Monoclonal Antibody
Dosing: Adult

Note: Do NOT substitute conventional trastuzumab products for or with ado-trastuzumab emtansine, fam-trastuzumab deruxtecan, pertuzumab/trastuzumab/hyaluronidase, or trastuzumab/hyaluronidase; products are different and are NOT interchangeable. Herzuma (trastuzumab-pkrb), Kanjinti (trastuzumab-anns), Ogivri (trastuzumab-dkst), Ontruzant (trastuzumab-dttb), and Trazimera (trastuzumab-qyyp) are approved as biosimilars to Herceptin. In Canada, Herzuma, Kanjinti, Ogivri, Ontruzant, and Trazimera are biosimilars to Herceptin (trastuzumab).

Breast cancer, adjuvant treatment, HER2+

Breast cancer, adjuvant treatment, HER2+: Note: Extending adjuvant treatment beyond 1 year is not recommended.

With concurrent paclitaxel or docetaxel:

Initial loading dose: IV: 4 mg/kg infused over 90 minutes, followed by

Maintenance dose: IV: 2 mg/kg infused over 30 minutes weekly for total of 12 weeks, followed 1 week later (when concurrent chemotherapy completed) by 6 mg/kg infused over 30 to 90 minutes every 3 weeks for total therapy duration of 52 weeks.

With concurrent docetaxel/carboplatin:

Initial loading dose: IV: 4 mg/kg infused over 90 minutes, followed by

Maintenance dose: IV: 2 mg/kg infused over 30 minutes weekly for total of 18 weeks, followed 1 week later (when concurrent chemotherapy completed) by 6 mg/kg infused over 30 to 90 minutes every 3 weeks for total therapy duration of 52 weeks.

Following completion of multimodality anthracycline-based chemotherapy:

Initial loading dose: IV: 8 mg/kg infused over 90 minutes, followed by

Maintenance dose: IV: 6 mg/kg infused over 30 to 90 minutes every 3 weeks for total therapy duration of 52 weeks.

Duration of therapy: The standard duration of adjuvant trastuzumab therapy in early breast cancer is 1 year (52 weeks); however, for patients unable to tolerate 1 year of trastuzumab, a noninferiority study comparing 12 months versus 6 months of adjuvant trastuzumab therapy in early breast cancer suggests disease-free survival may not be inferior with a 6-month duration (Earl 2018).

Breast cancer, early stage, locally advanced, or inflammatory, neoadjuvant treatment, HER2+

Breast cancer, early stage, locally advanced, or inflammatory, neoadjuvant treatment, HER2+ (off-label use): Trastuzumab, pertuzumab, and docetaxel (in patients with operable disease who had received no prior chemotherapy): IV: Initial: 8 mg/kg (cycle 1) followed by 6 mg/kg every 3 weeks for a total of 4 neoadjuvant cycles; postoperatively, administer 3 cycles of adjuvant FEC [fluorouracil, epirubicin, and cyclophosphamide] chemotherapy and continue trastuzumab to complete 1 year of treatment (Gianni 2012).

Breast cancer, metastatic, HER2+

Breast cancer, metastatic, HER2+:

Either as a single agent or in combination with paclitaxel:

Initial loading dose: IV: 4 mg/kg infused over 90 minutes, followed by

Maintenance dose: IV: 2 mg/kg infused over 30 minutes weekly until disease progression.

Off-label combinations: Note: There are multiple trastuzumab-containing regimens for the treatment of HER2+ metastatic breast cancer; commonly used regimens are listed below:

Trastuzumab, pertuzumab, and docetaxel (in patients with no prior anti-HER2 therapy or chemotherapy to treat metastatic disease): IV: Initial: 8 mg/kg followed by a maintenance dose of 6 mg/kg every 3 weeks until disease progression or unacceptable toxicity (Baselga 2012).

Trastuzumab, pertuzumab, and weekly paclitaxel: IV: Initial: 8 mg/kg followed by a maintenance dose of 6 mg/kg every 3 weeks until disease progression (Dang 2015).

Trastuzumab, tucatinib, and capecitabine (in patients with relapsed/refractory disease ± brain metastases): IV: Initial: 8 mg/kg followed by a maintenance dose of 6 mg/kg every 3 weeks (in combination with tucatinib and capecitabine); continue until disease progression or unacceptable toxicity (Murthy 2020).

