Mektovi 15mg Tablets
It is used to treat a type of skin cancer (melanoma).It is used to treat lung cancer.
Drug Class
Antineoplastic agent
Pharmacologic Class
MEK inhibitor
Pregnancy Category
Not available
FDA Approved
Jun 2018
DEA Schedule
Not Controlled
Overview
What is this medicine?
Mektovi (binimetinib) is a medicine used to treat a type of skin cancer called melanoma that has spread or cannot be removed by surgery. It works by blocking a specific protein (MEK) inside cancer cells that helps them grow. It is usually taken with another medicine called encorafenib (Braftovi).
How to Use This Medicine
Taking Your Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. You can take this medication with or without food. Continue taking it as directed by your doctor or healthcare provider, even if you're feeling well. If you vomit after taking a dose, do not take an extra dose. Instead, take your next dose at the usual time.
Storing and Disposing of Your Medication
Store this medication at room temperature in a dry place, avoiding the bathroom. Keep all medications in a safe location, out of reach of children and pets. Dispose of unused or expired medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so. If you're unsure about the best way to dispose of your medication, consult your pharmacist. You may also want to check if there are drug take-back programs in your area.
Missing a Dose
If you miss a dose, take it as soon as you remember. However, if it's almost time for your next dose (less than 6 hours), skip the missed dose and resume your regular schedule. Do not take two doses at the same time or take extra doses to make up for the missed one.
To use this medication correctly, follow your doctor's instructions and read all the information provided. You can take this medication with or without food. Continue taking it as directed by your doctor or healthcare provider, even if you're feeling well. If you vomit after taking a dose, do not take an extra dose. Instead, take your next dose at the usual time.
Storing and Disposing of Your Medication
Store this medication at room temperature in a dry place, avoiding the bathroom. Keep all medications in a safe location, out of reach of children and pets. Dispose of unused or expired medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so. If you're unsure about the best way to dispose of your medication, consult your pharmacist. You may also want to check if there are drug take-back programs in your area.
Missing a Dose
If you miss a dose, take it as soon as you remember. However, if it's almost time for your next dose (less than 6 hours), skip the missed dose and resume your regular schedule. Do not take two doses at the same time or take extra doses to make up for the missed one.
Lifestyle & Tips
- Take Mektovi exactly as prescribed by your doctor, usually twice a day, about 12 hours apart, with or without food.
- Do not crush, chew, or break the tablets. Swallow them whole.
- If you miss a dose, take it as soon as you remember, unless it is less than 6 hours until your next scheduled dose. In that case, skip the missed dose and take your next dose at the regular time. Do not take two doses at once.
- If you vomit after taking a dose, do not take an additional dose. Continue with your next scheduled dose.
- Avoid grapefruit and grapefruit juice, as they may interact with this medication.
- Use effective contraception during treatment and for at least 2 weeks after the last dose for females of reproductive potential, and for at least 2 weeks after the last dose for male patients with female partners of reproductive potential.
- Limit sun exposure and use protective clothing and sunscreen, as skin sensitivity may increase.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
45 mg orally twice daily (three 15 mg tablets twice daily), in combination with encorafenib
Dose Range:
45 - 45 mg
Condition-Specific Dosing:
BRAF_V600_mutated_melanoma:
45 mg orally twice daily, in combination with encorafenib 450 mg orally once daily.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
No dose adjustment required.
Moderate:
No dose adjustment required.
Severe:
No dose adjustment required.
Dialysis:
Not available (caution advised, as binimetinib is highly protein-bound and unlikely to be removed by dialysis).
Hepatic Impairment:
Mild:
No dose adjustment required.
Moderate:
Reduce binimetinib dose to 30 mg orally twice daily.
Severe:
Reduce binimetinib dose to 15 mg orally twice daily.
Pharmacology
Mechanism of Action
Binimetinib is a reversible, selective, allosteric inhibitor of mitogen-activated protein kinase (MEK) 1 and MEK2 activity. MEK proteins are upstream regulators of the extracellular signal-related kinase (ERK) pathway, which promotes cell proliferation. In BRAF-mutated melanoma, the BRAF protein is constitutively active, leading to uncontrolled activation of the MEK/ERK pathway. Binimetinib inhibits MEK activity, thereby blocking downstream signaling from BRAF and inhibiting cell proliferation in BRAF-mutated cancer cells.
