FINLEE Dispersible tablet Ref.[51662] Active ingredients: Dabrafenib

Treatment with Finlee should be initiated and supervised by a qualified physician experienced in the use of anti-cancer medicinal products.

Before taking Finlee, patients must have confirmation of BRAF V600E mutation assessed by a CE-marked in vitro diagnostic (IVD) medical device with the corresponding intended purpose. If the CE-marked IVD is not available, confirmation of BRAF V600E should be assessed by an alternative validated test.

Finlee is used in combination with trametinib powder for oral solution. See the summary of product characteristics (SmPC) for posology of trametinib powder for oral solution.

Finlee is not to be replaced with other dabrafenib formulations as bioequivalence was not shown (see section 5.2).

Posology

The recommended twice-daily dose of Finlee is determined by body weight (Table 1).

Table 1. Dosing regimen by body weight:

^* Round body weight to the nearest kg, if necessary.
The recommended dose for patients with a body weight less than 8 kg has not been established. Please refer to the trametinib powder for oral solution SmPC, “Posology” and “Method of administration”, for dosing instructions for treatment with trametinib when used in combination with Finlee.

Duration of treatment

Treatment with Finlee should continue until disease progression or until the development of unacceptable toxicity. There are limited data in patients older than 18 years of age with glioma, therefore continued treatment into adulthood should be based on benefits and risks to the individual patient as assessed by the physician.

Missed or delayed doses

If a dose of Finlee is missed, it should only be taken if it is more than 6 hours until the next scheduled dose. If vomiting occurs after taking Finlee, an additional dose should not be administered and the next dose should be taken at the next scheduled time.

Dose modification

The management of adverse reactions may require dose reduction, treatment interruption or treatment discontinuation (see Tables 2 and 3).

If treatment-related toxicities occur, then both dabrafenib and trametinib should be simultaneously dose reduced, interrupted or discontinued. Exceptions where dose modifications are necessary for only one of the two treatments are detailed below for uveitis, RAS mutation-positive non-cutaneous malignancies (primarily related to dabrafenib), left ventricular ejection fraction (LVEF) reduction, retinal vein occlusion (RVO), retinal pigment epithelial detachment (RPED) and interstitial lung disease (ILD)/pneumonitis (primarily related to trametinib).

Dose modifications or interruptions are not recommended for adverse reactions of cutaneous malignancies (see section 4.4).

Table 2. Dose modification schedule based on the grade of any adverse reactions (excluding pyrexia):

^* The intensity of clinical adverse reactions graded by the Common Terminology Criteria for Adverse Events (CTCAE)

Table 3. Recommended dose reduction levels for adverse reactions:

N/A=not applicable
Permanently discontinue Finlee if unable to tolerate 10 mg twice daily or a maximum of 3 dose reductions.

When an individual’s adverse reactions are under effective management, dose re-escalation following the same dosing steps as de-escalation may be considered. The dabrafenib dose should not exceed the recommended dose indicated in Table 1.

Dose modifications for selected adverse reactions

Pyrexia

If a patient’s temperature is ≥38°C, therapy with dabrafenib and trametinib should be interrupted. In case of recurrence, therapy can also be interrupted at the first symptom of pyrexia. Treatment with anti-pyretics such as ibuprofen or acetaminophen/paracetamol should be initiated. The use of oral corticosteroids should be considered in those instances in which anti-pyretics are insufficient. Patients should be evaluated for signs and symptoms of infection and, if necessary, treated in line with local practice (see section 4.4). Therapy should be restarted if the patient is symptom-free for at least 24 hours either (1) at the same dose level, or (2) reduced by one dose level if the pyrexia is recurrent and/or was accompanied by other severe symptoms including dehydration, hypotension or renal failure.

Dose modification exceptions (where only one of the two therapies is dose reduced) for selected adverse reactions

Uveitis

No dose modifications are required for uveitis as long as effective local therapies can control ocular inflammation. If uveitis does not respond to local ocular therapy, dabrafenib should be withheld until resolution of ocular inflammation, and then dabrafenib should be restarted reduced by one dose level. No dose modification of trametinib is required when taken in combination with dabrafenib (see section 4.4).

RAS mutation-positive non-cutaneous malignancies

The benefits and risks must be considered before continuing treatment with dabrafenib in patients with a non-cutaneous malignancy that has a RAS mutation. No dose modification of trametinib is required when taken in combination with dabrafenib (see section 4.4).

Left ventricular ejection fraction (LVEF) reduction/Left ventricular dysfunction

If an absolute decrease of >10% in LVEF compared to baseline occurs, and the ejection fraction is below the institution’s lower limit of normal (LLN), please refer to the trametinib powder for oral solution SmPC (section 4.2) for dose modification instructions for trametinib. No dose modification of dabrafenib is required when taken in combination with trametinib (see section 4.4).

Retinal vein occlusion (RVO) and retinal pigment epithelial detachment (RPED)

If patients report new visual disturbances such as diminished central vision, blurred vision or loss of vision at any time while on combination therapy with dabrafenib and trametinib, please refer to the trametinib powder for oral solution SmPC (section 4.2) for dose modification instructions for trametinib. No dose modification of dabrafenib is required when taken in combination with trametinib for confirmed cases of RVO or RPED.

