Rydapt

Acute Myeloid Leukemia (AML)

Rydapt is used to treat adults with newly diagnosed acute myeloid leukemia (AML) that has a specific genetic mutation called FLT3. For this condition, it is used in combination with standard chemotherapy drugs. Before starting treatment, a healthcare provider will perform a specific diagnostic test to confirm the presence of the FLT3 mutation.

Systemic Mastocytosis

Rydapt is also used to treat adults with advanced forms of systemic mastocytosis, a rare condition where the body produces too many mast cells that can accumulate in and damage organs. It is approved for the following specific types:

• Aggressive systemic mastocytosis (ASM): A form of the disease that causes organ dysfunction.
• Systemic mastocytosis with associated hematological neoplasm (SM-AHN): A condition where mastocytosis occurs alongside another blood or bone marrow disorder.
• Mast cell leukemia (MCL): A rare and aggressive form of leukemia involving mast cells.

Mechanism of Action

Rydapt is a type of targeted therapy known as a multi-kinase inhibitor. It works by interfering with the activity of specific enzymes called kinases, which act as switches for cell growth and survival. In certain cancers, these switches are stuck in the on position, causing cells to grow uncontrollably.

Targeting Specific Mutations

Rydapt is specifically designed to target and block several proteins, including:

• FLT3: In some cases of acute myeloid leukemia (AML), a mutation in the FLT3 gene causes leukemia cells to grow rapidly. Rydapt blocks this protein to help stop the spread of the cancer.
• KIT: In systemic mastocytosis, a mutation in the KIT protein leads to the overproduction of mast cells. By inhibiting KIT, Rydapt helps reduce the number of these cells in the body.

By blocking these signaling pathways, Rydapt helps slow or stop the progression of the disease and can lead to the destruction of cancer cells.

Common Side Effects

The most frequently reported side effects of Rydapt include:

• Nausea and vomiting
• Diarrhea or constipation
• Fatigue or weakness
• Headache
• Muscle, bone, or joint pain
• Mouth sores or redness
• Fever
• Upper respiratory tract infections
• Bruising or nosebleeds
• High blood sugar

Serious Side Effects

Rydapt can cause serious health issues that may require medical intervention. Contact a healthcare provider immediately if you experience:

• Lung problems: This medication may cause inflammation of the lungs (pneumonitis). Symptoms include new or worsening shortness of breath, cough, or chest pain.
• Low blood cell counts: Rydapt can significantly decrease the number of white blood cells, red blood cells, and platelets. This can lead to a higher risk of infection, anemia, and easy bruising or bleeding.
• Severe infections: Because it affects the immune system, Rydapt can increase the risk of developing serious or life-threatening infections.
• Heart rhythm changes: Some patients may develop a condition called QT prolongation, which affects the heart's electrical rhythm.
• Allergic reactions: Serious allergic reactions, including rash, swelling of the face or throat, and trouble breathing, have been reported.

Lung Inflammation

Rydapt may cause severe or life-threatening lung problems, including interstitial lung disease or pneumonitis. Symptoms to watch for include a new or worsening cough, chest pain, or difficulty breathing. Healthcare providers may monitor lung function and may interrupt or discontinue treatment if lung issues develop.

Embryo-Fetal Toxicity

This medication can cause harm to a developing fetus. The following precautions are typically recommended:

• Females of reproductive potential should have a pregnancy test before starting Rydapt.
• Effective contraception should be used by females during treatment and for at least 4 months after the last dose.
• Males with female partners of reproductive potential should use effective contraception during treatment and for at least 4 months after the last dose.

Breastfeeding

It is not known if Rydapt passes into breast milk. Due to the potential for serious adverse reactions in a breastfed child, breastfeeding is not recommended during treatment and for at least 4 months after the final dose.

Hypersensitivity

Serious allergic reactions have been reported. Signs of a reaction may include trouble breathing, flushing, chest pain, or swelling of the throat or tongue. Rydapt is contraindicated in patients with a known hypersensitivity to midostaurin or its ingredients.

Drug Interactions

Strong CYP3A4 inhibitors or inducers can significantly affect the concentration of Rydapt in the body. This may increase the risk of side effects or reduce the effectiveness of the medication.

Pregnancy

Rydapt can cause harm to a developing fetus if taken during pregnancy. It is important to discuss the potential risks and benefits with a healthcare provider before starting this medication.

For individuals who can become pregnant:

• A pregnancy test is typically performed before starting treatment to ensure the patient is not pregnant.
• Effective birth control should be used during treatment and for at least 4 months after the final dose.

For males with female partners who can become pregnant:

• Effective birth control should be used during treatment and for at least 4 months after the final dose to prevent pregnancy in a partner.

Breastfeeding

It is not known if Rydapt passes into human breast milk. Because of the risk of serious adverse reactions in a nursing infant, breastfeeding is not recommended during treatment and for at least 4 months after the last dose.

Fertility

This medication may affect fertility in both males and females, which could impact the ability to have children in the future. Patients should discuss any concerns regarding fertility and family planning with their healthcare team.

Dosage Forms

Rydapt is supplied as a soft capsule for oral administration. These capsules are typically provided in blister packs.

FDA Approval History

The U.S. Food and Drug Administration (FDA) approved Rydapt in April 2017. It was the first targeted therapy approved for use in combination with chemotherapy for patients with a specific genetic mutation in acute myeloid leukemia.

Approved Indications

Rydapt is currently approved for the following conditions:

• Acute Myeloid Leukemia (AML): For newly diagnosed adults whose cancer has a specific genetic marker called the FLT3 mutation. It is used in combination with standard induction and consolidation chemotherapy.
• Systemic Mastocytosis: For adults with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL).

Regulatory Requirements and Safety

For patients with AML, the FDA requires the use of an approved companion diagnostic test to confirm the presence of the FLT3 mutation before starting treatment. While Rydapt does not have a Boxed Warning, the FDA-approved labeling includes warnings regarding potential lung toxicity (interstitial lung disease) and risks to a developing fetus. There is currently no Risk Evaluation and Mitigation Strategy (REMS) program required for this medication.

Factors Influencing Cost

The price you pay for Rydapt depends on several variables, including:

• Insurance Coverage: Your out-of-pocket costs, such as copayments or coinsurance, are determined by your specific health insurance plan and its formulary.
• Treatment Plan: The total cost is affected by the dosage prescribed and the duration of treatment required for your specific condition.
• Specialty Pharmacy: Rydapt is a specialty medication and is typically dispensed through specialty pharmacies rather than standard retail pharmacies, which may affect pricing and delivery.

Financial Assistance

Because Rydapt is a high-cost specialty drug, there may be options available to help manage the expense. These often include:

• Manufacturer Support: The drug manufacturer may offer copay cards for patients with commercial insurance to help lower out-of-pocket expenses.
• Patient Assistance Programs: Programs may be available to provide the medication at a lower cost or for free to individuals who are uninsured or meet specific financial eligibility requirements.

Generic Availability

Rydapt is a brand-name medication containing the active ingredient midostaurin. Currently, there is no generic version of midostaurin available. Brand-name drugs typically cost more than generic alternatives because they are protected by patents that prevent other companies from manufacturing the same medication for a period of time.