Pharmacokinetics
Absorption:
Bioavailability:
Not available (absolute bioavailability not determined)
Tmax:
Approximately 1.6 hours (range: 0.5 to 4 hours)
FoodEffect:
A high-fat, high-calorie meal decreased binimetinib Cmax by 39% and AUC by 10%.
Distribution:
Vd:
Approximately 106 L
ProteinBinding:
>97%
CnssPenetration:
Limited (low brain-to-plasma ratio in animal studies)
Elimination:
HalfLife:
Approximately 10 to 17 hours
Clearance:
Not available
ExcretionRoute:
Primarily fecal (approximately 60% of dose), with minor renal excretion (approximately 30% of dose)
Unchanged:
Approximately 1.5% (renal) and 11% (fecal) of the dose excreted as unchanged drug.
Pharmacodynamics
OnsetOfAction:
Not precisely defined for anti-tumor effect; pharmacodynamic effects (e.g., pERK inhibition) can be observed within hours.
PeakEffect:
Not precisely defined for anti-tumor effect.
DurationOfAction:
Not precisely defined for anti-tumor effect; sustained inhibition of MEK/ERK pathway is expected with twice-daily dosing.
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Allergic Reaction: Rash, hives, itching, red, swollen, blistered, or peeling skin with or without fever, wheezing, tightness in the chest or throat, trouble breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Bleeding: Vomiting or coughing up blood, vomit that resembles coffee grounds, blood in the urine, black, red, or tarry stools, bleeding from the gums, abnormal vaginal bleeding, unexplained bruises or bruises that enlarge, or uncontrollable bleeding.
Respiratory Problems: Shortness of breath, difficulty breathing, cough, or fever.
High Blood Pressure: Severe headache, dizziness, fainting, or changes in vision.
Liver Problems: Dark urine, fatigue, decreased appetite, stomach pain or upset, light-colored stools, vomiting, or yellow skin and eyes.
Electrolyte Imbalance: Mood changes, confusion, muscle pain, cramps, or spasms, weakness, shakiness, balance problems, abnormal heartbeat, seizures, loss of appetite, or severe stomach upset or vomiting.
Infection: Fever, chills, or sore throat.
Muscle and Urinary Problems: Muscle pain or weakness, dark urine, or difficulty urinating.
Eye Problems: Eye pain, swelling, or redness.
Heart-Related Side Effects:
This medication may increase the risk of heart failure. Your doctor will monitor your heart function while you are taking this medication. If you experience any of the following symptoms, contact your doctor immediately:
New or worsening cough or shortness of breath
Swelling in the ankles or legs
Abnormal heartbeat
Sudden weight gain (more than 5 pounds in 24 hours)
Dizziness or fainting
Blood Clots:
Blood clots have been reported in people taking this medication. If you have a history of blood clots, inform your doctor. Seek medical attention immediately if you experience:
Chest pain or pressure
Coughing up blood
Shortness of breath
Swelling, warmth, numbness, color changes, or pain in a leg or arm
Difficulty speaking or swallowing
Eye Problems:
This medication may cause severe eye problems, including vision loss. If you experience any of the following symptoms, contact your doctor immediately:
Blurred vision
Vision loss
Changes in vision
Seeing color dots or halos
Sensitivity to bright lights
Common Side Effects:
Most people do not experience severe side effects, but some may occur. If you experience any of the following side effects, contact your doctor if they bother you or do not go away:
Dizziness, fatigue, or weakness
Stomach pain
Weight gain
Joint pain
* Constipation, diarrhea, vomiting, or stomach upset (these are common side effects, and your doctor can help you manage them)
Reporting Side Effects:
If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Allergic Reaction: Rash, hives, itching, red, swollen, blistered, or peeling skin with or without fever, wheezing, tightness in the chest or throat, trouble breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Bleeding: Vomiting or coughing up blood, vomit that resembles coffee grounds, blood in the urine, black, red, or tarry stools, bleeding from the gums, abnormal vaginal bleeding, unexplained bruises or bruises that enlarge, or uncontrollable bleeding.
Respiratory Problems: Shortness of breath, difficulty breathing, cough, or fever.
High Blood Pressure: Severe headache, dizziness, fainting, or changes in vision.
Liver Problems: Dark urine, fatigue, decreased appetite, stomach pain or upset, light-colored stools, vomiting, or yellow skin and eyes.
Electrolyte Imbalance: Mood changes, confusion, muscle pain, cramps, or spasms, weakness, shakiness, balance problems, abnormal heartbeat, seizures, loss of appetite, or severe stomach upset or vomiting.
