Active Ingredient: Selumetinib
Selumetinib as monotherapy is indicated for the treatment of symptomatic, inoperable plexiform neurofibromas (PN) in adult and paediatric patients with neurofibromatosis type 1 (NF1) aged 3 years and older.
For this indication, competent medicine agencies globally authorize below treatments:
For:
In case that patient age in years is ≥ 3
Oral, 25 milligrams selumetinib per square meter of body surface, once every 12 hours.
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.
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)
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