Finlee: detailed information

Package leaflet: Information for the patient

Finlee 10 mg dispersible tablets

dabrafenib
Please read this leaflet carefully before your child takes this medicine, because it contains important information.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor, pharmacist, or nurse.
This medicine has been prescribed for your child only. Do not give it to other people, even if their symptoms are the same as your child’s, as it may be harmful.
If your child experiences any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. See section 4.
The information in this leaflet is intended for you or your child, but throughout the leaflet the term “the child” will be used.

Contents of this leaflet

What Finlee is and what it is used for
What you need to know before giving Finlee
How to give Finlee
Possible side effects
How to store Finlee
Contents of the pack and other information

1. What Finlee is and what it is used for

Finlee is a medicine that contains the active substance dabrafenib.
This medicine is used in combination with another medicine (trametinib oral solution) in children aged 1 year and older to treat a type of brain tumour called glioma.
Finlee can be used in patients with:

low-grade glioma
high-grade glioma, when the patient has received at least one treatment with radiotherapy and/or chemotherapy.

Finlee is used to treat patients whose brain tumour has a specific mutation (alteration) in the gene called BRAF. This mutation causes the body to produce defective proteins, which in turn can lead to tumour development. Your doctor will test for this mutation before starting treatment.
In combination with trametinib, Finlee acts on these defective proteins and slows down or stops tumour growth. Also read the trametinib oral solution package leaflet.

2. What you should know before administering Finlee

Do not administer Finlee

if the child is allergic to dabrafenib or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to the doctor before administering Finlee. The doctor needs to know if the child:

has eye problems, including blockage of the vein draining the eye (retinal vein occlusion) or swelling of the eyes that may be caused by fluid leakage (chorioretinopathy).
has heart problems, such as heart failure or irregular heartbeat.
has or has had any kidney problems.
has or has had any liver problems.
has or has ever had any lung or breathing problems, including difficulty breathing often accompanied by dry cough, shortness of breath, and fatigue.
has or has had gastrointestinal problems such as diverticulitis (inflamed pouches in the colon) or metastases in the gastrointestinal tract.

Before the child starts taking Finlee, and during and after treatment, the doctor will perform checks to prevent complications.
Skin monitoring
Finlee can cause skin tumors. Generally, these skin changes remain localized and can be surgically removed, and treatment with Finlee can continue uninterrupted. The doctor may examine the child’s skin before and regularly during treatment.
Check the child’s skin monthly during treatment and for 6 months after stopping this medicine. Inform the doctor as soon as possible if you notice any skin changes such as a new wart, a sore or reddish bump that bleeds and does not heal, or a change in size or color of a mole.
Tumor lysis syndrome
If the child experiences any of the following symptoms, inform the doctor immediately, as this may be a life-threatening condition: nausea, shortness of breath, irregular heartbeat, muscle cramps, seizures, cloudy urine, reduced urine output, and fatigue. These may be caused by a group of metabolic complications that can occur during cancer treatment due to the breakdown products of dying cancer cells (tumor lysis syndrome or TLS), which may lead to changes in kidney function (see also section 4).
Children under 1 year of age
The effects of Finlee in children under 1 year of age are unknown. Therefore, Finlee is not recommended in this age group.
Patients over 18 years of age
Information on treatment of patients over 18 years of age with glioma is limited; therefore, continuation of treatment into adulthood should be evaluated by the doctor.
Other medicines and Finlee
Before starting treatment, inform the doctor, pharmacist, or nurse if the child is taking, has recently taken, or might take any other medicines, including those without a prescription.
Some medicines may affect how Finlee works or may increase the likelihood of the child experiencing side effects. Finlee may also affect how other medicines work. These include:

medicines used for birth control (contraceptives) containing hormones, such as pills, injections, or patches
medicines used to thin the blood, such as warfarin and acenocoumarol
medicines used to treat heart conditions, such as digoxin
medicines used to treat fungal infections, such as itraconazole, voriconazole, and posaconazole
medicines used to treat Cushing's syndrome, such as ketoconazole
certain medicines known as calcium channel blockers, used to treat high blood pressure, such as diltiazem, felodipine, nicardipine, nifedipine, or verapamil
medicines used to treat cancer, such as cabazitaxel
certain medicines used to lower blood fats (lipids), such as gemfibrozil
certain medicines used to treat psychiatric disorders, such as haloperidol
certain medicines known as antibiotics, such as clarithromycin, doxycycline, and telithromycin
certain medicines used to treat tuberculosis (TB), such as rifampicin
certain medicines used to lower cholesterol levels, such as atorvastatin and simvastatin
certain medicines known as immunosuppressants, such as cyclosporine, tacrolimus, and sirolimus
certain medicines known as anti-inflammatory agents, such as dexamethasone and methylprednisolone
certain medicines used to treat HIV, such as ritonavir, amprenavir, indinavir, darunavir, delavirdine, efavirenz, fosamprenavir, lopinavir, nelfinavir, tipranavir, saquinavir, and atazanavir
certain medicines used to aid sleep, such as diazepam, midazolam, zolpidem
certain medicines used to relieve pain, such as fentanyl and methadone
medicines used to treat seizures (epilepsy), such as phenytoin, phenobarbital, primidone, valproic acid, or carbamazepine
medicines known as antidepressants, such as nefazodone and medicines containing St. John's wort (Hypericum perforatum)

Inform the doctor, pharmacist, or nurse if the child is taking any of the medicines listed above (or if you are unsure). The doctor may decide to adjust the dose.
Pregnancy, breastfeeding, and fertility
Pregnancy

If the girl is pregnant or suspects she might be, consult the doctor or nurse before administering this medicine. Finlee may potentially harm the unborn baby.
If the girl becomes pregnant while taking this medicine, inform the doctor immediately.

Breastfeeding
It is not known whether Finlee passes into breast milk. If the girl is breastfeeding or planning to breastfeed, she must inform the doctor. The girl, her caregiver, and the doctor will decide whether to take Finlee or breastfeed.
Fertility
Finlee may reduce sperm count, and this may not return to normal levels after stopping treatment with Finlee.
Taking Finlee with trametinib oral solution: Trametinib may impair fertility in both males and females.
Before starting treatment with Finlee, discuss with the doctor options to improve the child’s chances of having children in the future.
Contraception

If the girl can become pregnant, she must use a reliable method of contraception (birth control) while taking Finlee in combination with trametinib oral solution and for at least 16 weeks after the last dose of Finlee in combination with trametinib.
Hormonal birth control methods (such as pills, injections, or patches) may not work properly while taking Finlee in combination with trametinib oral solution. An alternative effective method of birth control must be used to avoid the risk of pregnancy during treatment with this combination of medicines. Consult the doctor or nurse for advice.

Driving and using machines
Finlee may cause side effects that could affect the child’s ability to drive, ride a bicycle/scooter, operate machinery, or participate in other activities requiring alertness. If the child has vision problems, feels tired or weak, or has low energy levels, such activities should be avoided.
Descriptions of these effects can be found in section 4. Read all information in this leaflet for reference.
Discuss with the doctor, pharmacist, or nurse if you are unsure about anything. The child’s illness, symptoms, and treatment conditions may also affect their ability to participate in such activities.
Finlee contains potassium
This medicine contains potassium, less than 1 mmol (39 mg) per maximum daily dose, i.e., essentially ‘potassium-free’.
Finlee contains benzyl alcohol
This medicine contains <0.00078 mg of benzyl alcohol in each dispersible tablet.
Benzyl alcohol may cause allergic reactions.
Ask your doctor or pharmacist for advice if the girl is pregnant or breastfeeding. This is because large amounts of benzyl alcohol may accumulate in the child’s body and cause unwanted effects (such as metabolic acidosis).
Ask your doctor or pharmacist for advice if the child has liver or kidney disease. This is because large amounts of benzyl alcohol may accumulate in the child’s body and cause unwanted effects (such as metabolic acidosis).

3. How to administer Finlee

Administer this medicine to the child exactly as instructed by the doctor, pharmacist, or nurse. If you have any doubts, consult the doctor, pharmacist, or nurse.