Trastuzumab and lapatinib (in patients with progression on prior trastuzumab-containing therapy): IV: Initial: 4 mg/kg followed by a maintenance dose of 2 mg/kg every week (Blackwell 2010; Blackwell 2012).

Trastuzumab and an aromatase inhibitor: IV: Initial: 4 mg/kg followed by a maintenance dose of 2 mg/kg every week (in combination with anastrozole); continue until disease progression (Kaufman 2009).

Other trastuzumab combinations: IV: Initial: 8 mg/kg followed by a maintenance dose of 6 mg/kg every 3 weeks until disease progression or unacceptable toxicity (in combination with docetaxel or vinorelbine) (Andersson 2011) or 4 mg/kg loading dose followed by a maintenance dose of 2 mg/kg weekly until disease progression (in combination with docetaxel) (Marty 2005).

Colorectal cancer, metastatic, HER2+, with progression on conventional chemotherapy

Colorectal cancer, metastatic, HER2+, with progression on conventional chemotherapy (off-label use): IV: Initial: 4 mg/kg followed by a maintenance dose of 2 mg/kg every week (in combination with lapatinib) until disease progression or unacceptable toxicity (Sartore-Bianchi 2016).

Endometrial cancer, uterine serous, advanced or recurrent, HER2+

Endometrial cancer, uterine serous, advanced or recurrent, HER2+ (off-label use): IV: Initial: 8 mg/kg (cycle 1) followed by a maintenance dose of 6 mg/kg every 3 weeks (in combination with carboplatin and paclitaxel for ~6 cycles), followed by trastuzumab maintenance of 6 mg/kg every 3 weeks until disease progression or unacceptable toxicity (Fader 2018).

Gastric cancer, metastatic, HER2+

Gastric cancer, metastatic, HER2+:

In combination with cisplatin and either capecitabine or fluorouracil for 6 cycles followed by trastuzumab monotherapy (Bang 2010):

Initial loading dose: IV: 8 mg/kg infused over 90 minutes, followed by

Maintenance dose: IV: 6 mg/kg infused over 30 to 90 minutes every 3 weeks until disease progression.

Off-label dosing/combinations:

In combination with mFOLFOX: IV: 6 mg/kg on day 1 of cycle 1, followed by 4 mg/kg on day 1 every 2 weeks (in combination with fluorouracil, leucovorin, and oxaliplatin; modified FOLFOX regimen) until disease progression or unacceptable toxicity (Soulare 2015).

In combination with XELOX: IV: 8 mg/kg on day 1 of cycle 1, followed by 6 mg/kg on day 1 every 3 weeks (in combination with capecitabine and oxaliplatin; XELOX regimen) for up to 6 cycles; after 6 cycles of combination chemotherapy, trastuzumab ± capecitabine were continued until disease progression or unacceptable toxicity (Gong 2016; Rivera 2019).

Missed doses: A trastuzumab dose delay >1 week would require ~6 weeks to return to steady state range; if a maintenance dose is missed by >1 week, a reloading dose is required (Quartino 2018). If a trastuzumab dose is missed by 1 week or less, the usual maintenance dose (2 mg/kg weekly schedule or 6 mg/kg every 3 week schedule) should be administered as soon as possible (do not wait until the next planned cycle) and subsequent maintenance doses should be administered 7 or 21 days later (based on patient's maintenance dose/schedule); if a dose is missed by >1 week, then a re-loading dose (4 mg/kg if patient receives trastuzumab weekly; 8 mg/kg if on an every-3-week schedule) should be administered (over 90 minutes) as soon as possible, followed by the usual maintenance dose administered 7 or 21 days later (based on patient's maintenance dose/schedule).

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 to 90 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling, although no clinically significant pharmacokinetic differences have been observed.

CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

End-stage renal disease (ESRD) (with or without hemodialysis): 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: Older Adult

Refer to adult dosing.

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 (ASCO [Griggs 2021]).

Dosing: Adjustment for Toxicity: Adult

Cardiotoxicity:

Asymptomatic heart disease: Consider initiating treatment with heart failure medications (eg, angiotensin-converting enzyme inhibitors, beta-blockers) in patients with asymptomatic (stage B) heart disease (ASCO [Armenian 2017]).

