Rydapt

Name: Rydapt

What is midostaurin?

Midostaurin is a cancer medicine that interferes with the growth and spread of cancer cells in the body.

Midostaurin is used together with other cancer medicines to treat acute myeloid leukemia.

Midostaurin is also used to treat certain rare blood disorders, including systemic mastocytosis with mast cell leukemia or other cancers affecting the blood, bone marrow, or lymphatic tissue.

Midostaurin may be used only if your tumor has a specific genetic marker, for which your doctor will test.

Midostaurin may also be used for purposes not listed in this medication guide.

What should I discuss with my healthcare provider before taking midostaurin?

You should not use midostaurin if you are allergic to it.

To make sure midostaurin is safe for you, tell your doctor if you have ever had:

  • lung disease or breathing problems.

Midostaurin can harm an unborn baby or cause birth defects, whether the mother or father is taking this medicine.

  • If you are a woman, do not use midostaurin if you are pregnant. You may need to have a negative pregnancy test before starting this treatment. Use effective birth control to prevent pregnancy while you are using this medicine and for at least 4 months after your last dose.

  • If you are a man, use effective birth control if your sexual partner is able to get pregnant. An unborn baby can be harmed if a man fathers the child while he is using midostaurin. Keep using birth control for at least 4 months after your last dose.

  • Tell your doctor right away if a pregnancy occurs while either the mother or the father is taking midostaurin.

You should not breast-feed while using this medicine and for at least 4 months after your last dose.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Introduction

Midostaurin is an antineoplastic agent.

Uses for Rydapt

Midostaurin has the following uses:

Midostaurin is a kinase inhibitor indicated for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) that is FLT3 mutation-positive as detected by an FDA-approved test, in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation.

Midostaurin is also indicated for the treatment of adult patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL).1

Midostaurin has the following limitations of use:

Midostaurin is not indicated as a single-agent induction therapy for the treatment of patients with AML.1

Rydapt Dosage and Administration

General

Midostaurin is available in the following dosage form(s) and strength(s):

Capsules: 25 mg.1

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

  • AML: 50 mg orally twice daily with food.1

  • ASM, SM-AHN, or MCL: 100 mg orally twice daily with food.1

Cautions for Rydapt

Contraindications

Hypersensitivity to midostaurin or any of the excipients.1

Warnings/Precautions

Embryofetal Toxicity

Based on its mechanism of action and findings from animal reproduction studies, midostaurin may cause fetal harm when administered to pregnant women. In animal studies, midostaurin caused embryofetal toxicities, including late embryofetal 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 midostaurin therapy. Advise females of reproductive potential to use effective contraception during treatment with midostaurin and for at least 4 months after the last dose. Advise males with female partners to use effective contraception during treatment with midostaurin and for at least 4 months after the last dose.1

Pulmonary Toxicity

Cases of interstitial lung disease and pneumonitis, some fatal, have occurred in patients treated with midostaurin as monotherapy or with chemotherapy. Monitor patients for pulmonary symptoms. Discontinue midostaurin in patients who experience signs or symptoms of interstitial lung disease or pneumonitis without an infectious etiology.1

Specific Populations

Pregnancy

Risk Summary: Based on mechanism of action and findings in animal reproduction studies, midostaurin may cause fetal harm when administered to a pregnant woman. There are no available data on midostaurin use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. In animal reproduction studies, oral administration of midostaurin to pregnant rats and rabbits during organogenesis caused embryofetal toxicities, including late embryofetal 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 a fetus.1

The background risk of major birth defects and miscarriage for the indicated population are unknown. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.1

Animal Data: When midostaurin was administered to female rats prior to mating and through the first week of pregnancy at a dose of 60 mg/kg/day (approximately 0.1 times the human exposure at the recommended dose based on AUC), there were increases in pre- and post-implantation loss, including total litter loss, resulting in a reduction in the number of live embryos.1

During organogenesis, midostaurin administered at oral doses greater than or equal to 3 mg/kg/day (approximately 0.004 times the human exposure at the recommended dose by AUC) to pregnant female rats caused late embryofetal death. Dilated lateral brain ventricles were observed in offspring of rats given doses greater than or equal to 3 mg/kg/day. Extra rib and reduced fetal birth weight with effects on fetal growth (severe renal pelvic cavitation and widened anterior fontanelle) were observed in the absence of maternal toxicity at the highest dose of 30 mg/kg/day (approximately 0.05 times the human exposure at the recommended dose by AUC). Midostaurin administered orally to pregnant rabbits during organogenesis led to maternal toxicity with spontaneous abortions and some delay in fetal growth (reduced fetal birth weight) at doses greater than or equal to 10 mg/kg/day (approximately 0.01 times the human exposure at the recommended dose by AUC).1

