Trametinib (Specialist drug)

Treatment should only be initiated and supervised by a physician experienced in the administration of anti-cancer medicinal products, and patients must have confirmation of BRAF V600 mutation using a validated test before starting. When used in combination, the recommended dose of dabrafenib is 150 mg twice daily, and the once-daily trametinib dose should be taken at the same time each day with either the morning or the evening dose of dabrafenib. Duration: continue until the patient no longer derives benefit or unacceptable toxicity develops; in the adjuvant melanoma setting treat for 12 months unless there is disease recurrence or unacceptable toxicity. Missed dose: take a missed trametinib dose only if it is more than 12 hours until the next scheduled dose (for dabrafenib, only if more than 6 hours). Dose reductions: 1st reduction 1.5 mg once daily, 2nd reduction 1 mg once daily (dabrafenib 100 mg then 75 mg then 50 mg twice daily in combination); adjustment below 1 mg once daily is not recommended. Grade 2 (intolerable) or Grade 3 adverse reactions — interrupt until Grade 0 to 1 and reduce by one dose level; Grade 4 — discontinue permanently, or interrupt until Grade 0 to 1 and reduce by one dose level. Pyrexia: if temperature is 38 degrees C or above, interrupt therapy, treat with anti-pyretics (consider oral corticosteroids if insufficient) and restart when symptom-free for at least 24 hours, at the same or a reduced dose level. Trametinib should be interrupted for asymptomatic absolute LVEF decrease of more than 10% from baseline that is below the institutional lower limit of normal, and permanently discontinued for Grade 3 or 4 left ventricular dysfunction or clinically significant LVEF reduction not recovering within 4 weeks; permanently discontinue for retinal vein occlusion or for treatment-related ILD/pneumonitis; follow the SPC RPED table for retinal pigment epithelial detachment. Elderly: no initial dose adjustment in patients over 65 years, but more frequent dose adjustments may be needed. Hepatic impairment: no adjustment in mild impairment; use with caution in moderate or severe hepatic impairment. Paediatric population: safety and efficacy of trametinib tablets in children and adolescents under 18 years have not been established and no data are available. If a patient vomits after taking trametinib, the dose should not be retaken.