LVEF ≥16% decrease from baseline or LVEF below normal limits and ≥10% decrease from baseline: Withhold treatment for at least 4 weeks and repeat LVEF every 4 weeks. May resume trastuzumab treatment if LVEF returns to normal limits within 4 to 8 weeks and remains at ≤15% decrease from baseline value. Discontinue permanently for persistent (>8 weeks) LVEF decline or for >3 incidents of treatment interruptions for cardiomyopathy.

Hypersensitivity/infusion-related events:

Anaphylaxis or angioedema: Discontinue trastuzumab.

Mild-moderate infusion reactions: Decrease trastuzumab infusion rate.

Dyspnea or clinically significant hypotension: Interrupt trastuzumab infusion and manage as appropriate (monitor until symptoms resolve).

Severe or life-threatening infusion reactions: Discontinue trastuzumab.

Pulmonary toxicity:

Interstitial pneumonitis or acute respiratory distress syndrome: Discontinue trastuzumab.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution Reconstituted, Intravenous:

Herceptin: 440 mg (1 ea [DSC]) [contains benzyl alcohol, mouse (murine) and/or hamster protein]

Herzuma: Trastuzumab-pkrb 150 mg (1 ea); Trastuzumab-pkrb 420 mg (1 ea)

Herzuma: Trastuzumab-pkrb 420 mg (1 ea) [contains benzyl alcohol]

Ogivri: Trastuzumab-dkst 420 mg (1 ea) [contains polyethylene glycol]

Ontruzant: Trastuzumab-dttb 420 mg (1 ea) [contains benzyl alcohol]

Solution Reconstituted, Intravenous [preservative free]:

Herceptin: 150 mg (1 ea)

Kanjinti: Trastuzumab-anns 150 mg (1 ea); Trastuzumab-anns 420 mg (1 ea)

Ogivri: Trastuzumab-dkst 150 mg (1 ea); Trastuzumab-dkst 420 mg (1 ea) [contains polyethylene glycol]

Ontruzant: Trastuzumab-dttb 150 mg (1 ea)

Trazimera: Trastuzumab-qyyp 150 mg (1 ea); Trastuzumab-qyyp 420 mg (1 ea)

Generic Equivalent Available: US

No

Dosage Forms: Canada

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

Solution Reconstituted, Intravenous:

Herceptin: 440 mg (1 ea) [contains benzyl alcohol]

Herzuma: 150 mg (1 ea)

Herzuma: 440 mg (1 ea) [contains benzyl alcohol]

Kanjinti: 150 mg (1 ea); 420 mg (1 ea)

Ogivri: 150 mg (1 ea); 440 mg (1 ea) [contains polyethylene glycol (macrogol)]

Ontruzant: 150 mg (1 ea)

Ontruzant: 440 mg (1 ea) [contains benzyl alcohol]

Trazimera: 150 mg (1 ea)

Trazimera: 440 mg (1 ea) [contains benzyl alcohol]

Administration: Adult

IV: Administer by IV infusion; loading doses are infused over 90 minutes; maintenance doses may be infused over 30 minutes if tolerated. Do not administer with D5W. Do not administer IV push or by rapid bolus. Do not mix with any other medications.

Observe patients closely during the infusion for fever, chills, or other infusion-related symptoms. Treatment with acetaminophen, diphenhydramine, and/or meperidine is usually effective for managing infusion-related events.

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

Use: Labeled Indications

Breast cancer, adjuvant treatment: Treatment (adjuvant) of HER2-overexpressing node positive or node negative (estrogen receptor/progesterone receptor negative or with 1 high-risk feature) 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; or as a single agent following multimodality anthracycline-based therapy.

Breast cancer, metastatic: First-line treatment of HER2-overexpressing metastatic breast cancer (in combination with paclitaxel); single agent treatment of HER2-overexpressing breast cancer in patients who have received 1 or more chemotherapy regimens for metastatic disease.

Gastric cancer, metastatic: Treatment of HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma (in combination with cisplatin and either capecitabine or 5-fluorouracil) in patients who have not received prior treatment for metastatic disease.

Limitations of use: Patients should be selected for breast and gastric cancer therapy based on an approved companion diagnostic test for tumor specimen for HER2 overexpression or HER2 gene amplification. Due to differences in disease histopathology (eg, incomplete membrane staining, more frequent heterogeneous HER2 expression in gastric cancer), tests appropriate for the specific tumor type (breast or gastric) should be used to assess HER2 status.

