Professional Information

Add to List

Trastuzumab

Pronunciation: (traz-TOO-ze-mab)
Class: Monoclonal antibody

Trade Names:
Herceptin
- Injection, lyophilized powder for solution 440 mg

Pharmacology

User Reviews & Ratings

As a treatment for...	Avg User Ratings [?]
Salivary Gland Cancer	1 reviews Rate it!	10
Breast Cancer	0 reviews Rate it!	9.0
Breast Cancer, Adjuvant	0 reviews Rate it!	9.0

Showing 3 of 4 conditions - Show All...

Compare with other drugs.

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 weeks 16 and 32, serum concentrations reached steady state with C _min of 79 mcg/mL and C _max of 123 mcg/mL.

Trastuzumab pharmacokinetics are dose-dependent.

Distribution

Vd is 44 mL/kg.

Elimination

Trastuzumab kinetics are dose-dependent. Mean half-life increases and Cl decreases with increasing dose level. Mean half-life is 6 days (range, 1 to 32 days).

Indications and Usage

Adjuvant breast cancer

Adjuvant treatment of HER2-overexpressing node-positive or node-negative breast cancer: as part of a treatment regimen consisting of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel; with docetaxel and carboplatin; as a single agent following multimodality anthracycline-based therapy.

Metastatic breast cancer

In combination with paclitaxel for first-line treatment of HER2-overexpressing metastatic breast cancer; as a single agent for treatment of HER2-overexpressing breast cancer in patients who have received 1 or more chemotherapy regimens for metastatic disease.

Contraindications

None well documented.

Dosage and Administration

Breast Cancer, Adjunctive Treatment
Adults

IV Administer according to 1 of the following doses and schedules for a total of 52 wk of therapy.

During and Following Paclitaxel, Docetaxel, or Docetaxel/Carboplatin

Start with 4 mg/kg infused over 90 min, then administer in weekly doses of 2 mg/kg infused over 30 min during chemotherapy for the first 12 wk (paclitaxel or docetaxel) or for 18 wk (docetaxel/carboplatin). One wk after the last weekly dose of trastuzumab, administer trastuzumab 6 mg/kg infused over 30 to 60 min every 3 wk.

As a Single Agent Within 3 wk Following Completion of Multimodality Anthracycline-Based Chemotherapy Regimens

Start with 8 mg/kg infused over 90 min, then administer 6 mg/kg infused over 30 min every 3 wk.

Breast Cancer, Metastatic Treatment

IV Start with 4 mg/kg infused over 90 min alone or in combination with paclitaxel, followed by once-weekly doses of 2 mg/kg infused over 30 min until disease progression.

Dose Modification
Adults Infusion reactions

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

Adults Cardiomyopathy

IV 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 more 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.
For patients with known hypersensitivity to benzyl alcohol, which is the preservative in bacteriostatic water for injection, reconstitute with sterile water for injection.
Swirl gently to aid reconstitution. Do not shake.
Slight foaming of the product may be present upon reconstitution. Allow vial to stand undisturbed for approximately 5 min.

Storage/Stability

Store at 36° to 46°F prior to reconstitution. Store solution reconstituted with bacteriostatic water for injection under refrigeration at 36° to 46°F for up to 28 days. Do not freeze. If trastuzumab is reconstituted with sterile water for injection, use the solution immediately and discard any unused portion. Trastuzumab for infusion diluted in polyvinyl chloride 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

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

The following adverse reactions were reported with trastuzumab monotherapy.

Cardiovascular

CHF (7%); tachycardia (5%); decreased ejection fraction, hypertension (4%); cardiac arrhythmias, palpitations (3%).

CNS

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

Dermatologic

Rash (4%); acne, nail disorder, pruritus (2%).

EENT

Rhinitis (14%); pharyngitis (12%); nasopharyngitis (8%); epistaxis, pharyngolaryngeal pain (2%).

GI

Nausea (33%); diarrhea (25%); vomiting (23%); abdominal pain (22%); anorexia (14%); nausea and vomiting (8%); constipation, dyspepsia, upper abdominal pain (2%).

Genitourinary

UTI (5%); amniotic fluid deficiency, glomerulopathy (postmarketing).

Hematologic-Lymphatic

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

Hypersensitivity

Allergic reaction (3%).

Metabolic-Nutritional

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

Musculoskeletal

Back pain (22%); arthralgia (8%); bone pain (7%); myalgia (4%); muscle spasm (3%).

Respiratory

Cough (26%); dyspnea (22%); sinusitis (18%); upper respiratory infection (3%).

Miscellaneous

Pain (47%); chills and fever (40%); fever (36%); chills (32%); infection (20%); flu syndrome (10%); accidental injury, pyrexia (6%); influenza (4%); herpes simplex, influenza-like illness (2%); infusion reaction (postmarketing).

Precautions

Warnings

Cardiomyopathy

Administration can result in decreased LVEF and CHF. Risk is greatest with concurrent anthracycline-containing chemotherapy regimens.

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, interstitial pneumonitis, or acute respiratory distress syndrome.

Monitor

Measure baseline LVEF immediately prior to initiation of treatment; measure LVEF every 3 wk during and upon completion of therapy; repeat LVEF measurement at 4 wk intervals if treatment is withheld for left ventricular cardiac dysfunction; measure LFEV every 6 months for at least 2 yr following completion of trastuzumab treatment as a component of adjuvant therapy. Detection of HER2 protein overexpression is necessary for selection of patients appropriate for trastuzumab therapy because these are the only patients studied for whom benefit has been shown.

Pregnancy

Category D .

Lactation

Undetermined but human immunoglobulin G is excreted in breast milk.

Children

Safety and efficacy not established.

Elderly

The risk of cardiac dysfunction may be increased.

Embryo-fetal toxicity

Fetal harm can occur when administered during pregnancy. The risk of amniotic fluid deficiency occurring during the second and third trimesters is increased.

Neutropenia

Chemotherapy-induced neutropenia may be exacerbated by trastuzumab.

Overdosage

Symptoms

No information available.

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.
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; swelling in arms or legs; unexplained cough.
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 of general body weakness; any other bothersome or unexplained feeling or symptom.