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Finlee is a brand name for Dabrafenib. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Low-grade glioma Finlee in combination with trametinib is indicated for the treatment of paediatric patients aged 1 year and older with low-grade glioma (LGG) with a BRAF V600E mutation who require systemic therapy. High-grade glioma Finlee in combination with trametinib is indicated for the treatment of paediatric…
Verbatim from this product's EMA label. Tap a section to expand.
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.
2). 3 Posology The recommended twice-daily dose of Finlee is determined by body weight (Table 1). Table 1 Dosing regimen by body weight Body weight* Recommended dose (mg dabrafenib) twice daily Recommended dose (number of 10 mg tablets) twice daily 8 to 9 kg 20 mg 2 10 to 13 kg 30 mg 3 14 to 17 kg 40 mg 4 18 to 21 kg 50 mg 5 22 to 25 kg 60 mg 6 26 to 29 kg 70 mg 7 30 to 33 kg 80 mg 8 34 to 37 kg 90 mg 9 38 to 41 kg 100 mg 10 42 to 45 kg 110 mg 11 46 to 50 kg 130 mg 13 ≥51 kg 150 mg 15 *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.
Summary of the safety profile In clinical studies of paediatric patients treated with dabrafenib in combination with trametinib, the most common adverse reactions (reported at a frequency ≥20%) were: pyrexia (70%), rash (49%), headache (47%), vomiting (40%), fatigue (36%), dry skin (35%), diarrhoea (34%), haemorrhage (34%), nausea (29%), dermatitis acneiform (29%), abdominal pain (28%), neutropenia (26%), cough (24%) and transaminases increased (22%).
The most frequently reported severe (Grade 3/4) adverse reactions were: neutropenia (15%), pyrexia (11%), transaminases increased (6%) and weight increased (5%). 3). The safety profile in paediatric patients was largely consistent with the safety profile previously established in adult patients.
The following additional adverse reactions have so far only been reported in adult patients treated with dabrafenib capsules and trametinib tablets: cutaneous squamous cell carcinoma, seborrhoeic keratosis, peripheral neuropathy (including sensory and motor neuropathy), lymphoedema, dry mouth, actinic keratosis, renal failure, potentiation of radiation toxicity (common), melanoma, acrochordon, sarcoidosis, chorioretinopathy, pneumonitis, acute renal failure, nephritis, cardiac failure, left ventricular dysfunction, interstitial lung disease, rhabdomyolysis (uncommon), gastrointestinal perforation, haemophagocytic lymphohistiocytosis (rare), tumour lysis syndrome, myocarditis, Stevens-Johnson syndrome, drug reaction with eosinophilia and systemic symptoms, tattoo-associated skin reactions (frequency not known).
In addition, cases of biocular panuveitis or biocular iridocyclitis suggestive of Vogt-Koyanagi-Harada syndrome have been reported in adult patients. Tabulated list of adverse reactions The safety of dabrafenib in combination with trametinib has been evaluated in a pooled safety set of 171 paediatric patients across two studies in patients with BRAF V600 mutation-positive advanced solid tumours.
Finlee is intended for use in combination with trametinib powder for oral solution as there are limited efficacy data for dabrafenib monotherapy and for trametinib monotherapy in BRAF V600 mutation- positive glioma. The trametinib powder for oral solution SmPC must be consulted prior to intiation of treatment.
For additional information on warnings and precautions associated with trametinib treatment, please refer to the trametinib powder for oral solution SmPC. BRAF V600E testing The efficacy and safety of dabrafenib have not been established in patients with wild-type BRAF glioma.
1). New malignancies New malignancies, cutaneous and non-cutaneous, can occur when dabrafenib is used in combination with trametinib. 8). It is recommended that skin examination be performed prior to initiation of therapy with dabrafenib and monthly throughout treatment and for up to six months after treatment.
Monitoring should continue for 6 months following discontinuation of dabrafenib or until initiation of another anti-neoplastic therapy. Suspicious skin lesions should be managed with dermatological excision and do not require treatment modifications.
