females ofreproductive potential to use effective contraception during treatment and for 7 months following the last doseof HERCEPTIN HYLECTA [see Use in Specific Populations (8.1, 8.3) and Clinical Pharmacology (12.3)].
5.3 Pulmonary Toxicity
HERCEPTIN HYLECTA can result in serious and fatal pulmonary toxicity. Pulmonary toxicity includes dyspnea,interstitial pneumonitis, pulmonary infiltrates, pleural effusions, non-cardiogenic pulmonary edema, pulmonaryinsufficiency and hypoxia, acute respiratory distress syndrome, and pulmonary fibrosis. Patients withsymptomatic intrinsic lung disease or with extensive tumor involvement of the lungs, resulting in dyspnea at rest,appear to have more severe toxicity.
5.4 Exacerbation of Chemotherapy-Induced Neutropenia
HERCEPTIN HYLECTA may exacerbate chemotherapy-induced neutropenia. In randomized, controlled clinicaltrials with intravenous trastuzumab, the per-patient incidences of NCI-CTC Grade 3–4 neutropenia and of febrileneutropenia were higher in patients receiving trastuzumab in combination with myelosuppressive chemotherapyas compared to those who received chemotherapy alone. The incidence of septic death was similar among patientswho received trastuzumab and those who did not [see Adverse Reactions (6.1)].
5.5 Hypersensitivity and Administration-Related Reactions
Severe administration-related reactions (ARRs), including hypersensitivity and anaphylaxis, have been reportedwith HERCEPTIN HYLECTA. Patients experiencing dyspnea at rest due to complications of advancedmalignancy and comorbidities may be at increased risk of a severe or of a fatal ARR.
In the HannaH and SafeHER trials, 9% and 4.2% of patients experienced Grade 1-4 hypersensitivity andanaphylaxis, respectively. Grade 3-4 hypersensitivity and anaphylactic reactions occurred in 1% and <1% of thepatients treated with HERCEPTIN HYLECTA, respectively. In the SafeHER trial, 2 patients requiredpermanent treatment discontinuation with HERCEPTIN HYLECTA (1 patient due to a hypersensitivity reactionand 1 patient due to anaphylaxis). Serious and fatal reactions have been reported after treatment withintravenous trastuzumab products.
Closely monitor patients for systemic hypersensitivity reactions, especially during the first administration.
Permanently discontinue HERCEPTIN HYLECTA in patients who experience anaphylaxis or severehypersensitivity reactions. Medications to treat such reactions, as well as emergency equipment, should beavailable for immediate use. For patients experiencing reversible Grade 1 or 2 hypersensitivity reactions,consider pre-medication with an analgesic, antipyretic, or an antihistamine prior to readministration ofHERCEPTIN HYLECTA [see Adverse Reactions (6.1)].
ADVERSE REACTIONS
The following adverse reactions are discussed in greater detail in other sections of the label:
• Cardiomyopathy [see Warnings and Precautions (5.1)]
• Embryo-Fetal Toxicity [see Warnings and Precautions (5.2)]
• Pulmonary Toxicity [see Warnings and Precautions (5.3)]
• Exacerbation of Chemotherapy-Induced Neutropenia [see Warnings and Precautions (5.4)]
• Hypersensitivity and Administration-Related Reactions [see Warnings and Precautions (5.5)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates |
