Treatment should be initiated and supervised by a physician experienced in the use of anti-cancer medicinal products. Before taking Voranigo, patients must have confirmation of an isocitrate dehydrogenase-1 (IDH1) R132 or isocitrate dehydrogenase-2 (IDH2) R172 mutation using an appropriate diagnostic test.
The presence of an IDH1 R132 or IDH2 R172 mutation should be asessed by a CE-marked in vitro diagnostic (IVD) with the corresponding intended purpose. If the CE-marked IVD is not available, IDH1 R132 or IDH2 R172 mutation should be assessed by an alternative validated test.
Posology The recommended dose of Voranigo in adults and adolescents 12 years of age and older is 40 mg once daily for patients weighing at least 40 kg. No dose recommendation can be made in patients weighing less than 40 kg because of the lack of clinical data in this population.
Treatment should be continued as long as clinical benefit is observed or until treatment is no longer tolerated by the patient. Missed or delayed doses If a dose is missed or not taken at the usual time, it should be taken as soon as possible within 6 hours after the missed dose.
The next dose should be taken at the regularly scheduled time. If a dose is missed by more than 6 hours, it should be skipped and the next dose should be taken at the regularly scheduled time. If a dose is vomited, replacement tablets should not be taken.
The tablets should be taken as usual the following day. Precautions to be taken prior to administration and monitoring Complete blood counts and blood chemistries, including liver enzymes, should be assessed prior to starting treatment, every 2 weeks during the first 2 months and then once monthly for the first 2 years of treatment, and as clinically indicated thereafter.
4). Dose modifications for adverse reactions Dose interruption or dose reduction may be required based on individual safety and tolerability. The recommended dose reduction levels are provided in Table 1. The recommended Voranigo dose modifications and management for adverse reactions are provided in Table 2.
4) Grade 1 ALT or AST increase >ULN to 3 x ULN without concurrent total bilirubin >2 x ULN Continue Voranigo at current dose. Monitor liver enzymes weekly until recovery to <Grade 1. Grade 2 ALT or AST >3 to 5 x ULN without concurrent total bilirubin >2 x ULN First occurrence: Withhold Voranigo and monitor liver enzymes twice per week until recovery to ≤Grade 1 or baseline.
• Recovery in ≤28 days, resume Voranigo at the same dose. • Recovery in >28 days, resume Voranigo at reduced dose (see Table 1).
Recurrence:
Withhold Voranigo and monitor liver enzymes twice per week until recovery to ≤Grade 1 or baseline, and resume Voranigo at reduced dose (see Table 1). Grade 3 ALT or AST >5 to 20 x ULN without concurrent total bilirubin >2 x ULN First occurrence: Withhold Voranigo and monitor liver enzymes twice per week until recovery to ≤Grade 1 or baseline.
• Recovery in ≤28 days, resume Voranigo at reduced dose (see Table 1). • If not recovered in ≤28 days, permanently discontinue Voranigo.
Recurrence:
Permanently discontinue Voranigo and monitor liver enzymes twice per week until recovery to ≤Grade 1 or baseline. b Permanently discontinue Voranigo and monitor liver enzymes twice per week until recovery to ≤Grade 1 or baseline. Grade 4 Any ALT or AST >20 x ULN Permanently discontinue Voranigo and monitor liver enzymes twice per week until recovery to ≤Grade 1 or baseline.
Other adverse reactions Grade 3 First occurrence:
Withhold Voranigo until recovery to ≤Grade 1 or baseline. • Resume Voranigo at reduced dose (see Table 1).
Recurrence:
Permanently discontinue Voranigo. Grade 4 Permanently discontinue Voranigo. 0. b If an alternative aetiology is identified, consider resuming Voranigo at reduced dose (see Table 1) following resolution to Grade 1 or baseline. 2). 73 m2).
73 m2 or renal impairment requiring dialysis. 2). Hepatic impairment No starting dose adjustment is recommended for patients with mild or moderate (Child-Pugh class A or B) hepatic impairment. The pharmacokinetics of vorasidenib and AGI-69460 have not been studied in patients with severe hepatic impairment (Child-Pugh class C).
Vorasidenib should be used with caution in patients with severe hepatic impairment and this patient population should be closely monitored. 2). 1). Method of administration Voranigo is for oral […]