(encorafenib)

Prescribing Information
Download Prescribing Information

2 DOSAGE AND ADMINISTRATION

2 DOSAGE AND ADMINISTRATION

2.1 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 [see Warnings and Precautions (5.2), Clinical Studies (14.1)]. Information on FDA-authorized tests for the detection of BRAF V600E and V600K mutations in melanoma is available at: http://www.fda.gov/CompanionDiagnostics.

BRAF V600E Mutation-Positive Metastatic Colorectal Cancer (CRC)

Confirm the presence of a BRAF V600E mutation in plasma or tumor tissue prior to initiating BRAFTOVI [see Warnings and Precautions (5.2), Clinical Studies (14.2, 14.3)]. If no mutation is detected in a plasma specimen, test tumor tissue. Information on FDA-authorized tests for the detection of BRAF V600E mutations in CRC is available at: http://www.fda.gov/CompanionDiagnostics.

BRAF V600E Mutation-Positive Metastatic Non‑Small Cell Lung Cancer (NSCLC)

Confirm the presence of a BRAF V600E mutation in tumor or plasma specimens prior to initiating BRAFTOVI [see Warnings and Precautions (5.2), Clinical Studies (14.3)]. If no mutation is detected in a plasma specimen, test tumor tissue. Information on FDA-authorized tests for the detection of BRAF V600E mutations in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics.

2.2 Recommended Dosage for BRAF V600E or V600K Mutation-Positive Unresectable or Metastatic Melanoma and for BRAF V600E Mutation-Positive Metastatic Non-Small Cell Lung Cancer (NSCLC)

The recommended dosage of BRAFTOVI is 450 mg (six 75 mg capsules) orally once daily in combination with binimetinib until disease progression or unacceptable toxicity. Refer to the binimetinib prescribing information for recommended binimetinib dosing information.

2.3 Recommended Dosage for BRAF V600E Mutation-Positive Metastatic Colorectal Cancer (CRC)

The recommended dosage of BRAFTOVI is 300 mg (four 75 mg capsules) orally once daily until disease progression or unacceptable toxicity in combination with:

•
biweekly cetuximab and mFOLFOX6 (fluorouracil, leucovorin and oxaliplatin) or biweekly cetuximab and FOLFIRI (fluorouracil, leucovorin and irinotecan)[see Clinical Studies (14.2)]
•
weekly cetuximab [see Clinical Studies (14.2)].

2.4 Administration

BRAFTOVI may be taken with or without food [see Clinical Pharmacology (12.3)]. 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.

2.5 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 [see Warnings and Precautions (5.9)].

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)

When BRAFTOVI is administered in combination with cetuximab and mFOLFOX6 or FOLFIRI

•
Continue BRAFTOVI with mFOLFOX6 or FOLFIRI if cetuximab is permanently discontinued.
•
Permanently discontinue BRAFTOVI if cetuximab and mFOLFOX6 or FOLFIRI are permanently discontinued.

When BRAFTOVI is administered in combination with cetuximab

•
Permanently discontinue BRAFTOVI when cetuximab is permanently discontinued.

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 [see Warnings and Precautions (5.1)]

Noncutaneous RAS Mutation-positive Malignancies

Permanently discontinue BRAFTOVI.

Cardiomyopathy [see Warnings and Precautions (5.3)]

•
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 [see Dosage and Administration (2.3)].

•
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 [see Dosage and Administration (2.3)].
•
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 [see Warnings and Precautions (5.4)]

•
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 [see Warnings and Precautions (5.6)]

•
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 [see Warnings and Precautions (5.7)]

•
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)] [see Adverse Reactions (6.1)]

•
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) [see Warnings and Precautions (5)] and HFSR [see Adverse Reactions (6.1)]†

•
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.

2.6 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 [see Drug Interactions (7.1), Clinical Pharmacology (12.3)].

Table 4: Recommended Dose Reductions for BRAFTOVI for Coadministration with Strong or Moderate CYP3A4 Inhibitors
*
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 judgment when using BRAFTOVI with strong CYP3A4 inhibitors at the 150 mg dose level.

