Midostaurin

Midostaurin is a prescription medication used for the treatment of acute myeloid leukemia and systemic mastocytosis.

• Midostaurin is available under the following different brand names: Rydapt

Common side effects of Midostaurin include:

• low blood cell counts,
• fever,
• bruising,
• nosebleeds,
• high blood sugar,
• infection around a needle injection,
• mouth sores,
• cold symptoms (stuffy nose, sneezing, sore throat),
• trouble breathing,
• nausea,
• vomiting,
• stomach pain,
• constipation,
• diarrhea,
• muscle or bone pain,
• headache,
• tiredness, and
• swelling in the hands, feet, or ankle

Serious side effects of Midostaurin include:

• hives,
• difficulty breathing,
• swelling of the face, lips, tongue, or throat,
• warmth,
• redness,
• tingly feeling,
• chest pain,
• pain or sores in or around the mouth,
• redness inside the mouth,
• sore throat,
• wheezing,
• dry cough,
• shortness of breath,
• bruising, swelling, warmth, redness, oozing, or bleeding around the needle,
• increased thirst,
• increased urination,
• dry mouth,
• fruity breath odor,
• fever,
• chills,
• tiredness,
• skin sores,
• easy bruising,
• unusual bleeding,
• pale skin,
• cold hands and feet, and
• lightheadedness

Rare side effects of Midostaurin include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Capsule

• 25 mg

Acute Myeloid Leukemia (AML)

Adult dosage

• 50 mg orally twice daily (every 12 hours) on Days 8-21 of each cycle of induction with cytarabine and daunorubicin and on Days 8-21 of each cycle of consolidation with high-dose cytarabine

Systemic Mastocytosis (SM)

Adult dosage

• 100 mg orally twice daily (every 12 hours) with food

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Midostaurin has severe interactions with the following drug:
  • lefamulin
• Midostaurin has serious interactions with at least 110 other drugs.
• Midostaurin has moderate interactions with at least 19 other drugs.
• Midostaurin has minor interactions with no other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• Hypersensitivity; reactions have included anaphylactic shock, dyspnea, flushing, chest pain, and angioedema (eg, swelling of the airways or tongue, with or without respiratory impairment)

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Midostaurin?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Midostaurin?”

Cautions

• Cases of interstitial lung disease and pneumonitis, some fatal, reported with monotherapy or in combination with chemotherapy; monitor for pulmonary symptoms; discontinue if signs or symptoms of interstitial lung disease or pneumonitis occur without an infectious etiology
• Prolonged severe neutropenia and thrombocytopenia in pediatric patients with AML when coadministered with strong CYP3A4 inhibitor azole antifungal
• Based on its mechanism of action and findings from animal reproduction studies, midostaurin may cause fetal harm when administered to pregnant women (see Pregnancy)

Drug interaction overview

• Primarily metabolized by CYP3A4
• Strong CYP3A4 inhibitors
  • Coadministration with strong CYP3A inhibitors may increase midostaurin concentrations and risk of toxicity Consider alternative therapies that do not strongly inhibit CYP3A activity
  • Alternatively, if coadministered, monitor for increased risk of adverse reactions, especially during the first week of treatment
• Strong CYP3A inducers
  • Coadministration with strong CYP3A inducers may decrease midostaurin concentrations and reduce the efficacy
• Avoid coadministration with strong CYP3A inducers
• CYP2B6 substrates
• Therapy may decrease the systemic exposure to sensitive CYP2B6 substrate; dose adjustments for coadministered CYP2B6 substrate may be necessary
• Substrates transporters
  • Coadministration of midostaurin may increase the exposure of a breast cancer resistance protein (BCRP) and organic anion transporter polypeptide (OATP)1B1 substrate; dose adjustments for the coadministered BCRP or OATP1B1 substrates may be necessary with midostaurin

Pregnancy and Lactation

• A pregnancy exposure registry monitors pregnancy outcomes in women exposed to therapy during pregnancy; Females who may have been exposed to RYDAPT during pregnancy directly or through a male partner receiving RYDAPT therapy should contact the Novartis Pharmaceuticals Corporation at 1-888-669-6682 and/or at https://report.novartis.com /
• Based on the mechanism of action and findings in animal reproduction studies, may cause fetal harm when administered to pregnant women
• Administration to pregnant rats and rabbits during organogenesis 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
• Pregnancy testing: Recommended for females of reproductive potential within 7 days before initiating midostaurin
• Infertility: Based on findings in animals, midostaurin may impair fertility in females and males of reproductive potential
• Contraception
  • Females: The drug may cause fetal harm when administered to a pregnant woman; advise females of reproductive potential to use effective contraception during treatment and for 4 months after the last dose
  • Males: Males with female sexual partners of reproductive potential should use effective contraception during treatment and for at least 4 months after the last dose
• Lactation
  • Unknown if distributed in human breast milk
  • Orally administered midostaurin and its active metabolites pass into the milk of lactating rats within 1 hr of a 30-mg/kg/day dose, with approximately 5 times more in the milk of lactating rats compared with plasma
  • Because of the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment and for at least 4 months after the last dose