Dosage
The doctor will determine the correct dose of Finlee based on the child's body weight.
The doctor may decide that the child should take a lower dose if side effects occur.

How to administer
Read the instructions for use at the end of this leaflet for details on how to prepare and administer the solution of dispersible tablets.

Administer Finlee twice daily. Giving Finlee at the same time each day will help you remember when to administer the medicine. Administer each dose of Finlee approximately 12 hours apart. Trametinib oral solution is administered once daily. Administer trametinib oral solution either with the morning dose or with the evening dose of Finlee.
Administer Finlee on an empty stomach, at least 1 hour before or 2 hours after a meal. This means:
- After taking Finlee, the child must wait at least 1 hour before eating.
- After eating, the child must wait at least 2 hours before taking Finlee.
- If necessary, breastfeeding and/or formula feeding may be given on demand.

If you administer more Finlee than you should
If an overdose of Finlee is administered, contact the doctor, pharmacist, or nurse for advice. If possible, show them the Finlee packaging and this leaflet.

If you forget to administer Finlee
If you forget a dose and less than 6 hours have passed, administer it as soon as you remember.
If the missed dose is 6 hours or more overdue, skip that dose and administer the next dose at the usual time. Then continue administering Finlee at regular times as usual.
Do not administer a double dose to make up for a forgotten dose.

If the child vomits after taking Finlee
If the child vomits after taking Finlee, do not administer another dose until the next scheduled dose.

If you stop treatment with Finlee
Administer Finlee for the entire duration recommended by the doctor. Do not stop unless instructed by the doctor.
If you have any doubts about the use of this medicine, consult the doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Stop administering the medicine and contact the doctor urgently if the child
experiences any of the following symptoms:

Coughing up blood, blood in the urine, vomiting blood or material resembling coffee grounds, red or black tarry stools. These may be signs of bleeding.
Fever (temperature of 38°C or higher).
Chest pain or shortness of breath, sometimes with fever or cough. These may be signs of pneumonia or lung inflammation (interstitial lung disease).
Blurred vision, loss of vision, or other changes in eyesight. These may be signs of retinal detachment.
Redness of the eye, eye pain, increased sensitivity to light. These may be signs of uveitis.
Unexplained muscle pain, muscle cramps, or muscle weakness, dark urine. These may be signs of rhabdomyolysis.
Severe abdominal pain. This may be a sign of pancreatitis.
Fever, swollen lymph nodes, bruising, or rash occurring at the same time. These may be signs of a condition in which the immune system produces too many infection-fighting cells, leading to various symptoms (hemophagocytic lymphohistiocytosis).
Nausea, shortness of breath, irregular heartbeat, muscle cramps, seizures, cloudy urine, reduced urine output, and fatigue. These may be signs of a condition caused by the rapid breakdown of cancer cells, which can be fatal in some people (tumor lysis syndrome or TLS).
Reddish patches on the trunk, circular or target-shaped, with or without central blisters, skin peeling, mouth, throat, nose, genital, or eye ulcers. These may be signs of serious skin rashes, which can be life-threatening and may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome), widespread rash, fever, and swollen lymph nodes (DRESS).

Other possible side effects
Very common (may affect more than 1 in 10 people)

Headache
Dizziness
Cough
Diarrhea, nausea, vomiting, constipation, stomach ache
Skin problems such as rash, acne-like rash, dry or itchy skin, skin redness
Wart-like growths (cutaneous papilloma)
Nail infections
Pain in arms, legs, or joints
Lack of energy or feeling weak or tired
Weight gain
Upper respiratory tract infections with symptoms such as sore throat and stuffy nose (nasopharyngitis)
Increased liver enzymes in blood tests
Decreased levels of white blood cells (neutropenia, leukopenia)
Decreased levels of red blood cells (anemia)

Common (may affect up to 1 in 10 people)

