Class: Monoclonal antibody
- Injection, lyophilized powder for solution 440 mg
Recombinant DNA-derived humanized monoclonal antibody that selectively binds with high affinity to the extracellular domain of human epidermal growth receptor 2 (HER2). It inhibits the proliferation of human tumor cells that overexpress HER2 and mediates antibody-dependent cellular cytotoxicity.
At a dose of 500 mg, trastuzumab C max is 377 mcg/mL. Between weeks 16 and 32, serum concentrations reached steady state with a C min of 79 mcg/mL and a C max of 123 mcg/mL.
Trastuzumab pharmacokinetics are dose-dependent.
Vd is 44 mL/kg.
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) after an initial dose of 4 mg/kg followed by a weekly dose of 2 mg/kg. Mean half-life is 16 days (range, 11 to 23 days) after an initial dose of 8 mg/kg followed by a dose of 6 mg/kg every 3 wk.
Special PopulationsRenal Function Impairment
Disposition of trastuzumab is not altered based on serum creatinine (2 mg/dL or less).Age
Disposition of trastuzumab is not altered based on age.
Indications and UsageAdjuvant breast cancer
Adjuvant treatment of HER2-overexpressing node-positive or node-negative breast cancer (estrogen-receptor/progestin-receptor negative or with 1 high-risk feature): as part of a treatment regimen consisting of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel; with docetaxel and carboplatin; or 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.Metastatic gastric cancer
In combination with cisplatin and capecitabine or 5-fluorouracil for the treatment of patients with HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma who have not received prior treatment for metastatic disease.
None well documented.
Dosage and AdministrationBreast Cancer, Adjunctive Treatment
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
IV 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 90 min every 3 wk.As a Single Agent Within 3 Wk Following Completion of Multimodality Anthracycline-Based Chemotherapy Regimens
IV Start with 8 mg/kg infused over 90 min, then administer 6 mg/kg infused over 30 to 90 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.Metastatic Gastric Cancer
IV Start with 8 mg/kg as an IV infusion over 90 min, then administer 6 mg/kg infused over 30 to 90 min every 3 wk until disease progression.Dose Modification
IV Assess left ventricular ejection fraction (LVEF) prior to initiation of trastuzumab and frequently during treatment. Withhold trastuzumab for at least 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 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.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.
- For IV infusion only. Not for IV push or bolus administration.
- 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.
- Reconstitute each vial with 20 mL of bacteriostatic water for injection to yield a multidose solution containing trastuzumab 21 mg/mL. For patients with known hypersensitivity to benzyl alcohol, the preservative in bacteriostatic water for injection, reconstitute with sterile water for injection to yield a single-use solution.
- 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.
- Add appropriate volume of diluted trastuzumab solution to an infusion bag containing 250 mL of sodium chloride 0.9% injection. Gently invert the bag to mix the solution.
Store between 36° and 46°F prior to reconstitution. Store solution reconstituted with bacteriostatic water for injection under refrigeration between 36° and 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 InteractionsAntineoplastic agents (eg, anthracyclines [eg, doxorubicin])
The risk of symptomatic cardiac dysfunction is increased in patients receiving trastuzumab in combination with chemotherapy agents. The incidence and severity are highest when trastuzumab is used with anthracycline-containing chemotherapy regiments. Close clinical monitoring for signs of cardiac dysfunction is warranted.Paclitaxel
Trastuzumab serum levels may be elevated. Close clinical monitoring for signs of cardiac dysfunction is warranted.
The following adverse reactions were reported with trastuzumab monotherapy.
CHF (7%); tachycardia (5%); decreased ejection fraction, hypertension (4%); cardiac arrhythmias, palpitations (3%).
Asthenia (42%); headache (26%); insomnia (14%); dizziness (13%); paresthesia (9%); depression (6%); peripheral neuritis (2%); neuropathy (1%).
Rash (18%); acne, nail disorder, pruritus (2%).
Rhinitis (14%); pharyngitis (12%); nasopharyngitis (8%); epistaxis, pharyngolaryngeal pain (2%).
Nausea (33%); diarrhea (25%); vomiting (23%); abdominal pain (22%); anorexia (14%); nausea and vomiting (8%); constipation, dyspepsia, upper abdominal pain (2%).
UTI (5%); glomerulopathy (postmarketing).
Anemia (4%); leukopenia (3%).
Allergic reaction (3%).
Peripheral edema (10%); edema (8%).
Back pain (22%); arthralgia (8%); bone pain (7%); myalgia (4%); muscle spasm (3%).
Cough (26%); dyspnea (22%); sinusitis (9%); upper respiratory tract infection (3%).
Pain (47%); chills and fever (40%); fever (36%); chills (32%); infection (20%); flu syndrome (10%); pyrexia (6%); influenza (4%); herpes simplex, influenza-like illness (2%); infusion reaction, oligohydramnios (postmarketing).
Administration can result in decreased LVEF and CHF. Risk is greatest when coadministered with anthracycline-containing chemotherapy regimens.Embryofetal toxicity
Exposure during pregnancy can result in oligohydramnios and oligohydramnios sequence resulting in pulmonary hypoplasia, skeletal abnormalities and neonatal death.Infusion reactions and pulmonary toxicity
Administration can result in serious and fatal infusion reactions and pulmonary toxicity. 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.
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 years 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. Monitor women using trastuzumab during pregnancy for oligohydramnios.
Category D .
Undetermined, but human immunoglobulin G is excreted in breast milk.
Safety and efficacy not established.
The risk of cardiac dysfunction may be increased.
The provided diluent may contain benzyl alcohol, which has been associated with fatal “gasping syndrome” in premature infants.
Chemotherapy-induced neutropenia may be exacerbated by trastuzumab.
No information available.
- Advise patient, family, or caregiver that medication will be prepared and administered by a 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; intolerable reaction at the injection site; itching; rash; shortness of breath or difficulty breathing; swelling in the arms or legs; unexplained cough.
- Advise patient, family, or caregiver to report any of the following to health care provider: dizziness or loss of consciousness; persistent nausea, vomiting, diarrhea, or appetite loss; persistent or worsening of general body weakness; palpitations; weight gain of more than 5 lb in 24 h; any other bothersome or unexplained feeling or symptom.
- Advise pregnant women and women of childbearing potential that exposure can result in fetal harm. Instruct women with reproductive potential to use effective contraceptive methods during treatment and for a minimum of 6 mo following trastuzumab.
Copyright © 2009 Wolters Kluwer Health.