Ingrezza

Ingrezza (valbenazine) is a prescription medication used to treat tardive dyskinesia (TD) and chorea associated with Huntington's disease. These movement disorders cause involuntary, repetitive, or sudden body movements that can affect the face, mouth, arms, or legs.

Ingrezza helps reduce symptoms of tardive dyskinesia and chorea by regulating dopamine, a brain chemical involved in motor control.

Ingrezza is a once-a-day capsule that can be swallowed whole, or the Ingrezza Sprinkle capsule can be opened and sprinkled on soft food. Ingrezza capsules and sprinkle capsules can be taken with or without food.

Ingrezza is a VMAT2 inhibitor that works by blocking the vesicular monoamine transporter 2 (VMAT2) protein in nerve cells. VMAT2 controls how much dopamine is stored and released in the brain.

In tardive dyskinesia and Huntington’s chorea, excess or overly sensitive dopamine signaling contributes to uncontrolled movements. Ingrezza lowers the amount of dopamine available for release to help calm overactive movement signals and decrease involuntary movements.

Ingrezza controls the symptoms of movement disorders but does not cure the underlying movement disorders.

Ingrezza has been shown to significantly reduce involuntary movements in adults with tardive dyskinesia and chorea associated with Huntington’s disease, in Phase 3 clinical trials.

In the KINECT 3 trial (NCT02274558) for tardive dyskinesia, 40% of patients treated with Ingrezza achieved at least a 50% reduction in abnormal involuntary movements, as measured by the Abnormal Involuntary Movement Scale (AIMS), compared with 4.7% of placebo-treated patients.

For Huntington’s disease-related chorea, the KINECT-HD trial (NCT04102579) and supporting data from KINECT-HD2 (NCT04400331) demonstrated that patients taking Ingrezza had statistically significant improvements in Total Maximal Chorea (TMC) scores, indicating fewer and less severe involuntary movements.

Tardive dyskinesia (TD) and chorea both involve uncontrolled body movements, but they have different underlying causes.

Tardive dyskinesia is a nervous system disorder that causes repetitive, uncontrolled muscle movements, usually in the face (chewing, lip smacking, frowning, tongue movement, blinking, or eye movement). Tardive dyskinesia is often caused by long-term treatment with certain psychiatric medications.

Chorea is a movement disorder that results in sudden involuntary movements. Chorea can be caused by Huntington's disease (an inherited disease that causes the progressive breakdown of nerve cells in the brain).

The usual dose of Ingrezza is once a day, with or without food.

Ingrezza capsules are swallowed whole with a glass of water.

Ingrezza Sprinkle capsules may be opened and sprinkled over soft food (do not use milk or drinking water) and may be swallowed whole with water. Do not crush or chew.

Do not stop taking this medicine without first asking your doctor.

Take this medicine exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose. Use the medicine exactly as directed.

Your heart function may need to be checked using an electrocardiograph or ECG (sometimes called an EKG).

Ingrezza and Ingrezza sprinkle have a boxed warning for depression and suicidal ideation and behavior in patients with Huntington’s disease. A boxed warning is the strongest safety related warning issued by the FDA.

Before taking this medicine, tell your healthcare provider if you have Huntington’s disease and feel depressed, especially if your depression is not being treated or is not well controlled, or if you have any suicidal thoughts.Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings. This is especially important when this medicine is started and when the dose is changed.

Other Warnings

Ingrezza and Ingrezza sprinkle may cause other serious problems, including:

• Hypersensitivity reactions, including angioedema. Treatment should be discontinued if this occurs.
• Sleepiness and sedation, which may impair a patient’s ability to drive or operate hazardous machinery.
• QT prolongation: An increase in the QT interval may occur. Use should be avoided in patients with congenital long QT syndrome or arrhythmias associated with a prolonged QT interval.
• Neuroleptic Malignant Syndrome (NMS) may occur. Treatment should be discontinued if this syndrome is observed.
• Parkinsonism: Some patients have reported Parkinson-like symptoms, including severe cases, during the postmarketing period. The dose should be reduced or treatment discontinued if clinically significant Parkinson-like signs or symptoms develop.

