Capmaxen Capmatinib Tablets

I. Basic Drug Information

Generic Name: Capmatinib / Capmatinib Hydrochloride

Brand Name: Tabrecta / Capmaxen

English Name: Capmatinib / Capmatinib Hydrochloride

Dosage Form: Film-coated tablets

Common Strength: 200 mg/tablet; 56 tablets/box

Manufacturer: Everest Pharma Ltd (Bangladesh)

II. Pharmacological Action and Mechanism of Action

Capmatinib is a highly selective and potent MET tyrosine kinase inhibitor.

Mechanism of Action: It acts by selectively binding to c-Met (also known as the hepatocyte growth factor receptor), thereby inhibiting its phosphorylation and blocking the aberrant MET signaling pathway. This aberrant pathway—such as that caused by MET exon 14 skipping mutations—is a key driver of tumor growth in specific types of non-small cell lung cancer (NSCLC). By blocking this pathway, Capmatinib inhibits tumor cell proliferation and induces tumor cell death.

III. Indications

Indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors harbor mutations leading to MET exon 14 skipping. This indication is based on genomic testing; relevant diagnostic assays must be validated.

IV. Dosage and Administration

Recommended Dosage: 400 mg, taken orally twice daily (equivalent to two 200 mg tablets).

Administration Instructions:

Take twice daily, approximately 12 hours apart; may be taken with or without food.

Swallow tablets whole; do not break, crush, or chew.

Management of Missed Doses or Vomiting:

If a dose is missed, skip the missed dose and take the next scheduled dose at the regular time. Do not take an extra dose or double the dose to make up for a missed one.

If vomiting occurs after taking a dose, do not take an additional dose; continue with the next scheduled dose as planned.

Dosage Adjustment:

Based on the severity of adverse reactions, the physician may implement measures such as temporarily withholding the drug, reducing the dosage, or permanently discontinuing treatment. Common dosage adjustment steps are as follows: first dose reduction to 300 mg twice daily; second dose reduction to 200 mg twice daily. The table below summarizes the dose management principles for specific adverse reactions:

**Adverse Reaction Type** | **Severity/Criteria** | **Management Recommendation**

--------------------------|-----------------------|-----------------------------

Interstitial Lung Disease (ILD)/Pneumonitis | Any Grade | Permanently discontinue.

Hepatotoxicity | ALT/AST elevation > 3 times the Upper Limit of Normal (ULN) AND Total Bilirubin elevation > 2 times ULN | Permanently discontinue.

Pancreatic Toxicity | Occurrence of Pancreatitis (Grade 3 or 4) | Permanently discontinue.

Other Adverse Reactions | Grade 3 | Withhold treatment; resume at a reduced dose once resolved.

| Grade 4 | Permanently discontinue.

**V. Contraindications**

Contraindicated in patients with a history of severe hypersensitivity to capmatinib or to any of the excipients.

**VI. Warnings and Precautions**

1.  **Interstitial Lung Disease (ILD)/Pneumonitis:** Severe, fatal ILD/pneumonitis may occur. If new or worsening pulmonary symptoms (e.g., dyspnea, cough, fever) develop during treatment, patients should seek immediate medical attention and withhold treatment. Permanently discontinue treatment if ILD/pneumonitis is confirmed.

2.  **Hepatotoxicity:** May cause liver injury. Monitor liver function (ALT, AST, total bilirubin) prior to the start of treatment, every 2 weeks during treatment (for the first 3 months), and periodically thereafter. Withhold, reduce the dose, or permanently discontinue treatment based on severity.

3.  **Pancreatic Toxicity:** May cause pancreatitis and elevations in serum lipase/amylase. Monitor lipase and amylase levels prior to and periodically during treatment. Adjust treatment based on severity.

4.  **Risk of Photosensitivity Reactions:** May increase sensitivity to ultraviolet (UV) light. Advise patients to use sunscreen, wear protective clothing, and wear a hat to limit direct UV exposure.

5.  **Embryo-Fetal Toxicity:** May cause harm to the fetus. Females of reproductive potential and male partners must use effective contraception during treatment and for at least 1 week after the last dose. VII. Adverse Reactions

In clinical studies (N=373), the most common adverse reactions (incidence ≥ 20%) included:

Peripheral edema (59%)

Nausea (46%)

Musculoskeletal pain (40%)

Fatigue (34%)

Vomiting (28%)

Dyspnea (25%)

Decreased appetite (21%)

Cough (21%)

The most common Grade 3–4 laboratory abnormalities (incidence ≥ 5%) included:

Lymphopenia (14%)

Increased Alanine Aminotransferase (ALT) (9%)

Increased Lipase (9%)

VIII. Drug Interactions

Strong CYP3A4 Inducers (e.g., rifampin, phenytoin, carbamazepine, St. John’s wort): May decrease the plasma concentration of capmatinib, thereby affecting efficacy. Concomitant use should be avoided.

Other Medications: During treatment with capmatinib, patients should inform their physician before starting or discontinuing any other prescription medications, over-the-counter drugs, or herbal products.

