Trastuzumab

A to Z Drug Facts

Actions Recombinant DNA-derived humanized monoclonal antibody that selectively binds with high affinity to the extracellular domain of the HER2. It inhibits the proliferation of human tumor cells that overexpress HER2 and mediates antibody-dependent cellular cytotoxicity (ADCC).

 Indications Breast cancer.

 Contraindications None well documented.

 Route/Dosage

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 the initial loading dose was tolerated. Trastuzumab may be administered in an outpatient setting. Do not administer as an IV push or bolus.

Interactions There have been no formal drug interaction studies performed with trastuzumab in humans. Administration of paclitaxel in combination with trastuzumab resulted in a 2-fold decrease in trastuzumab clearance in a nonhuman primate study and in a 1.5-fold increase in trastuzumab serum levels in clinical studies. The incidence and severity of cardiac dysfunction increases in patients who receive trastuzumab in combination with anthracyclines and cyclophosphamide.

Lab Test Interferences None well documented.

 Adverse Reactions

CARDIOVASCULAR: CHF; peripheral edema; tachycardia; ventricular dysfunction. CNS: Headache; depression; dizziness; insomnia; neuropathy; paresthesia; peripheral neuritis; asthenia. DERMATOLOGIC: Acne (rare); herpes simplex; rash. GI: Moderate to low potential for nausea and vomiting; diarrhea (25%); anorexia; abdominal pain. GU: Urinary tract infection. HEMATOLOGIC: Mild anemia; leukopenia. HYPERSENSITIVITY: Allergic reactions rarely, including anaphylactoid reactions, asthma, hives, rash. METABOLIC: Peripheral edema. MUSCULOSKELETAL: Arthralgia; bone pain; back pain. RESPIRATORY: Cough; dyspnea; pharyngitis; rhinitis; sinusitis. OTHER: Chills; pain; fever; flu syndrome (eg, fever, chills, malaise); infection. Chills and fever reported in approximately 40% within 1 to 2 hr of the initial infusion. Rigors, dyspnea, and hypotension also may occur. Reactions are usually mild to moderate in severity and do not require discontinuation of therapy. The incidence decreases approximately 20% with subsequent doses.

 Precautions

Pregnancy: Category B. Lactation: Advise women to discontinue nursing during trastuzumab therapy and for 6 mo after the last dose because human IgG is excreted in breast milk, and the potential for absorption and harm to the infant is unknown. Children: Safety and efficacy have not been established. Elderly: The risk of cardiac dysfunction may be increased. The reported clinical experience is not adequate to determine whether older patients respond differently than younger patients. Cardiotoxicity: Signs and symptoms of cardiac dysfunction, such as dyspnea, increased cough, paroxysmal nocturnal dyspnea, peripheral edema, S₃ gallop, or reduced ejection fraction, have been observed. Hypersensitivity reactions, including anaphylaxis: Severe hypersensitivity reactions have been infrequently reported in patients with trastuzumab. Infusion reactions: In the postmarketing setting, rare occurrences of severe infusion reactions leading to fatal outcome have been associated with the use of trastuzumab. Pulmonary events: Patients with either symptomatic intrinsic pulmonary disease (eg, asthma, COPD) or extensive tumor involvement of the lungs (eg, lymphangitic spread of tumor, pleural effusions, parenchymal masses), resulting in dyspnea at rest, may be at increased risk for severe pulmonary adverse events.

 Administration/Storage

• Refrigerate.
• Reconstitute vial aseptically with 20 mL of bacteriostatic water for injection (supplied) or sterile water for injection (not supplied). The final concentration will be 21 mg/mL.
• Withdraw appropriate dose from vial and dilute in 250 mL 0.9% Sodium Chloride.
• Do not reconstitute or dilute with 5% Dextrose since aggregation may occur.
• Trastuzumab is stable for 28 days refrigerated.
• Trastuzumab solutions reconstituted with sterile water are preservative-free; use within 24 hr. The possibility of microbial contamination must be considered.
• Refrigerate diluted solutions and use within 24 hr when stored in PVC or polyethylene bags.

 Assessment/Interventions

• Frequently monitor patients for deteriorating cardiac function. Assess baseline cardiac function including history and physicial exam and at least 1 of the following: ECG, echocardiogram, and MUGA scan. Monitoring may not identify all patients who will develop cardiac dysfunction.
• Use with caution in patients with known hypersensitivity to trastuzumab, Chinese Hamster ovary cell proteins, or any component of this product.
• For patients with a known hypersensitivity to benzyl alcohol (the preservative in Bacteriostatic Water for Injection), reconstitute trastuzumab with Sterile Water for Injection, and discard following a single use.

Immunogenicity

• Human anti-human antibody to trastuzumab was detected in 1 patient.

 Patient/Family Education

• Explain name, action, and potential side effects of drug.
• 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 will be used in combination with other agents to achieve maximum benefit possible.
• Review dosing schedule with patient, family, or caregiver.
• Advise patient, family, or caregiver to immediately report any of the following to health care provider: rash; itching; hives; shortness of breath or difficulty breathing; unexplained cough; swelling in arms or legs; fever, chills, or other signs of infection.
• 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.
• Instruct patient not to take any prescription or OTC medications or dietary supplements unless advised to do so by health care provider.
• Instruct women of childbearing potential to notify health care provider if pregnant, planning to become pregnant, or breastfeeding.
• Advise patient that frequent follow-up visits, ECG, heart function tests, and laboratory tests will be required to monitor therapy and to keep appointments.

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Copyright © 2003 Facts and Comparisons
David S. Tatro
A to Z Drug Facts