Infection: Fever, chills, or sore throat.
Muscle and Urinary Problems: Muscle pain or weakness, dark urine, or difficulty urinating.
Eye Problems: Eye pain, swelling, or redness.
Heart-Related Side Effects:
This medication may increase the risk of heart failure. Your doctor will monitor your heart function while you are taking this medication. If you experience any of the following symptoms, contact your doctor immediately:
New or worsening cough or shortness of breath
Swelling in the ankles or legs
Abnormal heartbeat
Sudden weight gain (more than 5 pounds in 24 hours)
Dizziness or fainting
Blood Clots:
Blood clots have been reported in people taking this medication. If you have a history of blood clots, inform your doctor. Seek medical attention immediately if you experience:
Chest pain or pressure
Coughing up blood
Shortness of breath
Swelling, warmth, numbness, color changes, or pain in a leg or arm
Difficulty speaking or swallowing
Eye Problems:
This medication may cause severe eye problems, including vision loss. If you experience any of the following symptoms, contact your doctor immediately:
Blurred vision
Vision loss
Changes in vision
Seeing color dots or halos
Sensitivity to bright lights
Common Side Effects:
Most people do not experience severe side effects, but some may occur. If you experience any of the following side effects, contact your doctor if they bother you or do not go away:
Dizziness, fatigue, or weakness
Stomach pain
Weight gain
Joint pain
* Constipation, diarrhea, vomiting, or stomach upset (these are common side effects, and your doctor can help you manage them)
Reporting Side Effects:
If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- New or worsening shortness of breath, cough, or swelling in your ankles/legs (signs of heart problems)
- Blurred vision, eye pain, seeing 'floaters' or 'flashes of light', or any changes in your vision (signs of eye problems)
- New or worsening skin rash, redness, swelling, or blistering on your palms or soles (hand-foot syndrome)
- Muscle pain, tenderness, or weakness, especially if accompanied by dark urine (signs of muscle damage)
- Yellowing of your skin or eyes, dark urine, or pain in your upper right stomach area (signs of liver problems)
- Unusual bleeding or bruising (signs of bleeding problems)
- Severe or persistent diarrhea, nausea, or vomiting
- New or worsening headache, confusion, or seizures (signs of neurological problems)
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
If you are breastfeeding, as you should not breastfeed while taking this medication and for 3 days after your last dose.
To ensure safe treatment, it is crucial to discuss the following with your doctor and pharmacist:
All medications you are currently taking, including prescription and over-the-counter drugs, natural products, and vitamins.
Any existing health problems, as this medication may interact with other drugs or health conditions.
Before making any changes to your medication regimen, consult with your doctor to confirm that it is safe to take this medication with your other drugs and health conditions. Do not start, stop, or change the dose of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
If you are breastfeeding, as you should not breastfeed while taking this medication and for 3 days after your last dose.
To ensure safe treatment, it is crucial to discuss the following with your doctor and pharmacist:
All medications you are currently taking, including prescription and over-the-counter drugs, natural products, and vitamins.
Any existing health problems, as this medication may interact with other drugs or health conditions.
Before making any changes to your medication regimen, consult with your doctor to confirm that it is safe to take this medication with your other drugs and health conditions. Do not start, stop, or change the dose of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Encorafenib is administered in combination with binimetinib, so it is crucial to understand the warnings, benefits, and risks associated with both drugs. If you have any questions or concerns, discuss them with your doctor.
There is a risk of severe bleeding associated with this medication, which can be life-threatening. If you experience bleeding or have a history of bleeding problems, consult your doctor promptly.
This medication may also cause high blood pressure. Adhere to your doctor's instructions for regular blood pressure checks.
Regular monitoring of your blood work and heart function is necessary, as directed by your doctor. Additionally, you will need to undergo eye exams. It is important to note that this medication may increase the risk of developing certain types of cancer. Discuss this potential risk with your doctor.
Regular skin checks are also recommended. Inform your doctor immediately if you notice any skin changes, such as new warts, skin sores, reddish bumps that bleed or do not heal, or changes in the color or size of a mole.
This medication can cause harm to an unborn baby. A pregnancy test will be conducted before initiating treatment to confirm that you are not pregnant. If you may become pregnant, use effective birth control methods while taking this medication and for 30 days after your last dose. If you become pregnant, notify your doctor immediately.
If your partner may become pregnant, you may need to use birth control while taking this medication and for up to 1 week after your last dose. Consult your doctor to discuss the necessary precautions.