Note: Herzuma (trastuzumab-pkrb), Kanjinti (trastuzumab-anns), Ogivri (trastuzumab-dkst), Ontruzant (trastuzumab-dttb), and Trazimera (trastuzumab-qyyp) are approved as biosimilars to Herceptin (trastuzumab). In Canada, Herzuma, Kanjinti, Ogivri, Ontruzant, and Trazimera are biosimilars to Herceptin (trastuzumab).

Use: Off-Label: Adult

Breast cancer, locally advanced, inflammatory or early, HER2 positive (neoadjuvant treatment); Breast cancer, metastatic, HER2-positive (in combination with pertuzumab and docetaxel) in patients who have not received prior anti-HER2 therapy or chemotherapy to treat metastatic disease; Breast cancer, metastatic, HER2-positive (in combination with pertuzumab and weekly paclitaxel); Breast cancer, metastatic, HER2-positive (in combination with either docetaxel or vinorelbine); Breast cancer, metastatic, HER2-positive, hormone receptor-positive (in combination with an aromatase inhibitor); Breast cancer, metastatic, HER2-positive (in combination with lapatinib) which had progressed on prior trastuzumab containing therapy; Colorectal cancer, metastatic, HER2 overexpressing, with progression on conventional chemotherapy; Endometrial cancer (uterine serous), advanced or recurrent, HER2-positive

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

Herceptin may be confused with Herceptin Hylecta.

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

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.

Other safety concerns:

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

Conventional trastuzumab (Herceptin or trastuzumab biosimilars) may be confused with the Canadian product trastuzumab emtansine (Kadcyla); products are not interchangeable.

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

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Percentages reported with single-agent therapy.

>10%:

Cardiovascular: Decreased left ventricular ejection fraction (4% to 22%)

Dermatologic: Skin rash (4% to 18%)

Gastrointestinal: Abdominal pain (22%; upper abdominal pain: 2%), anorexia (14%), diarrhea (7% to 25%), nausea (6% to 33%), vomiting (4% to 23%)

Infection: Infection (20%)

Nervous system: Chills (5% to 32%), dizziness (4% to 13%), headache (10% to 26%), insomnia (14%), pain (47%)

Neuromuscular & skeletal: Asthenia (5% to 42%), back pain (5% to 22%)

Respiratory: Cough (5% to 26%), dyspnea (3% to 22%), pharyngitis (12%), rhinitis (2% to 14%)

Miscellaneous: Fever (6% to 36%), infusion related reaction (21% to 40%; severe infusion related reaction: 1%)

1% to 10%:

Cardiovascular: Cardiac arrhythmia (3%), cardiac failure (≤7%), edema (8%), hypertension (4%), palpitations (3%), peripheral edema (5% to 10%), tachycardia (5%)

Dermatologic: Acne vulgaris (2%), nail disease (2%), pruritus (2%)

Gastrointestinal: Constipation (2%), dyspepsia (2%)

Genitourinary: Urinary tract infection (3% to 5%)

Hematologic & oncologic: Anemia (4%; grade 3: <1%), leukopenia (3%)

Hypersensitivity: Hypersensitivity reaction (≤3%)

Infection: Influenza (4%), herpes simplex infection (2%)

Nervous system: Depression (6%), neuropathy (1%), paresthesia (2% to 9%), peripheral neuritis (2%)

Neuromuscular & skeletal: Arthralgia (6% to 8%), muscle spasm (3%), myalgia (4%), ostealgia (3% to 7%)

Respiratory: Epistaxis (2%), flu-like symptoms (2% to 10%), nasopharyngitis (8%), pharyngolaryngeal pain (2%), sinusitis (2% to 9%), upper respiratory tract infection (3%)

Miscellaneous: Accidental injury (6%)

<1%:

Cardiovascular: Cardiac disorder, ventricular dysfunction

Endocrine & metabolic: Thyroiditis (autoimmune)

Immunologic: Antibody development

Respiratory: Interstitial pneumonitis, pneumonitis, pulmonary hypertension, pulmonary infiltrates, respiratory failure

Frequency not defined:

Cardiovascular: Cardiomyopathy

Hematologic & oncologic: Neutropenia

Respiratory: Pulmonary fibrosis

Postmarketing:

Dermatologic: Madarosis of eyebrow (Agirgol 2020)

Genitourinary: Glomerulopathy, nephrotic syndrome, oligohydramnios

Hematologic & oncologic: Immune thrombocytopenia, tumor lysis syndrome

Hypersensitivity: Anaphylaxis, angioedema

Ophthalmic: Blurred vision (Ho 2013), conjunctivitis (Ho 2013), corneal disease (neovascularization inhibition) (Ho 2013), dry eye syndrome (Ho 2013), lacrimation (irritation related) (Ho 2013), maculopathy (bilateral ischemic) (Saleh 2011), vision loss (Saleh 2011)

Renal: Focal segmental glomerulosclerosis, glomerulonephritis (membranous, focal and fibrillary)

Respiratory: Acute respiratory distress syndrome, bronchospasm, hypoxia, non-cardiogenic pulmonary edema, pleural effusion

Contraindications

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

Canadian labeling: Known hypersensitivity to trastuzumab, Chinese hamster ovary cell proteins, or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Cardiomyopathy: Trastuzumab products are associated with symptomatic and asymptomatic reductions in left ventricular ejection fraction (LVEF) and heart failure; the incidence is highest in patients receiving trastuzumab with an anthracycline-containing chemotherapy regimen. Extreme caution should be used in patients with pre-existing cardiac disease or dysfunction. Prior or concurrent exposure to anthracyclines or radiation therapy significantly increases the risk of cardiomyopathy; other potential risk factors include advanced age, high or low body mass index, smoking, diabetes, hypertension, and hyper-/hypothyroidism. Patients who receive anthracyclines after completion or discontinuation of trastuzumab are at increased risk of cardiac dysfunction (anthracyclines should be avoided for at least 7 months after the last trastuzumab dose, and then monitor cardiac function closely if anthracyclines are used. Cardiomyopathy due to trastuzumab is generally reversible over a period of 1 to 3 months after discontinuation. Long-term (8 years) follow-up in the adjuvant setting (trastuzumab for 1 or 2 years administered sequentially following chemotherapy and radiation therapy) has demonstrated a low incidence of cardiac events, which were generally reversible in most patients (de Azambuja 2014). Trastuzumab is also associated with arrhythmias, hypertension, mural thrombus formation, stroke, and even cardiac death.

The American Society of Clinical Oncology (ASCO) has developed guidelines for prevention and monitoring of cardiac dysfunction in adult survivors of cancer (ASCO [Armenian 2017]). According to the guidelines, 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).

• Infusion reactions: Infusion reactions (including fatalities) have been associated with trastuzumab products. Most reactions occur during or within 24 hours of the first infusion. Infusion reactions may consist of fever and chills, and may also include nausea, vomiting, pain, headache, dizziness, dyspnea, hypotension, rash, and weakness. Re-treatment of patients who experienced severe hypersensitivity reactions has been attempted (with premedication). Some patients tolerated re-treatment, while others experienced a second severe reaction.

• Pulmonary toxicity: Trastuzumab may cause serious pulmonary toxicity (dyspnea, hypoxia, interstitial pneumonitis, pulmonary infiltrates, pleural effusion, noncardiogenic pulmonary edema, pulmonary insufficiency, acute respiratory distress syndrome, and/or pulmonary fibrosis). Use caution in patients with pre-existing pulmonary disease or patients with extensive pulmonary tumor involvement; these patient populations may have more severe toxicity. Pulmonary events may occur during or within 24 hours of administration; delayed reactions have occurred.

• Renal toxicity: Rare cases of nephrotic syndrome with evidence of glomerulopathy have been reported, with an onset of 4 to 18 months from trastuzumab initiation; complications may include volume overload and heart failure. The incidence of renal impairment was increased in metastatic gastric cancer patients when trastuzumab is added to chemotherapy.

Concurrent drug therapy issues:

• Chemotherapy: When used in combination with myelosuppressive chemotherapy, trastuzumab may increase the incidence of neutropenia (moderate-to-severe) and febrile neutropenia. The incidence of anemia may be higher when trastuzumab is added to chemotherapy.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some diluent may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP 1997; CDC 1982); some data suggest that benzoate displaces bilirubin from protein-binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer's labeling.

