How to Use Selumetinib (Koselugo)
Selumetinib (Koselugo) is a kinase inhibitor specifically used to treat symptomatic, unresectable plexiform neurofibromas (PN) in children aged 2 years and older with neurofibromatosis type 1 (NF1).
How to Use Selumetinib (Koselugo)
Recommended Dosage
(1) The standard recommended dose of selumetinib is 25 mg/m², taken orally twice daily (approximately every 12 hours) on an empty stomach until disease progression or intolerable toxicity occurs.
(2) An empty stomach is defined as refraining from eating for 2 hours before and 1 hour after each dose.
(3) The specific dosage should be calculated based on the patient's body surface area (BSA).
(4) For patients with a body surface area of 0.55-0.69 m², the dosage is 20 mg in the morning and 10 mg in the evening.
(5) For patients with a body surface area of 0.70-0.89 m², the dosage is 20 mg twice daily.
(6) Patients with a blood volume of 0.90-1.09 m²: 25 mg twice daily.
(7) Patients with a blood volume of 1.10-1.29 m²: 30 mg twice daily.
(8) Patients with a blood volume of 1.30-1.49 m²: 35 mg twice daily.
Precautions for Administration
(1) Administration: Must be swallowed whole. Do not chew, dissolve, or open the capsule. Patients unable to swallow whole capsules should not use this medication.
(2) Missed Dosage Management: If a dose is missed, take it as soon as you remember. If less than 6 hours have passed since the next dose, skip the missed dose and take the next dose as scheduled.
(3) Management of Vomiting: If vomiting occurs after administration, do not take an extra dose; continue with the next dose as scheduled.
Selmetinib (Koselugo) Dosage Adjustment
Cardiomyopathy
(1) If asymptomatic LVEF decreases by ≥10% and falls below the lower limit of normal, discontinue administration. Resume administration at a reduced dose after recovery.
(2) Permanent discontinuation of medication for symptomatic LVEF decrease or grade 3/4 LVEF decrease.
Ocular Toxicity
(1) Retinal Pigment Epithelial Detachment (RPED): Discontinue administration until recovery, then resume at a reduced dose.
(2) Retinal Vein Occlusion (RVO): Permanent discontinuation of medication.
Gastrointestinal Toxicity
(1) Grade 3 diarrhea: Discontinue administration until improvement to grade 0/1, then resume at the original dose.
(2) Permanent discontinuation if no improvement is observed within 3 days.
(3) Permanent discontinuation of medication for grade 4 diarrhea or grade 3/4 colitis.
Skin Toxicity
Grade 3/4 skin reaction: Discontinue administration until improvement, then resume at a reduced dose.
Crease Phosphokinase (CPK) Elevation
(1) Grade 4 CPK elevation or CPK elevation accompanied by myalgia: Discontinue administration until improvement to grade 0/1, then resume at a reduced dose.
(2) Permanent discontinuation if no improvement is observed within 3 weeks; permanent discontinuation of medication for rhabdomyolysis.
Special Populations for Koselugo (Selmetinib)
Patients with Hepatic Impairment
(1) Patients with mild hepatic impairment (Child-Pugh A) require no dose adjustment.
(2) Patients with moderate hepatic impairment (Child-Pugh B) reduce the dose to 20 mg/m² orally twice daily.
(3) Patients with severe hepatic impairment (Child-Pugh C) do not have a clearly defined recommended dose and should be used with caution.
Patients with Renal Impairment
(1) Patients with mild to moderate renal impairment require no dose adjustment.
(2) Patients with end-stage renal disease (ESRD) also require no dose adjustment.
Pregnant and Lactating Women
(1) Koselugo may cause fetal harm and is contraindicated in pregnant women.
(2) Women of childbearing age should use effective contraception during treatment and for one week after the last dose.
(3) Lactating women should discontinue breastfeeding during treatment and for one week after the last dose.
Pediatric Use
(1) Applicable to NF1 patients aged 2 years and older.
(2) Effectiveness in children under 2 years of age has not been established.
