Binimetinib

Reviewed on 8/16/2021

What Is Binimetinib Used For and How Does it Work?

Binimetinib is used in combination with encorafenib for patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test.

Binimetinib is available under the following different brand names: Mektovi.

What Are the Dosages of Binimetinib?

Dosages of Binimetinib:

Dosage Forms and Strengths

Tablet

  • 15mg

Dosage Considerations – Should be Given as Follows:

Melanoma

  • Indicated in combination with encorafenib for patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test
  • 45 mg orally twice daily in combination with encorafenib until disease progression or unacceptable toxicity

Dosage Modifications

If encorafenib is permanently discontinued, discontinue binimetinib.

Recommended dose reductions for binimetinib for adverse reactions.

  • First dose reduction: 30 mg orally twice daily
  • Subsequent modifications: Permanently discontinue if unable to tolerate 30 mg/day

Cardiomyopathy

  • Asymptomatic, absolute decrease in left ventricular ejection fraction (LVEF) of greater than 10% from baseline that is also below the lower limit of normal (LLN): Withhold for up to 4 weeks, evaluate LVEF every 2 weeks
  • Resume at a reduced dose if the following are present
    • LVEF is at or above the LLN and
    • The absolute decrease from baseline is up to 10% and
    • Patient is asymptomatic
    • If the LVEF does not recover within 4 weeks permanently discontinue
  • Symptomatic congestive heart failure or absolute decrease in LVEF of greater than 20% from baseline that is also below LLN: Permanently discontinue

Venous thromboembolism

  • Uncomplicated DVT or PE
    • Withhold drug; if improves to Grade 0-1, resume at a reduced dose
    • If no improvement, permanently discontinue
  • Life-threatening PE: Permanently discontinue

Serous retinopathy

  • Symptomatic serous retinopathy/retinal pigment epithelial detachments
  • Withhold drug for up to 10 days
    • If improves and becomes asymptomatic, resume at the same dose
    • If not improved, resume at a lower dose or permanently discontinue

Retinal vein occlusion

  • Any grade: Permanently discontinue

Uveitis

  • Grades 1-3
    • If Grade 1 or 2 does not respond to specific ocular therapy, or for Grade 3 uveitis, withhold for up to 6 weeks; if improved, resume at same or reduced dose
    • If not improved, permanently discontinue
  • Grade 4: Permanently discontinue

Interstitial lung disease

  • Grade 2
    • Withhold for up to 4 weeks; if improved to Grade 0-1, resume at a reduced dose
    • If not resolved within 4 weeks, permanently discontinue
  • Grades 3 or 4: Permanently discontinue

Hepatotoxicity

  • Grade 2 AST/ALT increased
    • Maintain binimetinib dose; if no improvement within 2 weeks, withhold dose until improved to Grade 0-1 or pretreatment/baseline levels and then resume at the same dose
  • Recurrent Grade 2 or first occurrence of any Grade 3 AST/ALT increased
    • Withhold for up to 4 weeks; if improves to Grade 0-1 or pretreatment/baseline level, resume at reduced dose
    • If no improvement, permanently discontinue
  • The first occurrence of any Grade 4 AST/ALT increased
    • Permanently discontinue OR
    • Withhold for up to 4 weeks; if improves to Grade 0-1 or pretreatment/baseline level, resume at reduced dose; if no improvement, permanently discontinue
  • Recurrent Grade 3 AST/ALT increased
    • Consider permanently discontinuing
  • Recurrent Grade 4 AST/ALT increased
    • Permanently discontinue

Rhabdomyolysis or CPK elevations

  • Grade 4 asymptomatic CPK elevation OR any Grade CPK elevation with symptoms or with renal impairment
  • Withhold 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

Dermatologic

  • Grade 2: If no improvement within 2 weeks, withhold drug until Grade 0-1; resume at the same dose if the first occurrence or reduce dose if recurrent
  • Grade 3: Withhold until Grade 0-1; resume at the same dose if the first occurrence or reduce dose if recurrent
  • Grade 4: Permanently discontinue

Other adverse reactions, including hemorrhage

  • Dose modification, when administered with encorafenib, is NOT recommended for palmar-plantar erythrodysesthesia syndrome (PPES), noncutaneous RAS mutation-positive malignancies, and QTc prolongation
  • Recurrent Grade 2 or first occurrence of any Grade 3
    • Withhold for up to 4 weeks; if improves to Grade 0-1 or pretreatment/baseline level, resume at reduced dose
    • If no improvement, permanently discontinue
  • The first occurrence of any Grade 4
    • Permanently discontinue OR
    • Withhold for up to 4 weeks; if improves to Grade 0-1 or pretreatment/baseline level, resume at reduced dose; if no improvement, permanently discontinue
  • Recurrent Grade 3
    • Consider permanently discontinuing
  • Recurrent Grade 4
    • Permanently discontinue

Hepatic impairment

  • Moderate (total bilirubin greater than 1.5 to up to 3 x ULN and any AST): 30 mg orally twice daily
  • Severe (total bilirubin greater than 3 x ULN and any AST): 30 mg orally twice daily

Renal impairment

  • No clinically important changes in binimetinib exposure were observed with severe renal impairment as compared with patients with normal renal function

Dosing Considerations

  • Confirm the presence of a BRAF V600E or V600K mutation in tumor specimens before initiating
  • Limitations of use: Not indicated for patients with wild-type BRAF melanoma
  • Safety and efficacy not established in pediatric patients

QUESTION

Self-examination is important in the detection of skin cancer. See Answer

What Are Side Effects Associated with Using Binimetinib?