There is a risk of severe bleeding associated with this medication, which can be life-threatening. If you experience bleeding or have a history of bleeding problems, consult your doctor promptly.
This medication may also cause high blood pressure. Adhere to your doctor's instructions for regular blood pressure checks.
Regular monitoring of your blood work and heart function is necessary, as directed by your doctor. Additionally, you will need to undergo eye exams. It is important to note that this medication may increase the risk of developing certain types of cancer. Discuss this potential risk with your doctor.
Regular skin checks are also recommended. Inform your doctor immediately if you notice any skin changes, such as new warts, skin sores, reddish bumps that bleed or do not heal, or changes in the color or size of a mole.
This medication can cause harm to an unborn baby. A pregnancy test will be conducted before initiating treatment to confirm that you are not pregnant. If you may become pregnant, use effective birth control methods while taking this medication and for 30 days after your last dose. If you become pregnant, notify your doctor immediately.
If your partner may become pregnant, you may need to use birth control while taking this medication and for up to 1 week after your last dose. Consult your doctor to discuss the necessary precautions.
Overdose Information
Overdose Symptoms:
- Symptoms of overdose are not well-established but may include exaggerated adverse effects such as cardiomyopathy, ocular toxicity, dermatologic reactions, or rhabdomyolysis.
What to Do:
In case of suspected overdose, contact a poison control center (e.g., 1-800-222-1222) or seek emergency medical attention immediately. There is no specific antidote. Treatment should be supportive.
Drug Interactions
Major Interactions
- Strong CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin): May increase binimetinib exposure. Avoid coadministration or reduce binimetinib dose.
- Strong CYP1A2 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's Wort): May decrease binimetinib exposure. Avoid coadministration.
- Strong UGT1A1 inhibitors (e.g., atazanavir, indinavir, nelfinavir, ritonavir): May increase binimetinib exposure. Avoid coadministration or reduce binimetinib dose.
- Strong UGT1A1 inducers (e.g., rifampin, phenobarbital, phenytoin): May decrease binimetinib exposure. Avoid coadministration.
Moderate Interactions
- Moderate CYP1A2 inhibitors (e.g., cimetidine, oral contraceptives): May increase binimetinib exposure. Monitor for adverse reactions.
- Moderate CYP1A2 inducers (e.g., omeprazole): May decrease binimetinib exposure. Monitor for efficacy.
- Moderate UGT1A1 inhibitors: May increase binimetinib exposure. Monitor for adverse reactions.
- Moderate UGT1A1 inducers: May decrease binimetinib exposure. Monitor for efficacy.
Monitoring
Baseline Monitoring
Left Ventricular Ejection Fraction (LVEF)
Rationale: Risk of cardiomyopathy/cardiac dysfunction.
Timing: Before initiating treatment.
Ophthalmologic examination
Rationale: Risk of ocular toxicities (e.g., retinal detachment, uveitis).
Timing: Before initiating treatment.
Liver function tests (ALT, AST, bilirubin)
Rationale: Risk of hepatotoxicity.
Timing: Before initiating treatment.
Creatine Phosphokinase (CPK)
Rationale: Risk of rhabdomyolysis/myopathy.
Timing: Before initiating treatment.
Electrolytes (e.g., potassium, magnesium, calcium)
Rationale: Risk of electrolyte abnormalities.
Timing: Before initiating treatment.
Dermatologic assessment
Rationale: Risk of dermatologic toxicities (e.g., rash, palmar-plantar erythrodysesthesia).
Timing: Before initiating treatment.
Routine Monitoring
Left Ventricular Ejection Fraction (LVEF)
Frequency: 1 month after initiation, then every 2-3 months thereafter, or as clinically indicated.
Target: Not available (monitor for decline)
Action Threshold: Symptomatic heart failure or asymptomatic LVEF decline below institutional lower limit of normal or >10% absolute decrease from baseline.
Ophthalmologic examination
Frequency: Periodically and promptly for any visual changes.
Target: Normal vision
Action Threshold: New or worsening visual disturbances, blurred vision, or other ocular symptoms.
Liver function tests (ALT, AST, bilirubin)
Frequency: Every 2 weeks for the first month, then monthly or as clinically indicated.
Target: Within normal limits or baseline
Action Threshold: Significant elevations (e.g., >3-5x ULN).
Creatine Phosphokinase (CPK)
Frequency: Monthly and as clinically indicated for muscle symptoms.
Target: Within normal limits or baseline
Action Threshold: Significant elevations (e.g., >5x ULN) or muscle pain/weakness.
