trastuzumab

High Alert

HER2-overexpressing metastatic gastric or gastroesophageal adenocarcinoma in patients who have not received prior treatment for metastatic disease (in combination with cisplatin and capecitabine or 5-fluorouracil).
HER2-overexpressing node-positive or node-negative breast cancer (as part of one of the following regimens: doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel; or docetaxel and carboplatin) (as adjuvant therapy).
HER2-overexpressing node-positive or node-negative breast cancer (to be used alone after multi-modality anthracycline-based therapy) (as adjuvant therapy).
HER2-overexpressing metastatic breast cancer (as first-line therapy) (in combination with paclitaxel).
HER2-overexpressing metastatic breast cancer in patients who have already received ≥1 other chemotherapy regimens for metastatic disease (as monotherapy).

Action ⬆ ⬇

A monoclonal antibody that binds to HER2 sites in breast cancer tissue and inhibits proliferation of cells that overexpress HER2 protein.

Therapeutic effects:

Regression of breast, gastric, or gastroesophageal cancer and metastases.

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Unknown.

Metabolism/Excretion: Unknown.

Half-Life: Unknown.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IV	unknown	unknown	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Pre-existing pulmonary conditions;
Hypersensitivity to trastuzumab, Chinese hamster ovary cell proteins, or other components of the product;
Hypersensitivity to benzyl alcohol (use sterile water for injection instead of bacteriostatic water, which accompanies the vial);
Rep: Women of reproductive potential;
Pedi: Safety not established in children;
Geri: Older adults may have risk of cardiotoxicity.

Patients with pre-existing cardiac dysfunction.

Adv. Reactions/Side Effects ⬆ ⬇

CV: ARRHYTHMIAS, HF, hypertension, tachycardia

Derm: rash, acne, herpes simplex

EENT: pharyngitis, rhinitis, sinusitis

F and E: edema

GI: abdominal pain, anorexia, diarrhea, nausea, vomiting

Hemat: anemia, leukopenia

MS: pain, arthralgia, bone pain

Neuro: depression, dizziness, headache, insomnia, neuropathy, paresthesia, peripheral neuritis, weakness

Resp: cough, dyspnea, INTERSTITIAL PNEUMONITIS, PULMONARY EDEMA, PULMONARY FIBROSIS

Misc: chills, fever, infection, flu-like syndrome, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA)

Interactions ⬆ ⬇

Drug-drug:

Concurrent use of anthracyclines, including daunorubicin, doxorubicin, or idarubicin, may ↑ risk of cardiotoxicity.
Paclitaxel may ↑ levels and risk of toxicity.

Route/Dosage ⬆ ⬇

Adjuvant Treatment of Breast Cancer

IV (Adults ): During and following paclitaxel, docetaxel, or docetaxel/carboplatin: 4 mg/kg initially, then 2 mg/kg once weekly during chemotherapy for the first 12 wk (paclitaxel or docetaxel) or 18 wk (docetaxel/carboplatin); 1 wk after the last weekly dose, give 6 mg/kg every 3 wk. Do not exceed treatment duration of 1 yr; As single agent within 3 wk following completion of multi-modality, anthracycline-based chemotherapy regimens: 8 mg/kg initially, then 6 mg/kg every 3 wk. Do not exceed treatment duration of 1 yr.

Metastatic Breast Cancer

IV (Adults ): 4 mg/kg initially, then 2 mg/kg once weekly until disease progression.

Metastatic Gastric Cancer

IV (Adults ): 8 mg/kg initially, then 6 mg/kg every 3 wk until disease progression.

Availability ⬆ ⬇

Lyophilized powder for injection: 150 mg/vial; 420 mg/vial

Assessment ⬆ ⬇

Assess for infusion-related symptoms (chills, fever, nausea, vomiting, pain [in some cases at tumor sites], headache, dizziness, dyspnea, hypotension, rash, and asthenia) following initial infusion. Severe reactions (bronchospasm, anaphylaxis, angioedema, hypoxia, severe hypotension) may occur during or immediately following the initial infusion. May be treated with epinephrine, corticosteroids, diphenhydramine, bronchodilators, and oxygen. Discontinue if dyspnea or severe hypotension occurs and discontinue permanently if severe reaction occurs.
Assess for signs and symptoms of HF (dyspnea, increased cough, paroxysmal nocturnal dyspnea, peripheral edema, S₃ gallop, reduced ejection fraction) prior to and frequently during therapy. Baseline cardiac assessment of history, physical exam, and left ventricular ejection fraction (LVEF) with ECG or multiple gated acquisition scan. Monitor LVEF every 3 mo and at completion of therapy, every 6 mo for 2 yr. Withhold trastuzumab 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. Repeat LVEF measures every 4 wk if dose is withheld. HF associated with trastuzumab may be severe, resulting in cardiac failure, death, and stroke. Trastuzumab should be discontinued upon the development of significant HF.
Monitor patient for signs of pulmonary hypersensitivity reactions (dyspnea, pulmonary infiltrates, pleural effusion, noncardiogenic pulmonary edema, pulmonary insufficiency, hypoxia, acute respiratory distress syndrome). Patients with symptomatic pulmonary disease or extensive lung tumor involvement are at increased risk. Infusion should be discontinued if severe symptoms occur.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.HER2 protein overexpression is used to determine whether treatment with trastuzumab is indicated. HER2 protein overexpression is detected by HercepTest (IHC assay) and PathVysion (FISH assay).
- May cause anemia and leukopenia.

