Ibrutinib (Specialist drug)

PREVIOUSLY UNTREATED MCL (560 mg once daily): Part I is 6 cycles of 21 days — ibrutinib on days 1-19 in combination with R-CHOP at cycles 1, 3 and 5, and R-DHAP (interchangeable with R-DHAOx) without ibrutinib at cycles 2, 4 and 6; Part II is ibrutinib daily for 24 months, started after recovery of peripheral blood counts, with rituximab added per national treatment guidelines. RELAPSED OR REFRACTORY MCL: 560 mg once daily as a single agent until progression or intolerance. CLL WITH VENETOCLAX: ibrutinib 420 mg once daily as a single agent for 3 cycles (1 cycle is 28 days) followed by 12 cycles of ibrutinib plus venetoclax. When given with anti-CD20 therapy on the same day, administer ibrutinib first. CYP3A4 DOSE ADJUSTMENT: reduce to 280 mg once daily with moderate CYP3A4 inhibitors; reduce to 140 mg once daily, or withhold for up to 7 days, with strong CYP3A4 inhibitors. TOXICITY: withhold for any new onset or worsening Grade 2 cardiac failure, Grade 3 cardiac arrhythmias, Grade 3 or higher non-haematological toxicity, Grade 3 or greater neutropenia with infection or fever, or Grade 4 haematological toxicity. On recovery to Grade 1 or baseline, restart per the SPC tables — for Grade 3/4 non-haematological toxicity, Grade 3/4 neutropenia with infection or fever, or Grade 4 haematological toxicity: MCL 560 mg, then 420 mg, then 280 mg on successive occurrences and discontinue on the fourth; CLL/WM 420 mg, then 280 mg, then 140 mg and discontinue on the fourth. For Grade 2 cardiac failure: MCL restart at 420 mg then 280 mg, CLL/WM restart at 280 mg then 140 mg, discontinue on the third occurrence. For Grade 3 cardiac arrhythmias: MCL restart at 420 mg, CLL/WM restart at 280 mg, discontinue on the second occurrence. Discontinue for Grade 3 or 4 cardiac failure or Grade 4 cardiac arrhythmias. MISSED DOSE: take as soon as possible the same day and return to the normal schedule the next day; do not take extra tablets. HEPATIC: 280 mg daily in mild impairment (Child-Pugh A), 140 mg daily in moderate impairment (Child-Pugh B); not recommended in severe impairment (Child-Pugh C). ELDERLY: no specific dose adjustment at 65 years or older. SURGERY: hold for at least 3 to 7 days pre- and post-surgery depending on the type of surgery and bleeding risk. PAEDIATRIC: the UK SPC states ibrutinib is not recommended in children and adolescents aged 0 to 18 years as efficacy has not been established. US LABELLING ONLY (a different indication, not covered by the UK SPC extract) — chronic graft-versus-host disease: patients 12 years and older 420 mg orally once daily; patients 1 to less than 12 years 240 mg/m2 orally once daily up to a maximum of 420 mg, given as capsules/tablets or 70 mg/mL oral suspension per the label's body-surface-area table. This is a body-surface-area regimen, not a per-kg dose, and must be verified against a children's formulary and current UK labelling before any paediatric use.