Current Daily Dose*

Dose for Coadministration with Moderate CYP3A4 Inhibitor

Dose for Coadministration with Strong CYP3A4 Inhibitor

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†

Medication Guide

MEDICATION GUIDE

MEDICATION GUIDE
BRAFTOVI® (braf-TOE-vee)
(encorafenib)
capsules

Important information: BRAFTOVI is used in combination with other medicines, including binimetinib, cetuximab, or cetuximab and fluorouracil-based chemotherapy. Read the Medication Guide that comes with binimetinib if BRAFTOVI is used with binimetinib. Talk to your healthcare provider about cetuximab, or cetuximab and mFOLFOX6 or FOLFIRI if used with BRAFTOVI.

What is the most important information I should know about BRAFTOVI?
BRAFTOVI can cause serious side effects, including:

Risk of new skin cancers. BRAFTOVI can cause skin cancers called cutaneous squamous cell carcinoma or basal cell carcinoma.
Talk to your healthcare provider about your risk for these cancers.
Check your skin and tell your healthcare provider right away about any skin changes, including a:

•
new wart
•
skin sore or reddish bump that bleeds or does not heal
•
change in size or color of a mole

Your healthcare provider should check your skin before treatment with BRAFTOVI, every 2 months during treatment, and for up to 6 months after you stop treatment with BRAFTOVI to look for any new skin cancers.

Your healthcare provider should also check for cancers that may not occur on the skin. Tell your healthcare provider about any new symptoms that develop during treatment with BRAFTOVI.

See "What are the possible side effects of BRAFTOVI?" for more information about side effects.

What is BRAFTOVI?
BRAFTOVI is a prescription medicine used:

•
in combination with a medicine called binimetinib to treat people with a type of skin cancer called melanoma:
o
that has spread to other parts of the body or cannot be removed by surgery, and
o
that has a certain type of abnormal "BRAF" gene
•
in combination with medicines called cetuximab and mFOLFOX6 (fluorouracil, leucovorin and oxaliplatin) or cetuximab and FOLFIRI (fluorouracil, leucovorin, and irinotecan) to treat adults with cancer of the colon or rectum (colorectal cancer):
o
that has spread to other parts of the body, and
o
that has a certain type of abnormal "BRAF" gene
•
in combination with a medicine called cetuximab to treat adults with cancer of the colon or rectum (colorectal cancer) after past treatment:
o
that has spread to other parts of the body, and
o
that has a certain type of abnormal "BRAF" gene
•
in combination with a medicine called binimetinib to treat adults with a type of lung cancer called non‑small‑cell lung cancer (NSCLC):
o
that has spread to other parts of the body, and
o
that has a certain type of abnormal "BRAF" gene

BRAFTOVI should not be used to treat people with wild-type‑BRAF melanoma, wild-type‑BRAF colorectal cancer, or wild-type‑BRAF NSCLC.

Your healthcare provider will perform a test to make sure that BRAFTOVI is right for you.
It is not known if BRAFTOVI is safe and effective in children.

Before taking BRAFTOVI, tell your healthcare provider about all of your medical conditions, including if you:

•
have had bleeding problems
•
have eye problems
•
have heart problems, including a condition called long QT syndrome
•
have been told that you have low blood levels of potassium, calcium, or magnesium
•
have liver or kidney problems
•
are pregnant or plan to become pregnant. BRAFTOVI can harm your unborn baby.

Females who are able to become pregnant:

 
o
Use effective nonhormonal birth control (contraception) during treatment with BRAFTOVI and for 2 weeks after the last dose of BRAFTOVI. Birth control methods that contain hormones (such as birth control pills, injections or transdermal systems) may not work as well during treatment with BRAFTOVI.
o
Talk to your healthcare provider about birth control methods that may be right for you during this time.
o
Your healthcare provider will do a pregnancy test before you start taking BRAFTOVI. Tell your healthcare provider right away if you become pregnant or think you might be pregnant during treatment with BRAFTOVI.
•
are breastfeeding or plan to breastfeed. It is not known if BRAFTOVI passes into your breast milk. Do not breastfeed during treatment with BRAFTOVI and for 2 weeks after the last dose of BRAFTOVI. Talk to your healthcare provider about the best way to feed your baby during this time.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
BRAFTOVI and certain other medicines can affect each other, causing side effects or affecting how BRAFTOVI or the other medicines work.
Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

How should I take BRAFTOVI?

