itis. Signs and symptoms include dyspnea, cough, fatigue, and pulmonary infiltrates. These events may or may not occur as sequelae of infusion reactions. In the randomized trial (Study 1), the overall frequency of pneumonitis was 1.2% [see Adverse Reactions (6.1)].
Permanently discontinue treatment with KADCYLA in patients diagnosed with ILD or pneumonitis.
Patients with dyspnea at rest due to complications of advanced malignancy and co-morbidities may be at increased risk of pulmonary toxicity.
5.5 Infusion-Related Reactions, Hypersensitivity Reactions
Treatment with KADCYLA has not been studied in patients who had trastuzumab permanently discontinued due to infusion-related reactions (IRR) and/or hypersensitivity; treatment with KADCYLA is not recommended for these patients.
Infusion-related reactions, characterized by one or more of the following symptoms – flushing, chills, pyrexia, dyspnea, hypotension, wheezing, bronchospasm, and tachycardia have been reported in clinical trials of KADCYLA. In the randomized trial (Study 1), the overall frequency of IRRs in patients treated with KADCYLA was 1.4% [see Adverse Reactions (6.1)]. In most patients, these reactions resolved over the course of several hours to a day after the infusion was terminated. KADCYLA treatment should be interrupted in patients with severe IRR. KADCYLA treatment should be permanently discontinued in the event of a life-threatening IRR [see Dosage and Administration (2.2)]. Patients should be observed closely for IRR reactions, especially during the first infusion.
One case of a serious, allergic/anaphylactic-like reaction has been observed in clinical trials of single-agent KADCYLA. Medications to treat such reactions, as well as emergency equipment, should be available for immediate use.
5.6 Thrombocytopenia
Thrombocytopenia, or decreased platelet count, was reported in clinical trials of KADCYLA (103 of 884 treated patients with ≥ Grade 3; 283 of 884 treated patients with any Grade). The majority of these patients had Grade 1 or 2 events (< LLN to ≥ 50,000/mm3) with the nadir occurring by day 8 and generally improving to Grade 0 or 1 (≥ 75,000 /mm3) by the next scheduled dose. In clinical trials of KADCYLA, the incidence and severity of thrombocytopenia were higher in Asian patients. Independent of race, the incidence of severe hemorrhagic events in patients treated with KADCYLA was low.
In the randomized trial (Study 1), the overall frequency of thrombocytopenia was 31.2% in the KADCYLA-treated group and 3.3% in the lapatinib plus capecitabine-treated group [see Adverse Reactions (6.1)]. The incidence of ≥ Grade 3 thrombocytopenia was 14.5% in the KADCYLA-treated group and 0.4% in the lapatinib plus capecitabine-treated group. In Asian patients, the incidence of ≥ Grade 3 thrombocytopenia was 45.1% in the KADCYLA-treated group and 1.3% in the lapatinib plus capecitabine-treated group.
Monitor platelet counts prior to initiation of KADCYLA and prior to each KADCYLA dose [see Dosage and Administration (2.2)]. KADCYLA has not been studied in patients with platelet counts <100,000/mm3 prior to initiation of treatment. In the event of decreased platelet count to Grade 3 or greater (< 50,000/mm3) do not administer KADCYLA until platelet counts recover to Grade 1 (≥ 75,000/mm3) [see Dosage and Administration (2.2)]. Patients with thrombocytopenia (< 100,000/mm3) and patients on anti-coagulant treat |
