API Crizotinib

Crizotinib More Info

Crizotinib is an oral small-molecule tyrosine kinase inhibitor (TKI) designed for targeted anti-cancer therapy. It exhibits high selectivity for specific oncogenic driver mutations, making it a cornerstone treatment for subsets of advanced non-small cell lung cancer (NSCLC) and other malignancies.​

Approved Indications​

First-line therapy for ALK-rearranged advanced NSCLC (the primary approved indication globally).​

Treatment of ROS1-rearranged advanced NSCLC (approved in major markets including the US, EU, and China).​

Orphan drug designation for NTRK fusion-positive solid tumors (in select regions, based on breakthrough efficacy in rare cancers).​

Mechanism of Action​

Crizotinib exerts its therapeutic effect through specific binding to aberrant tyrosine kinases:​

Inhibits ALK, ROS1, and NTRK fusion proteins, which are key drivers of cancer cell proliferation and survival.​

Blocks downstream signaling pathways (e.g., PI3K/Akt, MAPK) to induce cancer cell cycle arrest and apoptosis.​

Demonstrates minimal off-target activity, reducing toxicity to normal cells compared to conventional chemotherapy.​

Administration & Dosage​

Route: Oral (swallow whole; do not crush or chew).​

Standard dosage: 250 mg twice daily (every 12 hours), with or without food.​

Dose adjustments: May be reduced to 200 mg twice daily for adverse reaction management; further reduction to 250 mg once daily if needed (per physician guidance).​

Safety Profile​

Common Adverse Reactions (≥25%)​

Gastrointestinal: Nausea, diarrhea, vomiting, constipation.​

Neurological: Fatigue, dizziness, peripheral neuropathy.​

Ocular: Visual disturbances (e.g., blurred vision, photopsia) – usually mild and transient.​

Serious Adverse Reactions (Monitor Closely)​

Hepatotoxicity: Elevated liver transaminases (monitor LFTs at baseline and monthly).​

Interstitial lung disease (ILD)/pneumonitis: Discontinue if ILD is suspected.​

Cardiac: QT interval prolongation (avoid use with QT-prolonging drugs; monitor ECG).​

Hypersensitivity reactions: Rash, angioedema (discontinue immediately if severe).​

Contraindications & Precautions​

Contraindicated in patients with severe hypersensitivity to crizotinib or any excipients.​

Pregnancy: May cause fetal harm – females of reproductive age should use effective contraception during treatment and for 45 days post-discontinuation.​

Renal impairment: No dose adjustment needed for mild-to-moderate impairment; use with caution in severe impairment (limited data).​

Hepatic impairment: Avoid use in severe hepatic impairment; reduce dosage in moderate impairment.​

Drug Interactions​

Strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin): May increase crizotinib exposure – avoid concurrent use or reduce crizotinib dosage.​

Strong CYP3A inducers (e.g., rifampin, phenytoin): May decrease crizotinib efficacy – avoid concurrent use.​

CYP3A substrates (e.g., midazolam, cyclosporine): Crizotinib may increase their exposure – monitor for toxicity.​