•
Take BRAFTOVI exactly as your healthcare provider tells you. Do not change your dose or stop taking BRAFTOVI unless your healthcare provider tells you to.
•
Take BRAFTOVI by mouth 1 time each day.
•
BRAFTOVI may be taken with or without food.
•
Avoid grapefruit and grapefruit juice during treatment with BRAFTOVI. Grapefruit products may increase the amount of BRAFTOVI in your body.
•
If you miss a dose of BRAFTOVI, take it as soon as you remember. If it is within 12 hours of your next scheduled dose, take your next dose at your regular time. Do not make up for the missed dose.
•
Do not take an extra dose if you vomit after taking your scheduled dose. Take your next dose at your regular time.
•
If you stop treatment with binimetinib or cetuximab, talk to your healthcare provider about your BRAFTOVI treatment. Your BRAFTOVI dose may need to be changed or stopped.

What are the possible side effects of BRAFTOVI?
BRAFTOVI can cause serious side effects, including:

•
See "What is the most important information I should know about BRAFTOVI?"
•
Heart problems, including heart failure. BRAFTOVI can cause heart problems. Your healthcare provider will check your heart function before and during treatment with BRAFTOVI. Tell your healthcare provider right away if you get any of the following signs and symptoms of a heart problem:
o
feeling like your heart is pounding or racing
o
shortness of breath
o
swelling in your hands, ankles legs or feet
o
feeling faint or lightheaded
•
Liver problems. BRAFTOVI can cause liver problems. Your healthcare provider will perform blood tests to check your liver function before and during treatment with BRAFTOVI. Tell your healthcare provider if you get any of the following signs and symptoms of a liver problem:
o
yellowing of your skin or your eyes
o
dark or brown (tea-colored) urine
o
nausea or vomiting
o
loss of appetite
o
tiredness
o
bruising
o
bleeding
•
Bleeding problems. BRAFTOVI can cause serious bleeding problems, including in your stomach or brain, that can lead to death. Tell your healthcare provider and get medical help right away if you develop any signs of bleeding, including:
o
headaches, dizziness, or feeling weak
o
cough up blood or blood clots
o
vomit blood or your vomit looks like “coffee grounds”
o
red or black stools that look like tar
o
nose bleeds
•
Eye problems. BRAFTOVI can cause eye problems. Your healthcare provider should perform an eye exam regularly. Tell your healthcare provider right away if you develop any new or worsening symptoms of eye problems, including:
o
blurred vision, loss of vision, or other vision changes
o
see colored dots
o
see halos (blurred outline around objects)
o
eye pain, swelling, or redness
•
Changes in the electrical activity of your heart called QT prolongation. QT prolongation can cause irregular heartbeats that can be life threatening. Your healthcare provider should do tests before you start treatment with BRAFTOVI during your treatment to check your body salts (electrolytes). Tell your healthcare provider right away if you feel faint, lightheaded, dizzy or if you feel your heart beating irregularly or fast during treatment with BRAFTOVI. These symptoms may be related to QT prolongation.

Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with BRAFTOVI if you have certain side effects.

