TAFINLAR HARD CAPSULE 75MG

NOVARTIS (SINGAPORE) PTE LTD

NOVARTIS (SINGAPORE) PTE LTD

Therapeutic

Prescription Only

CAPSULE

**4 Dosage regimen and administration** Treatment with Tafinlar should be initiated by a physician experienced in the use of anticancer therapies. **Dosage regimen** **General target population** **Adults** The efficacy and safety of Tafinlar have not been established in patients with wild-type BRAF melanoma, wild-type BRAF NSCLC, or wild-type BRAF ATC ( _see section 12 Clinical Studies_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). Tafinlar should not be used in patients with wild-type BRAF melanoma, wild-type BRAF NSCLC, or wild-type BRAF ATC. Confirmation of BRAF V600 mutation using an approved/validated test is required for selection of patients appropriate for treatment with Tafinlar as monotherapy and in combination with trametinib ( _see section 12 Clinical Studies_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). When Tafinlar is used in combination with trametinib, please also refer to the full trametinib prescribing information. Tafinlar should be taken either at least one hour before, or at least two hours after a meal ( _see section 11 Clinical Pharmacology_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_), leaving an interval of approximately 12 hours between doses. Tafinlar should be taken at similar times every day. When Tafinlar 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 Tafinlar. If a dose of Tafinlar is missed, it should not be taken if it is less than 6 hours until the next scheduled dose. _Recommended Dosage for Unresectable or Metastatic Melanoma_ The recommended dose of Tafinlar either as monotherapy or in combination with trametinib is 150 mg 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. Treatment should continue until disease progression or the development of unacceptable toxicity ( _see Table 4-2_). _Recommended Dosage for the Adjuvant Treatment of Melanoma_ The recommended dose of Tafinlar in combination with trametinib is 150 mg 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 until disease recurrence or unacceptable toxicity for up to 1 year. _Recommended Dosage for NSCLC_ The recommended dose of Tafinlar in combination with trametinib is 150 mg 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. Treatment should continue until disease progression or the development of unacceptable toxicity ( _see Table 4-2_). _Recommended Dosage for ATC_ The recommended dose of Tafinlar in combination with trametinib is 150 mg 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. Treatment should continue until disease recurrence or unacceptable toxicity. **Dose adjustments** **Tafinlar as monotherapy and in combination with trametinib** The management of adverse events/adverse drug reactions may require treatment interruption, dose reduction, or treatment discontinuation. Dose modifications or interruptions are not recommended for adverse reactions of cutaneous squamous cell carcinoma (cuSCC) or new primary melanoma ( _see section 6 Warnings and Precautions_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). For pyrexia management guidance see section below. Recommended dose level reductions are provided in Table 4-1. Doses below 50 mg twice daily are not recommended.  The recommended dose modification schedule is provided in Table 4-2. 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 Tafinlar dose should not exceed 150 mg twice daily.  **Pyrexia management:** Therapy should be interrupted (Tafinlar when used as monotherapy, and both Tafinlar and Mekinist when used in combination) if a patient’s temperature is ≥38°C (100.4°F). 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. Patients should be evaluated for signs and symptoms of infection ( _see section 6 Warnings and Precautions_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). Tafinlar, or both Tafinlar and Mekinist when used in combination, should be restarted if patient is symptom free for at least 24 hours either (1) at the same dose level or (2) reduced by one dose level, if pyrexia is recurrent and/or was accompanied by other severe symptoms including dehydration, hypotension, or renal failure. The use of oral corticosteroids should be considered in those instances in which anti- pyretics are insufficient. If treatment-related toxicities occur when Tafinlar is used in combination with Mekinist then both treatments should be simultaneously dose reduced, interrupted or discontinued with the exceptions of uveitis shown below. **Exceptions where dose modifications are necessary for Tafinlar only:** **Uveitis management:** 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 Tafinlar until resolution of ocular inflammation and then restart Tafinlar reduced by one dose level. No dose modification of trametinib is required when taken in combination with Tafinlar. **Special Populations** **Renal impairment** No dose adjustment is required in patients with mild or moderate renal impairment. Based on the population pharmacokinetic analysis, mild and moderate renal impairment had no significant effect on the oral clearance of dabrafenib or on the concentrations of its metabolites ( _see section 11 Clinical Pharmacology, Pharmacokinetics_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). There are no clinical data in patients with severe renal impairment and the potential need for dose adjustment cannot be determined. Tafinlar should be used with caution in patients with severe renal impairment. **Hepatic impairment** No dose adjustment is required for patients with mild hepatic impairment. Based on the population pharmacokinetic analysis, mild hepatic impairment had no significant effect on the oral clearance of dabrafenib or on the concentrations of its metabolites ( _see section 11 Clinical Pharmacology, Pharmacokinetics_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). There are no clinical data in patients with moderate to severe hepatic impairment and the potential need for dose adjustment cannot be determined. 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. Tafinlar should be used with caution in patients with moderate or severe hepatic impairment. **Pediatric patients (below 18 years)** The safety and efficacy of Tafinlar in pediatric patients have not been established. Tafinlar is not recommended in this age group. **Geriatric patients (65 years of age or above)** No dosage adjustment is required in patients over 65 years of age ( _see section 11 Clinical Pharmacology, Pharmacokinetics_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_).