CARDIOMYOPATHY;

INFUSION REACTIONS, EMBRYO-FETAL TOXICITY; and

PULMONARY TOXICITY

FDA Approval Letter

CMS HCPCS Application Summaries and Coding Recommendations

Product NDC and Packaging

Full Prescribing Information, including Boxed Warnings

Trastuzumab products can result in sub-clinical and clinical cardiac failure. The incidence and severity was highest in patients receiving trastuzumab with anthracycline-containing chemotherapy regimens.

Trastuzumab products can cause left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death.

Trastuzumab products can also cause asymptomatic decline in left ventricular ejection fraction (LVEF).

Discontinue HERCESSI treatment in patients receiving adjuvant therapy and withhold HERCESSI in patients with metastatic disease for clinically significant decrease in left ventricular function.

Evaluate left ventricular function by echocardiogram or MUGA scan in all patients prior to and every 3 months during treatment with HERCESSI, and every 6 months for at least 2 years following completion of HERCESSI as a component of adjuvant therapy.

Repeat LVEF measurement at 4 week intervals if Hercessi is withheld for significant left ventricular cardiac dysfunction.

The safety of continuation or resumption of HERCESSI in patients with trastuzumab product-induced left ventricular cardiac dysfunction has not been studied.

With trastuzumab products, serious and fatal infusion reactions have been reported. Severe reactions, which include bronchospasm, anaphylaxis, angioedema, hypoxia, and severe hypotension were usually reported during or immediately following the initial infusion.

Interrupt HERCESSI infusion for dyspnea, clinically significant hypotension, and intervention of medical therapy administered (which may include epinephrine, corticosteroids, diphenhydramine, bronchodilators, and oxygen).

Monitor patients until symptoms completely resolve.

Discontinue HERCESSI for infusion reactions manifesting as anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome. Strongly consider permanent discontinuation in all patients with severe infusion reactions.

Infusion reactions consist of a symptom complex characterized by fever and chills, and on occasion include nausea, vomiting, pain (in some cases at tumor sites), headache, dizziness, dyspnea, hypotension, rash, and asthenia.

Exposure to trastuzumab products during pregnancy can result in oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Advise patients of these risks and the need for effective contraception.

Verify the pregnancy status of females of reproductive potential prior to the initiation of HERCESSI.

Advise females of reproductive potential to use effective contraception during treatment and for at least 7 months following the last dose of HERCESSI. Advise female patients to contact their healthcare provider with a known or suspected pregnancy.

Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for HERCESSI treatment and any potential adverse effects on the breastfed child from HERCESSI or from the underlying maternal condition. This consideration should also take into account the trastuzumab product wash out period of 7 months.

Trastuzumab products can result in serious and fatal pulmonary toxicity, which includes dyspnea, interstitial pneumonitis, pulmonary infiltrates, pleural effusions, noncardiogenic pulmonary edema, pulmonary insufficiency and hypoxia, acute respiratory distress syndrome, and pulmonary fibrosis. Such events can occur as sequelae of infusion reactions.

Patients with symptomatic intrinsic lung disease or with extensive tumor involvement of the lungs, resulting in dyspnea at rest, appear to have more severe toxicity.

Discontinue HERCESSI in patients experiencing pulmonary toxicity.

In randomized, controlled clinical trials, the per-patient incidences of NCI-CTC Grade 3-4 neutropenia and of febrile neutropenia were higher in patients receiving trastuzumab in combination with myelosuppressive chemotherapy as compared to those who received chemotherapy alone. The incidence of septic death was similar among patients who received trastuzumab and those who did not.

The most common adverse reactions associated with trastuzumab products in adjuvant and metastatic breast cancer are fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia. Adverse reactions requiring interruption or discontinuation of trastuzumab product treatment include CHF, significant decline in left ventricular cardiac function, severe infusion reactions, and pulmonary toxicity.

In the metastatic gastric cancer setting, the most common adverse reactions (≥ 10%) that were increased (≥ 5% difference) in the trastuzumab arm as compared to the chemotherapy alone arm were neutropenia, diarrhea, fatigue, anemia, stomatitis, weight loss, upper respiratory tract infections, fever, thrombocytopenia, mucosal inflammation, nasopharyngitis, and dysgeusia.

The most common adverse reactions which resulted in discontinuation of treatment in the trastuzumab containing arm in the absence of disease progression were infection, diarrhea, and febrile neutropenia.

as part of a treatment regimen containing doxorubicin, cyclophosphamide and either paclitaxel or docetaxel

as part of a treatment regimen with docetaxel and carboplatin

as a single agent following multi-modality anthracycline-based therapy

in combination with paclitaxel for the 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 one or more chemotherapy regimens for metastatic disease