HER2 testing either by immunohistochemistry (IHC) or fluorescence immunosorbent hybridization (FISH) must be performed in a specialized laboratory prior to initiation of Vivitra treatment. Vivitra treatment should only be initiated under supervision of an oncologist/physician experienced in the treatment of cancer patients.
Infusion-related reactions (IRRs) and hypersensitivity: Serious infusion related reactions reported infrequently to trastuzumab infusion include dyspnoea, hypotension, bronchospasm, respiratory distress, wheezing, anaphylaxis, urticaria, angioedema, reduced oxygen saturation, hypertension and supraventricular tachyarrhythmia. To reduce risk of occurrence of these events, pre-medication may be used. The majority of these events are reported during or within 2.5 hours of the start of the first infusion. It is recommended that the infusion should be discontinued or the rate of infusion slowed, if any infusion reaction occurs. The patient should be monitored until resolution of all observed symptoms. These symptoms can be treated with an analgesic/antipyretic, or an antihistamine. The majority of patients who experienced resolution of symptoms have subsequently received further trastuzumab infusions. In rare cases, infusion reactions have resulted in a fatal outcome. Patients at increased risk of a fatal infusion reaction include those who are experiencing dyspnoea at rest due to complications of advanced malignancy/comorbidities. Therefore, such patients should not be treated with trastuzumab. Delayed reactions with rapid clinical deterioration have also been reported with trastuzumab with fatalities within hours and up to one week following infusion. Rarely, infusion reaction and pulmonary symptoms were reported more than six hours after the start of trastuzumab infusion. Patients should be warned of the possibility of such delayed onset symptoms and should be instructed to contact their doctor when these symptoms occur.
Pulmonary events: Reported pulmonary events include: acute respiratory distress syndrome, pneumonia, interstitial lung disease, pneumonitis, pleural effusion, acute pulmonary edema, respiratory distress, and respiratory insufficiency. Severe pulmonary events with occasional fatalities have also been reported.
Prior or concomitant anticancer therapy such as gemcitabine, taxanes, vinorelbine and radiation therapy are associated with increased risk of interstitial lung disease. Patients experiencing dyspnoea at rest due to complications of advanced malignancy/comorbidities are at increased risk of a fatal infusion reaction. Therefore, such patients should not be treated with trastuzumab. Trastuzumab should be cautiously used in pneumonitis, especially in patients being treated with taxanes concomitantly.
Cardiac dysfunction: Trastuzumab therapy is associated with increased risk of developing congestive heart failure (NYHA class II-IV) or asymptomatic cardiac dysfunction. These cases may be moderate to severe and have been associated with death. These events have been reported in patients receiving trastuzumab therapy alone or in combination with docetaxel or paclitaxel, especially following anthracycline (doxorubicin or epirubicin) based chemotherapy.
Trastuzumab should be cautiously used in patients with increased cardiac risk, e.g. hypertension, coronary artery disease, congestive heart failure, LVEF <55% and older age. Baseline cardiac assessment including history, physical examination, electrocardiogram (ECG), echocardiogram, and/or multigated acquisition (MUGA) scan or magnetic resonance imaging (MRI) should be performed in all patients prior to start of trastuzumab treatment, especially those with prior anthracycline and cyclophosphamide (AC) exposure. A careful risk-benefit assessment should be made before deciding to treat with trastuzumab. Patients should be monitored to detect the development of cardiac dysfunction. Cardiac assessments, as performed at baseline, should be repeated every 3 months during treatment and every 6 months following discontinuation of treatment until 24 months from the last administration of trastuzumab.
Patients who receive anthracyclines after stopping trastuzumab may possibly be at increased risk of cardiac dysfunction, as trastuzumab persists in the circulation for up to 7 months after stopping trastuzumab treatment. Therefore, if possible, anthracycline-based therapy should be avoided for up to 7 months after stopping trastuzumab.
Cardiac function should be monitored during treatment (e.g. every 12 weeks) in all patients to identify patients who develop cardiac dysfunction. More frequent monitoring (e.g. every 6 - 8 weeks) may be performed in patients who develop asymptomatic cardiac dysfunction. Discontinuation of trastuzumab therapy should be considered if the patients have a continued decrease in left ventricular function, but remain asymptomatic, if no clinical benefit of trastuzumab therapy is evident.
The safety of continuation or resumption of trastuzumab has not been reported in patients who experience cardiac dysfunction. If LVEF drops ≥10 ejection fraction points from baseline and to below 50%, trastuzumab treatment should be suspended and repeat LVEF assessment performed within approximately 3 weeks. If LVEF has not improved, or declined further, or symptomatic CHF has developed, discontinuation of trastuzumab therapy should be strongly considered, unless the benefits of treatment outweigh the risks for the individual patient. All such patients should be referred to cardiologist for assessment and followed up.
Symptomatic cardiac failure developed during trastuzumab therapy should be treated with standard therapy for CHF. In the Metastatic breast cancer (MBC) setting, trastuzumab and anthracyclines should not be given concurrently in combination.
Benzyl alcohol, used as a preservative in BWFI in the 440 mg multidose vial, has been associated with toxicity in neonates and children up to 3 years old. When administering trastuzumab to a patient with a known sensitivity to benzyl alcohol, trastuzumab should be reconstituted with water for injection, and only one dose per trastuzumab vial should be used. Any unused portion must be discarded. Sterile water for injection, used to reconstitute the 150 mg single dose vial, does not contain benzyl alcohol.
Effects on Ability to Drive and Use Machines: Trastuzumab has negligible influence on the ability to drive or use machines. However, patients experiencing infusion-related symptoms should be advised not to drive and use machines until symptoms disappear.