MEKTOVI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MEKTOVI (MEKTOVI).
MEKTOVI (binimetinib) is a reversible, non-competitive inhibitor of mitogen-activated extracellular signal-regulated kinase 1 (MEK1) and MEK2. It inhibits the MAPK/ERK pathway, which is activated in tumors with BRAF mutations.
| Metabolism | Primarily metabolized by glucuronidation via UGT1A1 and UGT1A3, with minor contributions from CYP1A2 and CYP2C19. |
| Excretion | Primarily fecal (94% of total radioactivity) with minimal renal excretion (4% of total radioactivity). Unchanged drug accounts for approximately 27% of the dose in feces. |
| Half-life | Terminal elimination half-life is approximately 3.7 days (range 2.5–6.3 days) in patients with advanced solid tumors. This long half-life supports once-daily dosing. |
| Protein binding | Approximately 97–99% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Mean volume of distribution is 148 L (approximately 2.1 L/kg for a 70 kg patient). This large Vd indicates extensive tissue distribution. |
| Bioavailability | Absolute bioavailability is approximately 46% (range 32–63%) for the oral tablet formulation. Food does not significantly affect absorption. |
| Onset of Action | Time to maximum plasma concentration (Tmax) is 1.2–2.5 hours post-oral administration. Clinical response (e.g., tumor shrinkage) typically observed within weeks to months of continuous dosing. |
| Duration of Action | Sustained MEK inhibition throughout the dosing interval (24 hours) with once-daily dosing. Clinical duration of effect depends on treatment continuation until disease progression or unacceptable toxicity. |
45 mg orally twice daily, approximately 12 hours apart
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min) or ESRD. |
| Liver impairment | Mild (Child-Pugh A): No adjustment. Moderate (Child-Pugh B): Reduce dose to 30 mg orally twice daily. Severe (Child-Pugh C): Not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended; monitor for adverse effects due to potential age-related renal/hepatic function decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MEKTOVI (MEKTOVI).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or effects on milk production. M/P ratio not determined. Because of the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment and for 3 weeks after the final dose. |
| Teratogenic Risk | Category D. Based on its mechanism of action (MEK inhibitor), Mektovi (binimetinib) can cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies in pregnant women. Embryo-fetal toxicity has been demonstrated in animal studies at exposures below the human clinical exposure. Advise pregnant women of the potential risk to a fetus. First trimester: Highest risk for major malformations. Second and third trimesters: Risk of fetotoxicity and reduced fetal growth. |
■ FDA Black Box Warning
None.
| Serious Effects |
["None."]
| Precautions | ["Hemorrhage: Serious hemorrhagic events including fatal intracranial hemorrhage.","Venous thromboembolism: Monitor for pulmonary embolism and deep vein thrombosis.","Cardiomyopathy: Assess left ventricular ejection fraction before and during treatment.","Serous retinopathy and retinal vein occlusion: Monitor for visual disturbances; perform ophthalmologic evaluation.","Interstitial lung disease: Monitor for pulmonary symptoms.","Hepatotoxicity: Monitor liver function tests.","Rhabdomyolysis: Monitor creatine kinase.","Fetal harm: Can cause fetal harm; advise effective contraception."] |
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| Fetal Monitoring | Pregnancy testing should be performed prior to initiation of therapy and periodically during treatment. If patient becomes pregnant during treatment, apprise of potential hazard to fetus. Follow-up obstetric ultrasound should be considered to monitor fetal development. |
| Fertility Effects | Animal studies have shown impairment of male and female fertility at clinically relevant doses. May reduce male and female fertility in humans. Effects may not be reversible. |