Cardiomyopathy; Infusion Reactions, Pulmonary Toxicity; Embryo Fetal Toxocity
- Trastuzumab administration can result in sub-clinical and clinical cardiac failure manifesting as CHF and decreased left ventricular ejection fraction (LVEF).
- Left ventricular function should be evaluated in all patients prior to and during treatment with trastuzumab.
- The incidence and severity of left ventricular cardiac dysfunction was highest in patients who received the drug concurrently with anthracycline containing chemotherapy regimens.
- Discontinue trastuzumab treatment in patients receiving adjuvant therapy for breast cancer and strongly consider discontinuation of trastuzumab in patients with metastatic breast cancer who develop a clinically significant decrease in left ventricular function.
Infusion Reactions, Pulmonary Toxicity
- Trastuzumab administration can result in serious infusion reactions and pulmonary toxicity.
- Fatal infusion reactions have been reported.
- In most cases, symptoms occurred during or within 24 hours of administration of trastuzumab.
- Trastuzumab infusion should be interrupted for patients experiencing dyspnea or clinically significant hypotension.
- Patients should be monitored until signs and symptoms completely resolve.
- Discontinue trastuzumab for anaphylaxis, angloedema, interstitial pneumonitis or acute respiratory distress syndrome.
- Exposure to trastuzumab products during pregnancy can result in oligohydramnios, in some cases complicated by pulmonary hypoplasia and neonatal death. Advise patients of these risks and the need for effective contraception
MONITORING RECOMMENDATIONS RELATED TO BLACK BOX DATA
- Left ventricular function should be evaluated at baseline and frequently during therapy.
- Withhold dosing for at least 4 weeks and repeat LVEF assessment every 4 weeks for either of the following: greater than or equal to a 16% absolute decrease in LVEF from baseline values (pretreatment), LVEF below institutional limits of normal and greater than or equal to a 10% absolute decrease in LVEF from pretreatment values.
- Trastuzumab may be resumed if, within 4 to 8 weeks, the LVEF returns to normal limits and the absolute decrease from baseline is less than or equal to 15%.
- Permanently discontinue trastuzumab for a persistent (> 8 weeks) LVED decline or for suspension of trastuzumab dosing on more than 3 occasionas for cardiomyopathy.
Infusion Reaction (During Adjuvant Treatment or Treatment of Metastatic Disease
- Mild to moderate infusion reactions: decrease the rate of infusion
- Dyspnea or clinically significant hypotension: interrupt infusion
- Severe and life-threatening infusion reactions: Strongly consider permanent discontinuation of trastuzumab.
Patient Counseling Information