Frequent urination with pain or burning sensation (urinary tract infection)
Skin effects including skin infection (cellulitis), inflammation of hair follicles (folliculitis), inflamed scaly skin (generalized exfoliative dermatitis), thickening of the outer layer of skin (hyperkeratosis)
Decreased appetite
Low blood pressure (hypotension)
High blood pressure (hypertension)
Shortness of breath
Mouth pain or mouth ulcers, inflammation of the mucosa
Inflammation of the subcutaneous fat layer (panniculitis)
Unusual hair loss or thinning
Red, painful hands and feet (hand-foot syndrome)
Muscle spasms
Chills
Allergic reaction (hypersensitivity)
Dehydration
Vision problems including blurred vision
Decreased heart rate (bradycardia)
Fatigue, chest discomfort, dizziness, palpitations (reduced ejection fraction)
Swelling of tissues (edema)
Muscle pain (myalgia)
Fatigue, chills, sore throat, joint or muscle pain (flu-like illness)
Abnormal test results for creatine phosphokinase, an enzyme mainly found in the heart, brain, and skeletal muscle
Increased blood sugar levels
Low levels of sodium or phosphate in the blood
Decreased platelet count in the blood (cells that help blood clotting)
Increased sensitivity of the skin to sunlight

Uncommon (may affect up to 1 in 100 people)

Irregular heartbeat (atrioventricular block)
Inflammation of the intestine (colitis)
Cracked skin
Night sweats
Excessive sweating
Painful, raised red to dark red spots or ulcers on the skin, mainly on arms, legs, face, and neck, accompanied by fever (signs of acute febrile neutrophilic dermatosis)

In addition to the side effects listed above, the following side effects have been reported only in adult patients, but may also occur in children:

A condition affecting the nerves that may cause pain, loss of sensation, or tingling in the hands and feet and/or muscle weakness (peripheral neuropathy)
Dry mouth
Kidney failure
Benign skin tumor (acrochordon)
Inflammatory disease mainly affecting the skin, lungs, eyes, and lymph nodes (sarcoidosis)
Inflammation of the kidneys
A hole (perforation) in the stomach or intestine
Inflammation of the heart muscle that may cause shortness of breath, fever, palpitations, and chest pain
Localized skin reactions at tattoo sites
Worsening of side effects from radiation therapy

Reporting of side effects
If the child experiences any side effect, including those not listed in this leaflet, talk to the doctor, pharmacist, or nurse. You may also report side effects directly through the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Finlee

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial label and on the box after Exp.. The expiry date refers to the last day of that month.
Administer the solution no later than 30 minutes after the tablets have dissolved.
This medicine does not require any special storage temperature.
Store in the original packaging to protect the medicine from moisture.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Finlee contains

The active substance is dabrafenib. Each dispersible tablet contains dabrafenib mesylate equivalent to 10 mg of dabrafenib.
The other components are: mannitol (E 421), microcrystalline cellulose (E 460), crospovidone (E 1202), hypromellose (E 464), acesulfame potassium (E 950) (see section 2), magnesium stearate (E 470b), artificial berry flavour (maltodextrin, propylene glycol [E 1520], artificial flavours, triethyl citrate [E 1505], benzyl alcohol [E 1519] [see section 2]), and colloidal anhydrous silica (E 551).

