KOSELUGO Hard capsule Ref.[27820] Active ingredients: Selumetinib

Treatment with Koselugo should be initiated by a physician experienced in the diagnosis and the treatment of patients with NF1 related tumours.

Posology

The recommended dose of Koselugo 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 Koselugo capsules can be combined to attain the desired dose (Table 1).

Table 1. Recommended dose based on body surface area:

^a The recommended dose for patients with a BSA less than 0.55 m² has not been established.

Treatment with Koselugo should continue as long as clinical benefit is observed, or until PN progression or the development of unacceptable toxicity.

Missed dose

If a dose of Koselugo is missed, it should only be taken if it is more than 6 hours until the next scheduled dose.

Vomiting

If vomiting occurs after Koselugo is administered, an additional dose is not to be taken. The patient should continue with the next scheduled dose.

Dose adjustments

Interruption and/or dose reduction or permanent discontinuation of selumetinib may be required based on individual safety and tolerability (see sections 4.4 and 4.8).

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:

^a Based on BSA as shown in Table 1.
^b Permanently discontinue treatment in patients unable to tolerate Koselugo 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:

^* Common Terminology Criteria for Adverse Events (CTCAE)

Dose modification advice for left ventricular ejection fraction (LVEF) reduction

In cases of asymptomatic LVEF reduction of ≥10 percentage points from baseline and below the institutional lower level of normal (LLN), selumetinib treatment should be interrupted until resolution. Once resolved, selumetinib should be reduced by one dose level when resuming therapy (see Table 2).

In patients who develop symptomatic LVEF reduction or a grade 3 or 4 LVEF reduction, selumetinib should be discontinued and a prompt cardiology referral should be carried out (see section 4.4).

Dose modification advice for ocular toxicities

Selumetinib treatment should be interrupted in patients diagnosed with retinal pigment epithelial detachment (RPED) or central serous retinopathy (CSR) with reduced visual acuity until resolution; reduce selumetinib by one dose level when resuming therapy (see Table 2). In patients diagnosed with RPED or CSR without reduced visual acuity, ophthalmic assessment should be conducted every 3 weeks until resolution. In patients who are diagnosed with retinal vein occlusion (RVO), treatment with selumetinib should be permanently discontinued (see section 4.4).

Dose adjustments for co-administration with CYP3A4 or CYP2C19 inhibitors

Concomitant use of strong or moderate CYP3A4 or CYP2C19 inhibitors is not recommended and alternative agents should be considered. If a strong or moderate CYP3A4 or CYP2C19 inhibitor must be co-administered, the recommended Koselugo dose reduction is as follows:

• If a patient is currently taking 25 mg/m² twice daily, dose reduce to 20 mg/m² twice daily.
• If a patient is currently taking 20 mg/m² twice daily, dose reduce to 15 mg/m² twice daily (see Table 4 and section 4.5).

Table 4. Recommended dose to achieve 20 mg/m² or 15 mg/m² twice daily dose level:

Special populations

Renal impairment

Based on clinical trials no dose adjustment is recommended in patients with mild, moderate, severe renal impairment or those with end stage renal disease (ESRD) (see section 5.2).

Hepatic impairment

Based on clinical trials, no dose adjustment is recommended in patients with mild hepatic impairment. The starting dose should be reduced in patients with moderate hepatic impairment to 20 mg/m² BSA, twice daily (see Table 4). Koselugo is contraindicated for use in patients with severe hepatic impairment (see sections 4.3 and 5.2).

Ethnicity

Increased systemic exposure has been seen in adult Asian subjects, although there is considerable overlap with Western subjects when corrected for body weight. No specific adjustment to the starting dose is recommended for Asian patients, however these patients, should be closely monitored for adverse events (see section 5.2).

Paediatric population

The safety and efficacy of Koselugo in children less than 3 years of age has not been established. No data are available.

Elderly population

The safety and efficacy of Koselugo in adults with NF1-PN older than 65 years of age has not been established. No data are currently available in NF1-PN patients 65 years of age and older.

Method of administration

Koselugo is for oral use. It can be taken with or without food (see section 5.2).

The 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.

Koselugo should not be administered to patients who are unable or unwilling to swallow the capsule whole. Patients should be assessed for their ability to swallow a capsule before starting treatment. Standard medicine swallowing techniques are expected to be sufficient to swallow selumetinib capsules. For patients who have difficulties swallowing the capsule, referral to an appropriate health care professional such as a speech and language therapist could be considered to identify suitable methods that can be tailored to the particular patient.

There is no specific treatment for overdose. If overdose occurs, patients should be closely monitored for signs and symptoms of adverse reactions and treated supportively with appropriate monitoring as necessary. Dialysis is ineffective in the treatment of overdose.

3 years.

Do not store above 30°C.

Store in the original bottle in order to protect from moisture and light.

Keep the bottle tightly closed.

Koselugo 10 mg hard capsules: High-density polyethylene (HDPE) plastic bottle with white child-resistant polypropylene closure.

Koselugo 25 mg hard capsules: High-density polyethylene (HDPE) plastic bottle with blue child-resistant polypropylene closure.

Each bottle contains 60 hard capsules and a silica gel desiccant. Each carton contains one bottle.

Patients should be instructed not to remove the desiccant from the bottle.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.