alectinib

Alectinib is a selective oral inhibitor of anaplastic lymphoma kinase (ALK) used in the treatment of ALK-rearranged non-small cell lung cancer (NSCLC). It has notable activity against central nervous system metastases due to its ability to penetrate the brain, providing both systemic and intracranial disease control.

Medical uses include treatment of adults with ALK-positive NSCLC, especially after progression on crizotinib. In some regions, alectinib is also approved as first-line therapy based on trials showing improved progression-free survival and reduced intracranial progression compared with crizotinib.

Mechanistically, alectinib inhibits ALK tyrosine kinase signaling, thereby blocking downstream pathways that promote tumor cell growth and survival. It can overcome certain crizotinib-resistant ALK mutations and is active in CNS disease due to its pharmacologic properties.

Pharmacokinetics and metabolism involve oral administration with hepatic metabolism primarily by CYP3A4 and formation of active metabolites. Excretion is mainly via feces, and the drug has a relatively long elimination half-life, allowing twice-daily dosing.

Common adverse effects include constipation, fatigue, edema, and muscle pain, along with elevations in liver enzymes. Less frequent effects can include anemia or rash. Serious but uncommon adverse events may involve hepatotoxicity and, rarely, interstitial lung disease or other severe toxicities.

Drug interactions and cautions center on CYP3A: strong inhibitors or inducers can alter exposure to alectinib, necessitating dose adjustments or avoidance. Liver function should be monitored during therapy, and caution is advised in patients with hepatic impairment. Pregnancy should be avoided unless clearly indicated by a clinician.

Dosing is typically 600 mg taken orally twice daily, with or without food, with adjustments for hepatic impairment or drug interactions as specified in labeling.