Common side effects of Binimetinib include:

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

What Other Drugs Interact with Binimetinib?

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

Binimetinib has no listed severe interactions with other drugs.

Binimetinib has no listed serious interactions with other drugs.

Binimetinib has no listed moderate interactions with other drugs.

Binimetinib has no listed mild interactions with other drugs.

What Are Warnings and Precautions for Binimetinib?

Warnings

This medication contains binimetinib. Do not take Mektovi if you are allergic to binimetinib or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

  • None

Effects of Drug Abuse

  • No information available

Short-Term Effects

  • See "What Are Side Effects Associated with Using Binimetinib?"

Long-Term Effects

  • See "What Are Side Effects Associated with Using Binimetinib?"

Cautions

  • In the COLUMBUS trial, venous thromboembolism (VTE) occurred in 6% of patients receiving binimetinib in combination with encorafenib, including 3.1% of patients who developed pulmonary embolism
  • In patients with BRAF mutation-positive melanoma receiving binimetinib with encorafenib (n=690), 2 patients (0.3%) developed interstitial lung disease (ILD), including pneumonitis; assess new or progressive unexplained pulmonary symptoms or findings for possible ILD
  • Hepatotoxicity can occur when binimetinib is concomitantly used with encorafenib; monitor liver laboratory tests before initiating, monthly during treatment, and as clinically indicated
  • Rhabdomyolysis can occur when binimetinib is administered in combination with encorafenib; monitor CPK and creatinine levels before initiating treatment, periodically during treatment, and as clinically indicated; withhold, reduce dose, or permanently discontinue based on the severity of the adverse reaction
  • Hemorrhage can occur when encorafenib is administered in combination with binimetinib; hemorrhagic events include GI, hemorrhoidal, rectal, and intracranial hemorrhage, and hematochezia; withhold, reduce dose, or discontinue the drug
  • Based on findings from animal studies and its mechanism of action, fetal harm may occur when administered to a pregnant woman
  • Risks associated with combination treatment; refer to the encorafenib prescribing information for additional risk information

Ocular toxicities

  • Serous retinopathy
    • In the COLUMBUS trial, serous retinopathy occurred in 20% of patients, including retinal detachment (8%) and macular edema (6%)
    • Assess for visual symptoms at each visit
    • Perform an ophthalmologic examination at regular intervals for new or worsening visual disturbances, and follow new or persistent ophthalmologic findings
  • Retinal vein occlusion
    • Retinal vein occlusion (RVO) is a known class-related adverse reaction of MEK inhibitors and may occur
    • Perform ophthalmologic evaluation for patient-reported acute vision loss or other visual disturbance within 24 hours
  • Uveitis
    • Uveitis (e.g., iritis and iridocyclitis) was reported in patients treated with binimetinib in combination with encorafenib
    • Perform an ophthalmologic evaluation at regular intervals and for new or worsening visual disturbances, and to follow new or persistent ophthalmologic findings

Cardiomyopathy

  • Cardiomyopathy, manifesting as left ventricular dysfunction associated with symptomatic or asymptomatic decreases in ejection fraction, reported in patients treated with binimetinib in combination with encorafenib
  • Assess ejection fraction by echocardiogram or MUGA scan before initiating treatment, one month after initiating treatment, and then every 2-3 months during treatment
  • Safety of binimetinib in combination with encorafenib has not been established in patients with a baseline ejection fraction that is either below 50% or below the institutional lower limit of normal (LLN)
  • Closely monitor patients with cardiovascular risk factors

Pregnancy and Lactation

Based on animal reproduction studies and its mechanism of action, fetal harm may occur when binimetinib is administered to a pregnant woman. There are no available clinical data on the use of binimetinib during pregnancy. Pregnant women should be advised of the potential risk to a fetus.

Females of reproductive potential are advised to use effective contraception during treatment with binimetinib and for at least 30 days after the final dose. Nonhormonal contraceptives should be used during treatment and for at least 30 days after the final dose for patients taking encorafenib and binimetinib.

There are no data on the presence of binimetinib or its active metabolite in human milk, the effects of binimetinib on breastfed infants, or milk production. Because of the potential for serious adverse reactions from binimetinib in breastfed infants, women are advised not to breastfeed during treatment with binimetinib and for 3 days after the final dose.

SLIDESHOW

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References
https://reference.medscape.com/drug/mektovi-binimetinib-1000139

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