The most common side effects of BRAFTOVI when taken in combination with binimetinib for melanoma include:

•
fatigue
•
nausea
•
vomiting
•
abdominal pain
•
pain or swelling of your joints (arthralgia)

The most common side effects of BRAFTOVI when taken in combination with cetuximab and mFOLFOX6 for colorectal cancer include:

•
numbness, tingling or burning in your hands or feet (peripheral neuropathy)
•
nausea
•
fatigue
•
diarrhea
•
decreased appetite
•
rash
•
vomiting
•
bleeding (hemorrhage)
•
stomach-area (abdominal) pain
•
pain or swelling of your joints (arthralgia)
•
fever
•
constipation

The most common side effects of BRAFTOVI when taken in combination with cetuximab and FOLFIRI for colorectal cancer include:

•
nausea
•
diarrhea
•
fatigue
•
vomiting
•
hair loss (alopecia)
•
constipation
•
stomach-area (abdominal) pain
•
decreased appetite
•
rash

The most common side effects of BRAFTOVI when taken in combination with cetuximab for colorectal cancer include:

•
fatigue
•
nausea
•
diarrhea
•
acne-like rash (dermatitis acneiform)
•
stomach-area (abdominal) pain
•
decreased appetite
•
pain or swelling of your joints (arthralgia)
•
rash

The most common side effects of BRAFTOVI when taken in combination with binimetinib for NSCLC include:

•
fatigue
•
nausea
•
diarrhea
•
muscle or joint pain
•
vomiting
•
stomach-area (abdominal) pain
•
blurred vision, loss of vision, or other vision changes
•
constipation
•
shortness of breath
•
rash
•
cough

BRAFTOVI may cause fertility problems in males. This may affect your ability to father a child. Talk to your healthcare provider if this is a concern for you.

These are not all of the possible side effects of BRAFTOVI.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

You may also report side effects to Pfizer Inc. at 1-800-438-1985.

How should I store BRAFTOVI?

•
Store BRAFTOVI at room temperature between 68°F to 77°F (20°C to 25°C).
•
Store BRAFTOVI in the original bottle.
•
Keep the BRAFTOVI bottle tightly closed and protect it from moisture.
•
BRAFTOVI comes with a desiccant packet in the bottle to help protect your medicine from moisture. Do not remove the desiccant packet from the bottle.

Keep BRAFTOVI and all medicines out of the reach of children.

General information about the safe and effective use of BRAFTOVI.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use BRAFTOVI for a condition for which it was not prescribed. Do not give BRAFTOVI to other people, even if they have the same symptoms that you have. It may harm them. You can ask your healthcare provider or pharmacist for information about BRAFTOVI that is written for health professionals.

What are the ingredients in BRAFTOVI?
Active ingredient: encorafenib
Inactive ingredients: copovidone, poloxamer 188, microcrystalline cellulose, succinic acid, crospovidone, colloidal silicon dioxide, and magnesium stearate of vegetable origin
Capsule shell: gelatin, titanium dioxide, iron oxide red, iron oxide yellow, ferrosoferric oxide, monogramming ink (pharmaceutical glaze, ferrosoferric oxide, propylene glycol)
Distributed by: Array BioPharma Inc., a wholly owned subsidiary of Pfizer Inc. Boulder, Colorado 80301.
BRAFTOVI® is a registered trademark of Array BioPharma Inc. in the United States and various other countries.
LAB-1429-5.0
For more information, go to www.braftovi.com or call 1-844-792-7729.
© 2024 Array BioPharma Inc. All rights reserved.

This Medication Guide has been approved by the U.S. Food and Drug Administration.       Revised: 02/2026

Additional Resources

Chat online with Pfizer Medical Information regarding your inquiry on a Pfizer medicine or vaccine.

Speak with a Pfizer Medical Information Professional regarding your Pfizer medicine or vaccine inquiry.

Available 9AM-5PM ET Monday to Friday; excluding holidays.

 

Submit a medical question for a Pfizer medicine or a vaccine. 

The submission will be reviewed during our standard business hours.

To report an adverse event related to a Pfizer product and you are not part of a clinical trial* for this medication, click the link below to submit your information: 
Pfizer Safety Reporting Site

*If you are involved in a clinical trial for either product, adverse events should be reported to your coordinating study site.

If you cannot use the above website to report an adverse event related to a Pfizer medication, please call (800) 438-1985.

You may also contact the U.S. Food and Drug Administration (FDA) directly to report adverse events or product quality concerns either online at www.fda.gov/medwatch or by calling (800) 332-1088.