• Do not interchange: Conventional trastuzumab products and ado-trastuzumab emtansine or trastuzumab/hyaluronidase are not interchangeable. Verify product label prior to reconstitution and administration to prevent medication errors. Dosing and treatment schedules between conventional trastuzumab (Herceptin and trastuzumab biosimilars) and ado-trastuzumab emtansine (Kadcyla), fam-trastuzumab deruxtecan (Enhertu), pertuzumab/trastuzumab/hyaluronidase (Phesgo), or trastuzumab/hyaluronidase are different; confusion between the products may potentially cause harm to the patient.

Other warnings/precautions:

• HER2 expression: Establish 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. Due to differences in disease histopathology (eg, incomplete membrane staining and more frequent heterogeneous HER2 expression in gastric cancer), tests appropriate for the specific tumor type (breast or gastric) 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.

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.

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

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

Reproductive Considerations

[US Boxed Warning]: Advise patients of the risks of trastuzumab exposure in pregnancy and the need for effective contraception. Verify pregnancy status prior to initiation of therapy in patients who could become pregnant. Patients who could become pregnant should use effective contraception during treatment and for at least 7 months after the last trastuzumab dose.

Pregnancy Considerations

Trastuzumab inhibits human epidermal growth receptor 2 (HER2) protein, which has a role in embryonic development. [US Boxed Warning]: Trastuzumab exposure during pregnancy may result in oligohydramnios and oligohydramnios sequence (pulmonary hypoplasia, skeletal malformations, and neonatal death). Advise patients of these risks. Oligohydramnios (reversible in some cases) has been reported with trastuzumab use alone or with combination chemotherapy. Monitor for oligohydramnios if trastuzumab exposure occurs during pregnancy or within 7 months prior to conception; conduct appropriate fetal testing if oligohydramnios occurs.

Herceptin: If Herceptin is administered 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.

European Society for Medical Oncology guidelines for cancer during pregnancy recommend delaying treatment with trastuzumab (and other HER2-targeted agents) until after delivery in pregnant patients with HER2-positive disease (ESMO [Peccatori 2013]).

Breastfeeding Considerations

It is not known if trastuzumab is present in human milk.

Because many immunoglobulins are secreted in milk, and the potential for serious adverse reactions in the breastfed infant exists, the decision to discontinue trastuzumab or discontinue breastfeeding during treatment should take into account the 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.

Monitoring Parameters

Assessment for HER2 overexpression and HER2 gene amplification by validated immunohistochemistry or fluorescence in situ hybridization methodology (pretherapy); test should be specific for cancer type (breast vs gastric cancer). Evaluate pregnancy status prior to treatment (in patients who could become pregnant). Conduct a comprehensive cardiovascular assessment prior to treatment initiation, including a history and physical examination. Assess left ventricular ejection fraction (by ECG or MUGA scan) at baseline (immediately prior to trastuzumab initiation), every 3 months during trastuzumab therapy, every 4 weeks if trastuzumab is withheld for significant left ventricular cardiac dysfunction, and every 6 months for at least 2 years following completion of adjuvant trastuzumab therapy. Monitor vital signs during infusion; monitor for hypersensitivity or infusion reaction; if a reaction occurs, monitor carefully until symptoms resolve completely. Monitor for signs/symptoms of cardiac dysfunction or pulmonary toxicity. If pregnancy inadvertently occurs during treatment, monitor amniotic fluid volume.

Additional cardiovascular monitoring (ASCO [Armenian 2017]): Comprehensive assessment in patients with cancer that includes a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (modifiable risk factors such as smoking, hypertension, diabetes, dyslipidemia, and obesity should be actively managed before initiating potentially cardiotoxic therapies). Obtain an echocardiogram prior to initiating potentially cardiotoxic therapies. In patients who develop signs/symptoms of cardiac dysfunction during therapy, in addition to the above left ventricular ejection fraction (LVEF) monitoring recommendations, an echocardiogram is recommended for diagnostic workup; if echocardiogram is not available or feasible, a cardiac MRI (preferred) or MUGA scan may be utilized; obtain serum cardiac biomarkers (refer to a cardiologist if indicated). Routine echocardiographic surveillance may be utilized in patients with metastatic breast cancer receiving trastuzumab indefinitely.

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

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.

