Selumetinib

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.

• 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) ]. KOSELUGO is a kinase inhibitor 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).

• None. None.contraindicated

• KOSELUGO capsules: The recommended dosage is 25 mg/m 2 , swallowed whole, taken orally twice daily with or without food (see Table 1) . (2.1 , 2.2 ) • KOSELUGO oral granules: The recommended dosage is equivalent to 25 mg/m 2 , sprinkled onto or mixed with soft food and taken orally twice daily (see Table 2). ( 2.1 , 2.2 ) • Moderate hepatic impairment (Child-Pugh B): The recommended dosage is 20 mg/m 2 orally twice daily (see Tables 6 and 7) . ( 2.2 , 2.4 ) • Severe hepatic impairment (Child-Pugh C): The recommended dosage has not been established. ( 2.4 , 8.6 ) • Strong or Moderate CYP3A4 Inhibitors or Fluconazole: If coadministration with strong or moderate CYP3A4 inhibitors or fluconazole cannot be avoided, reduce the dose of KOSELUGO (see Tables 8 and 9) . ( 2.5 ) 2.1 Recommended Dosage The recommended dosage of KOSELUGO capsules ( see Table 1 ) and KOSELUGO oral granules ( see Table 2 ) for adult and pediatric patients 1 year of age and older, based on body surface area, is 25 mg/m 2 orally twice daily, until disease progression or unacceptable toxicity [see Dosage and Administration (2.2)]. Table 1 Recommended Dosage: KOSELUGO Capsules Body Surface Area The recommended dosage of KOSELUGO capsules for patients with a BSA less than 0.55 m 2 has not been established.

• Left Ventricular Dysfunction : Assess ejection fraction prior to initiating treatment, every 3 months during the first year, then every 6 months thereafter and as clinically indicated. Withhold, reduce the dose, or permanently discontinue KOSELUGO based on severity of adverse reaction. ( 2.3 , 5.1 ) • Ocular Toxicity : Conduct ophthalmic assessments prior to initiating KOSELUGO, at regular intervals during treatment and for new or worsening visual changes. Permanently discontinue KOSELUGO for retinal vein occlusion (RVO). Withhold KOSELUGO for retinal pigment epithelial detachment (RPED), monitor with optical coherence tomography assessments until resolution, and resume at reduced dose. ( 2.3 , 5.2 ) • Gastrointestinal Toxicity : Advise patients to start an anti-diarrheal agent immediately after the first episode of loose stool and to increase fluid intake. Withhold, reduce the dose, or permanently discontinue KOSELUGO based on severity of adverse reaction. ( 2.3 , 5.3 ) • Skin Toxicity : Monitor for severe skin rashes. Withhold, reduce the dose, or permanently discontinue KOSELUGO based on severity of adverse reaction. ( 2.3 , 5.4 ) • Increased Creatine Phosphokinase (CPK) : Increased CPK and rhabdomyolysis can occur. Obtain serum CPK prior to initiating KOSELUGO, periodically during treatment, and as clinically indicated. If increased CPK occurs, evaluate for rhabdomyolysis or other causes. Withhold, reduce the dose, or permanently discontinue KOSELUGO based on severity of adverse reaction.

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) ] Most common adverse reactions in pediatric patients (≥ 40%) are: vomiting, diarrhea, increased creatine phosphokinase, dry skin, paronychia, nausea, dermatitis acneiform, and pyrexia. ( 6.1 ) Most common adverse reactions in adult patients (≥ 40%) are rash (all), dermatitis acneiform, and diarrhea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca 1-800-236-9933 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience 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. The NF1 PN pediatric safety pool described in the WARNINGS AND PRECAUTIONS reflects exposure to KOSELUGO at the recommended dosage in 134 pediatric patients in SPRINKLE (N = 36) (NCT05309668), SPRINT Phase I (N = 24) (NCT01362803), SPRINT Phase II Stratum 1 (N = 50) [see Clinical Studies (14.1) ] , and Phase I Food Effect Study (N = 24) (NCT05101148).

• Lactation: Advise not to breastfeed. (8.2) 8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1) ] , KOSELUGO can cause fetal harm when administered to a pregnant woman. There are no available data on the use of KOSELUGO in pregnant women to evaluate drug-associated risk. In animal reproduction studies, administration of selumetinib to mice during organogenesis caused reduced fetal weight, adverse structural defects, and effects on embryofetal survival at exposures approximately > 5 times the human exposure at the clinical dose of 25 mg/m 2 twice daily ( see Data ). Advise pregnant women of the potential risk to the fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Human Data In KOMET, a first trimester spontaneous abortion was reported in a patient receiving KOSELUGO.