Patients should be instructed to inform their physicians immediately if new skin lesions develop. 7 Non-cutaneous malignancies In vitro experiments have demonstrated paradoxical activation of mitogen-activated protein kinase (MAP kinase) signalling in BRAF wild-type cells with RAS mutations when exposed to BRAF inhibitors.
8) when RAS mutations are present. RAS-associated malignancies have been reported in adult clinical studies, both with another BRAF inhibitor (chronic myelomonocytic leukaemia and non-cutaneous SCC of the head and neck) as well as with dabrafenib monotherapy (pancreatic adenocarcinoma, bile duct adenocarcinoma) and with dabrafenib in combination with trametinib (colorectal cancer, pancreatic cancer).
1.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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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).
4). 4 Table 2 Dose modification schedule based on the grade of any adverse reactions (excluding pyrexia) Grade (CTCAE)* Recommended dabrafenib dose modifications Grade 1 or Grade 2 (Tolerable) Continue treatment and monitor as clinically indicated.
Grade 2 (Intolerable) or Grade 3 Interrupt therapy until toxicity is Grade 0 to 1 and reduce by one dose level when resuming therapy. Refer to Table 3 for dose level guidance. Grade 4 Discontinue permanently, or interrupt therapy until Grade 0 to 1 and reduce by one dose level when resuming therapy.
Refer to Table 3 for dose level guidance. * 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 Body weight Recommended dose (mg dabrafenib) twice daily Reduced dose (number of 10 mg tablets) twice daily First reduction level Second reduction level Third reduction level 8 to 9 kg 20 mg 1 N/A N/A 10 to 13 kg 30 mg 2 1 N/A 14 to 17 kg 40 mg 3 2 1 18 to 21 kg 50 mg 3 2 1 22 to 25 kg 60 mg 4 3 2 26 to 29 kg 70 mg 5 4 2 30 to 33 kg 80 mg 5 4 3 34 to 37 kg 90 mg 6 5 3 38 to 41 kg 100 mg 7 5 3 42 to 45 kg 110 mg 7 6 4 46 to 50 kg 130 mg 9 7 4 ≥51 kg 150 mg 10 8 5 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. 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.
5 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 […]
3%) patients were 12 to <18 years of age at enrolment. 3 years. Adverse reactions (Table 4) are listed below by MedDRA system organ class ranked by frequency using the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1 000 to <1/100), rare (≥1/10 000 to <1/1 000), very rare (<1/10 000) and not known (cannot be estimated from the available data).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Table 4 Adverse reactions with dabrafenib in combination with trametinib Infections and infestations Very common Paronychia, nasopharyngitis*1 Common Urinary tract infection, cellulitis Neoplasms benign, malignant and unspecified (incl cysts and polyps) Very common Skin papilloma Blood and lymphatic system disorders Very common Neutropenia*2, anaemia, leukopenia* Common Thrombocytopenia* Immune system disorders Common Hypersensitivity Metabolism and nutrition disorders Common Dehydration, decreased appetite Nervous system disorders Very common Headache, dizziness*3 15 Eye disorders Common Vision blurred, visual impairment, uveitis*4 Uncommon Retinal detachment, periorbital oedema Cardiac disorders Common Ejection fraction decreased, bradycardia* Uncommon Atrioventricular block5 Vascular disorders Very common Haemorrhage*6 Common Hypertension, hypotension Respiratory, thoracic and mediastinal disorders Very common Cough* Common Dyspnoea Gastrointestinal disorders Very common Abdominal pain*, constipation, diarrhoea, nausea, vomiting Common Pancreatitis, stomatitis Uncommon Colitis* Skin and subcutaneous tissue disorders Very common Dermatitis acneiform*7, dry skin*8, pruritus, rash*9, erythema Common Dermatitis exfoliative generalised*10, alopecia, palmar-plantar erythrodysaesthesia syndrome, folliculitis, skin lesion, panniculitis, hyperkeratosis, photosensitivity*11 Uncommon Acute febrile neutrophilic dermatosis12, skin fissures, night sweats, hyperhidrosis Musculoskeletal and connective tissue disorders Very common Arthralgia, pain in extremity Common Myalgia*, muscle spasms*13 General disorders and administration site conditions Very common Pyrexia*, fatigue*14, weight increased Common Mucosal inflammation, face oedema*, chills, oedema peripheral, influenza-like illness Investigations Very common Transaminases increased*15 Common Hyponatraemia, hypophosphataemia, hyperglycaemia, blood alkaline phosphatase increased, gamma-glutamyltransferase increased, blood creatine phosphokinase increased *Denotes grouped term of two or more MedDRA preferred terms that were considered clinically similar.
