Gilteritinib (Specialist drug)

INDICATION: relapsed or refractory AML — FLT3 mutation (ITD or TKD) must be confirmed with a validated test before starting. Treatment should be initiated and supervised by a physician experienced in anti-cancer therapies. RESPONSE MAY BE DELAYED: continuation at the prescribed dose for up to 6 months should be considered to allow time for a clinical response. DOSE ESCALATION: in the absence of a composite complete remission (CRc) after 4 weeks of treatment, the dose can be increased to 200 mg (five 40 mg tablets) once daily if tolerated or clinically warranted. DOSE REDUCTION: the daily dose can be reduced from 120 mg to 80 mg, or from 200 mg to 120 mg. MONITORING: blood chemistries including creatine phosphokinase before initiation, on day 15 and monthly; ECG before initiation, on days 8 and 15 of cycle 1 and before the start of each of the next three subsequent months; pregnancy test within seven days before starting in females of reproductive potential. DOSE MODIFICATIONS: differentiation syndrome — give corticosteroids and start haemodynamic monitoring; interrupt if severe signs/symptoms persist more than 48 hours after starting corticosteroids, and resume at the same dose when they improve to Grade 2 or lower. Posterior reversible encephalopathy syndrome — discontinue. QTcF greater than 500 msec — interrupt, resume at a reduced dose (80 mg or 120 mg) when QTcF returns to within 30 msec of baseline or 480 msec or less. QTcF increased by more than 30 msec on day 8 of cycle 1 — confirm with ECG on day 9 and, if confirmed, consider reduction to 80 mg. Pancreatitis or other Grade 3 or higher treatment-related toxicity — interrupt until resolved or improved to Grade 1, then resume at a reduced dose (80 mg or 120 mg). PLANNED HSCT: interrupt one week before the conditioning regimen; treatment can be resumed 30 days after HSCT if engraftment was successful, there was no Grade 2 or higher acute graft-versus-host disease, and the patient is in CRc. MISSED DOSE: give as soon as possible on the same day and return to the normal schedule the next day; if vomiting occurs after dosing do not take another dose, return to the normal schedule the following day. HEPATIC: no adjustment for mild (Child-Pugh A) or moderate (Child-Pugh B) impairment; not recommended in severe (Child-Pugh C) impairment. ELDERLY: no dose adjustment at 65 years or older. PAEDIATRIC: safety and efficacy in children below 18 years have not been established; no data are available, and because of in vitro binding to 5HT2B there is a potential impact on cardiac development in patients under 6 months of age.