Description of the appearance of Finlee and contents of the pack
Finlee 10 mg dispersible tablets are white to pale yellow, round tablets, 6 mm in diameter,
marked with a "D" on one side and "NVR" on the other.
The bottles are white plastic with screw caps made of plastic.
The bottles also contain a desiccant in the form of silica gel in small cylindrical containers. The desiccants
must be kept inside the bottle and must not be ingested.
Finlee 10 mg dispersible tablets are available in packs containing 1 or 2 bottles (210 or 420
dispersible tablets) and 2 dosing scoops.
Marketing Authorisation Holder
Novartis Europharm Limited
Vista Building
Elm Park, Merrion Road
Dublin 4
Ireland
Manufacturer
Lek Pharmaceuticals d.d.
Verovškova ulica 57
1526, Ljubljana
Slovenia
Novartis Pharmaceutical Manufacturing LLC
Verovškova ulica 57
1000, Ljubljana
Slovenia
Novartis Farmacéutica S.A.
Gran Via de les Corts Catalanes 764
08013 Barcelona
Spain
Novartis Pharma GmbH
Sophie-Germain-Strasse 10
90443 Nuremberg
Germany
For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
België/Belgique/Belgien Lietuva
Novartis Pharma N.V. SIA Novartis Baltics Lietuvos filialas
Tél/Tel: +32 2 246 16 11 Tel: +370 5 269 16 50
България Luxembourg/Luxemburg
Novartis Bulgaria EOOD Novartis Pharma N.V.
Tel: +359 2 489 98 28 Tél/Tel: +32 2 246 16 11
Česká republika Magyarország
Novartis s.r.o. Novartis Hungária Kft.
Tel: +420 225 775 111 Tel.: +36 1 457 65 00
Danmark Malta
Novartis Healthcare A/S Novartis Pharma Services Inc.
Tlf.: +45 39 16 84 00 Tel: +356 2122 2872
Deutschland Nederland
Novartis Pharma GmbH Novartis Pharma B.V.
Tel: +49 911 273 0 Tel: +31 88 04 52 111
Eesti Norge
SIA Novartis Baltics Eesti filiaal Novartis Norge AS
Tel: +372 66 30 810 Tlf: +47 23 05 20 00
Ελλάδα Österreich
Novartis (Hellas) A.E.B.E. Novartis Pharma GmbH
Tel: +30 210 281 17 12 Tel: +43 1 86 6570
España Polska
Novartis Farmacéutica, S.A. Novartis Poland Sp. z o.o.
Tel: +34 93 306 42 00 Tel.: +48 22 375 4888
France Portugal
Novartis Pharma S.A.S. Novartis Farma - Produtos Farmacêuticos, S.A.
Tél: +33 1 55 47 66 00 Tel: +351 21 000 8600
Hrvatska România
Novartis Hrvatska d.o.o. Novartis Pharma Services Romania SRL
Tel: +385 1 6274 220 Tel: +40 21 31299 01
Ireland Slovenija
Novartis Ireland Limited Novartis Pharma Services Inc.
Tel: +353 1 260 12 55 Tel: +386 1 300 75 50
Ísland Slovenská republika
Vistor hf. Novartis Slovakia s.r.o.
Sími: +354 535 7000 Tel: +421 2 5542 5439
Italia Suomi/Finland
Novartis Farma S.p.A. Novartis Finland Oy
Tel: +39 02 96 54 1 Puh/Tel: +358 (0)10 6133 200
Κύπρος Sverige
Novartis Pharma Services Inc. Novartis Sverige AB
Tel: +357 22 690 690 Tel: +46 8 732 32 00
Latvija
SIA Novartis Baltics
Tel: +371 67 887 070
Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu.
INSTRUCTIONS FOR USE

SECTION A ADMINISTRATION USING DOSER
Dissolve the tablets in water before administering Finlee. Follow the instructions below to dissolve the tablets in water. If the Finlee solution comes into contact with the skin, wash the area thoroughly with water and soap. If the Finlee solution comes into contact with the eyes, rinse the eyes thoroughly with fresh water. In case of spillage, follow the instructions in the section “CLEANING UP SPILLS”.
1 Wash and dry hands before administering Finlee.
2 Add still drinking water to the doser: oApproximately 5 ml for 1 to 4 tablets oApproximately 10 ml for 5 to 15 tablets
3 Remove the child-resistant cap by pushing down on the cap and turning it counterclockwise.
4 Count the prescribed number of tablets in one hand and place them into the doser. The bottle contains 2 plastic containers with silica gel desiccant to keep the dispersible tablets dry. Replace the containers inside the bottle if they fall out. Do not discard the containers. Close the bottle with the cap. Store the closed bottle in the box, out of sight and reach of children.
5 Gently tilt the doser and stir gently with the handle of a stainless steel teaspoon until the tablets are completely dissolved (this may take 3 minutes or more). Once ready, the solution will appear cloudy white. Administer the solution within 30 minutes after the tablets have dissolved.
6 Ensure that the child drinks all of the solution from the doser.
7 Add approximately 5 ml of still drinking water to the empty doser and stir with the handle of a stainless steel teaspoon (there may be tablet residue inside the doser which could be difficult to see).
8 Ensure that the child drinks all of this solution from the doser as well.
9 If the prescribed number of tablets is between 5 and 15: repeat steps 7 to 8.
10 For cleaning instructions, see “SECTION C”.

