Acalabrutinib [Specialist drug]

Treatment should be initiated and supervised by a physician experienced in the use of anticancer medicinal products. SOURCE SCOPE: section 4.1 (therapeutic indications) was not part of the fetched bundle, so the CLL/MCL indication wording above comes from this page rather than from the quoted text; the 100 mg twice daily figure is quoted verbatim from section 4.2, which applies to monotherapy and to all the combination regimens it lists. The fetched product is the FILM-COATED TABLET presentation - Calquence also exists as hard capsules, which differ on gastric acid interactions (see below). DURATION BY REGIMEN: monotherapy or with obinutuzumab - continue until disease progression or unacceptable toxicity. With venetoclax with or without obinutuzumab - continue until disease progression, unacceptable toxicity or completion of 14 cycles (each cycle is 28 days); Calquence from Day 1 of Cycle 1 for a total of 14 cycles, venetoclax from Day 1 of Cycle 3 for 12 cycles (starting at 20 mg and increasing weekly to 50 mg, 100 mg, 200 mg and finally 400 mg); if obinutuzumab is included, 100 mg on Day 1 of Cycle 2 then 900 mg on Day 1 or 2, 1000 mg on Days 8 and 15 of Cycle 2, then 1000 mg on Day 1 of Cycles 3 to 7 (6 cycles total). With bendamustine and rituximab - Calquence from Day 1 of Cycle 1 (28-day cycles) continuously until progression or unacceptable toxicity; bendamustine 90 mg/m2 on Days 1 and 2 of each cycle for 6 cycles; rituximab 375 mg/m2 on Day 1 of each cycle for 6 cycles, with maintenance rituximab 375 mg/m2 on Day 1 of every other cycle for a maximum of 12 additional doses (Cycle 8 to Cycle 30) in patients achieving a partial or complete response. DOSE MODIFICATION (Table 1, monotherapy / with obinutuzumab / with venetoclax +/- obinutuzumab) for Grade 3 thrombocytopenia with bleeding, Grade 4 thrombocytopenia, Grade 4 neutropenia lasting longer than 7 days, or Grade 3 or greater non-haematological toxicity: first and second occurrence - interrupt, then resume at 100 mg approximately every 12 hours once toxicity resolves to Grade 1 or baseline; third occurrence - interrupt, then resume at a reduced frequency of 100 mg once daily; fourth occurrence - discontinue. CYP3A INTERACTIONS (Table 3): strong CYP3A inhibitor - avoid concomitant use; if used short-term (such as anti-infectives for up to seven days), interrupt Calquence. Moderate or mild CYP3A inhibitor - no dose adjustment, but monitor closely for adverse reactions with moderate inhibitors. Strong CYP3A inducer - avoid concomitant use. GASTRIC ACID REDUCING AGENTS: acalabrutinib TABLETS can be co-administered with proton pump inhibitors, H2-receptor antagonists and antacids. MISSED DOSE: if a dose is missed by more than 3 hours, take the next dose at its regularly scheduled time; a double dose should not be taken. ELDERLY: no dose adjustment required in patients aged 65 years and over. RENAL IMPAIRMENT: no dose adjustment for mild or moderate impairment (creatinine clearance greater than 30 mL/min); maintain hydration and monitor serum creatinine periodically. Use in severe renal impairment (creatinine clearance below 30 mL/min) only if benefit outweighs risk, with close monitoring for toxicity; there are no data in severe impairment or on dialysis. HEPATIC IMPAIRMENT: no dose adjustment for mild or moderate impairment (Child-Pugh A or B, or total bilirubin 1.5-3 times ULN with any AST), but monitor moderate impairment closely for toxicity; not recommended in severe impairment (Child-Pugh C or total bilirubin above 3 times ULN with any AST). CARDIAC: patients with severe cardiovascular disease were excluded from the Calquence clinical studies. SURGERY/BLEEDING: consider the benefit-risk of withholding Calquence for at least 3 days pre- and post-surgery; warfarin or other vitamin K antagonists should not be administered concomitantly. PAEDIATRIC: safety and efficacy in children and adolescents aged 0 to 18 years have not been established (no data available).