Mirdametinib

Brand Names: Gomekli

Drug Class: Kinase Inhibitor

Overview

11 DESCRIPTION GOMEKLI capsules and tablets for oral suspension contain mirdametinib, a kinase inhibitor. Mirdametinib is chemically known as (R)-N-(2,3-dihydroxypropoxy)-3,4-difluoro-2-((2- fluoro-4-iodophenyl)amino) benzamide. The molecular formula is C 16 H 14 F 3 IN 2 O 4 and the molecular weight is 482.20 g/mol.

Mechanism of Action

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Mirdametinib is an inhibitor of mitogen-activated protein kinase kinases 1 and 2 (MEK1/2). MEK1/2 proteins are upstream regulators of the extracellular signal-related kinase (ERK) pathway. In vitro, mirdametinib inhibited kinase activity of MEK1 and MEK2 and downstream phosphorylation of ERK. In a mouse model of NF1, oral dosing of mirdametinib inhibited ERK phosphorylation and reduced neurofibroma tumor volume and proliferation. 12.2 Pharmacodynamics Mirdametinib exposure-response relationships and the time course of pharmacodynamic response are not fully characterized.

Indications

  • 1 INDICATIONS AND USAGE GOMEKLI is indicated for the treatment of adult and pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection [see Clinical Studies (14) ]. GOMEKLI is a kinase inhibitor indicated for the treatment of adult and pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection. ( 1 )

Common Doses

  • 2 mg
  • 4 mg
  • 1 mg
  • 3 mg

Dosage

2 DOSAGE AND ADMINISTRATION The recommended dosage of GOMEKLI is 2 mg/m 2 orally twice daily, with or without food, for the first 21 days of each 28-day cycle. Continue treatment with GOMEKLI until disease progression or unacceptable toxicity. ( 2 ) 2.1 Recommended Evaluation and Testing Before Initiating GOMEKLI Prior to administration of GOMEKLI: conduct comprehensive ophthalmic assessment [see Warnings and Precautions (5.1) ]. assess ejection fraction (EF) by echocardiogram [see Warnings and Precautions (5.2) ]. 2.

Contraindications

  • 4 CONTRAINDICATIONS None. None. ( 4 )

Side Effects

  • 6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Ocular Toxicity [see Warnings and Precautions (5.1) ] Left Ventricular Dysfunction [see Warnings and Precautions (5.2) ] Dermatologic Adverse Reactions [see Warnings and Precautions (5.3) ] Embryo-Fetal Toxicity [see Warnings and Precautions (5.4) ] Adults: The most common adverse reactions (>25%) were rash, diarrhea, nausea, musculoskeletal pain, vomiting, and fatigue. ( 6.1 ) The most common Grade 3 or 4 laboratory abnormality (>2%) was increased creatine phosphokinase. ( 6.

Interactions

  • No major interactions listed on the FDA label. Always consult a healthcare professional.