Interstitial lung disease (ILD)/Pneumonitis

In patients treated with dabrafenib in combination with trametinib with suspected ILD or pneumonitis, including patients presenting with new or progressive pulmonary symptoms and findings including cough, dyspnoea, hypoxia, pleural effusion or infiltrates, pending clinical investigations, please refer to the trametinib powder for oral solution SmPC (section 4.2) for dose modification instructions for trametinib. No dose modification of dabrafenib is required when taken in combination with trametinib for cases of ILD or pneumonitis.

Special populations

Hepatic impairment

No dose adjustment is required in patients with mild hepatic impairment. There are no clinical data in patients with moderate to severe hepatic impairment and the potential need for dose adjustment cannot be determined (see section 5.2). Hepatic metabolism and biliary secretion are the primary routes of elimination of dabrafenib and its metabolites and patients with moderate to severe hepatic impairment may have increased exposure. Dabrafenib should be used with caution in patients with moderate or severe hepatic impairment.

Renal impairment

No dose adjustment is required in patients with mild or moderate renal impairment. There are no clinical data in patients with severe renal impairment and the potential need for dose adjustment cannot be determined (see section 5.2). Dabrafenib should be used with caution in patients with severe renal impairment.

Paediatric population

The safety and efficacy of combination therapy with dabrafenib and trametinib in children below 1 year of age have not been established. No data are available. Studies in juvenile animals have shown effects of dabrafenib which were not observed in adult animals (see section 5.3). Longer-term safety data in paediatric patients are currently limited.

Method of administration

Finlee is for oral use.

Finlee should be taken without food, at least one hour prior to or two hours after a meal (see section 5.2). Breast-feeding and/or baby formula may be given on demand if a patient is unable to tolerate the fasting conditions.

It is recommended that the doses of Finlee are taken at similar times every day, leaving an interval of approximately 12 hours between doses. The once-daily dose of trametinib should be taken at the same time each day with either the morning dose or the evening dose of Finlee.

If the patient is unable to swallow and has a nasogastric tube in situ, the Finlee tablet suspension can be administered via the tube.

Instructions for preparation and administration are provided in section 6.6.

No acute overdose symptoms have been reported in paediatric patients who received dabrafenib in combination with trametinib in clinical studies. There is no specific treatment for overdose. If overdose occurs, the patient should be treated supportively with appropriate monitoring as necessary.

Dispersible tablet: 2 years.

Dispersible tablet suspension: Use within 30 minutes of preparation.

This medicinal product does not require any special temperature storage conditions.

Store in the original package in order to protect from moisture.

Opaque white high-density polyethylene (HDPE) bottle with polypropylene child-resistant screw cap and a silica gel desiccant.

Each bottle contains 210 dispersible tablets and two 2 g desiccant canisters. Patients should be instructed to keep the desiccant canisters in the bottle and not to swallow them.

Packs containing:

• 1 bottle (210 dispersible tablets) and 2 dosing cups.
• 2 bottles (420 dispersible tablets) and 2 dosing cups.

Each dosing cup is 30 ml in volume with 5 ml graduated increments.

Not all pack sizes may be marketed.

Preparation of the dispersible tablet suspension:

• The prescribed dose of Finlee dispersible tablets should be placed in the dosing cup containing approximately 5 ml or 10 ml of still drinking water.
• The amount of still drinking water depends on the prescribed number of dispersible tablets. For a dose of 1 to 4 dispersible tablets, use approximately 5 ml of water; for a dose of 5 to 15 dispersible tablets, use approximately 10 ml of water.
• It may take 3 minutes (or more) to fully disperse the tablets.
• The contents should be gently stirred with the handle of a stainless steel teaspoon and then administered immediately.
• Administer the suspension no later than 30 minutes after preparation (after the tablets have fully dispersed). If more than 30 minutes have passed, do not use the suspension.
• After administration of the prepared suspension, there will be tablet residue inside the dosing cup. The residue may be difficult to see. Add approximately 5 ml of still drinking water to the empty dosing cup and stir with the handle of the stainless steel teaspoon to re-suspend any remaining particles. The entire contents of the dosing cup should be administered.

Administration using a feeding tube or an oral syringe:

• Once the suspension is prepared, withdraw all of the suspension from the dosing cup into a syringe compatible with a feeding tube or oral administration.
• If administering via a feeding tube, flush the feeding tube with still drinking water before administering, and dispense the suspension into the feeding tube as per the manufacturer’s instructions, and flush the feeding tube with still drinking water after administering.
• If administering via an oral syringe, place the end of the oral syringe inside the mouth with the tip touching the inside of either cheek. Slowly push the plunger all the way down to deliver the full dose.

A complete and illustrated set of instructions for use is provided at the end of the package leaflet “Instructions for use”.

Disposal:

The dosing cup can be used for up to 4 months after first use. After 4 months, the dosing cup can be thrown away in the household waste.

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