selumetinib

Selumetinib is an oral mitogen-activated protein kinase kinase 1 and 2 (MEK1/2) inhibitor.

Drug name

Common name: Selumetinib

Trade name: KOSELUGO®

Indications

For treatment:

Neurofibromatosis type 1 (NF1) in children 2 years of age and older: patients with symptomatic, inoperable plexiform neurofibromas (PN)

Specifications and Characteristics

Capsule :

10mg: white opaque hard capsule, printed with "SEL10" in black

25mg: blue opaque hard capsule, printed with "SEL25" in black

Main ingredients

Active ingredient: selumetinib (10 mg capsule contains 12.1 mg selumetinib sulfate; 25 mg capsule contains 30.25 mg selumetinib sulfate)

Excipients: Vitamin E polyethylene glycol succinate (TPGS)

Capsule shell ingredients: hypromellose, carrageenan, potassium chloride, titanium dioxide, etc.

Usage and dosage

Recommended dose : 25 mg/m² orally, twice a day (about 12 hours apart)

Medication requirements :

Take on an empty stomach (fast from 2 hours before meals to 1 hour after meals)

Swallow the capsule whole, do not chew, dissolve or open the capsule

If you miss a dose: ≤6 hours, you can take it again, >6 hours, skip it

After vomiting: No need to take a supplementary dose, just take the next dose as originally planned

Dose adjustment

Cardiotoxicity : Pause if asymptomatic LVEF decreases ≥10% and reduce dose after recovery; permanently discontinue if symptomatic LVEF decreases

Ocular toxicity : Suspension for retinal pigment epithelial detachment (RPED), reduce dose after recovery; permanent discontinuation for retinal vein occlusion (RVO)

Diarrhea : Suspension until improvement in grade 3, permanent discontinuation in grade 4

Hepatic insufficiency : Moderate (Child-PughB) reduce dose to 20 mg/m² twice daily

Precautions when using medication

Diet : Take strictly on an empty stomach (fasting from 2 hours before meals to 1 hour after meals)

Monitoring requirements :

Check cardiac function before treatment and every 3 months

Regular eye examination

Monitor CPK levels

Taboo : Avoid grapefruit and products, St. John's wort

Drug use for special groups

Pregnancy/lactation : Contraindicated, contraception is required during treatment and 1 week after discontinuation

Children : Safe and effective for NF1 patients aged ≥2 years

Hepatic insufficiency : Moderate dose reduction is required, severe dose is not recommended

Renal insufficiency : No dose adjustment required

Adverse reactions

Common (≥40%) : Vomiting (82%), rash (80%), abdominal pain (76%), diarrhea (70%), nausea (66%), dry skin (60%), fatigue (56%), fever (56%), acneiform rash (50%), stomatitis (50%)

Serious :

Cardiomyopathy (23%), grade 3 diarrhea (16%), grade 3 rash (8%)

Contraindications

No absolute contraindications

Drug interactions

Strong/moderate CYP3A4 inhibitor :Avoid combined use (such as itraconazole), and the dose needs to be reduced if combined use is necessary

Strong/moderate CYP3A4 inducer :Avoid combined use (such as rifampicin)

Vitamin K antagonist/antiplatelet drug : May increase bleeding risk

Storage method

Save at 25°C (77°F), allow short-term fluctuations of 15-30°C (59-86°F)

Keep the original packaging and do not remove the desiccant

Moisture-proof