Alkros ONE Capsule

Crizotinib is a kinase inhibitor indicated for the treatment of - adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK) or ROS1-positive as detected by an FDA-approved test. - pediatric patients 1 year of age and older and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) that is ALK-positive. o Limitations of Use: The safety and efficacy of Crizotinib have not been established in older adults with relapsed or refractory, systemic ALK-positive ALCL. - adult and pediatric patients 1 year of age and older with unresectable, recurrent, or refractory inflammatory myofibroblastic tumor (IMT) that is ALK-positive. ALK- or ROS1-Positive Metastatic Non-Small Cell Lung Cancer Crizotinib is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK) or ROS1-positive as detected by an FDA-approved test. Relapsed or Refractory, Systemic ALK-Positive Anaplastic Large Cell Lymphoma Crizotinib is indicated for the treatment of pediatric patients 1 year of age and older and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) that is ALK-positive. Limitations of Use: The safety and efficacy of Crizotinib have not been established in older adults with relapsed or refractory, systemic ALK-positive ALCL. Unresectable, Recurrent, or Refractory ALK-Positive Inflammatory Myofibroblastic Tumor Crizotinib is indicated for the treatment of adult and pediatric patients 1 year of age and older with unresectable, recurrent, or refractory inflammatory myofibroblastic tumor (IMT) that is ALK-positive.

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Source: US FDA prescribing information, via openFDA. Provided for general information only — it is not a substitute for your doctor's or pharmacist's advice. Always follow your prescriber's instructions.

• Hepatotoxicity: Fatal hepatotoxicity has occurred. Monitor with periodic liver testing. Temporarily suspend, dose reduce, or permanently discontinue Crizotinib. - Interstitial Lung Disease (ILD)/Pneumonitis: Permanently discontinue in patients with ILD/pneumonitis. - QT Interval Prolongation: Monitor electrocardiograms and electrolytes in patients who have a history of or predisposition for QTc prolongation, or who are taking medications that prolong QT. - Bradycardia: Crizotinib can cause bradycardia. Monitor heart rate and blood pressure regularly. - Severe Visual Loss: Crizotinib can cause visual changes including severe visual loss. Monitor and evaluate for ocular toxicity throughout treatment. Discontinue Crizotinib in patients with severe visual loss. - Gastrointestinal Toxicity in Pediatric and Young Adult Patients with ALCL or Pediatric Patients with IMT: Crizotinib can cause severe nausea, vomiting, diarrhea, and stomatitis. Provide standard antiemetic and antidiarrheal agents. - Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and use of effective contraception. Hepatotoxicity Drug-induced hepatotoxicity with fatal outcome occurred in 0.1% of the 1719 patients treated with Crizotinib for NSCLC across clinical trials. Concurrent elevations in ALT or AST ≥3 times the ULN and total bilirubin ≥2 times the ULN, with normal alkaline phosphatase, occurred in <1% of patients treated with Crizotinib. Increased ALT or AST >5 times the ULN occurred in 11% and 6% of patients, respectively. One percent (1.0%) of patients required permanent discontinuation due to elevated transaminases. Increased transaminases generally occurred within the first 2 months of treatment. In Study ADVL0912, of 121 patients ages 1 to ≤21 years treated with Crizotinib for relapsed or refractory tumors including ALCL and IMT, 71% and 79% had increases of AST and ALT, respectively, with increased ALT or AST >5 times the ULN in 6% each. Of the 26 patients with ALCL treated with Crizotinib, 65% and 81% had increases of AST and ALT, respectively, with increases >5 times the ULN in 4% each. Of the 14 pediatric patients with IMT treated with Crizotinib, 71% had increases of AST and 71% had increases of ALT. In Study A8081013, of the 7 adult patients with IMT treated with Crizotinib, 57% and 43% had increases of AST and ALT, respectively. Monitor liver function tests, including ALT, AST, and total bilirubin, every 2 weeks during the first 2 months of treatment, then once a month, and as clinically indicated, with more frequent repeat testing for increased liver transaminases, alkaline phosphatase, or total bilirubin in patients who develop increased transaminases. Abridged from the full prescribing information.

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Source: US FDA prescribing information, via openFDA. Provided for general information only — it is not a substitute for your doctor's or pharmacist's advice. Always follow your prescriber's instructions.

The following clinically significant adverse reactions are described elsewhere in the labeling: - Hepatotoxicity - Interstitial Lung Disease/Pneumonitis - QT Interval Prolongation - Bradycardia - Severe Visual Loss - Gastrointestinal Toxicity in Pediatric and Young Adult Patients with ALCL or Pediatric Patients with IMT The most common adverse reactions (≥25%) in adult patients with NSCLC are vision disorders, nausea, diarrhea, vomiting, edema, constipation, elevated transaminases, fatigue, decreased appetite, upper respiratory infection, dizziness, and neuropathy. The most common adverse reactions (≥35%) in patients with ALCL are diarrhea, vomiting, nausea, vision disorder, headache, musculoskeletal pain, stomatitis, fatigue, decreased appetite, pyrexia, abdominal pain, cough, and pruritus. Grade 3–4 laboratory abnormalities (≥15%) are neutropenia, lymphopenia, and thrombocytopenia. The most common adverse reactions (≥35%) in adult patients with IMT are vision disorders, nausea, and edema. The most common adverse reactions (≥35%) in pediatric patients with IMT are vomiting, nausea, diarrhea, abdominal pain, rash, vision disorder, upper respiratory tract infection, cough, pyrexia, musculoskeletal pain, fatigue, edema, constipation, and headache. Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The data in the Warnings and Precautions reflect exposure to Crizotinib in 1719 patients with NSCLC who received Crizotinib 250 mg twice daily enrolled on Studies 1 (including an additional 109 patients who crossed over from the control arm), 2, 3, a single-arm trial (n=1063) of ALK-positive NSCLC, and an additional ALK-positive NSCLC expansion cohort of a dose finding study (n=154). The data also reflect exposure to Crizotinib in 121 patients ages 1 to ≤21 years with relapsed or refractory tumors, including 26 patients with systemic ALCL and 14 pediatric patients with IMT, in a single-arm trial (Study ADVL0912). The data are also described for 7 adult patients with IMT treated with Crizotinib in a single-arm trial (Study A8081013). ALK- or ROS1-Positive Metastatic NSCLC The data described below is based primarily on 343 patients with ALK-positive metastatic NSCLC who received Crizotinib 250 mg orally twice daily from 2 open-label, randomized, active-controlled trials (Studies 1 and 2). Abridged from the full prescribing information.

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Source: US FDA prescribing information, via openFDA. Provided for general information only — it is not a substitute for your doctor's or pharmacist's advice. Always follow your prescriber's instructions.