Active Ingredient: Capmatinib
Capmatinib as monotherapy is indicated for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) harbouring alterations leading to mesenchymal-epithelial transition factor gene exon 14 (METex14) skipping, who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy.
For this indication, competent medicine agencies globally authorize below treatments:
For:
Oral, 400 milligrams capmatinib, 2 times daily.
The recommended dose of capmatinib is 400 mg orally twice daily with or without food.
Treatment should be continued based on individual safety and tolerability and as long as the patient is deriving clinical benefit from therapy.
If a dose of capmatinib is missed or vomiting occurs, the patient should not make up for the dose, but take the next dose at the scheduled time.
The recommended dose reduction schedule for the management of adverse reactions based on individual safety and tolerability is listed in Table 1.
Table 1. Capmatinib dose reduction schedule:
| Dose level | Dose and schedule | Number and strength of tablets |
|---|---|---|
| Starting dose | 400 mg twice daily | Two 200 mg tablets / twice daily |
| First dose reduction | 300 mg twice daily | Two 150 mg tablets / twice daily |
| Second dose reduction | 200 mg twice daily | One 200 mg tablet / twice daily |
Doses of capmatinib below 200 mg twice daily have not been investigated in clinical studies.
Recommendations for dose modifications of capmatinib for adverse reactions are provided in Table 2.
Table 2. Capmatinib dose modifications for the management of adverse reactions:
| Adverse reaction | Severity | Dose modification |
|---|---|---|
| Interstitial lung disease (ILD)/pneumonitis | Any grade treatment-related | Permanently discontinue capmatinib. |
| Isolated ALT and/or AST elevations from baseline, without concurrent total bilirubin increase | Grade 3 (>5.0 to ≤20.0 x ULN) | Temporarily withhold capmatinib until recovery to baseline ALT/AST grade. If recovered to baseline within 7 days, then resume capmatinib at the same dose, otherwise resume capmatinib at a reduced dose as per Table 1. |
| Grade 4 (>20.0 x ULN) | Permanently discontinue capmatinib. | |
| Combined elevations in ALT and/or AST with concurrent total bilirubin increase, in the absence of cholestasis or haemolysis | If patient develops ALT and/or AST >3 x ULN along with total bilirubin >2 x ULN, irrespective of baseline grade | Permanently discontinue capmatinib. |
| Isolated total bilirubin elevation from baseline, without concurrent ALT and/or AST increase | Grade 2 (>1.5 to ≤3.0 x ULN) | Temporarily withhold capmatinib until recovery to baseline bilirubin grade. If recovered to baseline within 7 days, then resume capmatinib at the same dose, otherwise resume capmatinib at a reduced dose as per Table 1. |
| Grade 3 (>3.0 to ≤10.0 x ULN) | Temporarily withhold capmatinib until recovery to baseline bilirubin grade. If recovered to baseline within 7 days, then resume capmatinib at a reduced dose as per Table 1, otherwise permanently discontinue capmatinib. | |
| Grade 4 (>10.0 x ULN) | Permanently discontinue capmatinib. | |
| Serum creatinine increased | Grade 2 (>1.5 to ≤3.0 x ULN) | Temporarily withhold capmatinib until recovery to baseline serum creatinine grade. If recovered to baseline, then resume capmatinib at the same dose level. |
| Grade 3 (>3.0 to ≤6.0 x ULN) | Temporarily withhold capmatinib until recovery to baseline serum creatinine grade. If recovered to baseline, then resume capmatinib at a reduced dose as per Table 1. | |
| Grade 4 (>6.0 x ULN) | Permanently discontinue capmatinib. | |
| Vomiting | Grade 2 | Temporarily withhold capmatinib until resolved to grade ≤1. If resolved to grade ≤1 then resume capmatinib the same dose level. |
| Grade 3 | Temporarily withhold capmatinib until resolved to grade ≤2. If resolved to grade ≤2 then resume capmatinib at a reduced dose as per Table 1. | |
| Grade 4 | Temporarily withhold capmatinib until resolved to grade ≤2. If resolved to grade ≤2 then resume capmatinib at a reduced dose as per Table 1. | |
| Other adverse reactions | Grade 2 | Maintain dose level. If intolerable, consider temporarily withholding capmatinib until resolved, then resume capmatinib at a reduced dose as per Table 1. |
| Grade 3 | Temporarily withhold capmatinib until resolved, then resume capmatinib at a reduced dose as per Table 1. | |
| Grade 4 | Permanently discontinue capmatinib. |
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; ULN, upper limit of normal.
Grading according to CTCAE Version 4.03 (CTCAE = Common Terminology Criteria for Adverse Events).
Baseline = at the time of treatment initiation.
Capmatinib should be taken orally twice daily with or without food. Patients with swallowing difficulties are recommended to take capmatinib tablets with food. The tablets should be swallowed whole to ensure that the full dose is administered.
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