Pirtobrutinib (Specialist drug)

PRESCRIBING: therapy should be initiated and supervised by physicians experienced in the use of anticancer therapies. DOSE INTERRUPTION: dosing should be interrupted until recovery to Grade 1 or baseline for Grade 3 neutropenia with fever and/or infection, Grade 4 neutropenia lasting 7 days or more, Grade 3 thrombocytopenia with bleeding, Grade 4 thrombocytopenia, or Grade 3 or 4 non-haematologic toxicity. Asymptomatic lymphocytosis is not regarded as an adverse reaction and patients experiencing it should continue treatment. In clinical studies adverse events in a limited number of patients were managed by dose reduction. MISSED DOSE: if more than 12 hours have passed after a missed dose, take the next dose at its scheduled time; an additional dose should not be taken. If vomiting occurs, do not take an additional dose but continue with the next scheduled dose. ELDERLY: no dose adjustment required based on age. HEPATIC IMPAIRMENT: no dose adjustment required for mild, moderate or severe hepatic impairment. PAEDIATRIC: safety and efficacy in children and adolescents under 18 years have not been established and no data are available. SURGERY: the benefit-risk of withholding pirtobrutinib for 3 to 5 days pre- and post-surgery should be considered, depending on the type of surgery and risk of bleeding. US LABELLING DIFFERENCES (from the openFDA provider in the same bundle — for cross-check, not applied to the UK dose above): the US label gives a stepwise dose reduction ladder of 200 mg then 100 mg then 50 mg once daily with discontinuation at the fourth occurrence; recommends reducing the dose to 100 mg once daily in severe renal impairment (eGFR 15-29 mL/min), which conflicts with the UK SPC statement that no adjustment is required in severe renal impairment; recommends reducing the dose by 50 mg if a strong CYP3A inhibitor cannot be avoided; and recommends increasing the dose to 300 mg (from 200 mg) if a moderate CYP3A inducer is unavoidable. SOURCE LIMITS: eMC §4.5 was not fetched and §4.4/§4.8 were truncated — the interactions listed in this draft come from section 7 of the US prescribing information contained in the same bundle and must be checked against the UK SPC §4.5.