Kesaiyou Selumetinib Hydrogen Sulfate Capsules

1. Indications and Usage
NF1 with PN: Indicated for pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have one or more symptomatic, unresectable plexiform neurofibromas (PN).
2. Dosage and Administration
Standard Dosage: 25 mg/m² administered orally twice daily (approximately every 12 hours).
Initial Dose Calculation: Doses should be calculated based on body surface area (BSA) and rounded to the nearest 5 mg or 10 mg capsule. The maximum single dose is 50 mg.
Administration: Must be taken on an empty stomach (no food for 2 hours before and 1 hour after dosing). Swallow capsules whole.
Dose Modifications: For toxicities, proceed with dose delays, reduction, or permanent discontinuation. For strong/moderate CYP3A4 or CYP2C19 inhibitors, the dose must be reduced.
3. Mechanism of Action
MEK Inhibition: Selumetinib is a selective, small-molecule inhibitor of mitogen-activated protein kinase kinases 1 and 2 (MEK1/2).
Pathway Blocking: It blocks the signaling of the RAS/RAF/MEK/ERK pathway, thereby inhibiting tumor cell proliferation and survival in NF1-PN.
4. Safety and Warnings
Cardiomyopathy: Elicit left ventricular ejection fraction (LVEF) evaluation prior to treatment initiation and every 3 months during treatment.
Ocular Toxicity: Monitor for retinal vein occlusion (permanent discontinuation required), retinal pigment epithelial detachment (suspend until resolved, then resume with dose reduction), and other ocular disorders.
Gastrointestinal and Dermatologic Toxicity: Monitor for severe diarrhea, diarrhea/colitis with cellular infiltration or tissue necrosis, and severe skin toxicity (dermatitis, rash).
Embryo-fetal Toxicity: Can cause fetal harm. Effective contraception is required for females and males during treatment and for at least one week after the final dose.
5. Adverse Reactions and Clinical Research
Most Common Adverse Reactions: Dermatitis acneiform, diarrhea, abdominal pain, fatigue, nausea, skin dryness, vomiting, arthralgia, myalgia, peripheral edema, and increased creatine kinase (CPK).
Clinical Research: Clinical trials demonstrated significant tumor shrinkage in children with NF1-PN.
6. Drug Interactions
CYP3A4 and CYP2C19 Inhibitors: Strong or moderate inhibitors (e.g., ketoconazole, itraconazole) significantly increase selumetinib exposure, necessitating a dosage reduction.
CYP3A4 Inducers: Strong inducers reduce selumetinib plasma concentrations, and concomitant use should generally be avoided.
P-gp Inhibitors: Concomitant use with P-glycoprotein (P-gp) inhibitors may increase absorption.
7. Pharmaceutical Information
Active Ingredient: Selumetinib (hydrogen sulfate).
Dosage Forms: Capsules available in strengths of 10 mg and 25 mg.
Storage: Store at 20°C to 25°C (68°F to 77°F); protect from moisture.