Pharmacokinetics

Excretion: In most patients, trastuzumab concentrations will decrease to ~3% (~97% washout) by 7 months following discontinuation.

Clearance: Every week dosing: 0.201 to 0.244 L/day; Every 3 week dosing: 0.173 to 0.337 L/day (Quartino 2018).

Pricing: US

Solution (reconstituted) (Herceptin Intravenous)

150 mg (per each): $1,870.10

Solution (reconstituted) (Herzuma Intravenous)

150 mg (per each): $1,683.00

420 mg (per each): $4,712.40

Solution (reconstituted) (Kanjinti Intravenous)

150 mg (per each): $1,632.08

420 mg (per each): $4,569.82

Solution (reconstituted) (Ogivri Intravenous)

150 mg (per each): $1,589.59

420 mg (per each): $4,436.71

Solution (reconstituted) (Ontruzant Intravenous)

150 mg (per each): $1,589.59

420 mg (per each): $4,450.85

Solution (reconstituted) (Trazimera Intravenous)

150 mg (per each): $1,453.32

420 mg (per each): $4,069.30

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.

Brand Names: International
  • Herceptin (AE, AR, AT, AU, BB, BE, BF, BG, BH, BJ, BM, BR, BS, BZ, CH, CI, CL, CN, CO, CR, CU, CY, CZ, DE, DK, DO, EC, EE, ES, ET, FI, FR, GB, GH, GM, GN, GR, GT, GY, HK, HN, HR, HU, ID, IE, IL, IN, IS, IT, JM, JO, JP, KE, KR, LB, LK, LR, LT, LU, LV, MA, ML, MR, MT, MU, MW, MX, MY, NE, NG, NI, NL, NO, NZ, PA, PE, PH, PL, PT, PY, QA, RO, RU, SA, SC, SD, SE, SG, SI, SK, SL, SN, SR, SV, TH, TN, TR, TT, TW, TZ, UA, UG, UY, VE, VN, ZA, ZM, ZW);
  • Herclon (HK);
  • Herticad (LK);
  • Herzuma (AT, BE, CZ, DE, DK, EE, ES, FI, FR, GB, HR, HU, IE, KR, LT, LU, LV, NL, PL, PT, RO, TW);
  • Kadcyla (AU, CH, FI, GR, NZ, RU, SE);
  • Kadjinti (FI);
  • Kanjinti (DE, EE, ES, GB, HR, IE, IS, LT, LV, NO, PL, SE, SK);
  • Ogivri (DE, EE, ES, HR, LT, LV, PL, SK, TW, ZW);
  • Ontruzant (AT, AU, CZ, DE, DK, EE, ES, FR, GB, HR, HU, LT, LV, NL, PL, PT, SE, SK);
  • Trastunix (BD);
  • Trazimera (AT, AU, CZ, DE, DK, EE, ES, FR, GB, HR, HU, IS, LB, LT, LV, NL, NO, NZ, PT, SK)


For country code abbreviations (show table)
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  31. Herzuma (trastuzumab) [product monograph]. Toronto, Ontario, Canada: Teva Canada Limited; April 2021.
  32. Herzuma (trastuzumab-pkrb) [prescribing information]. North Wales, PA: Teva Pharmaceuticals USA Inc; May 2019.
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  37. Kanjinti (trastuzumab-anns) [prescribing information]. Thousand Oaks, CA: Amgen Inc; October 2019.
  38. Kanjinti (trastuzumab) [product monograph]. Mississauga, Ontario, Canada: Amgen Canada Inc; August 2021.
  39. Kaufman B, Mackey JR, Clemens MR, et al. Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol. 2009;27(33):5529-5537. doi: 10.1200/JCO.2008.20.6847. [PubMed 19786670]
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  45. Ogivri (trastuzumab) [product monograph]. Etobicoke, Ontario, Canada: BGP Pharma ULC; December 2021.
  46. Ogivri (trastuzumab-dkst) [prescribing information]. Morgantown, WV: Mylan Pharmaceuticals Inc; February 2021.
  47. Ontruzant (trastuzumab-dttb) [prescribing information]. Jersey City, NJ: Organon LLC; June 2021.
  48. Ontruzant (trastuzumab) [product monograph]. Kirkland, Quebec, Canada: Organon Canada; January 2022.
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