PT at 50 mg twice daily, and if tolerated, increase to 100 mg twice daily.
Discontinue if low platelet count persists for > 21 days and is suspected to be related to RYDAPT.
Hemoglobin less than 8 g/L attributed to RYDAPT in patients without MCL, or life-threatening anemia attributed to RYDAPT in patients with baseline hemoglobin value of 8 -10 g/L Interrupt RYDAPT until hemoglobin greater than or equal to 8 g/L, then resume RYDAPT at 50 mg twice daily, and if tolerated, increase to 100 mg twice daily.
Discontinue if low hemoglobin persists for > 21 days and is suspected to be related to RYDAPT.
Grade 3/4 nausea and/or vomiting despite optimal anti-emetic therapy Interrupt RYDAPT for 3 days (6 doses), then resume RYDAPT at 50 mg twice daily, and if tolerated, increase to 100 mg twice daily.
Other Grade 3/4 non-hematological toxicities Interrupt RYDAPT until event has resolved to ≤ Grade 2, then resume RYDAPT at 50 mg twice daily, and if tolerated, increase to 100 mg twice daily.
ANC: Absolute Neutrophil Count
CTCAE severity: Grade 1 = mild symptoms; 2 = moderate symptoms; 3 = severe symptoms; 4 = life-threatening symptoms.
2.4 Recommended Administration
Administer prophylactic anti-emetics before treatment with RYDAPT to reduce the risk of nausea and vomiting.
Administer RYDAPT orally with food, twice daily at approximately 12 hour intervals [see Clinical Pharmacology (12.3)]. Do not open or crush RYDAPT capsules.
If a dose of RYDAPT is missed or vomited, do not make up the dose; take the next dose at the usual scheduled time.
Consider interval assessments of QT by EKG if RYDAPT is taken concurrently with medications that can prolong the QT interval.
3 DOSAGE FORMS AND STRENGTHS
25 mg capsules: pale orange oblong soft capsule with red ink imprint ‘PKC NVR’.
4 CONTRAINDICATIONS
RYDAPT is contraindicated in patients with hypersensitivity to midostaurin or to any of the excipients [see Description (11)]. Hypersensitivity reactions have included anaphylactic shock, dyspnea, flushing, chest pain, and angioedema (e.g., swelling of the airways or tongue, with or without respiratory impairment) [see Adverse Reactions (6.1)].
5 WARNINGS AND PRECAUTIONS
5.1 Embryo-Fetal Toxicity
Based on its mechanism of action and findings from animal reproduction studies, RYDAPT may cause fetal harm when administered to pregnant women. In animal studies, midostaurin caused embryo-fetal toxicities, including late embryo-fetal death and reduced fetal birth weight, with delays in fetal growth at doses lower than the recommended human dose. Advise pregnant women of the potential risk to the fetus. Verify the pregnancy status of females of reproductive potential within 7 days prior to initiating RYDAPT therapy. Advise females of reproductive potential to use effective contraception during treatment with RYDAPT and for at least 4 months after the last dose. Advise males with female partners to use effective contraception during treatment with RYDAPT and for 4 months after the last dose [see Use in Specific Populations (8.1, 8.3), Clinical Pharmacology (12.1)].
5.2 Pulmonary Toxicity
Cases of interstitial lung disease and pneumonitis, some fatal, have occurred in patients treated with RYDAPT as monotherapy or with chemotherapy. Monitor patients for pulmonary symptoms. Discontinue RYDAPT in patients who experience signs or symptoms of interstitial lung disease or pneumonitis without an infectious eti |
