Glasdegib (Specialist drug)

PRESCRIBING: should only be prescribed by or under the supervision of a physician experienced in the use of anticancer medicinal products. No starting dose adjustment is required on the basis of age, race, gender or body weight. DOSE REDUCTION: if a reduction is necessary, reduce to 50 mg orally once daily. MISSED OR VOMITED DOSE: if a dose is vomited do not give a replacement — wait for the next scheduled dose; if a dose is missed take it as soon as remembered unless more than 10 hours have passed since the scheduled time, in which case skip it; never take 2 doses at once. MONITORING: complete blood counts, electrolytes, renal and hepatic function before initiation and at least once weekly for the first month; serum creatine kinase before starting and as clinically indicated thereafter (for example if muscle signs or symptoms are reported); ECGs before initiation, approximately one week after initiation, then once monthly for the next two months. DOSE MODIFICATIONS: QTc 480-500 msec — assess and supplement electrolytes, review QT-prolonging concomitant medicines, monitor ECGs at least weekly for 2 weeks after resolution to 480 msec or less. QTc greater than 500 msec — interrupt, then resume at 50 mg once daily when QTc returns to within 30 msec of baseline or 480 msec or less; re-escalation to 100 mg daily may be considered if an alternative aetiology is identified. QTc prolongation with life-threatening arrhythmia — discontinue permanently. CK elevations: Grade 1 continue at the same dose with weekly CK monitoring; Grade 2 without renal impairment interrupt and resume at the same dose on resolution (re-introduce at 50 mg daily if symptoms recur); Grade 3 or 4 without renal impairment interrupt and, if renal function is not impaired and CK resolves to baseline, consider resuming at 50 mg daily; Grade 2-4 with renal impairment interrupt, hydrate, monitor CK and creatinine weekly, and resume at 50 mg daily only if both return to baseline, otherwise discontinue permanently. HAEMATOLOGIC: discontinue glasdegib and low-dose cytarabine permanently if platelets are less than 10 x 10^9/L or the neutrophil count is less than 0.5 x 10^9/L for more than 42 days in the absence of disease. NON-HAEMATOLOGIC Grade 3 — interrupt glasdegib and/or low-dose cytarabine until symptoms improve to Grade 1 or baseline, then resume at the same dose or a reduced dose of 50 mg (low-dose cytarabine at the same dose or reduced to 15 mg or 10 mg); Grade 4 — withhold until improvement to Grade 1 or baseline, then resume at 50 mg or discontinue at the prescriber's discretion. MODERATE CYP3A4 INDUCERS: avoid; if unavoidable increase glasdegib from 100 mg to 200 mg orally once daily (or from 50 mg to 100 mg once daily), and resume the previous dose 7 days after the inducer is stopped. PAEDIATRIC: safety and efficacy in patients under 18 years have not been established and glasdegib should not be used in the paediatric population. US LABELLING (cross-check): 100 mg orally once daily on days 1 to 28 in combination with cytarabine 20 mg subcutaneously twice daily on days 1 to 10 of each 28-day cycle; treat for a minimum of 6 cycles in patients without unacceptable toxicity to allow time for clinical response.