Koselugo

Selumetinib

Symptomatic, inoperable plexiform neurofibromas in paed patients ≥3 yr w/ neurofibromatosis type 1.

Recommended dose: 25 mg/m² bd (approx every 12 hr). Individualised dosing based on BSA up to max single dose: 50 mg. ≥1.9 m² 50 mg bd, 1.7-1.89 m² 45 mg bd, 1.5-1.69 m² 40 mg bd, 1.3-1.49 m² 35 mg bd, 1.1-1.29 m² 30 mg bd, 0.9-1.09 m² 25 mg bd, 0.7-0.89 m² 20 mg bd, 0.55-0.69 m² 20 mg in the morning & 10 mg in the evening. Dose adjustments for adverse events: ≥1.9 m² 1st dose reduction: 35 mg in the morning & evening. 2nd dose reduction: 25 mg in the morning & evening, 1.7-1.89 m² 1st dose reduction: 35 mg in the morning & 30 mg in the evening. 2nd dose reduction: 25 mg in the morning & 20 mg in the evening, 1.5-1.69 m² 1st dose reduction: 30 mg in the morning & evening. 2nd dose reduction: 25 mg in the morning & 20 mg in the evening, 1.3-1.49 m² 1st dose reduction: 25 mg in the morning & evening. 2nd dose reduction: 25 mg in the morning & 10 mg in the evening, 1.1-1.29 m² 1st dose reduction: 25 mg in the morning & 20 mg in the evening. 2nd dose reduction: 20 mg in the morning & 10 mg in the evening, 0.9-1.09 m² 1st dose reduction: 25 mg in the morning & 10 mg in the evening. 2nd dose reduction: 10 mg in the morning & evening, 0.7-0.89 m² 1st dose reduction: 20 mg in the morning & 10 mg in the evening. 2nd dose reduction: 10 mg in the morning & evening, 0.55-0.69 m² 1st dose reduction: 10 mg in the morning & evening. 2nd dose reduction: 10 mg once daily. Co-administration w/ CYP3A4 or CYP2C19 inhibitors Reduce dose to 20 mg/m² bd if patient is currently taking 25 mg/m² bd or reduce dose to 15 mg/m² bd if patient is currently taking 20 mg/m² bd. Moderate hepatic impairment Starting dose: 20 mg/m² bd.

Should be taken on an empty stomach: Swallow whole w/ water. Do not chew/dissolve/open cap.

Hypersensitivity. Severe hepatic impairment.

Permanently discontinue use if retinal vein occlusion is diagnosed. Interrupt therapy & reduce dose if retinal pigment epithelial detachment or central serous retinopathy is diagnosed & visual acuity is affected. History of impaired left ventricular function or baseline LVEF below institutional LLN. Skin & subcutaneous disorders. Not to be administered in patients w/ difficulty in swallowing. Asian patients. Perform LVEF echocardiogram evaluation prior to therapy. Conduct ophth evaluation prior to & if new visual disturbances occur. Monitor liver lab values prior to, at least mthly during 1st 6 mth & clinically thereafter. Not to be taken w/ vit E supplementation. Frequently perform anticoagulant assessment in concomitant use w/ anticoagulants or antiplatelets. May affect ability to drive & use machines. Not to be used in patients w/ severe hepatic impairment. Moderate hepatic impairment. Not recommended in women of childbearing potential not using contraception; advise both male & female patients of reproductive potential to use effective contraception during & for at least 1 wk after completion of treatment. Not recommended during pregnancy. Not to be used during lactation. Childn <3 yr.

Vomiting, diarrhoea, nausea, stomatitis; rash, dry skin, acneiform rash, paronychia, hair changes; asthenic events, pyrexia, peripheral oedema; increased blood CPK & creatinine, AST/ALT & BP, hypoalbuminaemia, decreased Hb, ejection fraction. Blurred vision; dyspnoea; dry mouth; facial oedema.

Increased C_max & AUC w/ strong CYP3A4 inhibitor eg, itraconazole; strong CYP2C19/moderate CYP3A4 inhibitor eg, fluconazole; erythromycin, fluoxetine. Avoid co-administration w/ strong CYP3A4 (eg, clarithromycin, grapefruit juice, oral ketoconazole) or CYP2C19 (eg, ticlopidine) inhibitors; moderate CYP3A4 (eg, erythromycin, fluconazole) or CYP2C19 (eg, omeprazole) inhibitors. Decreased C_max & AUC w/ strong CYP3A4 inducer eg, rifampicin. Avoid concomitant use w/ strong CYP3A4 inducers (eg, phenytoin, rifampicin, carbamazepine, St. John's wort) or moderate CYP3A4 inducers. Altered plasma conc of OAT3 substrates eg, MTX, furosemide. Avoid taking vit E supplements.

Targeted Cancer Therapy

L01EE04 - selumetinib ; Belongs to the class of mitogen-activated protein kinase (MEK) inhibitors. Used in the treatment of cancer.

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