SECTION B ADMINISTRATION VIA ORAL SYRINGE OR FEEDING TUBE
Minimum feeding tube size:

Dose	Minimum size
From 1 to 3 tablets	10 French gauge
From 4 to 15 tablets	12 French gauge
1 Follow steps 1 to 5 in “SECTION A” to dissolve the tablets, then proceed to step 2 in this section.
2 Draw up the entire solution from the dosing cup into a syringe compatible with a feeding tube or oral administration.
3a Oral syringe administration: Place the tip of the oral syringe inside the mouth, positioning it against the inside of one cheek. Slowly push the plunger all the way down to deliver the full dose. WARNING: Administering Finlee directly into the throat or pushing the plunger too quickly may cause choking.
3b Feeding tube administration: Deliver the solution into the feeding tube according to the manufacturer's instructions.
4 Add approximately 5 mL of plain drinking water to the empty dosing cup and stir with the handle of a stainless steel teaspoon to dissolve any residue (there will be tablet residue inside the dosing cup, which may be difficult to see).
5 Draw up the entire solution from the dosing cup into a syringe compatible with a feeding tube or oral administration.
6 Administer the solution through the feeding tube or into the cheek.
7 Repeat steps 4 to 6 for a total of 3 times to ensure the entire dose is administered.
8 For cleaning instructions, see “SECTION C”.

SECTION C CLEANING
Dosage Device

Rinse the dosage device with water immediately after administration. Do not use hot water, as the device may deform.
Remove excess water, then dry with clean paper towels.
Always keep the dosage device separate from other kitchen items to avoid contamination.
If both dosage devices become soiled and cannot be cleaned with water alone, contact your pharmacist for a new dosage device.

Measuring Spoon

Wash the measuring spoon by hand with warm water and soap, or place it in the dishwasher.

Oral Syringe
If used, clean the oral syringe as follows:

Fill a glass with hot soapy water.
Place the oral syringe into the glass with hot soapy water.
Draw water into the oral syringe and expel it again 4 or 5 times.
Separate the plunger from the barrel.
Rinse the glass, plunger, and barrel under hot tap water.
Allow the plunger and barrel to air-dry on a dry surface before next use.

The dosage device may be used for up to 4 months after first use. After 4 months, dispose of the
dosage device in household waste.
CLEANING OF SPILLS
Follow these steps if a spill of Finlee solution occurs:

Wear plastic gloves.
Completely absorb the solution using an absorbent material, such as paper towels soaked in a mixture of water and household disinfectant.
Repeat cleaning with fresh absorbent material at least 3 times until the area is clean.
Dry the area with paper towels.
Place all materials used for cleaning the spill into a sealable plastic bag.
Consult your pharmacist on how to dispose of the plastic bag.
Wash hands thoroughly with water and soap.

ANNEX IV
SCIENTIFIC CONCLUSIONS AND REASONS FOR THE VARIATION TO THE TERMS OF THE
MARKETING AUTHORISATION
Scientific Conclusions
Taking into account the assessment by the Pharmacovigilance and Risk Assessment Committee
(PRAC) of the Periodic Safety Update Report (PSUR) for dabrafenib, the scientific conclusions of the PRAC are as follows:
Considering the available data on radiation recall and sensitisation from clinical studies, the literature, and spontaneous reports, in some cases showing a close temporal relationship and localisation of the event within the irradiated area, and considering a plausible mechanism of action, the PRAC considers that a causal relationship between dabrafenib and enhanced radiation toxicity is at least a reasonable possibility. The PRAC concluded that the product information for medicinal products containing dabrafenib should be amended accordingly.
Having reviewed the PRAC recommendation, the Committee for Human Medicinal Products (CHMP) agrees with the general conclusions and the reasoning of the recommendation.
Reasons for the variation to the terms of the marketing authorisation
Based on the scientific conclusions regarding dabrafenib, the CHMP considers that the benefit-risk balance of medicinal products containing dabrafenib remains unchanged, subject to the proposed amendments to the product information.
The CHMP recommends a variation to the terms of the marketing authorisation.