Electrolytes
Frequency: Periodically and as clinically indicated.
Target: Within normal limits
Action Threshold: Significant abnormalities (e.g., hypokalemia, hypomagnesemia).
Dermatologic assessment
Frequency: Regularly and as clinically indicated.
Target: Normal skin
Action Threshold: Development or worsening of rash, palmar-plantar erythrodysesthesia, or other skin reactions.
Coagulation parameters (e.g., PT/INR, aPTT)
Frequency: Periodically and as clinically indicated for bleeding events.
Target: Within normal limits
Action Threshold: Abnormal values or signs of bleeding.
Symptom Monitoring
- New or worsening shortness of breath
- Swelling of ankles or legs
- Fatigue
- Dizziness
- Blurred vision
- Floaters or flashes of light
- Eye pain or redness
- Rash
- Skin dryness or itching
- Redness, swelling, or blistering of palms/soles
- Muscle pain or weakness
- Dark urine
- Nausea
- Vomiting
- Diarrhea
- Abdominal pain
- Unusual bleeding or bruising
- Headache
- Fever
Special Patient Groups
Pregnancy
Mektovi can cause fetal harm when administered to a pregnant woman. Based on animal studies and its mechanism of action, it is advised to avoid use during pregnancy. Females of reproductive potential should be advised to use effective contraception during treatment and for 2 weeks after the last dose. Male patients with female partners of reproductive potential should use effective contraception during treatment and for 2 weeks after the last dose.
Trimester-Specific Risks:
First Trimester:
High risk of embryo-fetal toxicity based on animal data (teratogenicity, embryolethality).
Second Trimester:
High risk of fetal toxicity based on animal data.
Third Trimester:
High risk of fetal toxicity based on animal data.
Lactation
It is not known whether binimetinib is excreted in human milk. Because of the potential for serious adverse reactions in a breastfed infant, advise women not to breastfeed during treatment with Mektovi and for 2 weeks after the last dose.
Infant Risk:
High (potential for serious adverse reactions)
Pediatric Use
The safety and effectiveness of Mektovi in pediatric patients have not been established. Its use is not recommended in this population.
Geriatric Use
No specific dose adjustment is required for patients âĨ65 years of age. Clinical studies did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. However, older patients may be more susceptible to adverse reactions.
Clinical Information
Clinical Pearls
- Mektovi (binimetinib) is always used in combination with encorafenib (Braftovi) for BRAF V600-mutated melanoma.
- Careful monitoring for cardiac, ocular, and dermatologic toxicities is crucial, especially during the initial months of therapy.
- Patients should be educated on the signs and symptoms of potential adverse effects and instructed to report them promptly.
- Dose modifications for adverse reactions are common and should be managed according to the prescribing information.
- Adherence to the twice-daily dosing schedule is important for optimal efficacy.
Alternative Therapies
- Pembrolizumab (Keytruda)
- Nivolumab (Opdivo)
- Ipilimumab (Yervoy)
- Nivolumab + Ipilimumab combination
- Vemurafenib (Zelboraf)
- Dabrafenib (Tafinlar)
Cost & Coverage
Average Cost:
Highly variable, typically >$10,000 per 30 tablets
Insurance Coverage:
Specialty Tier (requires prior authorization, often subject to step therapy and quantity limits)
General Drug Facts
If your symptoms or health problems do not improve or worsen over time, it is essential to contact your doctor for further evaluation and guidance. To ensure safe and effective treatment, never share your medication with others or take someone else's medication.
This medication is accompanied by a Medication Guide, a patient fact sheet that provides crucial information about its use. It is essential to read this guide carefully and review it again whenever your prescription is refilled. If you have any questions or concerns about this medication, consult with your doctor, pharmacist, or other healthcare provider for clarification.
In the event of a suspected overdose, immediately contact your local poison control center or seek emergency medical attention. When reporting the incident, be prepared to provide detailed information, including the name of the medication taken, the amount consumed, and the time it occurred.
This medication is accompanied by a Medication Guide, a patient fact sheet that provides crucial information about its use. It is essential to read this guide carefully and review it again whenever your prescription is refilled. If you have any questions or concerns about this medication, consult with your doctor, pharmacist, or other healthcare provider for clarification.
In the event of a suspected overdose, immediately contact your local poison control center or seek emergency medical attention. When reporting the incident, be prepared to provide detailed information, including the name of the medication taken, the amount consumed, and the time it occurred.