Source: European Medicines Agency (EU) Revision Year: 2023 Publisher: Daiichi Sankyo Europe GmbH, Zielstattstrasse 48, 81379 Munich, Germany
VANFLYTA is indicated in combination with standard cytarabine and anthracycline induction and standard cytarabine consolidation chemotherapy, followed by VANFLYTA single-agent maintenance therapy for adult patients with newly diagnosed acute myeloid leukaemia (AML) that is FLT3-ITD positive.
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.
ECGs should be performed, and electrolyte abnormalities should be corrected prior to initiation of treatment (see section 4.4).
VANFLYTA should be administered in combination with standard chemotherapy at a dose of 35.4 mg (2 × 17.7 mg) once daily for two weeks in each cycle of induction. For patients who achieve complete remission (CR) or complete remission with incomplete haematologic recovery (CRi), VANFLYTA should be administered at 35.4 mg once daily for two weeks in each cycle of consolidation chemotherapy followed by VANFLYTA single-agent maintenance therapy initiated at 26.5 mg once daily. After two weeks the maintenance dose should be increased to 53 mg (2 × 26.5 mg) once daily if the QT interval corrected by Fridericia’s formula (QTcF) is ≤450 ms (see Table 2 and section 4.4). Single-agent maintenance therapy may be continued for up to 36 cycles.
For additional dosing information see Tables 1 to 3.
Table 1. Dose regimen:
| VANFLYTA initiation | Inductiona | Consolidationb | Maintenance |
|---|---|---|---|
| Starting on day 8 (For 7 + 3 regimen)c | Starting on day 6 | First day of maintenance therapy | |
| Dose | 35.4 mg once daily | 35.4 mg once daily | • Starting dose of 26.5 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.
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.
VANFLYTA should be initiated only if QTcF is ≤450 ms (see section 4.4).
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. |
| QTcF ≥501 ms (Grade 3) | • Interrupt VANFLYTA. • Resume VANFLYTA at a reduced dose (see Table 3) when QTcF returns to <450 ms. • Do not escalate to 53 mg once daily during maintenance if QTcF >500 ms was observed during induction and/or consolidation, and it is suspected to be associated with VANFLYTA. Maintain the 26.5 mg once daily dose. |
| Recurrent QTcF ≥501 ms (Grade 3) | • Permanently discontinue VANFLYTA if QTcF >500 ms recurs despite appropriate dose reduction and correction/elimination of other risk factors (e.g., serum electrolyte abnormalities, concomitant QT prolonging medicinal products). |
| Torsade de pointes; polymorphic ventricular tachycardia; signs/symptoms of life- threatening arrhythmia (Grade 4) | • Permanently discontinue VANFLYTA. |
| Grade 3 or 4 non- haematologic adverse reactions | • Interrupt VANFLYTA. • Resume treatment at the previous dose if adverse reaction improves to ≤ Grade 1. • Resume treatment at a reduced dose (see Table 3) if adverse reaction improves to < Grade 3. • Permanently discontinue if Grade 3 or 4 adverse reaction persists beyond 28 days and is suspected to be associated with VANFLYTA. |
| Persistent Grade 4 neutropenia or thrombocytopenia without active bone marrow disease | • Reduce the dose (see Table 3). |
Grades are in accordance with National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 (NCI CTCAE v4.03).
Table 3. Dose adjustments by phase for adverse reactions and/or concomitant use with strong CYP3A inhibitors during treatment with VANFLYTA:
| Phase of treatment | Full dose | Dose Reductions | ||
|---|---|---|---|---|
| Adverse reaction | Concomitant strong CYP3A inhibitors | Adverse reaction and concomitant strong CYP3A inhibitors | ||
| Induction or Consolidation | 35.4 mg | 26.5 mg | 17.7 mg | Interrupt |
| Maintenance (first two weeks) | 26.5 mg | Interrupt | 17.7 mg | Interrupt |
| Maintenance (after two weeks) | 53 mg | 35.4 mg | 26.5 mg | 17.7 mg |
If a dose of VANFLYTA is missed or not taken at the usual time, the patient should take the dose as soon as possible on the same day and return to the usual schedule the following day. The patient should not take two doses on the same day.
If the patient vomits after taking VANFLYTA, the patient should not take an additional dose that day but take the next dose the following day at the usual time.
No dose adjustment is required in the elderly.
No dose adjustment is recommended for patients with mild or moderate hepatic impairment. VANFLYTA is not recommended for use in patients with severe hepatic impairment (Child-Pugh Class C), as safety and efficacy have not been established in this population.
No dose adjustment is recommended for patients with mild or moderate renal impairment.
VANFLYTA is not recommended for use in patients with severe renal impairment (CLcr <30 mL/min, estimated by Cockcroft-Gault), as safety and efficacy have not been established in this population.
The safety and efficacy of VANFLYTA in children and adolescents less than 18 years of age have not been established (see section 5.1). No data are available.
VANFLYTA is for oral use.
The tablets should be taken at approximately the same time each day with or without food.
There is no known antidote for overdoses of VANFLYTA. For a substantial overdose, supportive measures should be provided as necessary, with interruption of treatment, evaluation of haematology and ECG monitoring as well as attention to serum electrolytes and concomitant medicinal products that may predispose patients to QT interval prolongation and/or torsade de pointes. Patients should be managed with symptomatic and supportive care (see sections 4.2 and 4.4).
3 years.
This medicinal product does not require any special storage conditions.
Aluminium/aluminium perforated unit dose blisters.
VANFLYTA 17.7 mg film-coated tablets: Cartons containing 14 × 1 or 28 × 1 film-coated tablets.
VANFLYTA 26.5 mg film-coated tablets: Cartons containing 14 × 1, 28 × 1 or 56 × 1 film-coated tablets.
Not all pack sizes may be marketed.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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