Trepmac - Tablet Brigatinib - 90mg 30 Tablet(s) / Box Genvio Pharma Ltd. Indication: Non-Small Cell Lung Cancer Administration: Take with or without food Adult Dose: Non-Small Cell Lung Cancer Indicated for anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) in patients who have progressed on or are intolerant to crizotinib 90 mg PO qDay for the first 7 days; if 90 mg/day is tolerated, increase the dose to 180 mg PO qDay Continue until disease progression or unacceptable toxicity Hepatic impairment Mild or moderate (Child-Pugh A or B): No dose adjustment required Severe (Child-Pugh C): Reduce once daily dose by ~40% (eg, from 180 mg to 120 mg, 120 mg to 90 mg, or from 90 mg to 60 mg) Renal Dose: Renal impairment Mild or moderate (CrCl 30-89 mL/min): No dose adjustment required Severe (CrCl 15-29 mL/min): Reduce brigatinib dose by ~50% (eg, from 180 mg to 90 mg, or from 90 mg to 60 mg) Mode of Action: Tyrosine kinase inhibitor with in vitro activity at clinically achievable concentrations against multiple kinases, including ALK, ROS1, insulinlike growth factor-1 receptor (IGF-1R), and FLT-3, as well as EGFR deletion and point mutations Brigatinib inhibited autophosphorylation of ALK and ALK-mediated phosphorylation of the downstream signaling proteins STAT3, AKT, ERK1/2, and S6 in in vitro and in vivo assays Exhibited in vivo antitumor activity against 4 mutant forms of EML4-ALK, including G1202R and L1196M mutants identified in NSCLC tumors in patients who have progressed on crizotinib Also reduced tumor burden and prolonged survival in mice implanted intracranially with an ALK-driven tumor cell... Precaution: Risk of interstitial lung disease (ILD)/pneumonitis; HTN; bradycardia; visual disturbances (eg, blurred vision, diplopia, & reduced visual acuity); creatine phosphokinase (CPK) & pancreatic enzyme elevation; hyperglycemia. Withhold treatment in patients w/ Grade 3 or 4 CPK elevation; Grade 3 or 4 pancreatic enzyme elevation; inadequate hyperglycemic control. Discontinue in case of Grade 3 or 4 ILD/pneumonitis or recurrence of Grade 1 or 2 ILD/pneumonitis; Grade 4 HTN or recurrence of Grade 3 HTN; life-threatening bradycardia; Grade 4 visual disturbances. Use w/ caution in combination w/ antihypertensive agents causing bradycardia. Females of reproductive potential should use effective non-hormonal contraception during treatment... Side Effect: >10% Increased AST (38%) Hyperglycemia (38%) Increased ALT (34%) Nausea (33%) Fatigue (29%) Headache (28%) Increased CPK (27%) Increased amylase (27%) Dyspnea (27%) Vomiting (24%) Anemia (23%) Decreased appetite (22%) Prolonged aPTT (22%) Increased lipase (21%) Diarrhea (19%) Constipation (19%) Lymphopenia (19%) Cough (18%) Abdominal pain (17%) Increased alkaline phosphatase (15%) Decreased phosphorous (15%) Rash (15%) Pyrexia (14%) Arthralgia (14%) Peripheral neuropathy (13%) Muscle spasms (12%) Hypertension (11%) Pain in extremity (11%) Insomnia (11%) 1-10% Back pain (10%) Myalgia (9.2%) Visual disturbances (7.3%) Pneumonia (4.6%) Interstitial lung disease/pneumonitis (3.7%) <1% Hypoxia (0.9%) Pregnancy Category Note: Pregnancy Based on its mechanism of action and findings in animals, can cause fetal harm when administered to pregnant women Administration to pregnant rats during the period of organogenesis resulted in dose-related skeletal anomalies at doses as low as 12.5 mg/kg/day (~0.7 times the human exposure by AUC at 180 mg once daily), as well as increased postimplantation loss, malformations, and decreased fetal body weight at doses of 25 mg/kg/day (~1.26 times the human exposure at 180 mg once daily) or greater Infertility: Based on findings in male reproductive organs in animals, may cause reduced fertility in males Contraception Females:... Interaction: Increased plasma conc & adverse reactions w/ strong CYP3A inhibitors [eg, certain antivirals (boceprevir, cobicistat, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir), macrolide antibiotics (clarithromycin), antifungals (itraconazole, ketoconazole, posaconazole, voriconazole), conivaptan]; grapefruit or grapefruit juice. Decreased plasma conc & efficacy w/ strong CYP3A inducers (eg, rifampin, carbamazepine, phenytoin, St. John's Wort). Decreased conc & loss of efficacy of CYP3A substrates (eg, hormonal contraceptives).