Selumetinib oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of selumetinib.
Drugs List
Therapeutic Indications
Uses
Neurofibromas in patients with neurofibromatosis type 1
Monotherapy for the treatment of symptomatic, inoperable plexiform neurofibromas (PN) in paediatric patients with neurofibromatosis type 1 (NF1) aged 3 and above.
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Children
25mg per metre squared of body surface area (BSA), twice daily.
Recommended dose based on BSA
0.55 - 0.69 metres squared BSA: 20mg in the morning, 10mg in the evening
0.70 - 0.89 metres squared BSA: 20mg twice daily
0.90 - 1.09 metres squared BSA: 25mg twice daily
1.10 - 1.29 metres squared BSA: 30mg twice daily
1.30 - 1.49 metres squared BSA: 35mg twice daily
1.50 - 1.69 metres squared BSA: 40mg twice daily
1.70 - 1.89 metres squared BSA: 45mg twice daily
BSA greater than 1.90 metres squared: 50mg twice daily
Patients with Hepatic Impairment
Moderate hepatic impairment
Reduce dose to 20mg per metre squared BSA, twice daily.
Additional Dosage Information
Recommended dose reductions for adverse reactions
First dose reduction
Recommended dose based on BSA
0.55 - 0.69 metres squared BSA: 10mg twice daily
0.70 - 0.89 metres squared BSA: 20mg in the morning, 10mg in the evening
0.90 - 1.09 metres squared BSA: 25mg in the morning, 10mg in the evening
1.10 - 1.29 metres squared BSA: 25mg in the morning, 20mg in the evening
1.30 - 1.49 metres squared BSA: 25mg twice daily
1.50 - 1.69 metres squared BSA: 30mg twice daily
1.70 - 1.89 metres squared BSA: 35mg in the morning, 30mg in the evening
BSA greater than 1.90 metres squared: 35mg twice daily
Second dose reduction
Recommended dose based on BSA
0.55 - 0.69 metres squared BSA: 10mg once daily
0.70 - 0.89 metres squared BSA: 10mg twice daily
0.90 - 1.09 metres squared BSA: 10mg twice daily
1.10 - 1.29 metres squared BSA: 20mg in the morning, 10mg in the evening
1.30 - 1.49 metres squared BSA: 25mg in the morning, 10mg in the evening
1.50 - 1.69 metres squared BSA: 25mg in the morning, 20mg in the evening
1.70 - 1.89 metres squared BSA: 25mg in the morning, 20mg in the evening
BSA greater than 1.90 metres squared: 25mg twice daily
Dose modifications for adverse reactions
Grade 1 or 2 (tolerable) adverse reaction: Continue treatment and monitor as clinically appropriate
Grade 2 (intolerable) or Grade 3 adverse reaction: Interrupt treatment until toxicity resolves to grade 0 or 1, then resume therapy at one lower dose level. Consider discontinuation.
Grade 4 adverse reaction: Interrupt treatment until toxicity resolves to grade 0 or 1, then resume therapy at one lower dose level. Consider discontinuation.
Dose modifications for left ventricular ejection fraction (LVEF) reduction
Asymptomatic LVEF reduction of greater than or equal to 10 percentage points from baseline and below the institutional lower level of normal (LLN): Interrupt until resolution. Upon resolution, resume therapy at one lower dose level.
Symptomatic LVEF reduction/Grade 3 or 4 LVEF reduction: Discontinue and patient should be referred to a cardiologist promptly.
Dose modifications of ocular toxicities
Retinal pigment epithelial detachment (RPED) or central serous retinopathy (CSR) with reduced visual acuity: Interrupt until resolution. Upon resolution, resume therapy at one lower dose level.
RPED or CSR without reduced visual acuity: Perform ophthalmic assessment every 3 weeks until resolution.
Retinal vein occlusion (RVO): Permanently discontinue treatment.
Dose adjustments for co-administration with CYP3A4 or CYP2C19 inhibitors
If a strong or moderate CYP3A4 or CYP2C19 inhibitor must be co-administered, the dose of selumetinib should be reduced.
If the patient is taking 25mg per metre squared twice daily, reduce dose to 20mg per metre squared twice daily.
If the patient is taking 20mg per metre squared twice daily, reduce dose to 15mg per metre squared twice daily.
Recommended dose to achieve 20mg per metre squared twice daily dose level
0.55 - 0.69 metres squared BSA: 10mg twice daily
0.70 - 0.89 metres squared BSA: 20mg in the morning, 10mg in the evening
0.90 - 1.09 metres squared BSA: 20mg twice daily
1.10 - 1.29 metres squared BSA: 25mg twice daily
1.30 - 1.49 metres squared BSA: 30mg in the morning, 25mg in the evening
1.50 - 1.69 metres squared BSA: 35mg in the morning, 30mg in the evening
1.70 - 1.89 metres squared BSA: 35mg twice daily
BSA greater than 1.90 metres squared: 40mg twice daily
Recommended dose to achieve 15mg per metre squared twice daily dose level
0.55 - 0.69 metres squared BSA: 10mg once daily
0.70 - 0.89 metres squared BSA: 10mg twice daily
0.90 - 1.09 metres squared BSA: 20mg in the morning, 10mg in the evening
1.10 - 1.29 metres squared BSA: 25mg in the morning, 10mg in the evening
1.30 - 1.49 metres squared BSA: 25mg in the morning, 20mg in the evening
1.50 - 1.69 metres squared BSA: 25mg twice daily
1.70 - 1.89 metres squared BSA: 30mg in the morning, 25mg in the evening
BSA greater than 1.90 metres squared: 30mg twice daily
Missed doses
If a dose is missed, it should only be taken in it is more than 6 hours until the next scheduled dose.
