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

Drug name

Common name: Selumetinib

Product Name: KOSELUGO ®

indication

Used for treatment:

Neurofibromatosis type 1 (NF1) in children aged 2 years and above: patients with symptomatic and inoperable plexiform neurofibromatosis (PN)

Specifications and characteristics

Capsules:

10mg: White opaque hard capsule with black lettering "SEL10" printed on it

25mg: Blue opaque hard capsule with black lettering "SEL25" printed on it

main ingredients

Active ingredient: Smetinib (10mg capsules containing 12.1mg Smetinib sulfate); 25mg capsules containing 30.25mg sematinib sulfate

Accessories: Vitamin E Polyethylene Glycol Succinate (TPGS)

Capsule shell ingredients: Hydroxypropyl methylcellulose, carrageenan, potassium chloride, titanium dioxide, etc

Usage and Dosage

Recommended dosage: 25mg/m ² orally, twice daily (with an interval of approximately 12 hours)

Medication requirements:

Fasting (fasting from 2 hours before meals to 1 hour after meals)

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

When missed: ≤ 6 hours can be replenished,>6 hours can be skipped

After vomiting: No need for supplementation, take the next dose according to the original plan

Dose adjustment

Cardiotoxicity: Asymptomatic LVEF reduction of ≥ 10% paused, reduced after recovery; Symptomatic LVEF reduction and permanent discontinuation of medication

Eye toxicity: retinal pigment epithelial detachment (RPED) is temporarily suspended and reduced after recovery; Permanent discontinuation of medication for retinal vein occlusion (RVO)

Diarrhea: Level 3 suspension until improvement, Level 4 permanent discontinuation of medication

Liver dysfunction: Moderate (Child Pugh B) reduction to 20mg/m ² twice a day

Medication precautions

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

Monitoring requirements:

Check heart function before treatment and every 3 months

Regular ophthalmic examinations

Monitor CPK levels

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

Medication for special populations

Pregnancy/lactation: contraindicated, contraception is required during treatment and 1 week after discontinuation of medication

Children: NF1 patients aged ≥ 2 years are safe and effective

Liver dysfunction: Moderate dose reduction required, severe dose not recommended

Renal insufficiency: No need to adjust dosage

adverse reaction

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

Serious:

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

contraindication

No absolute contraindications

Drug interactions

Strong/medium acting CYP3A4 inhibitors: Avoid combination therapy (such as itraconazole), and reduce dosage when necessary

Strong/moderate CYP3A4 inducers: avoid combination use (such as rifampicin)

Vitamin K antagonists/antiplatelet drugs: may increase the risk of bleeding

Storage method

Store at 25 ° C (77 ° F), allowing for short-term fluctuations between 15-30 ° C (59-86 ° F)

Keep the original packaging and do not remove the desiccant

moisture-proof

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