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Trastuzumab

Pronouncation: (tras-TOOZ-oo-mab)
Class: Monoclonal antibody

Trade Names:
Herceptin
- Powder for injection, lyophilized 440 mg

Pharmacology

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As a treatment for...	Avg User Ratings [?]
Breast Cancer	0 comments Rate it!	9.0
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Recombinant DNA-derived humanized monoclonal antibody that selectively binds with high affinity to the extracellular domain of human epidermal growth factor receptor 2 (HER2). It inhibits the proliferation of human tumor cells that overexpress HER2 and mediates antibody-dependent cellular cytotoxicity.

Pharmacokinetics

Absorption

At a dose of 500 mg, trastuzumab C _max is 377 mcg/mL. Between wk 16 and 32, serum concentrations reached steady state with C _min 79 mcg/mL and C _max 123 mcg/mL.

Distribution

Vd is 44 mL/kg.

Elimination

Trastuzumab kinetics are dose-dependent. Mean t _½ increases and Cl decreases with increasing dose level. Mean t _½ is 5.8 days (range, 1 to 32 days).

Indications and Usage

Treatment of patients with metastatic breast cancer in which tumors overexpress HER2 protein and who have received treatment with 1 or more chemotherapy regimens; adjuvant treatment as part of a regimen containing doxorubicin, cyclophosphamide, and paclitaxel for patients with HER2-overexpressing, node-positive breast cancer; in combination with paclitaxel for the treatment of metastatic breast cancer in patients whose tumors overexpress the HER2 protein and who have not received chemotherapy treatment.

Contraindications

None well documented.

Dosage and Administration

Breast Cancer
Adults

IV The recommended initial loading dose is 4 mg/kg infused over 90 min. The recommended weekly maintenance dose is 2 mg/kg and can be infused over 30 min if initial loading dose was tolerated. Trastuzumab may be administered in an outpatient setting. Do not administer as an IV push or bolus.

Metastatic Breast Cancer
Adults

IV Administer until tumor progression.

Adjuvant Treatment of Breast Cancer
Adults

IV Do not coadminister trastuzumab with doxorubicin and cyclophosphamide. Following completion of doxorubicin and cyclophosphamide treatment, administer trastuzumab weekly for 52 wk. During the first 12 wk, coadminister trastuzumab with paclitaxel.

Dose Modification
Adults

IV Infusion reactions — Decrease the rate of infusion for mild or moderate infusion reactions. Interrupt the infusion in patients with dyspnea or clinically important hypotension. Consider discontinuation of trastuzumab for severe and life-threatening infusion reactions.

Adults

IV Cardiomyopathy — Assess left ventricular ejection fraction (LVEF) prior to initiation of trastuzumab and frequently during treatment. Withhold trastuzumab for at least 4 wk and repeat LVEF assessment every 4 wk for either of the following: 1) a 16% or greater absolute decrease in LVEF from pretreatment values; or 2) LVEF below institutional limits of normal and a 10% or more absolute decrease in LVEF from pretreatment levels. Trastuzumab treatment may be resumed if the LVEF returns to normal limits within 4 to 8 wk and the absolute decrease from baseline is 15% or less. Permanently discontinue trastuzumab treatment if LVEF declines for more than 8 wk or if trastuzumab dosing is suspended on more than 3 occasions for cardiomyopathy.

General Advice

For IV infusion only. Not for intradermal, subcutaneous, IM, IV push, IV bolus, or intra-arterial administration.
Dose is usually administered once every 7 days following initial loading dose.
The solution should be free of visible particulates, clear to slightly opalescent, and colorless to pale yellow.
Do not mix or dilute with other drugs, or administer through an IV line containing dextrose solutions.