1 nasopharyngitis includes pharyngitis 2 neutropenia includes neutrophil count decreased and febrile neutropenia 3 dizziness includes vertigo 4 uveitis includes iridocyclitis 5 atrioventricular block includes atrioventricular block first degree 6 haemorrhage includes epistaxis, haematuria, contusion, haematoma, international normalised ratio increased, anal haemorrhage, catheter site haemorrhage, cerebral haemorrhage, ecchymosis, extradural haematoma, gastrointestinal haemorrhage, haematochezia, petechiae, post-procedural haemorrhage, rectal haemorrhage, red blood cell count decreased, upper gastrointestinal haemorrhage, uterine haemorrhage, heavy menstrual bleeding and purpura 7 dermatitis acneiform includes acne and acne pustular 8 dry skin includes xerosis and xeroderma 9 rash includes rash maculo-papular, rash pustular, rash erythematous, rash papular, rash macular 10 dermatitis exfoliative generalised includes skin exfoliation and dermatitis exfoliative 11 photosensitivity includes photosensitivity reaction and sunburn 12 acute febrile neutrophilic dermatosis is an adverse drug reaction seen also […]
The benefits and risks should be considered before administering dabrafenib in patients with a prior or concurrent cancer associated with RAS mutations. Patients should be screened for occult pre-existing malignancies. Following discontinuation of dabrafenib, monitoring for non-cutaneous secondary/recurrent malignancies should continue for up to 6 months or until initiation of another anti-neoplastic therapy.
Abnormal findings should be managed according to clinical practices. 8). Major haemorrhagic events and fatal haemorrhages have occurred in adult patients taking dabrafenib in combination with trametinib. The potential for these events in patients with low platelet counts (<75 000/mm3) has not been established as such patients were excluded from clinical studies.
The risk of haemorrhage may be increased with concomitant use of antiplatelet or anticoagulant therapy. If haemorrhage occurs, patients should be treated as clinically indicated. 8), in some cases with a time to onset of several months.
In clinical studies in adult patients treated with dabrafenib, ophthalmological reactions, including uveitis, iridocyclitis and iritis, have been reported. Patients should be routinely monitored for visual signs and symptoms (such as change in vision, photophobia and eye pain) while on therapy.
No dose modifications are required as long as effective local therapies can control ocular inflammation. If uveitis does not respond to local ocular therapy, withhold dabrafenib until resolution of ocular inflammation and then restart dabrafenib reduced by one dose level.
No dose modification of trametinib is required when taken in combination with dabrafenib following diagnosis of uveitis. Cases of biocular panuveitis or biocular iridocyclitis suggestive of Vogt-Koyanagi-Harada syndrome have been reported in patients treated with dabrafenib in combination with trametinib.
Withhold dabrafenib until resolution of ocular inflammation and consider consulting an ophthalmologist. Systemic corticosteroid treatment may be necessary. RPED and RVO may occur with dabrafenib in combination with trametinib. 4). No dose modification of dabrafenib is required when taken in combination with trametinib following diagnosis of RVO or RPED.
8). Serious non-infectious febrile events were identified (defined as fever accompanied by severe rigors, dehydration, hypotension and/or acute renal insufficiency of pre-renal origin in patients with normal baseline renal function).
5 months. In adult patients with unresectable or metastatic melanoma who received dabrafenib in combination with trametinib and developed pyrexia, approximately half of the first occurrences of pyrexia happened within the first month of therapy and approximately one third of the patients had 3 or more events.
Patients with serious non-infectious febrile events responded well to dose interruption and/or dose reduction and supportive care. Therapy with dabrafenib and trametinib should be interrupted if the patient’s temperature is […]