Rydapt Dosage/Direction for Use

Treatment with Rydapt should be initiated by a physician experienced in the use of anti-cancer therapies.
Before taking midostaurin, AML patients must have confirmation of FLT3 mutation (internal tandem duplication [ITD] or tyrosine kinase domain [TKD]) using a validated test.
Posology: Rydapt should be taken orally twice daily at approximately 12-hour intervals. The capsules should be taken with food (see Interactions and Pharmacology: Pharmacokinetics under Actions).
Prophylactic antiemetics should be administered in accordance with local medical practice as per patient tolerance.
AML: The recommended dose of Rydapt is 50 mg orally twice daily.
Rydapt is dosed on days 8-21 of induction and consolidation chemotherapy cycles, and then for patients in complete response every day as single agent maintenance therapy until relapse for up to 12 cycles of 28 days each (see Indications/Uses). In patients receiving a haematopoietic stem cell transplant (SCT), Rydapt should be discontinued 48 hours prior to the conditioning regimen for SCT.
Dose modifications in AML: Recommendations for dose modifications of Rydapt in patients with AML are provided in Table 5. (See Table 5.)

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ASM, SM-AHN and MCL: The recommended starting dose of Rydapt is 100 mg orally twice daily.
Treatment should be continued as long as clinical benefit is observed or until unacceptable toxicity occurs.
Dose modifications in ASM, SM-AHN and MCL: Recommendations for dose modifications of Rydapt in patients with ASM, SM-AHN and MCL are provided in Table 6. (See Table 6.)

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Missed doses: If a dose is missed, the patient should take the next dose at the scheduled time.
If vomiting occurs, the patient should not take an additional dose of Rydapt, but should take the next scheduled dose.
Special populations: Elderly (≥65 years): No dose adjustment is required in patients aged over 65 years (see Pharmacology: Pharmacokinetics under Actions). In patients aged ≥60 years, Rydapt should be used only in patients eligible to receive intensive induction chemotherapy with adequate performance status and without significant comorbidities.
Renal impairment: No dose adjustment is required for patients with mild or moderate renal impairment. Clinical experience in patients with severe renal impairment is limited and no data are available in patients with end-stage renal disease (see Precautions and Pharmacology: Pharmacokinetics under Actions).
Hepatic impairment: No dose adjustment is required in patients with mild or moderate (Child-Pugh A or B) hepatic impairment (see Pharmacology: Pharmacokinetics under Actions). Exposure to midostaurin and its active metabolite CGP62221 is substantially lower in patients with severe hepatic impairment than that in patients with normal hepatic function (see Pharmacology: Pharmacokinetics under Actions). However, there are insufficient efficacy data in patients with severe hepatic impairment to suggest a dose adjustment is required.
Acute promyelocytic leukaemia: Rydapt has not been studied in patients with acute promyelocytic leukaemia and therefore its use is not recommended in this patient population.
Paediatric population: Rydapt should not be used in combination with intensive paediatric AML combination chemotherapy regimens including anthracyclines, fludarabine and cytarabine because of the risk of prolonged haematological recovery (such as prolonged severe neutropenia and thrombocytopenia) (see Precautions and Pharmacology: Pharmacodynamics under Actions).
Method of administration: Rydapt is for oral use.
The capsules should be swallowed whole with a glass of water. They should not be opened, crushed or chewed to ensure proper dosing and avoid the unpleasant taste of the capsule content.