Vanflyta

Treatment with VANFLYTA should be initiated by a physician experienced in the use of anti-cancer therapies. Before taking VANFLYTA, AML patients must have confirmation of FLT3-ITD positive AML using a CE-marked in vitro diagnostic (IVD) medical device with the corresponding intended purpose.

If a CE-marked IVD is not available, confirmation of FLT3-ITD positive AML should be assessed by an alternate validated test. 4). 7 mg) once daily for two weeks in each cycle of induction. 5 mg once daily. 4). Single-agent maintenance therapy may be continued for up to 36 cycles.

For additional dosing information see Tables 1 to 3. 5 mg once daily for two weeks if QTcF is ≤ 450 ms. • After two weeks, if QTcF is ≤ 450 ms, the dose should be increased to 53 mg once daily. Duration (28-day cycles) Two weeks in each cycle Two weeks in each cycle Once daily with no break between cycles for up to 36 cycles.

a Patients can receive up to 2 cycles of induction. b Patients can receive up to 4 cycles of consolidation. c For 5 + 2 regimen as the second induction cycle, VANFLYTA will be started on day 6. Haematopoietic stem cell transplantation For patients who proceed to haematopoietic stem cell transplantation (HSCT), VANFLYTA should be stopped 7 days before the start of a conditioning regimen.

It may be resumed after completion of the transplant based on white blood cell count (WBC) and at the discretion of the treating physician for patients with sufficient haematologic recovery and with ≤ Grade 2 graft-versus-host disease (GVHD), not requiring the initiation of new systemic GVHD therapy within 21 days, following the dosing recommendations described above.

4). For recommended dose modifications due to adverse reactions, see Table 2. For dose adjustments due to adverse reactions and/or concomitant use with strong CYP3A inhibitors, see Table 3.

Table 2:

Recommended dose modifications for adverse reactions Adverse reaction Recommended action QTcF 450-480 ms (Grade 1) • Continue VANFLYTA dose. QTcF 481-500 ms (Grade 2) • Reduce VANFLYTA dose (see Table 3) without interruption. • Resume VANFLYTA at the previous dose in the next cycle if QTcF has decreased to < 450 ms.

Monitor the patient closely for QT prolongation for the first cycle at the increased dose. 4 Adverse reaction Recommended action QTcF ≥ 501 ms (Grade 3) • Interrupt VANFLYTA. • Resume VANFLYTA at a reduced dose (see Table 3) when QTcF returns to < 450 ms.

9%). 7%). 3%). 4%). 6%). 8%). 1%). Tabulated list of adverse reactions The safety of VANFLYTA was investigated in QuANTUM-First, a randomised, double-blind, placebo-controlled study in adult patients with newly diagnosed FLT3-ITD positive AML.

Adverse reactions are listed according to MedDRA System Organ Class (SOC). Within each SOC, the adverse reactions are ranked by frequency with the most frequent reactions first, using the following convention: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000), very rare (< 1/10 000), not known (cannot be estimated from the available data).

Within each frequency category, adverse reactions are presented in order of decreasing seriousness. 4

8). QT interval prolongation may increase the risk of ventricular arrhythmias or torsade de pointes. Patients with congenital long QT syndrome and/or a previous history of torsade de pointes were excluded from the quizartinib development programme.

VANFLYTA must not be used in patients with congenital long QT syndrome. VANFLYTA should be used with caution in patients who are at significant risk of developing QT interval prolongation. , history of second-or third-degree heart block (without pacemaker), myocardial infarction within 6 months, uncontrolled angina pectoris, uncontrolled hypertension, congestive heart failure, history of clinically relevant ventricular arrhythmias or torsade de pointes), and patients receiving concomitant medicinal products known to prolong the QT interval.

2). Do not start treatment with VANFLYTA if the QTcF interval is greater than 450 ms. 6 During induction and consolidation, ECGs should be performed prior to initiation and then once weekly during quizartinib treatment or more frequently as clinically indicated.

During maintenance, ECGs should be performed prior to initiation and then once weekly for the first month following dose initiation and escalation, and thereafter as clinically indicated. The maintenance starting dose should not be escalated if the QTcF interval is greater than 450 ms (see Table 1).

2). ECG monitoring of the QT interval should be performed more frequently in patients who are at significant risk of developing QT interval prolongation and torsade de pointes. Monitoring and correction of hypokalaemia and hypomagnesaemia should be performed prior to and during treatment with VANFLYTA.

More frequent monitoring of electrolytes and ECGs should be performed in patients who experience diarrhoea or vomiting. 5). 5). , older than 65 years), compared to younger patients especially in the early treatment period. Patients older than 65 years of age should be closely monitored for the occurrence of severe infections during induction.

1. 4). 6).