(binimetinib)

Prescribing Information
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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 MEKTOVI [see Clinical Studies (14)]. Information on FDA-approved 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 Non-Small Cell Lung Cancer (NSCLC)

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

2.2 Recommended Dosage and Administration

The recommended dosage of MEKTOVI is 45 mg orally taken twice daily, approximately 12 hours apart, in combination with encorafenib until disease progression or unacceptable toxicity. Refer to the encorafenib prescribing information for recommended encorafenib dosing information.

MEKTOVI may be taken with or without food [see Clinical Pharmacology (12.3)]. Do not take a missed dose of MEKTOVI within 6 hours of the next dose of MEKTOVI.

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

2.3 Dosage Modifications for Adverse Reactions

If encorafenib is permanently discontinued, discontinue MEKTOVI.

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

Table 1: Recommended Dose Reductions for MEKTOVI for Adverse Reactions
ActionRecommended Dose

First Dose Reduction

30 mg orally twice daily

Subsequent Modification

Permanently discontinue if unable to tolerate MEKTOVI 30 mg orally twice daily

Dosage modifications for adverse reactions associated with MEKTOVI are presented in Table 2.

Table 2: Recommended Dosage Modifications for MEKTOVI for Adverse Reactions
Severity of Adverse Reaction*Dose Modification for MEKTOVI
*
National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
†
Dose modification of MEKTOVI when administered with encorafenib is not recommended for the following adverse reactions: palmar-plantar erythrodysesthesia syndrome (PPES), non-cutaneous RAS mutation-positive malignancies, and QTc prolongation.

Cardiomyopathy [see Warnings and Precautions (5.2)]

•
Asymptomatic, absolute decrease in LVEF of greater than 10% from baseline that is also below lower limit of normal (LLN)

Withhold MEKTOVI for up to 4 weeks, evaluate LVEF every 2 weeks.
Resume MEKTOVI at a reduced dose if the following are present:

•
LVEF is at or above the lower limit of 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 MEKTOVI.

•
Symptomatic congestive heart failure or absolute decrease in LVEF of greater than 20% from baseline that is also below LLN

Permanently discontinue MEKTOVI.

Venous Thromboembolism [see Warnings and Precautions (5.3)]

•
Uncomplicated deep venous thrombosis (DVT) or pulmonary embolism (PE)

Withhold MEKTOVI.

•
If improves to Grade 0-1, resume at a reduced dose.
•
If no improvement, permanently discontinue MEKTOVI.
•
Life threatening PE

Permanently discontinue MEKTOVI.

Serous Retinopathy [see Warnings and Precautions (5.4)]

•
Symptomatic serous retinopathy/Retinal pigment epithelial detachments

Withhold MEKTOVI for up to 10 days.

•
If improves and becomes asymptomatic, resume at same dose.
•
If not improved, resume at a lower dose level or permanently discontinue MEKTOVI.

Retinal Vein Occlusion (RVO) [see Warnings and Precautions (5.4)]

•
Any Grade

Permanently discontinue MEKTOVI.

Uveitis [see Warnings and Precautions (5.4)]

•
Grade 1-3

If Grade 1 or 2 does not respond to specific ocular therapy, or for Grade 3 uveitis, withhold MEKTOVI for up to 6 weeks.

•
If improved, resume at same or reduced dose.
•
If not improved, permanently discontinue MEKTOVI.
•
Grade 4

Permanently discontinue MEKTOVI.

Interstitial Lung Disease [see Warnings and Precautions (5.5)]

•
Grade 2

Withhold MEKTOVI for up to 4 weeks.

•
If improved to Grade 0-1, resume at a reduced dose.
•
If not resolved within 4 weeks, permanently discontinue MEKTOVI.
•
Grade 3 or Grade 4

Permanently discontinue MEKTOVI.

Hepatotoxicity [see Warnings and Precautions (5.6)]

•
Grade 2 AST or ALT increased

Maintain MEKTOVI dose.

