Usual Adult Dose for Melanoma - Metastatic

450 mg orally once a day in combination with binimetinib until disease progression or unacceptable toxicity
NOTE: If binimetinib is withheld, reduce encorafenib to a maximum dose of 300 mg once a day until binimetinib is resumed.

Comments:

• Confirm the presence of a BRAF V600E or V600K mutation in tumor specimens prior to initiating therapy.
• Refer to the binimetinib prescribing information for recommended dosing information.

Use: This drug, in combination with binimetinib, is indicated for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test

Usual Adult Dose for Colorectal Cancer

300 mg orally once a day in combination with cetuximab until disease progression or unacceptable toxicity

Comments:

• Confirm the presence of a BRAF V600E mutation in tumor specimens prior to initiating therapy.
• Refer to the cetuximab prescribing information for recommended dosing information.

Use: This drug, in combination with cetuximab, is indicated for the treatment of adult patients with metastatic colorectal cancer (CRC) with a BRAF V600E mutation, as detected by an FDA-approved test, after prior therapy

Renal Dose Adjustments

Mild to moderate renal impairment (CrCl 30 to less than 90 mL/min): No adjustment recommended.
Severe renal impairment (CrCl less than 30 mL/min): Dose adjustment may be required; however, no specific guidelines have been suggested.

Liver Dose Adjustments

Mild hepatic (Child-Pugh A) impairment: No adjustment recommended.
Moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment: Dose adjustment may be required; however, no specific guidelines have been suggested.

Dose Adjustments

BRAF V600E OR V600K MUTATION-POSITIVE UNRESECTABLE OR METASTATIC MELANOMA:

• If binimetinib is withheld, reduce encorafenib to a maximum dose of 300 orally mg once a day until binimetinib is resumed.
• If cetuximab is discontinued, discontinue binimetinib.

RECOMMENDED DOSE REDUCTIONS FOR ADVERSE REACTIONS for BRAF V600E or V600K Mutation-Positive Unresectable or Metastatic Melanoma:

• First dose reduction: 300 mg orally once a day
• Second dose reduction: 225 mg orally once a day
• Subsequent modification: Permanently discontinue this drug if unable tolerate 225 mg once a day.

BRAF V600E MUTATION-POSITIVE METASTATIC COLORECTAL CANCER (CRC):

• If cetuximab is discontinued, discontinue binimetinib.

RECOMMENDED DOSE REDUCTIONS FOR ADVERSE REACTIONS for BRAF V600E MUTATION-POSITIVE METASTATIC CRC:

• First dose reduction: 225 mg orally once a day
• Second dose reduction: 150 mg orally once a day
• Subsequent modification: Permanently discontinue this drug if unable tolerate 150 mg once a day.

BRAF V600E or V600K Mutation-Positive Unresectable or Metastatic Melanoma and BRAF V600E Mutation-Positive Metastatic Colorectal Cancer (CRC):
NEW PRIMARY MALIGNANCIES:

• Non-cutaneous RAS mutation-positive malignancies: Discontinue this drug.

UVEITIS:

• Grade 1 through 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 therapy.

QTc PROLONGATION:

• QTcF greater than 500 milliseconds (ms) and less than or equal to 60 ms increase from baseline: Withhold this drug until QTcF is less than or equal to 500 ms; resume at reduced dose; if more than one recurrence, permanently discontinue this drug.
• QTcF greater than 500 ms and greater than 60 ms increase from baseline: Permanently discontinue this drug.

HEPATOTOXICITY:

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

DERMATOLOGIC:

• Grade 2: If no improvement within 2 weeks, withhold this drug until Grade 0 or 1; resume at same dose.
• 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.

OTHER ADVERSE REACTIONS (INCLUDING HEMORRHAGE):

• Recurrent Grade 2 or first occurrence of any Grade 3: Withhold this drug for up to 4 weeks; if improves to Grade 0 or 1 or to pretreatment/baseline level, then resume at reduced dose; if no improvement, permanently discontinue this drug.
• First occurrence of any Grade 4: Permanently discontinue this drug OR withhold for up to 4 weeks; if improves to Grade 0 or 1 or to pretreatment/baseline level, then resume at reduced dose; if no improvement, permanently discontinue this drug.
• Recurrent Grade 3: Consider permanently discontinuing this drug.
• Recurrent Grade 4: Permanently discontinue this drug.

DOSE MODIFICATIONS FOR COADMINISTRATION OF STRONG OR MODERATE CYP450 3A4 INHIBITORS:
Avoid concurrent use of strong or moderate CYP450 3A4 inhibitors during therapy with this drug. If concomitant use of a strong or moderate CYP450 3A4 inhibitor is unavoidable, reduce the dose of this drug as follows:
Current daily dose 450 mg:

• Dose for coadministration with moderate CYP450 3A4 inhibitor: 225 mg
• Dose for coadministration with strong CYP450 3A4 inhibitor: 150 mg

Current daily dose 300 mg:

• Dose for coadministration with moderate CYP450 3A4 inhibitor: 150 mg
• Dose for coadministration with strong CYP450 3A4 inhibitor: 75 mg

Current daily dose 225 mg:

• Dose for coadministration with moderate CYP450 3A4 inhibitor: 75 mg
• Dose for coadministration with strong CYP450 3A4 inhibitor: 75 mg

Current daily dose 150 mg:

• Dose for coadministration with moderate CYP450 3A4 inhibitor: 75 mg
• Dose for coadministration with strong CYP450 3A4 inhibitor: 75 mg (

*NOTE: Encorafenib exposure at the 75 mg daily dose when coadministered with a strong CYP450 3A4 inhibitor is expected to be higher than at the 150 mg daily dose in the absence of a CYP450 3A4 inhibitor and similar to exposure at the 225 mg daily dose in the absence of a CYP450 3A4 inhibitor. Monitor patients closely for adverse reactions and use clinical judgement when using encorafenib with strong CYP450 3A4 inhibitors at the 150 mg dose level.

Precautions

CONTRAINDICATIONS:

• None

This drug is not recommended for use in children.

Consult WARNINGS section for additional precautions.

Dialysis

No adjustment recommended.

Other Comments

Administration advice:

• This drug may be taken with or without food.
• If a dose is missed, do not take it within 12 hours of the next dose.
• Do not take an additional dose if vomiting occurs after administration but continue with the next scheduled dose.

Storage requirements:

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

General:

• Do not use if safety seal under cap is broken or missing.
• Dispense in original bottle.
• Do not remove desiccant. Protect from moisture.
• Keep container tightly closed.

Frequently asked questions

• What is Braftovi used to treat?