(binimetinib)

Prescribing Information
Download Prescribing Information

6 ADVERSE REACTIONS

6 ADVERSE REACTIONS

The following adverse reactions are described elsewhere in the labeling:

•
New Primary Malignancies [see Warnings and Precautions (5.1)]
•
Cardiomyopathy [see Warnings and Precautions (5.2)]
•
Venous Thromboembolism [see Warnings and Precautions (5.3)]
•
Ocular Toxicities [see Warnings and Precautions (5.4)]
•
Interstitial Lung Disease [see Warnings and Precautions (5.5)]
•
Hepatotoxicity [see Warnings and Precautions (5.6)]
•
Rhabdomyolysis [see Warnings and Precautions (5.7)]
•
Hemorrhage [see Warnings and Precautions (5.8)]
•
Embryo-Fetal Toxicity [see Warnings and Precautions (5.9)]
•
Risks Associated with Combination Treatment [see Warnings and Precautions (5.10)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data described in WARNINGS AND PRECAUTIONS reflect exposure of 192 patients with BRAF V600 mutation-positive unresectable or metastatic melanoma to MEKTOVI 45 mg twice daily in combination with encorafenib 450 mg once daily in a randomized open-label, active-controlled trial (COLUMBUS) [see Clinical Studies (14.1)] or, for rare events, exposure of 690 patients with BRAF V600 mutation-positive melanoma to MEKTOVI 45 mg twice daily in combination with encorafenib once daily across multiple clinical trials (NCT03915951, NCT01909453).

The pooled safety population described in the WARNINGS AND PRECAUTIONS also reflect exposure of 98 patients with BRAF V600E mutation-positive metastatic non-small cell lung cancer to MEKTOVI 45 mg twice daily and encorafenib 450 mg once daily until disease progression or unacceptable toxicity in PHAROS [see Clinical Studies (14.2)].

BRAF V600E or V600K Mutation-Positive Unresectable or Metastatic Melanoma

The data described below reflect exposure of 192 patients with BRAF V600 mutation-positive unresectable or metastatic melanoma to MEKTOVI (45 mg twice daily) in combination with encorafenib (450 mg once daily) in COLUMBUS.

The COLUMBUS trial [see Clinical Studies (14.1)] excluded patients with a history of Gilbert's syndrome, abnormal left ventricular ejection fraction, prolonged QTc (>480 msec), uncontrolled hypertension, and history or current evidence of retinal vein occlusion. The median duration of exposure was 11.8 months for patients treated with MEKTOVI in combination with encorafenib and 6.2 months for patients treated with vemurafenib.

The most common (≥25%) adverse reactions in patients receiving MEKTOVI in combination with encorafenib were fatigue, nausea, diarrhea, vomiting, and abdominal pain.

Adverse reactions leading to dose interruptions of MEKTOVI occurred in 33% of patients receiving MEKTOVI in combination with encorafenib; the most common were left ventricular dysfunction (6%) and serous retinopathy (5%). Adverse reactions leading to dose reductions of MEKTOVI occurred in 19% of patients receiving MEKTOVI in combination with encorafenib; the most common were left ventricular dysfunction (3%), serous retinopathy (3%), and colitis (2%). Five percent (5%) of patients receiving MEKTOVI in combination with encorafenib experienced an adverse reaction that resulted in permanent discontinuation of MEKTOVI. The most common adverse reactions resulting in permanent discontinuation of MEKTOVI were hemorrhage in 2% and headache in 1% of patients.

Table 3 and Table 4 present adverse drug reactions and laboratory abnormalities, respectively, identified in COLUMBUS. The COLUMBUS trial was not designed to demonstrate a statistically significant difference in adverse reaction rates for MEKTOVI in combination with encorafenib, as compared to vemurafenib, for any specific adverse reaction listed in Table 3.

Table 3: Adverse Reactions Occurring in ≥10% of Patients Receiving MEKTOVI in Combination with Encorafenib in COLUMBUS*
Adverse ReactionMEKTOVI with
encorafenib
N=192		Vemurafenib
N=186
All
Grades
(%)		Grades
3 and 4†
(%)		All
Grades
(%)		Grades
3 and 4†
(%)
*
Grades per National Cancer Institute CTCAE v4.03.
†
Grade 4 adverse reactions limited to diarrhea (n=1) and hemorrhage (n=3) in the MEKTOVI with encorafenib arm and constipation (n=1) in the vemurafenib arm.
‡
Represents a composite of multiple, related preferred terms.