Contraindications
Adults aged 18 years and above
Children under 3 years
Breastfeeding
Left ventricular ejection fraction below lower limit of normal
Pregnancy
Severe hepatic impairment
Precautions and Warnings
Asian ancestry
Females of childbearing potential
Moderate hepatic impairment
Reduced left ventricular function
Advise ability to drive/operate machinery may be affected by side effects
Treatment to be initiated by specialist
Advise patient to have no food for 2 hours before and 1 hour after dose
Advise patient to have no food or drink for 2 hours before and 1 hour after
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Exclude pregnancy prior to initiation of treatment
Monitor hepatic function before treatment and during first 6 months
If visual disturbances occur, perform ophthalmic evaluation
Monitor LVEF at baseline and periodically during treatment
Monitor prothrombin times closely in patients on anticoagulant therapy
Advise patient to seek advice at first indications of pregnancy
Consider discontinuing treatment if grade 4 toxicity occurs
Discontinue if Grade 3 or 4 LVEF reduction occurs
Discontinue if retinal vein occlusion occurs
Discontinue if symptomatic LVEF reduction occurs
Discontinue treatment and/or reduce dose if LVEF decreases
Interrupt if central serous retinopathy with reduced visual acuity occurs
Interrupt if RPED with reduced visual acuity occurs
Interrupt or reduce dose if serous retinopathy occurs
Suspend treatment if grade 3 or intolerable grade 2 toxicities
Suspend treatment if LVEF decrease of 10% below baseline
Advise patient not to take St John's wort concurrently
Advise patient to avoid supplements containing vitamin E
Advise patient to avoid grapefruit products
Female: Contraception required during and for 1 week after treatment
Male & female: Barrier contraception required until 1 week after treatment
Male: Contraception required during and for 1 week after treatment
Choking risk in small children
Left ventricular ejection fraction (LVEF) reduction
LVEF should be evaluated by echocardiogram before initiation of treatment to establish baseline values. Prior to starting selumetinib treatment, patients should have an ejection fraction above the institutional lower limit of normal.
LVEF should be evaluated at 3 month intervals, or more frequently as clinically indicated, during treatment.
Ocular toxicity
Perform ophthalmological evaluation prior to treatment initiation and when patient reports new visual disturbances.
In patients diagnosed with RPED or CSR without reduced visual acuity, ophthalmic assessment should be performed every 3 weeks until resolution. If RPED or CSR is diagnosed and visual acuity is affected, selumetinib treatment should be interrupted and dose reduced when treatment is resumed. If RVO is diagnosed, selumetinib treatment should be permanently discontinued.
Liver laboratory abnormalities
Liver laboratory values should be monitored prior to initiation of selumetinib and at least monthly during the first 6 months of treatment.
Vitamin E supplementation
Patients should be advised not to take vitamin E supplements. Selumetinib capsules contain vitamin E as the excipient as D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS). High dose of vitamin E may increase the risk of bleeding in patients taking concomitant anticoagulant or antiplatelet treatment (e.g. warfarin or acetylsalicylic acid). Anticoagulant assessments should be conducted in these patients to detect when dose adjustments of the anticoagulant/antiplatelet treatment is required.
Risk of choking
Selumetinib capsules should be swallowed whole. Some patients may be at risk of choking and should not be administered to patients who are unable to swallow the capsule whole.
Pregnancy and Lactation
Pregnancy
Selumetinib is contraindicated during pregnancy.
The manufacturer recommends that selumetinib should not be used during pregnancy. There is no data on the use of selumetinib in pregnant women, however, animal studies have shown reproductive toxicity including embryofoetal death, structural defects and reduced foetal weights.
Lactation
Selumetinib is contraindicated during breastfeeding.
The manufacturer recommends that selumetinib should not be used during breastfeeding. It is unknown whether selumetinib, or its metabolites, are excreted in human milk. However, selumetinib and its metabolites are excreted in the milk of lactating mice. Therefore a risk to the breast-fed child cannot be excluded and breastfeeding should be discontinued during treatment with selumetinib.
Side Effects
Alopecia
Anaemia
Asthenia
Blurred vision
Central serous chorioretinopathy
Changes in hair colour
Creatine phosphokinase increased
Decreased ejection fraction
Dermatitis acneiform
Detachment of the retinal pigment epithelium
Diarrhoea
Dry mouth
Dry skin
Dyspnoea
Erythematous rash
Facial oedema
Haemoglobin decrease
Hair disorder
Hypoalbuminaemia
Increase in serum ALT/AST
Increased blood pressure
Macular rash
Maculopapular rash
Nausea
Paronychia
Periorbital oedema
Peripheral oedema
Pyrexia
Rash
Retinal vein occlusion
Retinal vein thrombosis
Serum creatinine increased
Stomatitis
Vomiting
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: December 2021
Reference Sources
Summary of Product Characteristics: Koselugo 10 mg hard capsules. AstraZeneca UK Limited. Revised August 2021.
Summary of Product Characteristics: Koselugo 25 mg hard capsules. AstraZeneca UK Limited. Revised August 2021.
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.