Dabrafenib

SCOPE: this is the adult capsule dose, and it is the dose for this page's primary indication - BRAF V600-mutant melanoma in combination with trametinib (page specialty Oncology, existing entry '150mg BD (with trametinib for melanoma)'). The label gives no indication-specific adult variation: the same 150 mg twice daily applies across its adult indications (melanoma as a single agent and with trametinib, NSCLC, anaplastic thyroid cancer, other BRAF V600E solid tumours). VERBATIM (section 2 Highlights): 'The recommended dosage of TAFINLAR in adult patients is 150 mg (two 75 mg capsules) orally twice daily. The recommended dosage for TAFINLAR in pediatric patients is based on body weight. Take TAFINLAR at least 1 hour before or 2 hours after a meal.' (Section 2.2): 'The recommended dosage for TAFINLAR capsules in adult patients is 150 mg taken orally twice daily.' ADMINISTRATION (section 2.3): 'Take TAFINLAR at the same time each day, approximately 12 hours apart. Do not take a missed dose of TAFINLAR within 6 hours of the next dose of TAFINLAR. If vomiting occurs after TAFINLAR administration, do not take an additional dose. Take the next dose at its scheduled time.' STRENGTHS (section 3): capsules 50 mg and 75 mg; tablets for oral suspension 10 mg - so 'two 75 mg capsules' is pinned to marketed strengths. PATIENT SELECTION (section 2.1): 'Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with TAFINLAR as a single agent'; 'Confirm the presence of BRAF V600E or V600K mutation in tumor specimens prior to initiation of treatment with TAFINLAR and trametinib'. The UK SPC adds that the mutation must be confirmed 'by a CE-marked in vitro diagnostic (IVD) medical device with the corresponding intended purpose' or, if unavailable, 'by an alternative validated test'. DURATION (section 2.2): 'until disease progression or unacceptable toxicity' for unresectable or metastatic melanoma, metastatic NSCLC, locally advanced or metastatic anaplastic thyroid cancer and solid tumours; in the adjuvant melanoma setting 'until disease recurrence or unacceptable toxicity for up to 1 year'. COMBINATION: 'Refer to the trametinib prescribing information for recommended trametinib dosing information.' NO MAXIMUM DOSE is stated for the adult regimen, so maxDose is deliberately left empty. The only ceiling wording in the bundle is in the UK Finlee SPC and belongs to the paediatric weight-banded table ('The dabrafenib dose should not exceed the recommended dose indicated in Table 1'); 'Permanently discontinue Finlee if unable to tolerate 10 mg twice daily or a maximum of 3 dose reductions' is a count of dose reductions, not a dose ceiling, and neither is carried across. DOSE MODIFICATION FRAMEWORK (UK SPC section 4.2 - stated for the paediatric product, the only modification table this bundle retrieved in full): Grade 1 or tolerable Grade 2, continue treatment and monitor as clinically indicated; intolerable Grade 2 or Grade 3, interrupt therapy until toxicity is Grade 0 to 1 and reduce by one dose level on resuming; Grade 4, discontinue permanently, or interrupt until Grade 0 to 1 and reduce by one dose level. If treatment-related toxicities occur both dabrafenib and trametinib are simultaneously reduced, interrupted or discontinued, except for uveitis and RAS mutation-positive non-cutaneous malignancies (dabrafenib only) and LVEF reduction, retinal vein occlusion, retinal pigment epithelial detachment and ILD/pneumonitis (trametinib only). PYREXIA (UK SPC section 4.2): 'If a patient's temperature is 38 degrees C or above, therapy with dabrafenib and trametinib should be interrupted... 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... 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.' US section 2.4 (Dosage Modifications for Adverse Reactions) is truncated in this bundle - verify the adult modification table against the full prescribing information.

WEIGHT-BANDED, NOT PER-KG - dosePerKg is deliberately null so nothing is fed to the weight calculator. TABLETS FOR ORAL SUSPENSION / FINLEE DISPERSIBLE TABLETS, twice-daily dose by body weight (identical bands in US Table 2 and UK SPC Table 1; 'Round body weight to the nearest kg, if necessary'): 8 to 9 kg = 20 mg; 10 to 13 kg = 30 mg; 14 to 17 kg = 40 mg; 18 to 21 kg = 50 mg; 22 to 25 kg = 60 mg; 26 to 29 kg = 70 mg; 30 to 33 kg = 80 mg; 34 to 37 kg = 90 mg; 38 to 41 kg = 100 mg; 42 to 45 kg = 110 mg; 46 to 50 kg = 130 mg; 51 kg or greater = 150 mg. 'The recommended dose for patients with a body weight less than 8 kg has not been established.' CAPSULES in paediatric patients (US Table 1): 26 to 37 kg = 75 mg twice daily; 38 to 50 kg = 100 mg twice daily; 51 kg or greater = 150 mg twice daily - 'A recommended dosage of TAFINLAR capsules has not been established in patients who weigh less than 26 kg.' AGE LIMITS: US section 8.4 - safety and effectiveness are established in paediatric patients 1 year of age and older, in combination with trametinib, for BRAF V600E unresectable or metastatic solid tumours and for low-grade glioma requiring systemic therapy; 'The safety and effectiveness of TAFINLAR in combination with trametinib have not been established for these indications in pediatric patients less than 1 year old'; 'The safety and effectiveness of TAFINLAR as a single agent in pediatric patients have not been established.' UK SPC section 4.2: '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.' INDICATION CAUTION: the paediatric indication in the UK Finlee SPC is BRAF V600E-mutant GLIOMA in combination with trametinib, and the US paediatric indications are solid tumours and low-grade glioma - none of these is the melanoma indication this page leads with. CONCENTRATION is null because the oral suspension has no fixed mg/mL: 'Prepare the oral suspension with approximately 5 mL of water for 1 to 4 tablets, and approximately 10 mL of water for 5 to 15 tablets in the provided dosing cup'; 'Discard the oral suspension if not administered within 30 minutes after preparation.' Administration by feeding tube is possible: '10 French gauge or larger for 1 to 3 tablets; 12 French gauge or larger for 4 to 15 tablets'. DOSE-REDUCTION LEVELS by band are tabulated in UK SPC Table 3 (e.g. 51 kg or greater: first reduction 10 tablets, second 8, third 5, of the 10 mg tablet).