In an oral pre- and postnatal development study in the rat, adverse effects upon maternal performance included dams with signs of dystocia and a lower live litter size at 30 mg/kg/day (approximately 0.05 times the human exposure at the recommended dose by AUC). For the F1 offspring, lower body weights, accelerated complete eye opening and delayed auricular startle ontogeny were noted at 30 mg/kg/day.1

Lactation

There are no data on the presence of midostaurin or its active metabolites in human milk, the effect on the breastfed infant, or the effect on milk production. Orally administered midostaurin and its active metabolites pass into the milk of lactating rats within 1 hour of a 30 mg/kg/day dose, with approximately 5 times more in the milk of lactating rats compared to plasma.

Because of the potential for serious adverse reactions in breastfed infants from midostaurin, advise women not to breastfeed during treatment with midostaurin and for at least 4 months after the last dose.1

Females And Males of Reproductive Potential

Pregnancy testing is recommended for females of reproductive potential within seven days prior to initiating midostaurin.1

Midostaurin may cause fetal harm when administered to a pregnant woman Advise females of reproductive potential to use effective contraception during treatment with midostaurin and for at least 4 months after the last dose.1

Males with female sexual partners of reproductive potential should use effective contraception during midostaurin treatment and for at least 4 months after stopping treatment with midostaurin.1

Based on findings in animals, midostaurin may impair fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible.1

Pediatric Use

Safety and effectiveness of midostaurin have not been established in pediatric patients.1

Geriatric Use

Of the 142 patients with advanced SM in clinical studies of midostaurin, 64 (45%) were aged 65 and over, and 16 (11%) were aged 75 years and over. No overall differences in safety or response rate were observed between the subjects aged 65 and over compared with younger subjects. Greater sensitivity of older individuals cannot be ruled out.1

Clinical studies in AML with midostaurin did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.1

In general, administration for elderly patients should be cautious, based on patient’s eligibility for concomitant chemotherapy and reflecting the greater frequency of concomitant disease or other drug therapy.1

Common Adverse Effects

  • AML: The most common adverse reactions (≥20%) were febrile neutropenia, nausea, mucositis, vomiting, headache, petechiae, musculoskeletal pain, epistaxis, device-related infection, hyperglycemia, and upper respiratory tract infection.1

  • ASM, SM-AHN, or MCL: The most common adverse reactions (≥20%) were nausea, vomiting, diarrhea, edema, musculoskeletal pain, abdominal pain, fatigue, upper respiratory tract infection, constipation, pyrexia, headache, and dyspnea.1

Advice to Patients

Advise the patient to read the FDA-approved patient labeling (Patient Information).1

  • Pulmonary Adverse Reactions: Inform patients to seek medical attention for new cough, chest discomfort, or shortness of breath.1

  • Gastrointestinal Adverse Reactions: Inform patients that midostaurin can cause nausea, vomiting, and diarrhea. Advise patients to contact their healthcare provider if these symptoms occur or are persisting despite supportive medications.1

  • Embryofetal Toxicity: Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with midostaurin and for at least 4 months after the last dose. Advise females to inform their healthcare provider of a known or suspected pregnancy.1

    Advise male patients with female partners of reproductive potential to use effective contraception during treatment with midostaurin and for at least 4 months after the last dose.1

  • Lactation: Advise women not to breastfeed during treatment with midostaurin and for at least 4 months after the final dose.1

  • Infertility: Advise females and males of reproductive potential that midostaurin may impair fertility.1

Indications and Usage for Rydapt

Acute Myeloid Leukemia

Rydapt is indicated, in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation chemotherapy, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) who are FLT3 mutation-positive, as detected by a FDA approved test [see Dosage and Administration (2.1), Clinical Studies (14.1)].

Limitations of Use

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

Systemic Mastocytosis

Rydapt is indicated for the treatment of adult patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL).

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)].

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What should I avoid while taking Rydapt?

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

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