IX. Use in Specific Populations

Pregnant Women: Based on its mechanism of action, this drug may cause fetal harm; therefore, it is contraindicated.

Lactating Women: Breastfeeding is not recommended during treatment and for at least 1 week after the last dose.

Pediatric and Adolescent Patients: Safety and efficacy have not been established.

Geriatric Patients: In clinical studies, no overall differences in safety or efficacy were observed between patients aged 65 and older and younger patients.

X. Storage

Store at room temperature (20–25°C).

Once the bottle is opened, the contents should be used within 6 weeks; any remaining tablets should be discarded thereafter.

Keep out of reach of children.

Important Note

This package insert is based on official information and is provided for reference purposes only; it does not substitute for professional medical advice. All treatment decisions must be made by an oncologist following a comprehensive assessment of the patient's condition.

How to Choose: Gumetinib / Berotinib / Capmatinib / Tepotinib? Gumetini, Boretini, Capmatinib, and Tepotinib all belong to the Class Ib category of MET tyrosine kinase inhibitors. They are primarily used to treat non-small cell lung cancer (NSCLC) characterized by MET gene abnormalities—specifically, *MET* exon 14 skipping mutations. Their commonality lies in their targeted action against the MET pathway; however, they differ in terms of their region of development, market approval status, clinical data, side effect profiles, pricing, and accessibility.

**I. Basic Comparison of the Four Drugs**

**Gumetini:** Developed by Haihe Biopharma (China); currently approved for market use only in China.

**Boretini:** Developed by Anshi Biopharma (China); currently approved for market use only in China.

**Capmatinib:** Developed by Novartis (Switzerland); approved for market use by the U.S. FDA, in the EU, and in China.

**Tepotinib:** Developed by Merck (Germany); approved for market use by the U.S. FDA, in the EU, and in China.

**II. Key Distinctions**

**1. Efficacy and Clinical Evidence**

**Capmatinib**

One of the earliest MET inhibitors to receive global approval.

Supported by mature clinical data and demonstrates a high response rate.

Also shows efficacy in patients with brain metastases.

**Tepotinib**

A frequently recommended drug in international clinical guidelines.

Generally well-tolerated and convenient to administer orally.

Widely utilized in elderly patient populations.

**Gumetini**

Independently developed in China.

Clinical data derived from domestic patients is highly representative of the Asian population.

Offers a high cost-effectiveness ratio.

**Boretini**

Market penetration and widespread adoption are currently lower than those of the other three drugs.

**2. Comparison of Side Effects (Common)**

All four drugs belong to the Class Ib category of MET inhibitors. This classification signifies a high degree of precision in targeting the MET receptor; they specifically target the mutation while minimizing off-target effects on other cellular pathways, thereby reducing the incidence of side effects.

**Gumetini:** Edema (swelling), nausea, abnormal liver function.

**Capmatinib:** Peripheral edema, nausea, fatigue.

**Tepotinib:** Edema is the most common side effect; others include diarrhea and elevated creatinine levels.

**Boretini:** Side effect profile is similar to the common reactions associated with other MET inhibitors.

It is worth noting that MET inhibitors, as a class, commonly induce edema (swelling of the legs or face); this is a characteristic feature of this category of therapeutic agents. 3. Price and Accessibility (Chinese Market)

Gumitinib: Relatively affordable

Boretinib: Moderate cost

Capmatinib: Relatively expensive; imported medication

Tepotinib: Relatively expensive; imported medication

III. How to Choose?

If you are undergoing treatment in China:

Limited budget → Prioritize Gumitinib

Seeking established international clinical data → Capmatinib / Tepotinib

Patients with brain metastases → Capmatinib may be a preferred choice

Need for medical insurance coverage/accessibility → Domestic medications are a more practical option

IV. Brief Summary

Gumitinib: High cost-effectiveness (domestic)

Boretinib: High-potential option (domestic)

Capmatinib: Mainstream, reliable international choice

Tepotinib: Mainstream, reliable international choice

Product Specifications

Product Name: Capmatinib Hydrochloride Tablets 200 mg * 56 Tablets/Box (Capmaxen)

Common Name: Capmatinib Hydrochloride Tablets

Active Ingredient: Capmatinib Hydrochloride

Dosage Form: Oral film-coated tablets

Specification: 200 mg/tablet; 56 tablets/box

Manufacturer: Everest Pharma Ltd. (Bangladesh)

Indications: Used for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors harbor a mutation leading to MET exon 14 skipping.

This indication is based on genetic testing; the relevant testing method must be validated.

Dosage and Administration: Recommended dose: 400 mg, twice daily (equivalent to two 200 mg tablets), taken orally.

Administration Method:

Take twice daily, approximately 12 hours apart; may be taken with or without food.

Swallow tablets whole; do not break, crush, or chew.

Handling of Missed Doses or Vomiting:

If a dose is missed, skip the missed dose and take the next scheduled dose at the regular time. Do not take an extra dose or double the dose.

If vomiting occurs after taking the medication, do not take an additional dose; take the next scheduled dose at the regular time.