Tucatinib (Specialist drug)

eMC SPC for TUKYSA 150 mg film-coated tablets. Treatment should be initiated and supervised by a physician experienced in the administration of anti-cancer medicinal products. COMBINATION REGIMEN (§4.2 Table 1): tucatinib 300 mg orally twice daily continuously, WITH capecitabine 1000 mg/m² orally twice daily on Days 1 to 14 every 21 days (within 30 minutes after a meal — tucatinib may be taken at the same time as capecitabine), AND trastuzumab either intravenously (initial dose 8 mg/kg on Day 1, then 6 mg/kg every 21 days) or subcutaneously (600 mg every 21 days). Refer to the SmPCs for capecitabine and trastuzumab; the treatment components can be administered in any order. MISSED DOSE: take the next dose at the regularly scheduled time. DOSE REDUCTIONS (§4.2 Table 2): 300 mg twice daily → first reduction 250 mg twice daily → second reduction 200 mg twice daily → third reduction 150 mg twice daily; permanently discontinue in patients unable to tolerate 150 mg orally twice daily. Interrupt until recovery to ≤ Grade 1 then resume at the same dose for Grade 3 diarrhoea without antidiarrhoeal treatment or Grade 2 bilirubin (>1.5 to 3 × ULN); resume at the next lower dose level for Grade 3 diarrhoea despite antidiarrhoeal treatment, Grade 3 ALT/AST (>5 to 20 × ULN), Grade 3 bilirubin (>3 to 10 × ULN) or other Grade 3 reactions; permanently discontinue for Grade 4 diarrhoea, Grade 4 ALT/AST (>20 × ULN), Grade 4 bilirubin (>10 × ULN), ALT or AST >3 × ULN with bilirubin >2 × ULN, or any other Grade 4 reaction. CYP2C8: if co-administration with a strong CYP2C8 inhibitor cannot be avoided, reduce the starting dose to 100 mg orally twice daily and resume the previous dose 3 elimination half-lives after the inhibitor is stopped. HEPATIC: no adjustment in mild or moderate impairment; for severe hepatic impairment (Child-Pugh C) a reduced starting dose of 200 mg orally twice daily is recommended. ELDERLY: no dose adjustment at ≥65 years; not investigated above 80 years. PAEDIATRIC: the safety and efficacy of TUKYSA in paediatric patients have not been established and no data are available. Note that eMC §4.5 was not captured in the fetched bundle; the US label indication set additionally includes HER2-positive RAS wild-type unresectable or metastatic colorectal cancer at the same 300 mg twice-daily dose in combination with trastuzumab.