Koselugo®Selumetinib Hydrogen Sulfate Capsules

1. Indications and Usage
Neurofibromatosis Type 1 (NF1): Treatment of pediatric patients 3 years of age and older with symptomatic, inoperable plexiform neurofibromas (PNs) associated with NF1 .
Note: Approved specifically for children; data for adult use as initial treatment is limited .
2. Dosage and Administration
Administration: Oral administration. Capsules must be swallowed whole with water (do not crush, chew, or open). Can be taken with or without food .
Standard Dose:
Recommended Dose: 25 mg/m² twice daily (approximately every 12 hours).
Calculation: Dose is calculated based on Body Surface Area (BSA) and rounded to the nearest 5 mg or 10 mg (maximum single dose 50 mg) .
Missed Dose: If a dose is missed, take it as soon as possible if it is more than 6 hours before the next scheduled dose. Otherwise, skip the missed dose.
Vomiting: If vomiting occurs after administration, do not re-administer the dose .
3. Mechanism of Action
Selumetinib is a selective inhibitor of mitogen-activated protein kinase 1 and 2 (MEK1 and MEK2).
MEK proteins are upstream regulators of the ERK signaling pathway, which promotes cell proliferation.
In NF1, the loss of neurofibromin function leads to overactivation of this pathway.
By inhibiting MEK, selumetinib blocks ERK phosphorylation, thereby reducing tumor cell proliferation and inducing apoptosis .
4. Safety and Warnings
Embryo-Fetal Toxicity: May cause fetal harm. Contraception is required for females of reproductive potential during treatment and for 1 week after the final dose .
Cardiomyopathy: Can cause a decrease in left ventricular ejection fraction (LVEF). Echocardiograms are recommended before initiation and periodically during treatment .
Ocular Toxicity: Retinal vein occlusion (RVO) and uveitis may occur. Periodic ophthalmologic examinations are recommended .
Rash and Acneiform Rash: Severe skin reactions are common. Dermatologic monitoring is necessary.
Elevated Creatine Phosphokinase (CPK): Monitor CPK levels periodically, especially in patients with muscle pain or weakness .
5. Adverse Reactions
Common adverse reactions (incidence ≥20%) in pediatric patients include:
Gastrointestinal: Vomiting, diarrhea, nausea, abdominal pain.
Dermatologic: Acneiform rash, dry skin, paronychia (nail bed inflammation), pruritus.
General: Fatigue, fever (pyrexia), stomatitis .
6. Drug Interactions
CYP3A4 and CYP2C19 Inhibitors: Avoid co-administration with strong or moderate inhibitors (e.g., ketoconazole, clarithromycin) as they increase Selumetinib exposure. If unavoidable, dose reduction is required .
CYP3A4 Inducers: Avoid co-administration with strong inducers (e.g., rifampin) as they reduce efficacy .
7. Pharmaceutical Information
Chemical Name: 5-[(4-Bromo-2-chlorophenyl)amino]-4-fluoro-6-[2-(hydroxyethoxy)carbamoyl]-1-methyl-1H-benzimidazole hydrogen sulfate .
Molecular Formula: C17H15BrClFN4O3 · H2SO4 .
Storage: Store at 25°C (77°F); excursions permitted to 15°C-30°C (59°F-86°F). Keep out of reach of children .