Braftovi Dosage

Generic name: ENCORAFENIB 75mg
Dosage form: capsule
Drug class: Multikinase inhibitors

Medically reviewed by Drugs.com. Last updated on Sep 18, 2024.

Patient Selection

BRAF V600E or V600K Mutation-Positive Unresectable or Metastatic Melanoma

Confirm the presence of a BRAF V600E or V600K mutation in tumor specimens prior to initiating BRAFTOVI. Do not take a missed dose of BRAFTOVI within 12 hours of the next dose of BRAFTOVI.

Do not take an additional dose if vomiting occurs after BRAFTOVI administration but continue with the next scheduled dose.

Dosage Modifications for Adverse Reactions

BRAF V600E or V600K Mutation-Positive Unresectable or Metastatic Melanoma or BRAF V600E Mutation-Positive Metastatic NSCLC

If binimetinib is withheld, reduce BRAFTOVI to a maximum dose of 300 mg (four 75 mg capsules) once daily until binimetinib is resumed.

Dose reductions for adverse reactions associated with BRAFTOVI are presented in Table 1.

Table 1: Recommended Dose Reductions for BRAFTOVI for Adverse Reactions – Melanoma or NSCLC

Action	Recommended Dose
First Dose Reduction	300 mg (four 75 mg capsules) orally once daily
Second Dose Reduction	225 mg (three 75 mg capsules) orally once daily
Subsequent Modification	Permanently discontinue if unable to tolerate BRAFTOVI 225 mg (three 75 mg capsules) once daily

BRAF V600E Mutation-Positive Metastatic Colorectal Cancer (CRC)

If cetuximab is discontinued, discontinue BRAFTOVI.

Dose reductions for adverse reactions associated with BRAFTOVI are presented in Table 2.

Table 2: Recommended Dose Reductions for BRAFTOVI for Adverse Reactions – CRC
Action	Recommended Dose
First Dose Reduction	225 mg (three 75 mg capsules) orally once daily
Second Dose Reduction	150 mg (two 75 mg capsules) orally once daily
Subsequent Modification	Permanently discontinue if unable to tolerate BRAFTOVI 150 mg (two 75 mg capsules) once daily

BRAF V600E or V600K Mutation-Positive Unresectable or Metastatic Melanoma, BRAF V600E Mutation-Positive Metastatic Colorectal Cancer (CRC), or BRAF V600E Mutation-Positive NSCLC

Dosage modifications for adverse reactions associated with BRAFTOVI are presented in Table 3.

Table 3: Recommended Dosage Modifications for BRAFTOVI for Adverse Reactions
Severity of Adverse Reaction*	Dose Modification for BRAFTOVI
* National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. † Dose modification of BRAFTOVI when administered with binimetinib or with cetuximab is not recommended for new primary cutaneous malignancies; ocular events other than uveitis, iritis, and iridocyclitis; interstitial lung disease/pneumonitis; creatine phosphokinase (CPK) elevation; rhabdomyolysis; and venous thromboembolism.
New Primary Malignancies
Non-Cutaneous RAS Mutation-positive Malignancies	Permanently discontinue BRAFTOVI.
Cardiomyopathy
• Symptomatic congestive heart failure or absolute decrease in LVEF of greater than 20% from baseline that is also below LLN	Reduce BRAFTOVI by one dose level. • If LVEF improves to at least institutional LLN and absolute decrease to less than or equal to 10% compared to baseline, continue BRAFTOVI at the reduced dose. • If no improvement, withhold BRAFTOVI until improves to at least institutional LLN and absolute decrease to less than or equal to 10% compared to baseline and then resume at the reduced dose or reduce dose an additional dose level.
Hepatotoxicity
• Grade 2 AST or ALT increased	Maintain BRAFTOVI dose. • If no improvement within 4 weeks, withhold BRAFTOVI until improves to Grade 0-1 or to pretreatment/baseline levels and then resume at same dose.
• Grade 3 or 4 AST or ALT increased	See Other Adverse Reactions.
Uveitis
• Grade 1–3	If Grade 1 or 2 does not respond to specific ocular therapy, or for Grade 3 uveitis, withhold BRAFTOVI for up to 6 weeks. • If improved, resume at same or reduced dose. • If not improved, permanently discontinue BRAFTOVI.
• Grade 4	Permanently discontinue BRAFTOVI.
QTc Prolongation
• QTcF greater than 500 ms and less than or equal to 60 ms increase from baseline	Withhold BRAFTOVI until QTcF less than or equal to 500 ms. Resume at reduced dose. • If more than one recurrence, permanently discontinue BRAFTOVI.
• QTcF greater than 500 ms and greater than 60 ms increase from baseline	Permanently discontinue BRAFTOVI.
Dermatologic [other than Hand-foot Skin Reaction (HFSR)]
• Grade 2	If no improvement within 2 weeks, withhold BRAFTOVI until Grade 0–1. Resume at same dose.
• Grade 3	Withhold BRAFTOVI until Grade 0–1. Resume at same dose if first occurrence or reduce dose if recurrent.
• Grade 4	Permanently discontinue BRAFTOVI.
Other Adverse Reactions (including Hemorrhage) and HFSR†
• Recurrent Grade 2 or • First occurrence of any Grade 3	Withhold BRAFTOVI for up to 4 weeks. • If improves to Grade 0–1 or to pretreatment/baseline level, resume at reduced dose. • If no improvement, permanently discontinue BRAFTOVI.
• First occurrence of any Grade 4	Permanently discontinue BRAFTOVI or Withhold BRAFTOVI for up to 4 weeks. • If improves to Grade 0–1 or to pretreatment/baseline level, then resume at reduced dose. • If no improvement, permanently discontinue BRAFTOVI.
• Recurrent Grade 3	Consider permanently discontinuing BRAFTOVI.
• Recurrent Grade 4	Permanently discontinue BRAFTOVI.

Refer to the binimetinib or cetuximab prescribing information for dose modifications for adverse reactions associated with each product, as appropriate.

Dose Modifications for Coadministration With Strong or Moderate CYP3A4 Inhibitors

Avoid coadministration of BRAFTOVI with strong or moderate CYP3A4 inhibitors. If coadministration is unavoidable, reduce the BRAFTOVI dose according to the recommendations in Table 4. After the inhibitor has been discontinued for 3 to 5 elimination half-lives, resume the BRAFTOVI dose that was taken prior to initiating the CYP3A4 inhibitor.

Table 4: Recommended Dose Reductions for BRAFTOVI for Coadministration With Strong or Moderate CYP3A4 Inhibitors
Current Daily Dose*	Dose for Coadministration with Moderate CYP3A4 Inhibitor	Dose for Coadministration with Strong CYP3A4 Inhibitor
* Current daily dose refers to recommended dose of BRAFTOVI based on indication or reductions for adverse reactions based on dosing recommendations in Table 1 (Melanoma) and Table 2 (CRC). † Encorafenib exposure at the 75 mg QD BRAFTOVI dosage when coadministered with a strong CYP3A4 inhibitor is expected to be higher than at the 150 mg QD dosage in the absence of a CYP3A4 inhibitor and similar to exposure at the 225 mg QD dosage in the absence of a CYP3A4 inhibitor. Monitor patients closely for adverse reactions and use clinical judgement when using BRAFTOVI with strong CYP3A4 inhibitors at the 150 mg dose level.
450 mg	225 mg (three 75 mg capsules)	150 mg (two 75 mg capsules)
300 mg	150 mg (two 75 mg capsules)	75 mg
225 mg	75 mg	75 mg
150 mg	75 mg	75 mg†