Selumetinib (INN), sold under the brand name Koselugo, is a medication for the treatment of children, two years of age and older, with neurofibromatosis type I (NF-1), a genetic disorder of the nervous system causing tumors to grow on nerves. It is taken by mouth. Common side effects include headache, abdominal pain and other problems of the gastrointestinal tract, fatigue, muscle pain, as well as dry skin and other skin problems. Selumetinib was approved for medical use in the United States in April 2020, and in the European Union in June 2021. The U.S. Food and Drug Administration considers it to be a first-in-class medication.
Medical uses Selumetinib is used for the treatment of neurofibromas in those with neurofibromatosis type I (NF-1). This is a rare, progressive condition caused by a mutation or flaw in the gene coding for the protein neurofibromin 1. NF-1 is usually diagnosed in early childhood and appears in an estimated one out of every 3,000 infants. It is characterized by changes in skin coloring (pigmentation), neurologic and skeletal impairments and risk for development of benign and malignant tumors throughout life. It is approved specifically for children who have symptomatic, inoperable plexiform neurofibromas, which are tumors involving the nerve sheaths (coating around nerve fibers) and can grow anywhere in the body, including the face, extremities, areas around the spine and deep in the body where they may affect organs. Between 30% and 50% of children born with NF-1 develop one or more plexiform neurofibromas. In November 2025, selumetinib was approved for medical use in the US for adults with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas). The US Food and Drug Administration previously approved selumetinib capsules and granules for people aged one year of age and older for this indication.
Adverse effects The US prescribing information includes warnings and precautions for left ventricular dysfunction, ocular toxicity, gastrointestinal toxicity, skin toxicity, increased creatine phosphokinase, increased levels of vitamin E and increased risk of bleeding (Koselugo capsules), and embryo-fetal toxicity. adverse reactions observed in adults receiving selumetinib were consistent with the known selumetinib safety profile. Common side effects are headache, nausea, vomiting, abdominal pain, diarrhea, fatigue, musculoskeletal pain (pain in the body affecting bones, muscles, ligaments, tendons and nerves), fever, dry skin, acneiform rash (acne) and other rashes, stomatitis (inflammation of the mouth and lips), paronychia (infection in the skin that surrounds a toenail or fingernail) and pruritus (itching). Selumetinib can also cause serious side effects including heart failure (manifested as ejection fraction decrease, or when the muscle of the left ventricle of the heart is not pumping as well as normal) and eye toxicity (acute and chronic damage to the eye) including retinal vein occlusion, retinal pigment epithelial detachment and impaired vision. Selumetinib can also cause increased creatinine phosphokinase (CPK). CPK is an enzyme found in the heart, brain and skeletal muscles. When muscle tissue is damaged, CPK leaks into a person's blood, which can be a sign of rhabdomyolysis (breakdown of skeletal muscle due to direct or indirect muscle injury). Further, selumetinib capsules contain vitamin E, and users are at an increased risk of bleeding if their daily intake of vitamin E exceeds the recommended or safe limits.
Pregnancy Based on findings from animal studies, selumetinib may cause harm to a newborn baby when administered to a pregnant woman. The FDA advises health care professionals to tell women of reproductive age, and men with female partners of reproductive potential, to use effective contraception during treatment with selumetinib, and for one week after the last dose.
Interactions As selumetinib is thought to be metabolized by the liver enzymes CYP3A4 and CYP2C19, use of moderate to strong CYP3A4 inhibitors (such as grapefruit juice) and of the CYP2C19 inhibitor fluconazole is discouraged for people taking selumetinib.
Pharmacology
Mechanism of action Selumetinib is a kinase inhibitor, more specifically a selective inhibitor of the enzyme mitogen-activated protein kinase kinase (MAPK kinase or MEK) subtypes 1 and 2. These enzymes are part of the MAPK/ERK pathway, which regulates cell proliferation (i.e., growth and division) and is overly active in many types of cancer.
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