Encorafenib Dosage

Medically reviewed by Drugs.com. Last updated on Apr 26, 2024.

Usual Adult Dose for Non-Small Cell Lung Cancer

450 mg orally once a day in combination with binimetinib
Duration of therapy: Until disease progression or unacceptable toxicity

Comments:

• Prior to initiating therapy, confirm the presence of indicated BRAF mutation in tumor (or plasma, if appropriate) specimens using a US FDA-approved test.
• Refer to the binimetinib manufacturer product information for dosing recommendations.
• If binimetinib is withheld or discontinued, decrease the dose of this drug to 300 mg orally once a day.

Uses:

• In combination with binimetinib, for the treatment of unresectable or metastatic melanoma with a BRAF V600E or V600K mutation
• In combination with binimetinib, for the treatment of metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation

Usual Adult Dose for Melanoma - Metastatic

450 mg orally once a day in combination with binimetinib
Duration of therapy: Until disease progression or unacceptable toxicity

Comments:

• Prior to initiating therapy, confirm the presence of indicated BRAF mutation in tumor (or plasma, if appropriate) specimens using a US FDA-approved test.
• Refer to the binimetinib manufacturer product information for dosing recommendations.
• If binimetinib is withheld or discontinued, decrease the dose of this drug to 300 mg orally once a day.

Uses:

• In combination with binimetinib, for the treatment of unresectable or metastatic melanoma with a BRAF V600E or V600K mutation
• In combination with binimetinib, for the treatment of metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation

Usual Adult Dose for Colorectal Cancer

300 mg orally once a day in combination with cetuximab
Duration of therapy: Until disease progression or unacceptable toxicity

Comments:

• Prior to initiating therapy, confirm the presence of indicated BRAF mutation in tumor specimens using a US FDA-approved test.
• Refer to the cetuximab manufacturer product information for dosing recommendations.
• If cetuximab is discontinued, this drug should also be discontinued.

Use: In combination with cetuximab, for the treatment of metastatic colorectal cancer (CRC) with a BRAF V600E mutation after prior therapy

Renal Dose Adjustments

Mild or moderate renal dysfunction (CrCl 30 to 89 mL/min): No adjustment recommended
Severe renal dysfunction (CrCl less than 30 mL/min): A recommended dose has not been established.

Liver Dose Adjustments

LIVER DYSFUNCTION:
Mild liver dysfunction (Child-Pugh A): No adjustment recommended
Moderate or severe liver dysfunction (Child-Pugh B or C): A recommended dose has not been established.

HEPATOXICITY:

• Grade 2 AST/ALT increased: Maintain the dose; if no improvement within 4 weeks, withhold this drug until improved to grade 0 or 1, or to pretreatment/baseline levels; then, resume at same dose.
• Recurrent grade 2 or first occurrence of any grade 3 AST/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. Permanently discontinue this drug if there is no improvement.
• First occurrence of any grade 4 AST/ALT increased: Permanently discontinue this drug OR withhold therapy 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.
• Recurrent grade 3 AST/ALT increased: Consider permanently discontinuing this drug.
• Recurrent grade 4 AST/ALT increased: Permanently discontinue this drug.

Dose Adjustments

MELANOMA or NSCLC:
Stepwise Dose Reductions for Adverse Reactions:

• First dose reduction: Decrease to 300 mg orally once a day
• Second dose reduction: Decrease to 225 mg orally once a day
• Third dose reduction: Permanently discontinue therapy if unable to tolerate 225 mg orally once a day.

If Therapy with Binimetinib is Withheld: Reduce encorafenib dose to a maximum of 300 mg orally once a day until combination therapy is resumed.

COLORECTAL CANCER:
Stepwise Dose Reductions for Adverse Reactions:

• First dose reduction: Decrease to 225 mg orally once a day
• Second dose reduction: Decrease to 150 mg orally once a day
• Third dose reduction: Permanently discontinue therapy if unable to tolerate 150 mg orally once a day.

If Therapy with Cetuximab is Discontinued: Discontinue treatment with encorafenib.

DOSE MODIFICATIONS FOR SELECTED ADVERSE REACTIONS:
New Primary Malignancies:

• Non-cutaneous RAS mutation-positive malignancies: Permanently discontinue this drug.
• Cutaneous malignancies: Dose modification is not recommended.

Cardiomyopathy:

• Symptomatic congestive heart failure or absolute decrease in left ventricular ejection fraction (LVEF) greater than 20% from baseline and below lower limit of normal (LLN): Reduce by 1 dose level
• If improvement to at least LLN and absolute decrease is 10% or less as compared to baseline, continue at reduced dose
• If no improvement, withhold treatment until improvement to at least LLN and absolute decrease is 10% or less as compared to baseline; then, resume at reduced dose or reduce an additional dosing level.

