Active Ingredient: Selumetinib
Selumetinib as monotherapy is indicated for the treatment of symptomatic, inoperable plexiform neurofibromas (PN) in paediatric patients with neurofibromatosis type 1 (NF1) aged 3 years and above.
For this indication, competent medicine agencies globally authorize below treatments:
Oral
50 - 50 mg per m² of body surface area (BSA)
From 25 To 25 mg per m² of body surface area (BSA) 2 time(s) per day every day
The recommended dose of selumetinib is 25 mg/m² of body surface area (BSA), taken orally twice daily (approximately every 12 hours).
Dosing is individualised based on BSA (mg/m²) and rounded to the nearest achievable 5 mg or 10 mg dose (up to a maximum single dose of 50 mg). Different strengths of selumetinib capsules can be combined to attain the desired dose (Table 1).
Table 1. Recommended dose based on body surface area:
| Body surface area (BSA)a | Recommended dose |
|---|---|
| 0.55–0.69 m² | 20 mg in the morning and 10 mg in the evening |
| 0.70–0.89 m² | 20 mg twice daily |
| 0.90–1.09 m² | 25 mg twice daily |
| 1.10–1.29 m² | 30 mg twice daily |
| 1.30–1.49 m² | 35 mg twice daily |
| 1.50–1.69 m² | 40 mg twice daily |
| 1.70–1.89 m² | 45 mg twice daily |
| ≥1.90 m² | 50 mg twice daily |
a The recommended dose for patients with a BSA less than 0.55 m² has not been established.
Treatment with selumetinib should continue as long as clinical benefit is observed, or until PN progression or the development of unacceptable toxicity. There is limited data in patients older than 18, therefore continued treatment into adulthood should be based on benefits and risks to the individual patient as assessed by the physician. However, start of treatment with selumetinib in adults is not appropriate.
If a dose of selumetinib is missed, it should only be taken if it is more than 6 hours until the next scheduled dose.
If vomiting occurs after selumetinib is administered, an additional dose is not to be taken. The patient should continue with the next scheduled dose.
Interruption and/or dose reduction or permanent discontinuation of selumetinib may be required based on individual safety and tolerability. Recommended dose reductions are given in Table 2 and may require the daily dose to be divided into two administrations of different strength or for treatment to be given as a once daily dose.
Table 2. Recommended dose reductions for adverse reactions:
| Body surface area (BSA) | Initial selumetinib dosea (mg/twice daily) | First dose reduction (mg/dose) | Second dose reduction (mg/dose)b | ||
|---|---|---|---|---|---|
| Morning | Evening | Morning | Evening | ||
| 0.55–0.69 m² | 20 mg in the morning and 10 mg in the evening | 10 | 10 | 10 once daily | |
| 0.70–0.89 m² | 20 | 20 | 10 | 10 | 10 |
| 0.90–1.09 m² | 25 | 25 | 10 | 10 | 10 |
| 1.10–1.29 m² | 30 | 25 | 20 | 20 | 10 |
| 1.30–1.49 m² | 35 | 25 | 25 | 25 | 10 |
| 1.50–1.69 m² | 40 | 30 | 30 | 25 | 20 |
| 1.70–1.89 m² | 45 | 35 | 30 | 25 | 20 |
| ≥1.90 m² | 50 | 35 | 35 | 25 | 25 |
a Based on BSA as shown in Table 1.
b Permanently discontinue treatment in patients unable to tolerate selumetinib after two dose reductions.
Dose modifications for the management of adverse reactions associated with this medicinal product are presented in Table 3.
Table 3. Recommended dose modifications for adverse reactions:
| CTCAE Grade* | Recommended dose modification |
|---|---|
| Grade 1 or 2 (tolerable – can be managed with supportive care) | Continue treatment and monitor as clinically indicated |
| Grade 2 (intolerable – cannot be managed with supportive care) or Grade 3 | Interrupt treatment until toxicity is grade 0 or 1 and reduce by one dose level when resuming therapy (see Table 2) |
| Grade 4 | Interrupt treatment until toxicity is grade 0 or 1, reduce by one dose level when resuming therapy (see Table 2). Consider discontinuation |
* Common Terminology Criteria for Adverse Events (CTCAE)
Selumetinib should be taken on an empty stomach with no food or drink other than water 2 hours prior to dosing and 1 hour after dosing.
The selumetinib capsules should be swallowed whole with water. The capsules should not be chewed, dissolved, or opened, because this could impair drug release and affect the absorption of selumetinib.
Selumetinib should not be administered to patients who are unable or unwilling to swallow the capsule whole.
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