Midostaurin

What is midostaurin used for?

Midostaurin is a prescription medicine that is used to treat a type of leukemia. It is used to treat mastocytosis.

Description

Midostaurin is a kinase inhibitor for oral use. The molecular formula for midostaurin is C35H30N4O4. The molecular weight is 570.65 g/mol. The chemical name of midostaurin is Benzamide, N-[(9S,10R,11R,13R)-2,3,10,11,12,13-hexahydro-10-methoxy-9-methyl-1-oxo-9,13-epoxy-1H,9H-diindolo[1,2,3-gh:3′,2′,1′-lm]pyrrolo[3,4-j][1,7]benzodiazonin-11-yl]-N-methyl-. The chemical structure of midostaurin is shown below:

RYDAPT is supplied as a soft capsule containing 25 mg of midostaurin. The capsule contains 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.

Mechanism of Action

Midostaurin is a small molecule that inhibits multiple receptor tyrosine kinases. In vitro biochemical or cellular assays have shown that midostaurin or its major human active metabolites CGP62221 and CGP52421 inhibit the activity of wild type FLT3, FLT3 mutant kinases (ITD and TKD), KIT (wild type and D816V mutant), PDGFRα/β, as well as members of the serine/threonine kinase PKC (protein kinase C) family.

Midostaurin demonstrated the ability to inhibit FLT3 receptor signaling and cell proliferation, and it induced apoptosis in leukemic cells expressing ITD and TKD mutant FLT3 receptors or overexpressing wild type FLT3 and PDGF receptors. Midostaurin also demonstrated the ability to inhibit KIT signaling, cell proliferation and histamine release and induce apoptosis in mast cells.

Before taking midostaurin, tell your doctor:

• If you are allergic to midostaurin; any part of this medicine; or any other drugs, foods, or substances. Tell your doctor about the allergy and what signs you had.
• If you are taking any of these drugs: Carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, or St. John’s wort.
• If you are breast-feeding. Do not breast-feed while you take midostaurin or for 4 months after your last dose.

This is not a list of all drugs or health problems that interact with midostaurin.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take midostaurin with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

What are some things I need to know or do while I take midostaurin?

• Tell all of your health care providers that you take midostaurin. This includes your doctors, nurses, pharmacists, and dentists.
• If you drink grapefruit juice or eat grapefruit often, talk with your doctor.
• If you have high blood sugar (diabetes), talk with your doctor. This medicine may raise blood sugar.
• Check your blood sugar as you have been told by your doctor.
• Tell your doctor if you have signs of high blood sugar like confusion, feeling sleepy, more thirst, more hungry, passing urine more often, flushing, fast breathing, or breath that smells like fruit.
• You may have more chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu.
• You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Some people have had lung problems with midostaurin. Sometimes, this has been deadly. Call your doctor right away if you have signs of lung problems like shortness of breath or other trouble breathing, cough that is new or worse, or fever.
• Call your doctor right away if you have signs of a blood clot like chest pain or pressure; coughing up blood; shortness of breath; swelling, warmth, numbness, change of color, or pain in a leg or arm; or trouble speaking or swallowing.
• This medicine may affect fertility. Fertility problems may lead to not being able to get pregnant or father a child.
• This medicine may cause harm to an unborn baby. A pregnancy test will be done before you start midostaurin to show that you are NOT pregnant.
• Women must use birth control while taking midostaurin and for some time after the last dose. Ask your doctor how long to use birth control. If you get pregnant, call your doctor right away.
• Men with a partner who may get pregnant must use birth control while taking midostaurin and for some time after the last dose. Ask your doctor how long to use birth control. If your partner gets pregnant, call the doctor right away.

How is midostaurin best taken?

Use midostaurin as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take midostaurin with food.
• Swallow whole. Do not chew, open, or crush.
• Keep taking midostaurin as you have been told by your doctor or other health care provider, even if you feel well.
• Other drugs may be given before midostaurin to help avoid side effects.
• If you throw up after taking a dose, do not repeat the dose. Take your next dose at your normal time.

What do I do if I miss a dose?

• Skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

What are the side effects of midostaurin that I need to call my doctor about immediately?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
• Signs of skin infection like oozing, heat, swelling, redness, or pain.
• Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
• Signs of electrolyte problems like mood changes, confusion, muscle pain or weakness, a heartbeat that does not feel normal, seizures, not hungry, or very bad upset stomach or throwing up.
• Signs of high or low blood pressure like very bad headache or dizziness, passing out, or change in eyesight.
• Flushing.
• Chest pain.
• Pinpoint red spots on the skin.
• Sweating a lot.
• Shortness of breath, a big weight gain, or swelling in the arms or legs.
• A heartbeat that does not feel normal.
• Very bad dizziness or passing out.
• Not able to focus.
• Shakiness.
• Feeling very tired or weak.
• Any unexplained bruising or bleeding.
• Throwing up blood or throw up that looks like coffee grounds.
• Black, tarry, or bloody stools.

What are some other side effects of midostaurin?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Mouth irritation or mouth sores.
• Headache.
• Muscle or joint pain.
• Bone pain.
• Nosebleed.
• Signs of a common cold.
• Trouble sleeping.
• Dry skin.
• Weight gain.
• Feeling dizzy, tired, or weak.
• Stomach pain.
• Constipation, diarrhea, throwing up, and upset stomach are common with midostaurin. If these happen, talk with your doctor about ways to lower these side effects. Call your doctor right away if any of these effects bother you, do not go away, or get very bad.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-332-1088. You may also report side effects at https://www.fda.gov/medwatch.

If overdose is suspected:

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

How do I store and/or throw out midostaurin?

• Store in the original container at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.

Label

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