General Disorders and Administration Site Conditions

  Fatigue‡

43

3

46

6

  Pyrexia‡

18

4

30

0

  Peripheral edema‡

13

1

15

1

Gastrointestinal Disorders

  Nausea

41

2

34

2

  Diarrhea

36

3

34

2

  Vomiting‡

30

2

16

1

  Abdominal pain‡

28

4

16

1

  Constipation

22

0

6

1

Skin and Subcutaneous Tissue Disorders

  Rash‡

22

1

53

13

Nervous System Disorders

  Dizziness‡

15

3

4

0

Visual Disorders

  Visual impairment‡

20

0

4

0

  Serous retinopathy/RPED‡

20

3

2

0

Vascular Disorders

  Hemorrhage‡

19

3

9

2

  Hypertension‡

11

6

11

3

Other clinically important adverse reactions occurring in <10% of patients who received MEKTOVI in combination with encorafenib were:

Gastrointestinal disorders: Colitis

Skin and subcutaneous tissue disorders: Panniculitis, Photosensitivity

Immune system disorders: Drug hypersensitivity

Table 4: Laboratory Abnormalities Occurring in ≥10% (All grades) of Patients Receiving MEKTOVI in Combination with Encorafenib in COLUMBUS*
Laboratory AbnormalityMEKTOVI
with encorafenib
N=192		Vemurafenib
N=186
All
Grades
(%)		Grades
3 and 4
(%)		All
Grades
(%)		Grades
3 and 4
(%)
*
Grades per National Cancer Institute CTCAE v4.03.

Hematology

  Anemia

36

3.6

34

2.2

  Leukopenia

13

0

10

0.5

  Lymphopenia

13

2.1

30

7

  Neutropenia

13

3.1

4.8

0.5

Chemistry

  Increased Creatinine

93

3.6

92

1.1

  Increased Creatine Phosphokinase

58

5

3.8

0

  Increased Gamma Glutamyl Transferase

45

11

34

4.8

  Increased ALT

29

6

27

2.2

  Increased AST

27

2.6

24

1.6

  Increased Alkaline Phosphatase

21

0.5

35

2.2

  Hyponatremia

18

3.6

15

0.5

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

The safety of MEKTOVI in combination with encorafenib is described in 98 patients with BRAF V600E mutation-positive metastatic NSCLC who received MEKTOVI (45 mg twice daily) in combination with encorafenib (450 mg once daily) in an open-label, single-arm trial (PHAROS).

The PHAROS trial [see Clinical Studies (14.2)] excluded patients with abnormal LVEF, prolonged QTc (>480 ms), uncontrolled hypertension, and history or current evidence of retinal vein occlusion. The median duration of treatment for MEKTOVI and encorafenib was 8.4 and 9.2 months respectively.

The most common (≥25%) adverse reactions in patients receiving MEKTOVI were fatigue, nausea, diarrhea, musculoskeletal pain, vomiting, abdominal pain, visual impairment, constipation, dyspnea, rash, and cough.

Adverse reactions leading to dose interruptions of MEKTOVI occurred in 62% of patients receiving MEKTOVI; the most common (≥5%) were diarrhea (17%); nausea (15%); fatigue (9%); AST increased (7%); ALT increased, anemia, musculoskeletal pain, vomiting (6% each); and acute kidney injury, hemorrhage, and LV dysfunction/cardiomyopathy (5% each). Adverse reactions leading to dose reductions of MEKTOVI occurred in 33% of patients receiving MEKTOVI; the most common (≥5%) were diarrhea (8%), nausea (6%), and AST increased (5%). A total of 17% of patients receiving MEKTOVI experienced an adverse reaction that resulted in permanent discontinuation of MEKTOVI; the most common (≥2%) were diarrhea (3.1%); musculoskeletal pain, LV dysfunction/cardiomyopathy, fatigue, nausea, rash, visual impairment, and vomiting (2% each). None of the other adverse reactions leading to permanent discontinuation of MEKTOVI occurred in more than 1 patient.

Serious adverse reactions occurred in 38% of patients who received MEKTOVI in combination with encorafenib. Serious adverse reactions in ≥2% of patients included hemorrhage (6%); diarrhea (4.1%); anemia, dyspnea, pneumonia (3.1% each); arrhythmia, device related infection, edema, myocardial infarction, and pleural effusion (2% each). Fatal adverse reactions occurred in 2% of patients who received MEKTOVI (45 mg twice-daily) in combination with encorafenib, including intracranial hemorrhage and myocardial infarction (1% each).

Table 5 and Table 6 present adverse drug reactions and laboratory abnormalities, respectively, identified in PHAROS.

