Posology : מינונים

4.2     Posology and method of administration

Treatment with Rydapt should be initiated by a physician experienced in the use of anti-cancer therapies.

Dosage for AML

Usual dosage
The recommended dose of Rydapt is 50 mg twice daily (see Table 1.1).

Initiation of therapy

Rydapt is dosed on days 8 to 21 of induction and consolidation chemotherapy cycles.
Maintenance therapy

Thereafter, Rydapt is administered twice daily as single-agent maintenance therapy for 12 months.

Table 1.1 Dosage for AML
Induction                 Consolidation              Single-agent chemotherapy              chemotherapy               maintenance therapy (1 to 2 cycles, 21 days   (up to 4 cycles, 21 days   (12 cycles, 28 days per per cycle)                per cycle)                 cycle)
Use of midostaurin               On days 8 to 21,          On days 8 to 21,           On days 1 to 28, 50 mg twice daily         50 mg twice daily          50 mg twice daily Dose modification due to adverse effects/interactions

Recommendations for dose modifications of Rydapt in patients with AML are shown in Table 1.2.

Table 1.2 Rydapt dose interruption, reduction, and discontinuation – recommendations for patients with AML
Criteria                                                   Rydapt dosing During maintenance therapy: Grade 4                        Interrupt Rydapt until ANC ≥1.0 × 109/liter, then neutropenia (ANC <0.5 × 109/liter)                         resume Rydapt at 50 mg twice daily.
If neutropenia (ANC <1.0 × 109/liter) persists
>2 weeks and is suspected to be related to Rydapt,
discontinue Rydapt.
ANC: absolute neutrophil count


Dosing for advanced SM
Usual dosage

The recommended starting dose of Rydapt is 100 mg twice daily.

Treatment duration
Treatment should be continued as long as clinical benefit is observed or until unacceptable toxicity occurs.

Dose modification due to adverse effects/interactions

Recommendations for dose modifications of Rydapt in patients with advanced SM are shown in Table 2.



Table 2        Rydapt dose interruption, reduction, and discontinuation – recommendations for patients with advanced SM
Criteria                                                            Rydapt dosing 9
ANC <1.0 × 10 /liter in patients who did not have severe            Interrupt Rydapt until ANC ≥1.5 × 109/liter, then resume Rydapt at neutropenia at baseline.                                            50 mg twice daily. If well tolerated, gradually increase to 100 mg twice daily.
If ANC <1.0 × 109/liter recurs and is suspected to be related to
Rydapt, discontinue Rydapt.
Grade 3/4 nausea and/or vomiting despite optimal anti-emetic        Interrupt Rydapt for 3 days (6 doses), then resume Rydapt at 50 mg therapy                                                             per day and, if well tolerated, gradually increase dose to 100 mg twice daily
ANC: absolute neutrophil count
Common Terminology Criteria for Adverse Events (CTCAE) severity: grade 1 = mild symptoms; grade 2 = moderate symptoms; grade 3 = severe symptoms; grade 4 = life-threatening symptoms.


Special dosage instructions
Patients with hepatic impairment

No dose adjustment is required in patients with mild or moderate (Child-Pugh A or B) hepatic impairment. (see section 5.2). 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 section 5.2). However, there are insufficient efficacy data in patients with severe hepatic impairment to suggest a dose adjustment is required.

Patients with renal impairment

No dose adjustment is required in patients with mild or moderate renal impairment. Clinical experience in patients with severe renal impairment is limited. No data are available on patients with end-stage renal disease (see section 5.2).
Elderly patients
No dose adjustment is required in patients over 65 years of age (see section 5.2).

Children and adolescents

Rydapt is not indicated for children and adolescent under 18 years old.
Method of administration

Rydapt should be taken orally, twice daily at approximately 12-hour intervals. Rydapt should be taken with food to prevent nausea (see section 4.5 or 5.2)

Prophylactic anti-emetics should be administered in accordance with local medical practice as per patient tolerance.

Rydapt capsules should be swallowed whole with a glass of water. Rydapt capsules must not be opened, crushed or chewed.

If a dose is missed, the forgotten dose should not be taken and the patient should wait and take the next scheduled dose at the scheduled time.

If vomiting occurs during treatment, the patient should not take an additional dose before taking the next scheduled dose.