Implementation ⬆ ⬇

Do not confuse trastuzumab with ado-trastuzumab.
Fatalities have occurred with chemotherapeutic agents. Before administering, clarify all ambiguous orders; double check single, daily, and course-of-therapy dose limits; have second practitioner independently double check original order, dose calculations and infusion pump settings.
May be administered in the outpatient setting.
If a dose is missed by ≤1 wk, administer usual maintenance dose as soon as possible. Do not wait until next planned cycle. Administer subsequent maintenance doses 7 days or 21 days later according to the weekly or three-weekly schedules, respectively. If a dose is missed by >1 wk, administer a reloading dose as soon as possible. Administer subsequent maintenance doses 7 days or 21 days later according to weekly or three-weekly schedules, respectively.

IV Administration:

Intermittent Infusion: Reconstitution: Reconstitute each vial with 20 mL of bacteriostatic water for injection, directing the stream of diluent into lyophilized cake of trastuzumab.Concentration: 21 mg/mL. Swirl the vial gently; do not shake. May foam slightly; allow the vial to stand undisturbed for 5 min. Solution should be clear to slightly opalescent and colorless to pale yellow, without particulate matter. Label vial immediately in the area marked "Do not use after" with the date 28 days from the date of reconstitution. Stable for 24 hr at room temperature or 28 days if refrigerated. If patient is allergic to benzyl alcohol, use sterile water for injection for reconstitution. Use immediately and discard any unused portion. Diluent: Calculate to volume required for the desired dose, withdraw, and add it to an infusion containing 250 mL of 0.9% NaCl. Invert bag gently to mix.
Rate: Infuse the 4 mg/kg loading dose over 90 min and the weekly 2 mg/kg dose over 30 min or 6 mg/kg dose over 30–90 min every 3 wk, or 8 mg/kg dose over 90 min if the loading dose was well tolerated. Do not administer as an IV push or bolus.

Patient/Family Teaching ⬆ ⬇

Explain purpose of trastuzumab to patient.
Instruct patient to notify health care professional promptly if new onset or worsening shortness of breath, cough, swelling of the ankles/legs, swelling of the face, palpitations, weight gain of more than 5 pounds in 24 hr, dizziness or loss of consciousness occur. Caution patient to avoid crowds and persons with known infections.
Advise patient not to receive any vaccinations without advice of health care professional.
Rep: May cause fetal harm. Advise females of reproductive potential to notify health care professional immediately if pregnancy is planned or suspected or if breastfeeding. Caution patient to use effective contraception during and for 7 mo following last dose. Monitor infants exposed to trastuzumab for oligohydramnios, pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Advise women who are breastfeeding to discontinue nursing or discontinue trastuzumab. Encourage women who may be exposed during pregnancy to report exposure to the Genentech Adverse Event Line at 1-888-835-2555.

Evaluation/Desired Outcomes ⬆ ⬇

Regression of breast, gastric, or gastroesophageal cancer and metastases.

US Brand Names ⬆ ⬇

Herceptin, Herzuma, Kanjinti, Ogivri, Ontruzant, Trazimera

Code ⬆

NDC Code

50242- Genentech, Inc.
- 50242-132- Herceptin
  - 50242-132-01- 1 VIAL, SINGLE-DOSE in 1 CARTON (50242-132-01) > 15 mL in 1 VIAL, SINGLE-DOSE

50242- Genentech, Inc.
- 50242-132- Herceptin
  - 50242-132-10- 10 VIAL, SINGLE-DOSE in 1 CARTON (50242-132-10) > 15 mL in 1 VIAL, SINGLE-DOSE

50242- Genentech, Inc.
- 50242-134- Herceptin
  - 50242-134-68- 1 KIT in 1 CARTON (50242-134-68) * 20 mL in 1 VIAL, MULTI-DOSE * 20 mL in 1 VIAL

50242- Genentech, Inc.
- 50242-333- Herceptin
  - 50242-333-01- 1 KIT in 1 CARTON (50242-333-01) * 20 mL in 1 VIAL, MULTI-DOSE * 20 mL in 1 VIAL

67457- Mylan Institutional LLC
- 67457-847- OGIVRI
  - 67457-847-44- 1 KIT in 1 CARTON (67457-847-44) * 20 mL in 1 VIAL, MULTI-DOSE (67457-845-50) * 20 mL in 1 VIAL (67457-846-20)

67457- Mylan Institutional LLC
- 67457-991- OGIVRI
  - 67457-991-15- 1 VIAL in 1 CARTON (67457-991-15) > 15 mL in 1 VIAL

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