Midostaurin

What is Midostaurin?

• Midostaurin (Rydapt) is a kinase inhibitor used for the treatment of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and advanced systemic mastocytosis.

Midostaurin skeletal

Midostaurin molecule ball

Midostaurin molecule spacefill

What are the uses of this medicine?

Midostaurin (Rydapt) is used to treat adults:

• newly diagnosed with a certain type of acute myeloid leukemia (AML), in combination with certain chemotherapy medicines
• Your healthcare provider will perform a test to make sure Rydapt is right for you.
• with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL).

Limitations of Use:

• Rydapt is not indicated as a single-agent induction therapy for the treatment of patients with AML.

How does this medicine work?

• Midostaurin (mye" doe staw' rin) is a potent small molecule multi-kinase inhibitor with specific activity against FLT3 (FMS-like tyrosine kinase 3), a tyrosine kinase receptor that is mutated in to up one-third of patients with acute myeloid leukemia (AML).
• The mutated FLT3 activates an intracellular signaling cascade of RAS-MEK-PI3K-AKT-STAT-5, promoting unregulated cell growth and proliferation. Midostaurin also has activity against other kinases including Kit, platelet derived growth factor receptor, vascular endothelial growth factor receptor 2 and members of the protein kinase C family.
• Midostaurin has been found to induce objective responses in a proportion of patients with refractory AML with detectable FLT3 mutations and in patients with advanced systemic mastocytosis.

Who Should Not Use this medicine ?

This medicine cannot be used in patients who:

• are allergic to midostaurin or any of the ingredients in Rydapt.

What drug interactions can this medicine cause?

Tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following:

• boceprevir (no longer available in the U.S.; Victrelis)
• carbamazepine (Carbatrol, Equetro, Tegretol, others)
• clarithromycin (Biaxin, in Prevpac); diltiazem (Cardizem, Cartia, Tiazac, others)
• enzalutamide (Xtandi)
• idelalisib (Zydelig)
• itraconazole (Onmel, Sporanox)
• ketoconazole (Nizoral)
• medications used to treat human immunodeficiency virus (HIV) such as cobicistat (Tybost, in Evotaz, in Genvoya, in Prezcobix, in Stribild), elvitegravir (Vitekta), indinavir (Crixivan), nelfinavir (Viracept), ritonavir (Norvir, in Kaletra, in Technivie, in Viekira), saquinavir (Invirase) and tipranavir (Aptivus)
• mitotane (Lysodren)
• nefazodone
• phenytoin (Dilantin, Phenytek)
• posaconazole (Noxafil)
• rifampin (Rifadin, Rimactane, in Rifamate, in Rifater)
• troleandomycin (not available in the U.S.)
• voriconazole (Vfend)
• Tell your doctor what herbal products you are taking, especially St. John's wort.

Is this medicine FDA approved?

• Midostaurin received accelerated approval for these indication in the United States in 2017.

How should this medicine be used?

• Select patients for the treatment of AML with Rydapt based on the presence of FLT3 mutation positivity.

Recommended dosage: Recommended Dosage in Acute Myeloid Leukemia:

• The recommended dose of Rydapt for patients with AML is 50 mg orally twice daily with food.

Aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL):

• The recommended dose of Rydapt is 100 mg orally twice daily with food.

Administration:

• Take Rydapt 2 times a day (about every 12 hours apart).
• Take Rydapt with food.
• Do not open or crush Rydapt capsules.
• If you miss a dose of Rydapt, take your next dose at your scheduled time. Do not take an extra dose to make up for a missed dose.
• If you vomit after taking a dose of Rydapt, do not take an extra dose. Take your next dose at your scheduled time.
• Your healthcare provider will prescribe medicines to help prevent the nausea and vomiting during treatment with Rydapt.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Capsules: 25 mg

This medicine is available in fallowing brand namesː

• Rydapt

What side effects can this medication cause?

The most common side effects of Rydapt in people with AML include:

• low white blood cell counts with fever (febrile neutropenia)
• nausea
• redness, pain, or ulcers on the inside your mouth (mucositis)
• vomiting
• headache
• bruising
• muscle or bone pain
• nose bleeds
• device-related infection
• high blood sugar levels (hyperglycemia)
• upper respiratory tract infection
• abnormal electrocardiogram (QT prolongation)

The most common side effects of Rydapt in people with ASM, SM-AHN, or MCL include:

• nausea
• vomiting
• diarrhea
• swelling in your hands, feet, or ankles
• muscle or bone pain
• stomach-area pain
• tiredness
• upper respiratory tract infection
• constipation
• fever
• headache
• trouble breathing

Rydapt may cause serious side effects, including:

• Lung problems

What special precautions should I follow?

• Based on its mechanism of action and findings from animal reproduction studies, Rydapt may cause fetal harm when administered to pregnant women. Advise females of reproductive potential to use effective contraception during treatment with Rydapt and for 4 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with Rydapt and for 4 months after the last dose.
• 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.
• Inform patients that Rydapt can cause nausea, vomiting, and diarrhea. Advise patients to contact their healthcare provider if these symptoms occur or are persisting despite supportive medications.
• Advise women not to breastfeed during treatment with Rydapt and for 4 months after the last dose.
• Advise females and males of reproductive potential that Rydapt may impair fertility.

What to do in case of emergency/overdose?

• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.

Can this medicine be used in pregnancy?

• Based on mechanism of action and findings in animal reproduction studies, Rydapt may cause fetal harm when administered to a pregnant woman.
• Advise pregnant women of the potential risk to a fetus.
• There is a pregnancy registry that monitors the health of females and their babies exposed to Rydapt during pregnancy. Females who have taken Rydapt during pregnancy or have been exposed to Rydapt during pregnancy through a male partner taking Rydapt should contact Novartis Pharmaceuticals Corporation at 1-888-669-6682.

Can this medicine be used in children?

• Safety and effectiveness of Rydapt have not been established in pediatric patients.

What are the active and inactive ingredients in this medicine?

• Active ingredient: midostaurin
• Inactive ingredients: carmine, corn oil mono-di-triglycerides, dehydrated alcohol, ferric oxide red, ferric oxide yellow, gelatin, glycerin 85%, hypromellose 2910, polyethylene glycol 400, polyoxyl 40 hydrogenated castor oil, propylene glycol, purified water, titanium dioxide, and vitamin E.

Who manufactures and distributes this medicine?

Distributed by:

• Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, New Jersey

What should I know about storage and disposal of this medication?

• Store Rydapt at room temperature at 68°F to 77°F (20°C to 25°C).
• Keep Rydapt in the original container to protect from moisture.

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• Dailymed label info on Midostaurin
• FDA Midostaurin

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