•
If no improvement within 2 weeks, withhold MEKTOVI until improved to Grade 0-1 or to pretreatment/baseline levels and then resume at the same dose.
•
Grade 3 or 4 AST or ALT increased

See Other Adverse Reactions.

Rhabdomyolysis or Creatine Phosphokinase (CPK) elevations [see Warnings and Precautions (5.7)]

•
Grade 4 asymptomatic CPK elevation or
•
Any Grade CPK elevation with symptoms or with renal impairment

Withhold MEKTOVI dose for up to 4 weeks.

•
If improved to Grade 0-1 resume at a reduced dose.
•
If not resolved within 4 weeks, permanently discontinue MEKTOVI.

Dermatologic [other than palmar plantar erythrodysesthesia syndrome (PPES)] [see Adverse Reactions (6.1)]

•
Grade 2

If no improvement within 2 weeks, withhold MEKTOVI until Grade 0-1. Resume at same dose if first occurrence or reduce dose if recurrent.

•
Grade 3

Withhold MEKTOVI until Grade 0-1. Resume at same dose if first occurrence or reduce dose if recurrent.

•
Grade 4

Permanently discontinue MEKTOVI.

Other Adverse Reactions (including Hemorrhage) [see Warnings and Precautions (5.8), Adverse Reactions (6.1)]†

•
Recurrent Grade 2 or
•
First occurrence of any Grade 3

Withhold MEKTOVI for up to 4 weeks.

•
If improves to Grade 0-1 or to pretreatment/baseline levels, resume at reduced dose.
•
If no improvement, permanently discontinue MEKTOVI.
•
First occurrence of any Grade 4

Permanently discontinue MEKTOVI, or
Withhold MEKTOVI for up to 4 weeks.

•
If improves to Grade 0-1 or to pretreatment/baseline levels, then resume at a reduced dose.
•
If no improvement, permanently discontinue MEKTOVI.
•
Recurrent Grade 3

Consider permanently discontinuing MEKTOVI.

•
Recurrent Grade 4

Permanently discontinue MEKTOVI.

Refer to the encorafenib prescribing information for dose modifications for adverse reactions associated with encorafenib.

2.4 Dosage Modifications for Moderate or Severe Hepatic Impairment

For patients with 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 3 × ULN and any AST) hepatic impairment, the recommended dosage is 30 mg orally taken twice daily [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].

Medication Guide

MEDICATION GUIDE

     

MEDICATION GUIDE

MEKTOVI® (mek-TOE-vee)

(binimetinib)

tablets

Important Information: If your healthcare provider prescribes MEKTOVI with encorafenib, please read the Medication Guide that comes with encorafenib.

What is the most important information I should know about MEKTOVI when taken in combination with encorafenib?

MEKTOVI when taken in combination with encorafenib may cause serious side effects, including:

•
Risk of new skin cancers. MEKTOVI, when used with encorafenib, may 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:
o
new wart
o
skin sore or reddish bump that bleeds or does not heal
o
change in size or color of a mole
 
Your healthcare provider should check your skin before treatment with MEKTOVI, when taken in combination with encorafenib, every 2 months during treatment, and for up to 6 months after you stop treatment 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 MEKTOVI when taken in combination with encorafenib.

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

What is MEKTOVI?

MEKTOVI is a prescription medicine used:

•
in combination with a medicine called encorafenib 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 a medicine called encorafenib 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

Your healthcare provider will perform a test to make sure that MEKTOVI is right for you.

It is not known if MEKTOVI is safe and effective in children.

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

•
have heart problems
•
have had blood clots
•
have eye problems
•
have lung or breathing problems
•
have liver or kidney problems
•
have any muscle problems
•
have bleeding problems
•
have high blood pressure (hypertension)
•
are pregnant or plan to become pregnant. MEKTOVI can harm your unborn baby.
o
Females who are able to become pregnant should use effective birth control (contraception) during treatment with MEKTOVI and for at least 30 days after the last dose of MEKTOVI.
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 MEKTOVI. Tell your healthcare provider right away if you become pregnant or think you might be pregnant during treatment with MEKTOVI.
•
are breastfeeding or plan to breastfeed. It is not known if MEKTOVI passes into your breast milk. Do not breastfeed during treatment with MEKTOVI and for 3 days after the last dose of MEKTOVI. 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.