Metabolism

Selumetinib pharmacokinetics were observed at steady state in adult and pediatric patients with NF1 and are presented as mean (CV%) unless otherwise indicated. The maximum plasma concentration (C max ) is 792 (49) ng/mL and systemic exposure (AUC) is 2141 (55) ng•h/mL following KOSELUGO 25 mg/m 2 twice daily.

Dialysis is not effective as KOSELUGO is highly protein bound and is extensively metabolized.

• Apr 10, 2020NDANDA213756Astrazeneca
• Sep 10, 2025NDANDA219943Astrazeneca

1. 1Blood Creatine Phosphokinase Increased1087.8%
2. 2Rash1087.8%
3. 3Off Label Use1057.6%
4. 4Paronychia815.9%
5. 5Dermatitis Acneiform695.0%
6. 6Diarrhoea684.9%
7. 7Nausea654.7%
8. 8Acne644.6%
9. 9Fatigue634.6%
10. 10Alopecia543.9%
11. 11Death523.8%
12. 12Vomiting473.4%
13. 13Abdominal Pain382.8%
14. 14Headache372.7%
15. 15Pain372.7%

The 10 most recently updated of 139 ClinicalTrials.gov registrations naming Selumetinib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Targeted Therapy Directed by Genetic Testing in Treating Patients With Locally Advanced or Advanced Solid Tumors, The ComboMATCH Screening Trial
  Recruiting · Phase 2 · Interventional · 2,900 enrolled · National Cancer Institute (NCI)
  NCT05564377updated 2026-06-12
• Testing the Combination of Anti-Cancer Drugs, Selumetinib and DS-8201a, for Advanced Pancreatic Ductal Adenocarcinoma
  Not yet recruiting · Phase 1 · Phase 2 · Interventional · 31 enrolled · National Cancer Institute (NCI)
  NCT07619521updated 2026-06-11
• Pharmacokinetics, Safety and Efficacy of the Selumetinib Granule Formulation in Children Aged ≥1 to <7 Years With NF1-related Symptomatic, Inoperable PN
  Active not recruiting · Phase 1 · Phase 2 · Interventional · 36 enrolled · AstraZeneca
  NCT05309668updated 2026-06-09
• Testing the Use of the Combination of Selumetinib and Olaparib or Selumetinib Alone Targeted Treatment for RAS Pathway Mutant Recurrent or Persistent Ovarian and Endometrial Cancers, A ComboMATCH Treatment Trial
  Recruiting · Phase 2 · Interventional · 165 enrolled · National Cancer Institute (NCI)
  NCT05554328updated 2026-06-03
• Real-World Treatment Study of Koselugo (Selumetinib)
  Recruiting · Observational · 200 enrolled · AstraZeneca
  NCT06360406updated 2026-06-01
• AZD6244 Hydrogen Sulfate for Children With Nervous System Tumors
  Active not recruiting · Phase 1 · Phase 2 · Interventional · 99 enrolled · National Cancer Institute (NCI)
  NCT01362803updated 2026-06-01
• Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
  Active not recruiting · Phase 2 · Interventional · 1,377 enrolled · National Cancer Institute (NCI)
  NCT03155620updated 2026-06-01
• Selumetinib for the Prevention of Plexiform Neurofibroma Growth in NF Type 1
  Recruiting · Phase 2 · Interventional · 200 enrolled · University of Alabama at Birmingham
  NCT06188741updated 2026-05-29
• A Study of the Drugs Selumetinib vs. Carboplatin and Vincristine in Patients With Low-Grade Glioma
  Recruiting · Phase 3 · Interventional · 170 enrolled · National Cancer Institute (NCI)
  NCT04166409updated 2026-05-29
• AZD6244 (ARRY-142886) Solid Oral Dosage Formulation in Participants With Advanced Solid Malignancies
  Active not recruiting · Phase 1 · Interventional · 58 enrolled · AstraZeneca
  NCT00463814updated 2026-05-29

Frequently asked questions

How does Selumetinib work?

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.

What is Selumetinib used for?

According to FDA labeling, Selumetinib carries indications including: 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) ]. KOSELUGO is a kinase inhibitor 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).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Selumetinib?

Selumetinib is classified as Mitogen-activated protein kinase (MEK) inhibitors, Kinase Inhibitor, Mitogen-Activated Protein Kinase Kinase 1 Inhibitors, Mitogen-Activated Protein Kinase Kinase 2 Inhibitors, Protein Kinase Inhibitors, Cellular Proliferation Alteration.

What are the brand names for Selumetinib?

Selumetinib is marketed under brand names including Koselugo.

What are the contraindications for Selumetinib?

Selumetinib labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.