Mektovi

/ Medison

The recommended dosage of this medical product is 45 mg orally taken twice daily, approximately 12 hours apart, in combination with encorafenib until disease progression or unacceptable toxicity.
For full details see prescribing information.

BRAF V600E or V600K Mutation-Positive Unresectable or Metastatic Melanoma
Treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation. In combination with encorafenib.
BRAF V600E Mutation-Positive metastatic non-small cell lung cancer (NSCLC)
Treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) adenocarcinoma with a BRAF V600E mutation, as detected by an approved test. In combination with encorafenib.

Hypersensitivity to the active substance or to any of the excipients

New Primary Malignancies
New primary malignancies, cutaneous and non-cutaneous, can occur when binimetinib is used in combination with encorafenib.
In PHAROS, cutaneous squamous cell carcinoma and skin papilloma each occurred in 2% of patients who received binimetinib in combination with encorafenib.
Monitor patients for new malignancies prior to initiation of treatment, while on treatment, and after discontinuation of treatment.
Cardiomyopathy
Cardiomyopathy, presenting as left ventricular dysfunction with symptomatic or asymptomatic decreases in ejection fraction, has been reported in patients treated with binimetinib in combination with encorafenib. Grade 3 left ventricular dysfunction events have been observed. Most events resolved.
Assess ejection fraction by echocardiogram or MUGA scan prior to initiating treatment, one month after initiating treatment, and then every 2 to 3 months during treatment. The 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). Patients with cardiovascular risk factors should be monitored closely.
Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction.
Venous Thromboembolism
In COLUMBUS, venous thromboembolism (VTE) occurred in 6% of patients receiving binimetinib in combination with encorafenib, including 3.1% of patients who developed pulmonary embolism. In PHAROS, VTE occurred in 7% of patients receiving binimetinib in combination with encorafenib, including 1% of patients who developed pulmonary embolism.
Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction.
Ocular Toxicities
Serous Retinopathy
Serous retinopathy, including retinal detachment and macular edema, has been reported in patients receiving binimetinib in combination with encorafenib. Events were generally symptomatic but not associated with blindness. No patient permanently discontinued therapy due to serous retinopathy, although dose interruption or reduction was occasionally required.
Assess for visual symptoms at each visit. Perform an ophthalmologic examination at regular intervals, for new or worsening visual disturbances, and to follow new or persistent ophthalmologic findings. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction.
Retinal Vein Occlusion
RVO is a known class-related adverse reaction of MEK inhibitors and may occur in patients treated with binimetinib in combination with encorafenib. In patients with BRAF mutation-positive melanoma receiving binimetinib with encorafenib (n=690), 1 patient experienced RVO (0.1%).
The safety of this medical product has not been established in patients with a history of RVO or current risk factors for RVO including uncontrolled glaucoma or a history of hyperviscosity or hypercoagulability syndromes.
Perform ophthalmologic evaluation for patient-reported acute vision loss or other visual disturbance within 24 hours. Permanently discontinue in patients with documented RVO.
Uveitis
Uveitis, including iritis and iridocyclitis, has been reported in patients treated with binimetinib in combination with encorafenib. In COLUMBUS, the incidence of uveitis among patients treated with binimetinib in combination with encorafenib was 4%. In PHAROS, uveitis occurred in 1% of patients receiving binimetinib in combination with encorafenib.
Assess for visual symptoms at each visit. Perform an ophthalmologic evaluation at regular intervals and for new or worsening visual disturbances, and to follow new or persistent ophthalmologic findings. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction.
Interstitial Lung Disease
In patients with BRAF mutation-positive melanoma receiving binimetinib with encorafenib (n=690), 2 patients (0.3%) developed interstitial lung disease (ILD), including pneumonitis. In PHAROS, 1 patient (1%) receiving binimetinib with encorafenib developed pneumonitis.
Assess new or progressive unexplained pulmonary symptoms or findings for possible ILD. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction.
Hepatotoxicity
Hepatotoxicity can occur when binimetinib is administered in combination with encorafenib. In COLUMBUS, the incidence of Grade 3 or 4 increases in liver function laboratory tests in patients receiving binimetinib in combination with encorafenib was 6% for alanine aminotransferase (ALT), 2.6% for aspartate aminotransferase (AST), and 0.5% for alkaline phosphatase. No patient experienced Grade 3 or 4 serum bilirubin elevation. In PHAROS, the incidence of Grade 3 or 4 increases in liver function laboratory tests in patients receiving binimetinib in combination with encorafenib was 10% for AST, 9% for ALT, and 3.2% for alkaline phosphatase.
Monitor liver laboratory tests before initiation, monthly during treatment, and as clinically indicated. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction.
Rhabdomyolysis
Rhabdomyolysis can occur when binimetinib is administered in combination with encorafenib. In COLUMBUS, elevation of laboratory values of serum CPK occurred in 58% of patients treated with binimetinib in combination with encorafenib. In patients with BRAF mutation-positive melanoma receiving binimetinib with encorafenib (n=690), rhabdomyolysis was reported in 1 patient (0.1%). In PHAROS, elevation of laboratory values of serum creatine kinase (CK) occurred in 41% of patients treated with binimetinib in combination with encorafenib. No patient experienced rhabdomyolysis.
Monitor CPK and creatinine levels prior to initiation, periodically during treatment, and as clinically indicated. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction.
Hemorrhage
Hemorrhage, including fatal intracranial events, has been observed in patients treated with binimetinib in combination with encorafenib. Reported cases have included Grade 3 or higher events, most commonly gastrointestinal hemorrhage (rectal hemorrhage, hematochezia, and hemorrhoidal hemorrhage, anal hemorrhage and hemothorax).
Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction.
Embryo-Fetal Toxicity
Based on findings from animal studies and its mechanism of action, binimetinib can cause fetal harm when administered to a pregnant woman. Binimetinib was embryotoxic and abortifacient when administered to rabbits during the period of organogenesis at doses greater than or equal to those resulting in exposures approximately 5 times the human exposure at the recommended clinical dose of 45 mg twice daily.
Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 30 days after the final dose.
For full details see prescribing information.

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.
For full details see prescribing information.

No clinically important drug interactions have been observed

Verify the pregnancy status of females of reproductive potential prior to initiating treatment. Advise females of reproductive potential to use effective contraception during treatment and for at least 30 days after the last dose.
Pregnancy: There are no available clinical data on the use of binimetinib during pregnancy. Advise pregnant women and females of reproductive potential of the potential risk to a fetus.
Lactation: There are no data on the presence of binimetinib or its active metabolite in human milk, or the effects of binimetinib on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment and for 3 days after the last dose

Since binimetinib is 97% bound to plasma proteins, hemodialysis is likely to be ineffective in the treatment of overdose