Child: As monotherapy for the treatment of symptomatic and inoperable plexiform neurofibromas: ≥3 years with a BSA of ≥0.55 m2: Recommended dose: 25 mg/m2 12 hourly. Dosing is individualised based on BSA (mg/m2) with each dose rounded to the nearest 5 mg or 10 mg dose up to a Max single dose of 50 mg. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability. Dosage and treatment recommendations may vary among countries and individual products (refer to specific product guidelines).
What are the brands available for Selumetinib in Singapore?
≥3 years with a BSA of ≥0.55 m2: Severe (Child-Pugh class C): Contraindicated. Moderate (Child-Pugh class B): 20 mg/m2 12 hourly.
Administration
Selumetinib May be taken with or without food. Swallow whole & do not chew/dissolve/open.
Contraindications
Severe hepatic impairment. Pregnancy.
Special Precautions
Patient with history of heart failure, reduced LVEF, or baseline LVEF below LLN; history of visual impairment. Not indicated for use in adults. Do not administer to patients who are unable or unwilling to swallow the whole capsule. Patient of Asian descent. Moderate hepatic impairment. Children.
Adverse Reactions
Significant: LVEF reduction; ocular toxicities (e.g. blurred vision, cataracts, ocular hypertension, photophobia, periorbital edema, visual impairment, retinal vein occlusion, retinal pigment epithelial detachment, central serous retinopathy); dermatological toxicities (e.g. acneiform eruption, maculopapular rash, paronychia, xeroderma); colitis; increased ALT, AST, and creatine phosphokinase. Blood and lymphatic system disorders: Anaemia, lymphocytopenia. Cardiac disorders: Cardiomyopathy, sinus tachycardia. Eye disorders: Chorioretinopathy. Gastrointestinal disorders: Nausea, vomiting, dry mouth, abdominal pain, diarrhoea, constipation, stomatitis. General disorders and administration site conditions: Fatigue, asthenia, pyrexia, peripheral oedema, facial oedema. Investigations: Decreased serum albumin, Hb, neutrophils; increased blood creatinine, amylase, serum lipase, alkaline phosphatase; increased or decreased serum K or Na; weight gain. Musculoskeletal and connective tissue disorders: Musculoskeletal pain. Nervous system disorders: Headache. Renal and urinary disorders: Haematuria, proteinuria, acute renal failure. Respiratory, thoracic and mediastinal disorders: Dyspnoea, hypoxia, epistaxis. Skin and subcutaneous tissue disorders: Rash, dry skin, pruritus, dermatitis, eczema, alopecia, hair colour change. Vascular disorders: Hypertension.
PO: Z (Animal studies showed embryofoetal harm and death. Avoid during pregnancy.)
Patient Counseling Information
This drug may cause fatigue, body weakness or vision problems, if affected, do not drive or operate machinery. Women of childbearing potential must use proven birth control methods during therapy and for 1 week after stopping the treatment. Males with female partners of childbearing potential must also use effective contraception during treatment and for 1 week after the last dose. Do not breastfeed during therapy and for 1 week after the last dose.
Monitoring Parameters
Confirm pregnancy status in women of childbearing potential before treatment initiation. Monitor LFTs (at baseline and as clinically indicated); serum CPK (prior treatment, periodically during treatment, and as clinically indicated); and anticoagulant parameters (e.g. INR or prothrombin time) to individuals receiving antiplatelets or vitamin-K antagonists. Evaluate LVEF by echocardiogram at baseline then every 3 months within the 1st year of treatment, then every 6 months thereafter or as clinically indicated. Perform comprehensive ophthalmic evaluation before treatment initiation, at regular intervals during therapy, and if new or worsening visual changes occur. Conduct HBV screening including HBsAg, HBV core antibody, total Ig or IgG, and antibody to HBV surface antigen before or at the beginning of systemic chemotherapy. Assess for signs and symptoms of new or worsening visual disturbances; gastrointestinal toxicity (e.g. severe diarrhoea); rhabdomyolysis; and severe skin reactions.
Drug Interactions
Plasma concentration may be increased with strong or moderate CYP3A4 inhibitors (e.g. erythromycin, clarithromycin, ketoconazole, fluconazole, itraconazole) and strong or moderate CYP2C19 inhibitors (e.g. fluoxetine, omeprazole, ticlopidine). Plasma concentration may be decreased with strong or moderate CYP3A4 inducers (e.g. carbamazepine, phenytoin, rifampicin). Enhanced risk of bleeding with vitamin E, vitamin K antagonists (e.g. warfarin), or antiplatelet agents. May alter the plasma concentration of organic anion transporter-3 (OAT3) substrates (e.g. furosemide, methotrexate) and P-gp substrates (e.g. digoxin, fexofenadine).
Food Interaction
Plasma concentration may be increased with grapefruit juice. Plasma concentration may be decreased with St. John’s wort.
Action
Description: Mechanism of Action: Selumetinib, an antineoplastic agent, is a selective mitogen-activated extracellular kinase (MEK) inhibitor. It inhibits MEK protein kinases 1 and 2, which are upstream regulators of the extracellular signal-related kinase (ERK) pathway. Both MEK and ERK are involved in the RAS-regulated Raf-MEK-ERK pathway. Inhibition of MEK in the pathway causes the prevention of tumour cell proliferation and survival. Pharmacokinetics: Absorption: Rapidly absorbed. Bioavailability: 62%. Time to peak plasma concentration: 1-1.5 hours. Distribution: Plasma protein binding: Approx 98.4%; 96.1% to serum albumin and <35% to α-1 acid glycoprotein. Metabolism: Metabolised in the liver by CYP3A4 (and to a lesser extent by CYP2C19, CYP2C9, CYP1A2, CYP2E1, and CYP3A5); undergoes glucuronidation by UGT1A1 and UGT1A3. CYP2C19 and CYP1A2 (with some contribution by CYP2C9 and CYP2A6) produce the active metabolite N-desmethyl selumetinib, which undergoes the same metabolic pathways as selumetinib. Excretion: Via faeces (59%; 19% as unchanged drug); urine (33%; <1% as unchanged drug). Elimination half-life: 6.2 hours.
Chemical Structure
Selumetinib Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 10127622, Selumetinib. https://pubchem.ncbi.nlm.nih.gov/compound/Selumetinib. Accessed June 26, 2024.
Storage
Store between 15-30°C. Protect from light and moisture.
L01EE04 - selumetinib ; Belongs to the class of mitogen-activated protein kinase (MEK) inhibitors. Used in the treatment of cancer.
References
Anon. Selumetinib Sulfate. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 11/03/2024.Anon. Selumetinib. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 11/03/2024.Buckingham R (ed). Selumetinib. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 11/03/2024.Koselugo 10 mg and 25 mg Hard Capsules (AstraZeneca Sdn Bhd). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 11/03/2024.Koselugo 10 mg Hard Capsules (AstraZeneca UK Limited). MHRA. https://products.mhra.gov.uk. Accessed 11/03/2024.Koselugo 25 mg Hard Capsules (AstraZeneca UK Limited). MHRA. https://products.mhra.gov.uk. Accessed 11/03/2024.Koselugo Capsule (AstraZeneca Pharmaceuticals LP). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 11/03/2024.Paediatric Formulary Committee. Selumetinib. BNF for Children [online]. London. BMJ Group, Pharmaceutical Press, and RCPCH Publications. https://www.medicinescomplete.com. Accessed 11/03/2024.Selumetinib. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 11/03/2024.
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