Ingrezza

Conditions Treated

Ingrezza is primarily used to treat two specific conditions involving involuntary movements:

• Tardive Dyskinesia (TD): This is a movement disorder characterized by repetitive, uncontrollable muscle movements. These movements often affect the face, tongue, lips, or jaw (such as grimacing, smacking the lips, or rapid eye blinking) but can also involve the arms, legs, and torso. TD is typically caused by the long-term use of certain psychiatric medications, such as antipsychotics.
• Chorea Associated with Huntington’s Disease: Chorea refers to involuntary, irregular, and unpredictable movements that can look like dancing, jerking, or twitching. Huntington’s disease is an inherited condition that causes the progressive breakdown of nerve cells in the brain, and chorea is one of its common symptoms.

Healthcare providers prescribe this medication to help reduce the frequency and severity of these movements when they interfere with a person's daily activities or quality of life.

Mechanism of Action

Ingrezza is classified as a vesicular monoamine transporter 2 (VMAT2) inhibitor. It works by blocking a specific protein in the brain called VMAT2, which is responsible for moving certain chemicals into nerve cells.

Regulating Brain Chemicals

The primary chemical affected by this medication is dopamine. Dopamine is a natural substance that helps the brain control muscle movements. In people with certain movement disorders, there may be an imbalance or overactivity of dopamine in the parts of the brain that manage motor function.

By blocking the VMAT2 protein, Ingrezza reduces the amount of dopamine released in the brain. This reduction helps to:

• Control involuntary, repetitive body movements.
• Manage jerky or irregular motions associated with chorea.

Although the way the drug interacts with the VMAT2 protein is established, the precise mechanism by which it improves specific movement symptoms is not completely understood.

Common Side Effects

The most frequently reported side effect of Ingrezza is sleepiness or drowsiness. Other common side effects may include:

• Fatigue
• Dry mouth
• Constipation
• Blurred vision
• Headache
• Nausea or vomiting
• Joint pain
• Restlessness

Serious Side Effects

Some side effects require immediate medical attention. Seek help right away if you experience any of the following:

• Movement Problems: New or worsening tremors, stiffness, drooling, or difficulty with balance and walking (parkinsonism).
• Heart Rhythm Issues: A fast, pounding, or irregular heartbeat, or feeling lightheaded.
• Allergic Reactions: Severe rash, hives, or swelling of the face, tongue, or throat.
• Neuroleptic Malignant Syndrome: High fever, muscle rigidity, confusion, and increased sweating.
• Mental Health Changes: Sudden changes in mood, worsening depression, or suicidal thoughts.

Suicidal Thoughts and Behavior

Ingrezza carries a boxed warning regarding the risk of depression and suicidal thoughts or actions in patients with Huntington’s disease. Healthcare providers typically monitor patients for any new or worsening symptoms of depression, suicidal ideation, or unusual changes in mood or behavior.

Heart Rhythm Changes

This medication can cause a condition called QT prolongation, which affects the heart's electrical rhythm. This risk may be higher in individuals with pre-existing heart conditions or those taking other medications that also affect heart rhythm.

Somnolence and Drowsiness

Ingrezza can cause significant sleepiness or drowsiness, which may impair the ability to drive or operate heavy machinery. It is important to understand how the medication affects alertness before engaging in potentially dangerous activities.

Movement Disorders (Parkinsonism)

Some people may develop parkinsonism, a group of movement problems that include shaking, body stiffness, or trouble with balance and walking. These symptoms usually resolve after the medication is discontinued.

Allergic Reactions

Serious allergic reactions, including swelling of the face, lips, or throat (angioedema), have been reported. Immediate medical attention is necessary if signs of a severe reaction appear.

Pregnancy

There is currently limited data on the use of Ingrezza in pregnant women. It is not known whether the medication will cause harm to an unborn baby. If you are pregnant or planning to become pregnant, you should discuss your treatment options and any potential risks with your doctor.

Breastfeeding

It is unknown if Ingrezza passes into breast milk. Because of the risk of serious side effects in a nursing child, it is recommended that you do not breastfeed while taking this medication. If you discontinue the drug, you should wait at least five days after your last dose before breastfeeding.

Available Forms

Ingrezza is provided in two oral capsule formats:

• Oral Capsules: These are standard capsules intended to be swallowed whole.
• Sprinkle Capsules: These capsules are designed for patients who have difficulty swallowing. They can be swallowed whole or opened and the contents sprinkled onto soft food, such as applesauce or yogurt, before consumption.

FDA Approval History

The U.S. Food and Drug Administration (FDA) first approved Ingrezza in April 2017. It was the first drug specifically indicated for the treatment of adults with tardive dyskinesia, a movement disorder often caused by the long-term use of certain psychiatric medications. In August 2023, the FDA expanded its approval to include the treatment of chorea (involuntary movements) associated with Huntington’s disease.

Boxed Warning

Ingrezza includes a boxed warning, which is the most serious warning required by the FDA. This warning is specific to the treatment of chorea in patients with Huntington’s disease and highlights the following risks:

• Increased risk of depression
• Suicidal thoughts or behavior

Healthcare providers are advised to monitor patients for any new or worsening symptoms of depression, suicidal ideation, or unusual changes in behavior. The risks of these side effects must be balanced against the clinical need for the medication.

Regulatory Status

Ingrezza is a prescription-only medication and is not classified as a controlled substance. It is available as an oral capsule and is typically dispensed through specialty pharmacies.

Insurance and Out-of-Pocket Costs

The amount you pay for Ingrezza depends largely on your insurance plan. Most commercial insurance plans, Medicare Part D, and Medicaid provide some level of coverage, though the medication is often placed in a high-cost specialty tier. This may result in significant co-pays or coinsurance requirements.

Specialty Pharmacy Distribution

Ingrezza is generally not available at all retail pharmacies. It is typically distributed through specialty pharmacies that focus on complex medications. These pharmacies often provide additional support, such as help with insurance authorization and delivery coordination.

Financial Assistance Programs

Several options may be available to help reduce the cost of treatment:

• Co-pay Savings Cards: Patients with commercial insurance may be eligible for savings cards from the manufacturer that lower out-of-pocket expenses.
• Patient Assistance Programs: Non-profit organizations and the drug manufacturer may offer programs for patients who are uninsured or have limited financial resources.
• Start Programs: Some programs allow patients to receive a limited supply of the medication for free while waiting for insurance approval.