Uveitis (including Iritis and Iridocyclitis):

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

QTc Prolongation:

• QTcF greater than 500 milliseconds (ms), with 60 ms or less increase from baseline: Withhold this drug until QTcF is 500 ms or less; then, resume at reduced dose. If more than 1 recurrence, permanently discontinue this drug.
• QTcF greater than 500 ms, with greater than 60 ms increase from baseline: 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 at reduce dose if recurrent.
• Grade 4: Permanently discontinue this drug.

Other Adverse Reactions (Including Hemorrhage and Hand-Foot Skin Reaction):

• Recurrent grade 2 or first occurrence of any grade 3: Withhold this drug for up to 4 weeks; if improvement to grade 0 or 1, or to pretreatment/baseline level, resume at reduced dose. Permanently discontinue this drug if there is no improvement.
• First occurrence of any grade 4: Permanently discontinue this drug OR withhold therapy for up to 4 weeks. If improvement to grade 0 or 1 or to baseline level, 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.

COADMINISTRATION WITH STRONG OR MODERATE CYP450 3A4 INHIBITORS:
General Recommendations:

• Avoid concomitant use of strong or moderate CYP450 3A4 inhibitors during therapy; drug exposure is expected to be significantly higher.
• Use clinical judgment with close patient monitoring and dose adjustment (when indicated) if concomitant use cannot be avoided.
• After discontinuing use of CYP450 3A4 inhibitor for 3 to 5 half-lives, resume this drug at the prior dose.

Dose Reductions During Concomitant Use with a Moderate or Strong CYP450 3A4 Inhibitor:

• Current dose 450 mg once a day:
• Moderate inhibitor: Decrease dose to 225 mg once a day
• Strong inhibitor: Decrease dose to 150 mg once a day
• Current dose 300 mg once a day:
• Moderate inhibitor: Decrease dose to 150 mg once a day
• Strong inhibitor: Decrease dose to 75 mg once a day
• Current dose 225 mg once a day:
• Moderate or strong inhibitor: Decrease dose to 75 mg once a day
• Current dose 150 mg once a day:
• Moderate or strong inhibitor: Decrease dose to 75 mg once a day

Comments:

• Dose modification of this drug when administered with binimetinib or with cetuximab is not recommended for ocular events other than uveitis, iritis, and iridocyclitis, interstitial lung disease/pneumonitis, creatine phosphokinase elevation, rhabdomyolysis, and venous thromboembolism.
• Consult the binimetinib or cetuximab manufacturer product information for adverse reaction dose modifications associated with each product, as appropriate.

Precautions

CONTRAINDICATIONS: None

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Comments:

• This drug is highly bound to plasma proteins; efficient removal via hemodialysis is unlikely.

Other Comments

Administration advice:

• For oral use
• Consult the manufacturer product information prior to treatment for detailed recommendations.
• Before starting therapy, confirm the presence of indicated BRAF mutations in tumor and/or plasma specimens using a US FDA-approved test.
• Administer with or without food.
• If a dose is missed, do not administer an additional dose if it is within 12 hours of the next dose.
• If vomiting occurs after administration, do not administer an additional dose; 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).
• Protect from moisture; keep desiccant in bottle and container tightly closed.

General:

• Limitation of use: This drug is not indicated for treatment of patients with wild-type BRAF melanoma, wild-type BRAF CRC, or wild-type BRAF NSCLC.
• Information on US FDA-approved tests for the detection of BRAF mutations is available at: http://www.fda.gov/CompanionDiagnostics

Monitoring:

• Cardiovascular: For left ventricular dysfunction (prior to therapy, after 1 month, and then every 2 to 3 months thereafter); for QT prolongation or for risk thereof (prior to and during therapy as indicated)
• Dermatologic: Skin evaluations (prior to therapy, every 2 months during therapy, and for 6 months after discontinuation)
• Hepatic: Liver function tests (prior to and during therapy as clinically indicated)
• Metabolic: Electrolytes (prior to and during therapy; correct abnormalities as indicated)
• Ocular: Ophthalmic evaluations (at regular intervals during therapy)
• Oncologic: For new non-cutaneous malignancies (prior to, during, and after therapy)

Patient advice:

• Read the US FDA-approved patient labeling (Medication Guide).
• Prior to treatment, ensure confirmation of BRAF V600E or V600K mutation, as indicated.
• Tell your healthcare provider about all of the medicines you take.
• Inform your health care provider immediately for change or development of any new skin lesion.
• Report any symptoms of heart failure, liver dysfunction, unusual bleeding, vision changes, or syncope to your health care provider.
• Patients of childbearing potential: Contact your health care provider regarding a known or suspected pregnancy. Use effective non-hormonal contraception during treatment and for 2 weeks after the last dose.
• Breastfeeding is not recommended during treatment.

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Further information

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