Binimetinib is often used in combination with encorafenib. These two drugs target the same signaling pathway at different points and can synergistically slow cancer cell growth.
Used Dosage of Binimetinib
1. Adult Metastatic Melanoma
When used in combination with encorafenib, the dosage is 45 mg orally every 12 hours until disease progression or unacceptable toxicity.
2. Non-Small Cell Lung Cancer
When used in combination with encorafenib, the dosage is 45 mg orally every 12 hours until disease progression or unacceptable toxicity.
Dosage Recommendations for Binimetinib
1. Binimetinib can be taken with food or on an empty stomach.
2. If a dose is missed, it is not necessary to take a missed dose if the next dose is less than 6 hours away.
3. If vomiting occurs after taking the medication, no additional dose is needed; take the next scheduled dose as planned.
Bimetatinib Dosage Adjustment
Initial Dose Reduction: 30 mg orally every 12 hours.
Subsequent Adjustments: If the dose of 30 mg every 12 hours cannot be tolerated, permanently discontinue binimetinib.
If cannefenib is permanently discontinued, binimetinib should also be discontinued.
Bimetatinib Dosage Adjustment in Special Populations
1. Dosage Adjustment in Renal Impairment
Dose adjustment is not recommended.
2. Dosage Adjustment in Hepatic Impairment
Mild Hepatic Impairment: Dosage adjustment is not recommended.
Moderate or Severe Hepatic Impairment: The recommended dose is 30 mg orally twice daily.
Dose Adjustment for Specific Adverse Reactions of Binimetinib
1. Cardiomyopathy
(1) Asymptomatic, with an absolute decrease in left ventricular ejection fraction (LVEF) of more than 10% from baseline and below the lower limit of normal (LLN)
Discontinue binimetinib treatment for a maximum of 4 weeks; assess LVEF every 2 weeks. If LVEF recovers to the lower limit of normal or above, and the absolute decrease from baseline is ≤10%, and the patient is asymptomatic, binimetinib treatment can be resumed at a reduced dose. If LVEF does not recover within 4 weeks, permanently discontinue binimetinib.
(2) Symptomatic congestive heart failure, or an absolute decrease in LVEF of more than 20% from baseline and below LLN
Permanently discontinue binimetinib.
2. Venous Thromboembolism
(1) Uncomplicated deep vein thrombosis (DVT) or pulmonary embolism (PE)
Discontinue binimetinib treatment. If symptoms improve to grade 0 or 1, treatment can be resumed at a reduced dose. If there is no improvement, binimetinib should be permanently discontinued.
(2) Life-threatening pulmonary embolism
Permanently discontinue binimetinib.
3. Serous retinopathy
(1) Symptomatic serous retinopathy/retinal pigment epithelium detachment
Suspend binimetinib treatment for up to 10 days. If symptoms improve and disappear, treatment can be resumed at the original dose.
(2) If there is no improvement
Treatment can be resumed at a reduced dose or binimetinib can be permanently discontinued.
4. Retinal vein occlusion (RVO)
Any grade: Permanently discontinue binimetinib.
5. Uveitis
(1) Grade 1, 2, or 3
If Grade 1 or 2 uveitis is unresponsive to specific ocular treatment, or if it is Grade 3 uveitis, discontinue binimetinib treatment for up to 6 weeks. If symptoms improve, treatment can be resumed at the original dose or a reduced dose. If there is no improvement, permanently discontinue binimetinib.
(2) Grade 4
Permanently discontinue binimetinib.
6. Interstitial Lung Disease
Grade 2: Discontinue binimetinib treatment for up to 4 weeks. If symptoms improve to Grade 0 or 1, treatment can be resumed at a reduced dose. If there is no improvement within 4 weeks, permanently discontinue binimetinib.
Grade 3 or 4: Permanently discontinue binimetinib.
7. Hepatotoxicity
(1) Grade 2: Elevated AST or ALT
Maintain the current dose. (1) If there is no improvement within 2 weeks, discontinue binimetinib treatment until it returns to grade 0 or 1 or pre-treatment/baseline levels, then resume treatment at the original dose.
(2) First occurrence of grade 3 AST or ALT elevation
Discontinue binimetinib treatment for a maximum of 4 weeks. If it returns to grade 0 or 1 or pre-treatment/baseline levels, treatment can be resumed at a reduced dose. If there is no improvement, permanently discontinue binimetinib.
(3) Recurrent grade 3 AST or ALT elevation
Consider permanently discontinuing binimetinib.
(4) First occurrence of grade 4 AST or ALT elevation
Permanently discontinue binimetinib, or discontinue binimetinib treatment for a maximum of 4 weeks. If it returns to grade 0 or 1 or pre-treatment/baseline levels, treatment can be resumed at a reduced dose. If there is no improvement, permanently discontinue binimetinib.
(5) Recurrent Grade 4 AST or ALT elevation
Permanently discontinue binimetinib.
8. Rhabdomyolysis or elevated creatine phosphokinase (CPK)
(1) Grade 4 asymptomatic CPK elevation, or any grade of CPK elevation with symptoms or renal impairment
Suspend binimetinib treatment for up to 4 weeks. If improvement to Grade 0 or 1, treatment can be resumed at a reduced dose. If no relief is achieved within 4 weeks, permanently discontinue binimetinib.
9. Skin reaction
Grade 2: If no improvement is achieved within 2 weeks, suspend binimetinib treatment until Grade 0 or 1 is achieved. Treatment can be resumed at the original dose upon first occurrence, and at a reduced dose upon recurrence.
Grade 3: Suspend binimetinib treatment until Grade 0 or 1 is achieved. Treatment can be resumed at the original dose upon first occurrence, and at a reduced dose upon recurrence.
Grade 4: Permanently discontinue binimetinib.
10. Other Adverse Reactions (including bleeding)
(1) Relapse of Grade 2 or first occurrence of any Grade 3
Suspend binimetinib treatment for up to 4 weeks. If improvement to Grade 0 or 1, treatment can be resumed at a reduced dose. If no improvement is achieved within 4 weeks, permanently discontinue binimetinib.
(2) First occurrence of any Grade 4
Permanently discontinue binimetinib, or suspend binimetinib treatment for up to 4 weeks. If improvement to Grade 0 or 1 or pre-treatment/baseline levels, treatment can be resumed at a reduced dose. If no improvement is achieved, permanently discontinue binimetinib.
