Capmatinib Hydrochloride

• Non-Small Cell Lung Cancer (NSCLC):
  Approved for treatment of adult patients with metastatic NSCLC harboring mutations that cause mesenchymal-epithelial transition (MET) exon 14 skipping alterations, confirmed by an FDA-approved test.
• Off-label Uses:
  Investigational use in other MET-driven malignancies such as papillary renal cell carcinoma and hepatocellular carcinoma under clinical trials.

• Adults (NSCLC):
  Recommended dose: 400 mg orally twice daily (total 800 mg daily).
  Tablets should be swallowed whole with water, with or without food.
• Dose Adjustments:
• For moderate hepatic impairment (Child-Pugh B), reduce dose to 400 mg once daily.
• Use with caution in severe hepatic impairment; no formal recommendations.
• No dose adjustment needed for mild to moderate renal impairment; severe renal impairment data limited.
• Duration:
  Continued until disease progression or unacceptable toxicity.

Capmatinib hydrochloride is a highly selective, potent small molecule inhibitor of the MET receptor tyrosine kinase. It blocks the ATP-binding site of MET, thereby inhibiting phosphorylation and downstream signaling pathways such as RAS/MAPK, PI3K/AKT, and STAT3 involved in tumor cell proliferation, survival, migration, and invasion. By targeting MET exon 14 skipping mutations that lead to abnormal MET activation, capmatinib effectively reduces tumor growth and metastasis in MET-driven cancers.

• Absorption:
  Oral bioavailability is moderate; peak plasma concentration reached approximately 2 hours post-dose.
• Distribution:
  Volume of distribution is large, indicating extensive tissue distribution; highly protein bound (~96%).
• Metabolism:
  Primarily metabolized in the liver via CYP3A4 and aldehyde oxidase pathways.
• Half-life:
  Terminal half-life approximately 6–7 hours.
• Elimination:
  Excreted mainly via feces (~78%) and urine (~15%) as metabolites.

• Pregnancy:
  No adequate human data; animal studies show fetal harm. Use only if potential benefit justifies risk. Women of childbearing potential should use effective contraception during treatment and for 1 week after last dose.
• Lactation:
  Unknown if excreted in human milk; breastfeeding not recommended during treatment and for 1 week after last dose.

• Primary: Antineoplastic Agent
• Subclass: MET receptor tyrosine kinase inhibitor

• Known hypersensitivity to capmatinib or any formulation components.
• Concomitant use with strong CYP3A4 inducers is contraindicated.

• Risk of interstitial lung disease (ILD)/pneumonitis; monitor for new or worsening respiratory symptoms and discontinue if confirmed.
• Hepatotoxicity: Monitor liver function tests regularly.
• Photosensitivity reactions reported; advise sun protection.
• QT interval prolongation potential; monitor ECG in patients with risk factors.
• Embryo-fetal toxicity; pregnancy prevention required.
• Use caution in patients with hepatic or renal impairment.

Common (≥20%):

• Peripheral edema
• Nausea
• Fatigue
• Vomiting
• Dyspnea
• Decreased appetite

Less common:

• Increased serum creatinine
• Rash
• Diarrhea
• Cough
• Elevated liver enzymes

Serious/Rare:

• Interstitial lung disease/pneumonitis
• Hepatotoxicity
• QT prolongation

• CYP3A4 inhibitors: Increase capmatinib levels; dose adjustment may be required.
• CYP3A4 inducers: Decrease capmatinib plasma concentrations; avoid concomitant use.
• Drugs prolonging QT interval may increase risk of arrhythmias.
• No significant interactions via other CYP isoforms reported.

• FDA granted accelerated approval for MET exon 14 skipping mutation-positive NSCLC based on response rates.
• EMA approval followed with similar indications.
• Ongoing trials are evaluating combination regimens and expanded indications.
• Updated safety monitoring guidelines emphasize vigilance for ILD and hepatotoxicity.

• Store at controlled room temperature, 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep container tightly closed.
• Keep out of reach of children.