Table 5: Adverse Reactions Occurring in ≥10% of Patients Receiving MEKTOVI in Combination with Encorafenib in PHAROS*
*
Grades per National Cancer Institute CTCAE v4.03.
†
One Grade 5 adverse reaction of hemorrhage occurred.
‡
Fatigue includes fatigue, asthenia.
§
Edema includes edema peripheral, generalized edema, swelling, localized edema, face edema.
Diarrhea includes diarrhea, colitis.
#
Abdominal pain includes abdominal pain, abdominal pain upper, abdominal discomfort, epigastric discomfort.
Þ
Visual impairment includes vision blurred, visual impairment, vitreous floaters, photophobia, visual acuity reduced, photopsia.
ß
Musculoskeletal pain includes back pain, arthralgia, pain in extremity, myalgia, musculoskeletal chest pain, non-cardiac chest pain, neck pain.
à
Rash includes rash, rash macular, rash maculo-papular, rash papular, rash pustular,dermatitis acneiform, palmar-plantar erythrodysesthesia syndrome, eczema, skin exfoliation.
è
Pruritis includes pruritus, pruritus genital.
ð
Dyspnea includes dyspnea, dyspnea exertional.
ø
Cough includes cough, productive cough.
ý
Dizziness includes dizziness, balance disorder.
£
Hemorrhage includes anal hemorrhage, hemothorax, gastrointestinal hemorrhage, hematochezia, hematuria, hemoptysis, hemorrhage intracranial, hyphema, small intestinal hemorrhage, upper gastrointestinal hemorrhage, vaginal hemorrhage.
¥
Left ventricular dysfunction/cardiomyopathy includes ejection fraction decreased, cardiac failure, cardiac failure congestive.

 

 

Adverse Reaction

MEKTOVI

with encorafenib

N=98

All

Grades

(%)

Grade 3 and 4†

(%)

General Disorders and Administration Site Conditions

   Fatigue‡

61

8

   Edema§

23

1

   Pyrexia

22

0

Gastrointestinal Disorders

   Nausea

58

3.1

   Diarrhea

52

7

   Vomiting

37

1

   Abdominal pain#

32

1

   Constipation

27

0

Eye Disorders

   Visual impairmentÞ

29

2

Musculoskeletal and Connective Tissue Disorders

   Musculoskeletal painß

48

4.1

Skin and Subcutaneous Tissue Disorders

   Rashà

27

3.1

   Pruritisè

16

0

   Dry skin

13

0

   Alopecia

12

0

Respiratory, Thoracic and Mediastinal Disorders

   Dyspneað

27

8

   Coughø

26

0

Nervous System Disorders

   Dizzinessý

17

1

   Headache

11

0

Metabolism and Nutrition Disorders

   Decreased appetite

14

1

Vascular Disorders

   Hemorrhage†£

12

4.1

   Hypertension

10

5

Cardiac Disorders

   Left ventricular dysfunction/cardiomyopathy¥

11

1

Investigations

   Weight increased

11

1

Psychiatric Disorders

   Insomnia

10

0

Other clinically important adverse reactions occurring in <10% of patients who received MEKTOVI in combination with encorafenib were:

Nervous system disorders: Peripheral neuropathy, Dysgeusia, Facial paresis

Gastrointestinal disorders: Pancreatitis

Skin and subcutaneous tissue disorders: Hyperkeratosis, Erythema, Photosensitivity

Immune system disorders: Drug hypersensitivity

Table 6: Laboratory Abnormalities Occurring in ≥10% (All Grades) of Patients Receiving MEKTOVI with Encorafenib in PHAROS*
*
Grades per National Cancer Institute CTCAE v4.03.
†
Based on the number of patients with available baseline and at least one on-treatment laboratory test.

 

 

Laboratory Abnormality†

MEKTOVI with encorafenib

All

Grades

(%)

Grades

3 and 4

(%)

Hematology

    Anemia

47

11

    Lymphopenia

24

6

    Thrombocytopenia

20

1.1

    Leukopenia

12

0

    Neutropenia

12

1.1

Chemistry

    Increased creatinine

91

3.2

    Hyperglycemia

48

6

    Increased creatine kinase

41

3.3

    Lipase increased

40

14

    Increased ALT

34

9

    Hypoalbuminemia

32

0

    Increased AST

31

10

    Increased alkaline phosphatase

31

3.2

    Hyperkalemia

31

2.1

    Hyponatremia

26

11

    Serum amylase increased

22

1.1

    Hypocalcemia

12

2.1

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

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.