KOSELUGO (selumetinib) for adults with neurofibromatosis type 1 with symptomatic, inoperable plexiform neurofibromas

Initial US Approval:

2020

Key Clinical Studies:

KOMET (NCT04924608)

Drug Class/Description:

Kinase inhibitor

Indications and Usage:

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). 

Dosage and Administration:

• KOSELUGO capsules: The recommended dosage is 25 mg/m², swallowed whole, taken orally twice daily with or without food. 
• KOSELUGO oral granules: The recommended dosage is equivalent to 25 mg/m², sprinkled onto or mixed with soft food and taken orally twice daily.
• Moderate hepatic impairment (Child-Pugh B): The recommended dosage is 20 mg/m² orally twice daily. 
• Severe hepatic impairment (Child-Pugh C): The recommended dosage has not been established.
• 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.

Dosage Forms and Strengths:

Capsules: 10 mg and 25 mg of selumetinib.

Oral Granules: 5 mg and 7.5 mg of selumetinib.

Contraindications:

None.

Warnings and Precautions:

• 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.
• 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.
• 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.
• Skin Toxicity: Monitor for severe skin rashes. Withhold, reduce the dose, or permanently discontinue KOSELUGO based on severity of adverse reaction.
• 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.
• Increased Vitamin E Levels and Increased Risk of Bleeding (KOSELUGO Capsules): KOSELUGO capsules contain vitamin E and daily intake of vitamin E that exceeds the recommended or safe limits may increase the risk of bleeding. An increased risk of bleeding may occur in patients co-administered vitamin-K antagonists or anti-platelet agents. KOSELUGO oral granules do not contain vitamin E.
• Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of reproductive potential of the potential risk to a fetus and to use effective contraception 

Adverse Reactions:

Most common adverse reactions in pediatric patients (≥ 40%) are: vomiting, diarrhea, increased creatine phosphokinase, dry skin, paronychia, nausea, dermatitis acneiform, and pyrexia. 

Most common adverse reactions in adult patients (≥ 40%) are rash (all), dermatitis acneiform, and diarrhea.

Drug Interactions:

• Strong or Moderate CYP3A4 Inhibitors or Fluconazole: Avoid coadministration of strong or moderate CYP3A4 inhibitors or fluconazole with KOSELUGO. If coadministration cannot be avoided, reduce the dose of KOSELUGO.
• Strong or Moderate CYP3A4 Inducers: Avoid concomitant use of strong and moderate CYP3A4 inducers. 

Use in Specific Populations:

Lactation: Advise not to breastfeed. 

Adapted From:

https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/219943s002lbl.pdf

 

Every health-care provider should make their own determination regarding specific safe and appropriate patient care practices, including drug dosages and indications. The provider should always consult the most recent prescribing/product information. FDA Focus information is not guaranteed to be accurate, complete, or current. JADPRO and its editors, authors, reviewers, and commentators cannot be held responsible for any liability incurred as a consequence of the application of any of the information listed within.