Capmatinib

412.4190832

412.42

1592732-453-0

TY34L4F9OZ

DTXSID90145595

C90564

L - Antineoplastic and immunomodulating agents

85.1

2.9

1.4

1.717

|Danger|H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]|P201, P202, P260, P264, P270, P273, P281, P301+P310, P308+P313, P314, P321, P330, P391, P405, and P501|The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

Data regarding toxicity and overdose of capmatinib are limited. Embryo-fetal toxicity has been documented in animal models - both males and females using capmatinib should use effective contraception throughout the course of therapy and for 1 week following cessation of therapy.

Plasma protein binding is approximately 96% and is independent of drug serum concentration.

Capmatinib is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping as detected by an FDA-approved test.|FDA Label|Treatment of lung malignant neoplasms|Drug: Capmatinibhydrochloride

Capmatinib inhibits the overactivity of c-Met, a receptor tyrosine kinase encoded by the _MET_ proto-oncogene. Mutations in _MET_ are involved in the proliferation of many cancers, including non-small cell lung cancer (NSCLC). Capmatinib may cause photosensitivity reactions in patients following ultraviolet (UV) exposure - patients undergoing therapy with capmatinib should be advised to use sunscreen and protective clothing to limit exposure to UV radiation. Instances of interstitial lung disease/pneumonitis, which can be fatal, occurred in patients being treated with capmatinib. Patients presenting with signs or symptoms of lung disease (e.g. cough, dyspnea, fever) should have capmatinib immediately withheld, and capmatinib should be permanently discontinued if no other feasible causes of the lung-related symptoms are identified.

The oral bioavailability of capmatinib is estimated to be >70%. Following oral administration, maximum plasma concentrations are achieved within 1 to 2 hours (T_max). Co-administration with a high-fat meal increased capmatinib AUC by 46% with no change in C_max (as compared to fasted conditions), and co-administration with a low-fat meal had no clinically meaningful effects on exposure.|Following oral administration of radiolabeled capmatinib, approximately 78% of the radioactivity is recovered in feces, of which ~42% is unchanged parent drug, and 22% is recovered in the urine, of which a negligible amount remains unchanged parent drug.|The apparent volume of distribution at steady-state is 164 L.|The mean apparent clearance of capmatinib at steady-state is 24 L/h.

Capmatinib undergoes metabolism primarily via CYP3A4 and aldehyde oxidase. Specific biotransformation pathways and metabolic products have yet to be elucidated.

The elimination half-life is 6.5 hours.

Aberrant activation of c-Met has been documented in many cancers, including non-small cell lung cancer (NSCLC). Mutations that result in the skipping of _MET_ exon 14 lead to the formation of a mutant c-Met with a missing regulatory domain - these mutant proteins have a reduced ability to negatively regulate, leading to a pathological increase in their downstream activity. Capmatinib inhibits the phosphorylation of both wild-type and mutant variants of c-Met triggered by the binding of its endogenous ligand, hepatocyte growth factor - in doing so, it prevents c-Met-mediated phosphorylation of downstream signaling proteins, as well as the proliferation and survival of c-Met-dependent tumor cells.

2-fluoro-4-(7-((quinolin-6-yl)methyl)imidazo(1,2-b)(1,2,4)triazin-2-yl)benzoic acid

Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients