Inrebic

Conditions Treated

Inrebic is used to treat adults with intermediate-2 or high-risk myelofibrosis. Myelofibrosis is a serious bone marrow disorder that disrupts the body's normal production of blood cells, often leading to extensive scarring in the bone marrow.

This medication is approved for several forms of the condition, including:

• Primary myelofibrosis: A condition that occurs on its own without a known prior bone marrow disease.
• Post-polycythemia vera myelofibrosis: A type that develops in people who previously had polycythemia vera (a condition with too many red blood cells).
• Post-essential thrombocythemia myelofibrosis: A type that develops in people who previously had essential thrombocythemia (a condition with too many platelets).

Treatment Goals

The primary goal of treatment with Inrebic is to reduce the size of an enlarged spleen (splenomegaly), which is a common complication of myelofibrosis. It is also used to help improve symptoms associated with the disease, such as:

• Night sweats
• Itching
• Bone or joint pain
• Feeling of fullness or discomfort under the left ribs
• Fatigue

Mechanism of Action

Inrebic belongs to a class of medications known as kinase inhibitors. It specifically targets enzymes called Janus Associated Kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3). These enzymes play a critical role in the signaling pathways that control the production and growth of blood cells.

In people with myelofibrosis, these signaling pathways are often overactive, sometimes due to a specific genetic mutation. This overactivity causes the bone marrow to produce too many blood cells and develop fibrous scar tissue. This process can lead to an enlarged spleen and other debilitating symptoms.

By binding to and inhibiting these JAK2 and FLT3 enzymes, Inrebic helps to:

• Interrupt the abnormal signals that drive the overproduction of blood cells.
• Reduce the inflammation and cell growth associated with the disease.
• Shrink the size of an enlarged spleen.
• Improve general symptoms related to myelofibrosis.

Common Side Effects

Many people taking Inrebic experience mild to moderate side effects. These may include:

• Diarrhea, nausea, or vomiting
• Constipation
• Headache
• Dizziness
• Muscle or joint pain
• Feeling unusually tired or weak

Serious Side Effects

Inrebic can cause severe complications that require immediate medical attention. Contact a healthcare provider right away if you experience:

• Brain problems (Encephalopathy): Symptoms such as confusion, memory loss, vision changes, or difficulty with balance and coordination. This may be related to low levels of vitamin B1 (thiamine).
• Low blood cell counts: Significant decreases in red blood cells (anemia) or platelets, which may lead to shortness of breath, pale skin, unusual bruising, or bleeding.
• Liver problems: Yellowing of the skin or the whites of the eyes (jaundice), dark-colored urine, or pain in the upper right stomach area.
• Kidney issues: Changes in how often you urinate or swelling in the feet and ankles.
• Heart and blood vessel risks: As a JAK inhibitor, this medication may increase the risk of serious heart-related events like heart attack or stroke, as well as blood clots in the legs or lungs.
• Increased cancer risk: There may be a higher risk of developing certain cancers, including lymphoma and skin cancer.

Serious Brain Damage (Encephalopathy)

Inrebic has a boxed warning because it can cause serious and potentially fatal brain damage, including a condition called Wernicke’s encephalopathy. This condition is often related to low levels of thiamine (vitamin B1). Healthcare providers typically check thiamine levels before starting treatment and periodically during therapy. If thiamine levels are low, they are usually corrected before the medication is started. Treatment is stopped immediately if encephalopathy is suspected.

Heart Events, Blood Clots, and Cancer

As a Janus kinase (JAK) inhibitor, Inrebic may increase the risk of several serious health conditions, particularly in people who are current or former smokers or have other cardiovascular risk factors:

• Heart-related events: There is an increased risk of major cardiovascular events, such as heart attack and stroke.
• Blood clots: Serious blood clots may form in the legs (deep vein thrombosis), lungs (pulmonary embolism), or arteries.
• Cancer: There is an increased risk of developing certain cancers, including lymphoma and lung cancer.
• Death: There is an increased risk of death from all causes for people taking certain JAK inhibitors.

Blood Cell Changes

Treatment with Inrebic can lead to low levels of red blood cells (anemia) and platelets (thrombocytopenia). Healthcare providers monitor blood counts regularly to manage these risks, which may require dose adjustments, interruptions, or blood transfusions.

Gastrointestinal Problems

Severe nausea, vomiting, and diarrhea are common side effects. These symptoms usually occur within the first few weeks of treatment. Healthcare providers may recommend anti-nausea or anti-diarrheal medications to manage these effects or may adjust the Inrebic dose if symptoms are severe.

Liver and Pancreas Monitoring

Inrebic can cause elevations in liver enzymes and pancreatic enzymes, such as amylase and lipase. Periodic blood tests are used to monitor liver and pancreas health during treatment to ensure these levels do not become dangerously high.

Pregnancy

Inrebic can cause fetal harm when administered to a pregnant woman. Animal studies have shown that the active ingredient, fedratinib, may lead to embryo-fetal toxicity. If you are pregnant or planning to become pregnant, discuss the potential risks and benefits with your healthcare provider.

Females who are able to become pregnant are typically advised to use effective birth control during treatment with Inrebic and for at least one month after the final dose. If you suspect you have become pregnant while taking this medication, notify your doctor immediately.

Breastfeeding

It is not known whether Inrebic passes into human breast milk or how it might affect a nursing infant. Because of the potential for serious adverse reactions, it is recommended that you do not breastfeed during treatment and for at least one month after your last dose. Consult your healthcare provider to discuss the safest way to feed your baby during this time.

Dosage Forms

Inrebic is supplied as a capsule intended for oral administration. It is not available in other forms such as liquids or injections.

Administration

• The medication is taken by mouth.
• Capsules should be swallowed whole and not opened, crushed, or chewed.
• The capsules may be taken with or without food.
• Taking the medication with a high-fat meal may help reduce the occurrence of nausea and vomiting.

FDA Approval and Indications

The U.S. Food and Drug Administration (FDA) approved Inrebic in August 2019. It is indicated for the treatment of adults with intermediate-2 or high-risk primary or secondary myelofibrosis. This includes myelofibrosis that occurs on its own (primary) or myelofibrosis that develops from other bone marrow disorders, such as polycythemia vera or essential thrombocythemia.

Boxed Warning

Inrebic carries a Boxed Warning, which is the FDA’s most serious warning for a medication. This warning is for serious and potentially fatal encephalopathy, including Wernicke’s encephalopathy. This condition involves brain damage that can occur if thiamine (vitamin B1) levels become too low.

To manage this risk, the FDA requires the following regulatory safeguards:

• Healthcare providers must test thiamine levels in all patients before starting Inrebic.
• Thiamine levels must be monitored periodically while the patient is taking the medication.
• If thiamine deficiency is detected, treatment should be delayed or stopped until levels are corrected.
• If a patient shows signs of brain toxicity or encephalopathy, the medication must be discontinued immediately.

JAK Inhibitor Class Warnings

Inrebic belongs to a class of drugs known as Janus kinase (JAK) inhibitors. The FDA has issued safety communications for this class of drugs regarding an increased risk of serious heart-related events, such as heart attack or stroke, as well as cancer, blood clots, and death. While these risks were primarily identified in studies of JAK inhibitors used for inflammatory conditions, the FDA requires warnings about these potential risks for the entire drug class.

Insurance and Pharmacy Factors

The out-of-pocket cost for Inrebic is largely determined by your health insurance plan. Most plans categorize this medication as a specialty drug, which may require a higher copayment or coinsurance. Because it is a specialty medication, it is often only available through specific specialty pharmacies rather than local retail stores.

Availability of Generics

Currently, there is no generic version of fedratinib (Inrebic) available. Brand-name medications typically cost more than generics because they are protected by patents that prevent other companies from making the same drug for a period of time.

Financial Support Programs

Patients who have difficulty affording Inrebic may be eligible for financial assistance. These options often include:

• Copay Assistance: Programs designed for patients with commercial insurance to reduce their monthly out-of-pocket expenses.
• Patient Assistance Programs: Support for individuals who do not have insurance or whose insurance does not cover the medication.

It is recommended to speak with your healthcare provider or pharmacist to explore available cost-saving options and to verify coverage with your insurance provider.