Usual Adult Dose for Melanoma - Metastatic

45 mg orally every 12 hours in combination with encorafenib until disease progression or unacceptable toxicity

Comments:

• Refer to the encorafenib prescribing information for encorafenib dosing information.
• This drug may be taken with or without food.
• Do not take a missed dose within 6 hours of the next dose.
• Do not take an additional dose if vomiting occurs after administration but continue with the next scheduled dose.

Renal Dose Adjustments

No adjustment recommended.

Liver Dose Adjustments

• Mild hepatic impairment (total bilirubin greater than 1 and less than or equal to 1.5 x the upper limit of normal (ULN) and any AST or total bilirubin less than or equal to ULN and AST greater than ULN: No adjustment recommended.
• Moderate (total bilirubin greater than 1.5 and less than or equal to 3 × ULN and any AST) or severe (total bilirubin levels greater than or equal to 3 × ULN and any AST) hepatic impairment: The recommended dose is 30 mg orally 2 times a day.

Dose Adjustments

If encorafenib is permanently discontinued, discontinue this drug.

Recommended Dose Reductions for Adverse Reactions:

• First dose reduction: 30 mg orally every 12 hours
• Subsequent modification: Permanently discontinue this drug if unable to tolerate 30 mg orally every 12 hours.

• Asymptomatic, absolute decrease in LVEF of greater than 10% from baseline that is also below lower limit of normal (LLN): Withhold this drug for up to 4 weeks; evaluate LVEF every 2 weeks. Resume this drug at a reduced dose if LVEF is at or above the lower limit or normal AND absolute decrease from baseline is 10% or less AND patient is asymptomatic. If the LVEF does not recover within 4 weeks permanently discontinue this drug.
• Symptomatic congestive heart failure or absolute decrease in LVEF or greater than 20% from baseline that is also below LLN: Permanently discontinue this drug.

• Uncomplicated deep venous thrombosis (DVT) or pulmonary embolism (PE): Withhold this drug. If improves to Grade 0 or 1, resume at a reduced dose. If no improvement, permanently discontinue this drug.
• Life threatening PE: Permanently discontinue this drug.

• Symptomatic serous retinopathy/retinal pigment epithelial detachments: Withhold this drug for up to 10 days. If improves and becomes asymptomatic, resume at the same dose. If not improved, resume at a lower dose level or permanently discontinue this drug.

• Any grade: Permanently discontinue this drug.

• Grade 1, 2, or 3: If Grade 1 or 2 does not respond to specific ocular therapy, or for Grade 3 uveitis, withhold this drug for up to 6 weeks. If improved, resume at same or reduced dose. If not improved, permanently discontinue this drug.
• Grade 4: Permanently discontinue this drug.

• Grade 2: Withhold this drug for up to 4 weeks. If improved to Grade 0 or 1, resume a reduced dose. If not resolved within 4 weeks, permanently discontinue this drug.
• Grade 3 or 4: Permanently discontinue this drug.

• Grade 2 AST or ALT increased: Maintain the dose. If no improvement within 2 weeks, withhold this drug until improved to Grade 0 or 1 or to pretreatment/baseline levels and then resume at the same dose.
• First occurrence of Grade 3 AST or ALT increased: Withhold this drug for up to 4 weeks. If improves to Grade 0 or 1 or to pretreatment/baseline levels, resume at reduced dose. If no improvement, permanently discontinue this drug.
• Recurrent Grade 3 AST or ALT increased: Consider permanently discontinuing this drug.
• First occurrence of Grade 4 AST or ALT increased: Permanently discontinue this drug OR withhold this drug for up to 4 weeks. If improves to Grade 0 or 1 or to pretreatment/baseline levels, then resume at a reduced dose. If no improvement, permanently discontinue this drug.
• Recurrent Grade 4 AST or ALT increased: Permanently discontinue this drug.

• Grade 4 asymptomatic CPK elevation OR any Grade CPK elevation with symptoms or with renal impairment: Withhold this drug for up to 4 weeks. If improved to Grade 0 or 1 resume at a reduced dose. If not resolved within 4 weeks, permanently discontinue this drug.

• Grade 2: If no improvement within 2 weeks, withhold this drug until Grade 0 to 1. Resume at same dose if first occurrence or reduce dose if recurrent.
• Grade 3: Withhold this drug until Grade 0 or 1. Resume at same dose if first occurrence or reduce dose if recurrent.
• Grade 4: Permanently discontinue this drug.

• Recurrent Grade 2 or first occurrence of any Grade 3: Withhold this drug for up to 4 weeks. If improved to Grade 0 or 1 resume at a reduced dose. If not resolved within 4 weeks, permanently discontinue this drug.
• First occurrence of any Grade 4: Permanently discontinue this drug OR withhold this drug for up to 4 weeks. If improves to Grade 0 or 1 or to pretreatment/baseline levels, then resume at a reduced dose. If no improvement, permanently discontinue this drug.

Precautions

CONTRAINDICATIONS:

• None

Dialysis

This drug is 95% bound to plasma proteins; therefore, it is unlikely to be removed by hemodialysis.

Other Comments

Administration advice:

• Refer to the encorafenib prescribing information for encorafenib dosing information.
• This drug may be taken with or without food.
• Do not take a missed dose within 6 hours of the next dose.
• Do not take an additional dose if vomiting occurs after administration but continue with the next scheduled dose.

• Store at 20C to 25C (68F to 77F); excursions permitted between 15C and 30C (59F and 86F).

Frequently asked questions

• What is Mektovi used to treat?