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 MEKTOVI?

•
Take MEKTOVI exactly as your healthcare provider tells you to take it. Do not change your dose or stop taking MEKTOVI unless your healthcare provider tells you to.
•
Take MEKTOVI in combination with encorafenib by mouth 2 times a day, about 12 hours apart.
•
MEKTOVI may be taken with or without food.
•
If you miss a dose of MEKTOVI, take it as soon as you remember. If it is within 6 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 encorafenib, talk to your healthcare provider about whether your MEKTOVI treatment may need to be stopped.

What are the possible side effects of MEKTOVI?

MEKTOVI may cause serious side effects, including:

•
Heart problems, including heart failure. MEKTOVI, when taken with encorafenib, can cause heart problems. Your healthcare provider should check your heart function before and during treatment with MEKTOVI. Call your healthcare provider right away if you have 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 of your ankles and feet
o
feeling lightheaded
•
Blood clots. MEKTOVI, when taken with encorafenib, can cause blood clots in your arms or legs, which can travel to your lungs and can lead to death. Get medical help right away if you have the following symptoms:
o
chest pain
o
sudden shortness of breath or trouble breathing
o
pain in your legs with or without swelling
o
swelling in your arms and legs
o
a cool pale arm or leg
•
Eye problems. MEKTOVI, when taken with encorafenib, can cause eye problems. Your healthcare provider should perform an eye exam regularly during treatment with MEKTOVI. 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
•
Lung or breathing problems. MEKTOVI, when taken with encorafenib, can cause lung or breathing problems. Tell your healthcare provider if you have any new or worsening symptoms of lung or breathing problems, including:
o
shortness of breath
o
cough
•
Liver problems. MEKTOVI, when taken with encorafenib, can cause liver problems. Your healthcare provider should perform blood tests to check your liver function before and during treatment with MEKTOVI. Tell your healthcare provider if you have 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
•
Muscle problems (rhabdomyolysis). MEKTOVI, when taken with encorafenib, can cause muscle problems that can be severe. Treatment with MEKTOVI may increase the level of an enzyme in your blood called creatine phosphokinase (CPK) and can be a sign of muscle damage. Your healthcare provider should perform a blood test to check your levels of CPK before and during treatment. Tell your healthcare provider right away if you develop any of these symptoms:
o
weakness
o
muscle aches or pain
o
dark, reddish urine
•
Bleeding problems. MEKTOVI, when taken with encorafenib, can cause serious bleeding problems, including in your brain or stomach, 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 stool that look like tar

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

The most common side effects of MEKTOVI when taken with encorafenib for melanoma include:

•
fatigue
•
nausea
•
diarrhea
•
vomiting
•
stomach-area (abdominal) pain

The most common side effects of MEKTOVI when taken with encorafenib 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

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

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 MEKTOVI?

•
Store MEKTOVI at room temperature between 68°F to 77°F (20°C to 25°C).

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

General information about the safe and effective use of MEKTOVI.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use MEKTOVI for a condition for which it was not prescribed. Do not give MEKTOVI 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 MEKTOVI that is written for health professionals.

What are the ingredients in MEKTOVI?

Active ingredient: binimetinib

Inactive ingredients: lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, magnesium stearate (vegetable source), and colloidal silicon dioxide

Tablet coating: polyvinyl alcohol, polyethylene glycol, titanium dioxide, talc, ferric oxide yellow, ferrosoferric oxide

Distributed by: Array BioPharma Inc., a wholly owned subsidiary of Pfizer Inc., Boulder, Colorado 80301.

MEKTOVI® is a registered trademark of Array BioPharma Inc. in the United States and various other countries.

For more information, go to www.BRAFTOVIMEKTOVI.com or call 1-844-792-7729.

©2020 Array BioPharma Inc. All rights reserved.

LAB-1427-2.0

This Medication Guide has been approved by the U.S. Food and Drug Administration.
Revised: 10/2023

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