Storage/Stability

Store vials of powder for injection in refrigerator (36° to 46°F). Trastuzumab reconstituted with supplied bacteriostatic water for injection is stable for 28 days after reconstitution if stored in refrigerator. Do not freeze. Discard any remaining reconstituted solution after 28 days. If trastuzumab is reconstituted with sterile water for injection, use the solution immediately and discard any unused portion. Trastuzumab for infusion diluted in polyvinylchloride or polyethylene bags containing sodium chloride 0.9% injection may be stored in refrigerator (36° to 46°F) for no more than 24 h.

Drug Interactions

Anthracyclines, cyclophosphamide

Incidence and severity of cardiac dysfunction may be increased.

Anticoagulants (eg, warfarin)

The risk of bleeding may be increased.

Paclitaxel

Trastuzumab serum levels may be elevated.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Incidences of the following adverse reactions were reported with trastuzumab monotherapy.

Cardiovascular

Any cardiac dysfunction, CHF (7%); tachycardia (5%)

CNS

Asthenia (42%); headache (26%); insomnia (14%); dizziness (13%); paresthesia (9%); depression (6%); peripheral neuritis (2%); neuropathy (1%).

Dermatologic

Rash (18%); acne, herpes simplex (2%).

EENT

Rhinitis (14%); pharyngitis (12%).

GI

Nausea (33%); diarrhea (25%); vomiting (23%); anorexia (14%); nausea and vomiting (8%).

Genitourinary

UTI (5%); fibrillary glomerulonephritis, focal glomerulosclerosis, membranous glomerulonephritis, nephrotic syndrome with glomerulopathy (postmarketing).

Hematologic-Lymphatic

Anemia (4%); leukopenia (3%).

Metabolic-Nutritional

Peripheral edema (10%); edema (8%).

Musculoskeletal

Back pain (22%); bone pain (7%); arthralgia (6%).

Respiratory

Increased cough (26%); dyspnea (22%); sinusitis (9%).

Miscellaneous

Pain (47%); chills and fever (40%); fever (36%); chills (32%); infusional toxicity (21%); infection (20%); flu syndrome (10%); accidental injury (6%); allergic reaction (3%).

Precautions

Warnings

Cardiomyopathy

Administration can result in ventricular dysfunction and CHF. Increased risk with concurrent anthracycline and cyclophosphamide.

Infusion reactions and pulmonary toxicity

Administration can result in serious infusion reactions and pulmonary toxicity, which, in rare instances, are fatal. Usually, symptoms occur during or within 24 h of administration. In patients experiencing dyspnea or clinically important hypotension, interrupt treatment and monitor until signs and symptoms resolve. Consider discontinuing therapy for infusion reactions manifesting as anaphylaxis, angioedema, pneumonitis, or acute respiratory distress syndrome.

Pregnancy

Category B .

Lactation

Undetermined. Advise women to discontinue breast-feeding during trastuzumab therapy and for 6 mo after the last dose because human immunoglobulin G is excreted in breast milk, and the potential for absorption and harm to the infant is unknown.

Children

Safety and efficacy not established.

Elderly

The risk of cardiac dysfunction may be increased.

Benzyl alcohol

For patients with known hypersensitivity to benzyl alcohol (a preservative in bacteriostatic water for injection), reconstitute with sterile water for injection.

Neutropenia

Chemotherapy-induced neutropenia may be exacerbated by trastuzumab.

Patient Information

Advise patient, family, or caregiver that medication will be prepared and administered by health care provider in a health care setting.
Advise patient, family, or caregiver that medication may be used in combination with other chemotherapy agents to achieve max benefit possible.
Advise patient, family, or caregiver to immediately report any of the following to health care provider: fever, chills, or other signs of infection; hives; itching; intolerable reaction at the injection site; rash; shortness of breath at night; shortness of breath or difficulty breathing; unexplained cough; swelling in arms or legs.
Advise patient, family, or caregiver to report any of the following to health care provider: persistent nausea, vomiting, diarrhea, or appetite loss; persistent or worsening general body weakness; any other bothersome or unexplained feeling or symptom.