3.      How to take Koselugo

[...]

Your doctor may reduce your dose if you have certain side effects while you are taking Koselugo (see section 4 ‘Possible side effects’) or the doctor may interuptinterrupt treatment or stop it permanently.

How to take

·              Take Koselugo twice a day, about 12 hours apart.

·              Take the capsules on an empty stomach. This means that:

o    you must wait at least 2 hours before taking Koselugo after eating and

·           after taking Koselugo you must wait at least 1 hour before you eat, with or without food.

·           Swallow the capsules whole with water.

·           Do not chew, dissolve, or open the capsules.

·           If you have, or think you might have difficulty swallowing capsules whole, talk to your doctor before starting treatment.  

[...]

6.      Contents of the pack and other information

[...]

Manufacturer

AstraZeneca AB

Global External Sourcing (GES)

Karlebyhusentrén Astraallén

Gärtunaporten

SE-151 85152 57 Södertälje

Sweden

[...]

This leaflet was last revised in 0510/2023

4.2    Posology and method of administration

[...]

Method of administration

Koselugo is for oral use. It shouldcan be taken on an empty stomach with noor without food or drink other than water 2 hours prior to dosing and 1 hour after dosing (see sections 4.5 andsection 5.2).

4.5    Interaction with other medicinal products and other forms of interaction

[...]

Co-administration with medicinal products that are strong inhibitors of CYP3A4 (e.g., clarithromycin, grapefruit juice, oral ketoconazole) or CYP2C19 (e.g., ticlopidine) should be avoided. Co‑administration with medicinal products that are moderate inhibitors of CYP3A4 (e.g., erythromycin and fluconazole) and CYP2C19 (e.g., omeprazole) should be avoided.

5.2    Pharmacokinetic properties

[...]

In adolescent patients with NF1 and inoperable PN treated with multiple doses of 25 mg/m² bid, co‑administration of selumetinib with a low-fat meal resulted in 24% lower C_max when compared to fasting administration. Selumetinib AUC was reduced by 8%, and t_max was delayed by approximately 0.57 hours (see section 4.2).

A population PK analysis including children and adolescent patients with NF1 and inoperable PN, adult patients with advanced solid malignancies and healthy adult subjects taken from 15 studies showed that concomitant administration of a low or high fat meal resulted in a mean decrease in the exposure (AUC) of selumetinib when compared to fasted administration (23.1% and 20.7%, respectively) which was not considered clinically relevant.

9.      DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 17 June 2021

Date of latest renewal: 25 April 202231 May 2023

10.    DATE OF REVISION OF THE TEXT

31^st May19 October 2023

4.      Possible side effects

[...]

Possible serious side effects

Eye (vision) problems

Koselugo can cause eye problems. Tell your doctor straight away if you get blurred vision (a very common side effect that may affect up tomore than 1 in 10 people) or any other changes to your sight during treatment. Your doctor may ask you to stop taking this medicine or send you to a specialist,

[...]

Very common (may affect more than 1 in 10 people)

·           being sick (vomiting), feeling sick (nausea)

·           diarrhoea

·           inflammation of the mouth (stomatitis)

·           skin and nail problems - signs may include dry skin, rash, redness around the fingernails

·           hair thinning (alopecia), hair colour change

·           feeling tired, weak or lacking energy

·           fever (pyrexia)

·           swelling of the hands or feet (peripheral oedema)

·           a slight decrease in the amount of blood that the heart is pumping (ejection fraction decreased) – signs may include shortness of breath or swelling in your legs, ankles or feet

·           high blood pressure (hypertension)

·           reduced level of albumin, an essential liver protein in the blood (shown in blood tests)

·           reduced haemoglobin, the oxygen-carrying protein in red blood cells (shown in blood tests)

·           increase in enzymes (shown in blood tests) suggesting stress on the liver, kidney injury or muscle breakdown

6.      Contents of the pack and other information

This leaflet was last revised in 06/202105/2023

This medicine has been given ‘conditional approval’. This means that there is more evidence to come about this medicine. The European Medicines Agency will review new information on thethis medicine at least every year and this leaflet will be updated as necessary.

SmPC updated following approval of the annual license renewal and the addition of SPRINT DC02 data

New leaflet for new product