capmatinib

Action and Spectrum

Actions and Spectrum: 

capmatinib is a selective inhibitor of the MET receptor tyrosine kinase. The MET receptor plays a role in cell growth, survival, and invasion, and it can be overactivated in certain types of cancer, including NSCLC. capmatinib works by binding to the MET receptor and inhibiting its activity, disrupting the signaling pathways contributing to cancer growth and spread. By targeting this specific pathway, capmatinib aims to inhibit the growth and progression of MET-driven cancers. 

capmatinib is specifically indicated for treating metastatic NSCLC with a mutation known as MET exon 14 skipping mutation. This mutation leads to abnormal MET receptor activity and is associated with a more aggressive form of NSCLC. It targets this specific genetic alteration and inhibits the abnormal signaling that drives cancer growth in patients with this mutation. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

All grades 

Increased creatinine (62%) 

Nausea (44%) 

Decreased lymphocytes (44%) 

Increased ALT (37%) 

Fatigue (32%) 

Decreased albumin (68%) 

Peripheral edema (52%) 

Increased alkaline phosphatase (32%) 

Increased lipase (26%) 

Dyspnea (24%) 

Decreased sodium (23%) 

Increased potassium (23%) 

Decreased leukocytes (23%) 

Vomiting (28%) 

Increased AST (25%) 

Decreased hemoglobin (24%) 

Decreased phosphate (23%) 

1-10% 

All grades 

Decreased weight  

<10% 

ILD/pneumonitis 

Acute kidney injury  

Urticaria 

Pruritus  

Cellulitis 

Grade 3 to 4 

Fatigue (8%) 

Increased GGT (7%) 

Dyspnea (7%) 

Increased AST (4.9%) 

Peripheral edema (9%) 

Increased ALT (8%) 

Increased lipase (7%) 

Decreased sodium (6%) 

Black Box Warning

Black box warning: 

None 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

None 

Caution: 

• Adverse Reactions: Like any medication, capmatinib can have side effects. Common adverse reactions may include nausea, diarrhea, fatigue, peripheral edema (swelling in the extremities), vomiting, and decreased appetite. More severe side effects, such as interstitial lung disease or hepatotoxicity, might also occur. Patients should be monitored closely for any unusual or severe symptoms. 
• Drug Interactions: capmatinib can interact with other medications, potentially affecting their effectiveness or causing adverse reactions.  
• Liver Function: capmatinib is metabolized by the liver, so individuals with liver impairment may need adjusted dosing or close monitoring.  
• Allergies and Hypersensitivity: Patients with known hypersensitivity or allergies to capmatinib or any of its components should not take the medication. 
• Cardiovascular Effects: Some targeted therapies, including capmatinib, might affect the cardiovascular system. Patients with a history of heart conditions should be carefully monitored. 

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

capmatinib is a tyrosine kinase inhibitor (TKI) that targets the MET receptor. It treats non-small cell lung cancer (NSCLC) with specific genetic alterations, particularly the MET exon 14 skipping mutation. 

Pharmacodynamics:  

• MET Inhibition: capmatinib is designed to inhibit the activity of the MET receptor tyrosine kinase. The MET receptor is activated by its ligand, hepatocyte growth factor (HGF). This leads to the activation of downstream signaling pathways that regulate various cellular processes, including cell proliferation, survival, and migration. 
• Downstream Signaling Pathways: When the MET receptor is activated, it triggers signaling cascades such as the PI3K-Akt and Ras-MAPK pathways, which are involved in cell growth and survival. In cancer, abnormal MET activation can promote uncontrolled cell growth and metastasis. By inhibiting MET with capmatinib, these pathways are disrupted. 
• Anti-Tumor Effects: The main pharmacodynamic effect of capmatinib is the suppression of tumor growth and metastasis in cancers where the MET pathway is aberrantly activated, such as NSCLC with the MET exon 14 skipping mutation. By inhibiting the MET pathway, capmatinib reduces the proliferation and survival of cancer cells, leading to a decrease in tumor size and metastatic potential. 
• Biomarker-Driven Therapy: One of the critical aspects of capmatinib’s pharmacodynamics is its specificity for tumors with specific genetic alterations, such as the MET exon 14 skipping mutation. This genetic alteration leads to a hyperactive MET pathway. In these cases, capmatinib’s targeted inhibition of MET can lead to a more effective and specific treatment approach. 

Pharmacokinetics: 

Absorption 

The drug is well-absorbed after oral administration. Bioavailability is greater than 70%, indicating that a significant portion of the administered dose reaches the systemic circulation. 

Distribution 

The protein binding of capmatinib is approximately 96%, which means that a large portion of the drug is bound to proteins in the bloodstream. The volume of distribution (Vd) at steady-state is 164 L, indicating that capmatinib is distributed widely throughout the body’s tissues. 

Metabolism 

capmatinib is primarily metabolized by two enzymes: cytochrome P450 3A4 (CYP3A4) and aldehyde oxidase. This metabolism leads to the formation of metabolites that are then excreted. 

Elimination and Excretion 

The half-life of capmatinib is approximately 6.5 hours. The drug is cleared from the body at approximately 24 L/hr. It is excreted through both feces and urine. Around 42% of the administered dose in the feces is excreted unchanged. In the urine, approximately 22% of the administered dose is excreted unchanged. Steady-state is reached by day 3 following twice-daily (BID) dosing. The time to reach peak plasma concentration (Cmax) is 1-2 hours after administration.

Adminstartion

Administration: 

Oral administration 

• May be consumed with or without meals.  
• Do not crush, chew, or break pills; swallow them whole.  
• Missed dosage or nausea: Don’t take a make-up dosage; take the following dose appropriately. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: capmatinib 

Why do we use capmatinib? 

capmatinib is a targeted therapy medication primarily used to treat a specific type of lung cancer known as non-small cell lung cancer (NSCLC) with a particular genetic alteration.