Tafinlar Dosage/Direction for Use

Treatment with dabrafenib should be initiated and supervised by a qualified physician experienced in the use of anticancer medicinal products.
Before taking dabrafenib, patients must have confirmation of tumour BRAF V600 mutation using a validated test.
The efficacy and safety of dabrafenib have not been established in patients with wild-type BRAF melanoma or wild-type BRAF NSCLC. Dabrafenib should therefore not be used in patients with wild-type BRAF melanoma or wild-type BRAF NSCLC (see Precautions and Pharmacology: Pharmacodynamics under Actions).
Posology: The recommended dose of dabrafenib, either used as monotherapy or in combination with trametinib, is 150 mg (two 75 mg capsules) twice daily (corresponding to a total daily dose of 300 mg). The recommended dose of trametinib, when used in combination with dabrafenib, is 2 mg once daily.
Duration of treatment: Treatment should continue until the patient no longer derives benefit or the development of unacceptable toxicity (see Table 13). In the adjuvant melanoma setting, patients should be treated for a period of 12 months unless there is disease recurrence or unacceptable toxicity.
Missed doses: If a dose of dabrafenib is missed, it should not be taken if it is less than 6 hours until the next scheduled dose.
If a dose of trametinib is missed, when dabrafenib is given in combination with trametinib, the dose of trametinib should only be taken if it is more than 12 hours until the next scheduled dose.
Dose modification: Two dabrafenib capsule strengths, 50 mg and 75 mg, are available to effectively manage dose modification requirements.
The management of adverse reactions may require treatment interruption, dose reduction, or treatment discontinuation (see Tables 12 and 13).
Dose modifications or interruptions are not recommended for adverse reactions of cutaneous squamous cell carcinoma (cuSCC) or new primary melanoma (see Precautions).
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, withhold dabrafenib until resolution of ocular inflammation and then restart dabrafenib reduced by one dose level (see Precautions).
Recommended dose level reductions and recommendations for dose modifications are provided in Tables 12 and 13, respectively. (See Tables 12 and 13.)

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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 150 mg twice daily.
Pyrexia: If a patient's temperature is ≥38°C therapy should be interrupted (dabrafenib when used as monotherapy, and both dabrafenib and trametinib when used in combination). 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 Precautions). Dabrafenib, or both dabrafenib and trametinib when used in combination, 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.
If treatment-related toxicities occur when dabrafenib is used in combination with trametinib, then both treatments should be simultaneously dose reduced, interrupted or discontinued. Exceptions where dose modifications are necessary for only one of the two treatments are detailed as follows 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 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 Precautions).
RAS-mutation-positive non-cutaneous malignancies: The benefits and risks should 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.
Left ventricular ejection fraction (LVEF) reduction/Left ventricular dysfunction: If dabrafenib is being used in combination with trametinib and absolute decrease of >10% in LVEF compared to baseline and the ejection fraction is below the institution's lower limit of normal (LLN), refer to the trametinib SmPC for dose modification instructions for trametinib. No dose modification of dabrafenib is required when taken in combination with trametinib.
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, refer to the trametinib SmPC 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, refer to the trametinib SmPC 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.
Renal impairment: No dose adjustment is required for patients with mild or moderate renal impairment. There are no clinical data in subjects with severe renal impairment and the potential need for dose adjustment cannot be determined (see Pharmacology: Pharmacokinetics under Actions). Dabrafenib should be used with caution in patients with severe renal impairment when administered as monotherapy or in combination with trametinib.
Hepatic impairment: No dose adjustment is required for patients with mild hepatic impairment. There are no clinical data in subjects with moderate to severe hepatic impairment and the potential need for dose adjustment cannot be determined (see Pharmacology: Pharmacokinetics under Actions). 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 when administered as monotherapy or in combination with trametinib.
Special populations: Non-Caucasian patients: Limited safety and efficacy data have been collected on dabrafenib in non-Caucasian patients. The population pharmacokinetic analysis showed no significant differences in the pharmacokinetics of dabrafenib between Asian and Caucasian patients. No dabrafenib dose adjustment is needed in Asian patients.
Elderly: No adjustment of the initial dose is required in patients >65 years of age.
Paediatric population: The safety and efficacy of dabrafenib in children and adolescents (<18 years) have not yet been established. No clinical data are available. Studies in juvenile animals have shown adverse effects of dabrafenib which had not been observed in adult animals (see Pharmacology: Toxicology: Preclinical safety data under Actions).
Method of administration: Tafinlar is for oral use. The capsules are to be swallowed whole with water. They should not be chewed or opened and should not be mixed with food or liquids due to chemical instability of dabrafenib.
It is recommended that the doses of dabrafenib be taken at similar times every day, leaving an interval of approximately 12 hours between doses. When dabrafenib and trametinib are taken in combination, 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 dabrafenib.
Dabrafenib should be taken at least one hour before, or at least 2 hours after a meal.
If a patient vomits after taking dabrafenib, the patient should not retake the dose and should take the next scheduled dose.
Refer to trametinib SmPC for information on method of administration when given in combination with dabrafenib.