Selumetinib (1 brand name, 1 dosage form, 1 route)
Available dosage forms: CAPSULE.
Routes of administration: ORAL.
Brand Names
- KOSELUGO
Indications and Usage
KOSELUGO is indicated for the treatment of adult and pediatric patients 1 year of age and older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN) [see Dosage and Administration (2)].
Contraindications
None.
Adverse Reactions
The following clinically significant adverse reactions are described elsewhere in the labeling: •Left Ventricular Dysfunction [see Warnings and Precautions (5.1)] •Ocular Toxicity [see Warnings and Precautions (5.2)] •Gastrointestinal Toxicity [see Warnings and Precautions (5.3)] •Skin Toxicity [see Warnings and Precautions (5.4)] •Increased Creatine Phosphokinase [see Warnings and Precautions (5.5)]
Mechanism of Action
Selumetinib 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. Both MEK and ERK are critical components of the RAS-regulated RAF-MEK-ERK pathway, which is often activated in different types of cancers. In genetically modified mouse models of NF1 that generate neurofibromas that recapitulate the genotype and phenotype of human NF1, oral dosing of selumetinib inhibited ERK phosphorylation, and reduced neurofibroma numbers, volume, and proliferation.
Overdosage
Dialysis is not effective as KOSELUGO is highly protein bound and is extensively metabolized.