You should not use this medicine if you are allergic to valbenazine or any ingredients contained in this medicine.

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

emotional or mental problems (such as depression, nervousness, anxiety, anger, agitation, psychosis, or previous suicidal thoughts or attempts);

• heart disease;
• long QT syndrome or other heart rhythm disorder;
• congestive heart failure;
• a heart attack;
• liver disease; or
• kidney disease.

Pregnancy

Ingrezza may cause fetal harm. Tell your doctor if you are pregnant, become pregnant, or plan to become pregnant.

Breastfeeding

Do not breastfeed while using this medicine and for at least 5 days after your last dose.

Common Ingrezza side effects

• headache, dizziness, drowsiness;
• problems with balance or coordination;
• dry mouth;
• feeling restless;
• constipation; or
• blurred vision.
• rash or hives; or
• trouble getting to sleep or staying asleep.

Serious Ingrezza side effects

Also, see the Warnings section below.

Get emergency medical help if you have signs of an allergic reaction to this medicine: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• extreme drowsiness;
• fast, slow, or uneven heartbeats;
• pounding heartbeats or fluttering in your chest;
• shortness of breath; or
• a light-headed feeling, like you might pass out; or
• Parkinson-like symptoms - tremors, shaking, stiffness, problems with balance or walking.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Usual Adult Ingrezza Dose for Tardive Dyskinesia:

Initial Dose: 40 mg orally once a day

Maintenance Dose: Increase to 80 mg orally once a day after one week at the initial dose; however, a continuation of the initial dose may be considered for some patients.

Usual Adult Dose for Chorea associated with Huntington’s disease:

Initial dose: 40 mg once daily.

Maintenance Dose: Increase the dose in 20 mg increments every two weeks to the recommended dosage of 80 mg once daily.

General Ingrezza dosing information

• Administer with or without food.
• Sprinkle capsules may be opened and sprinkled over soft food (do not use milk or drinking water).
• Sprinkle capsules may be swallowed whole with water. Do not crush or chew.
• The recommended dosage for patients with moderate or severe hepatic impairment is 40 mg once daily.
• The recommended dosage for known CYP2D6 poor metabolizers is 40 mg once daily.

Ingrezza formulations and strengths

• Ingrezza capsules 40 mg, 60 mg, and 80 mg.
• Ingrezza Sprinkle capsules: 40 mg, 60 mg, and 80 mg.

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.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Valbenazine may impair your thinking or reactions. Avoid driving or hazardous activity until you know how this medicine will affect you. Dizziness or drowsiness can cause falls, accidents, or severe injuries.

Review the Ingrezza Package Insert or the Ingrezza Sprinkle Package Insert for more detailed information about this medicine. Discuss any medical questions you have with your doctor or other health care provider. This is not all the information you need to know about this medicine for safe and effective use, and it does not take the place of talking to your doctor about your treatment.

Other drugs may interact with this medicine, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.

It is important to tell your doctor if you take any of these medicines.

• Monoamine oxidase inhibitors (MAOIs), including if you have stopped taking an MAOI within the last 14 days.
• Strong CYP3A4 inducers
• Strong CYP3A4 inhibitors
• Strong CYP2D6 inhibitors
• digoxin.

Not all possible drug interactions are listed here.

• Store capsules at 59°F to 86°F (15°C to 30°C).
• Store Sprinkle capsules between 68°F to 77°F (20°C to 25°C).
• Keep the bottle tightly closed to protect sprinkle capsules from moisture.
• Sprinkle capsule granules added to soft food can be stored for up to 2 hours at room temperature between 68°F to 77°F (20°C to 25°C). After 2 hours, throw away any unused portion.

Ingrezza manufacturer Neurocrine Biosciences, Inc., San Diego, CA 92130, U.S.A.

Active ingredient: valbenazine

Inactive ingredients:

Ingrezza capsules: hypromellose, isomalt, magnesium stearate, pregelatinized starch, and silicified microcrystalline cellulose. The capsule shells contain candurin silver fine, FD&C Blue#1, FD&C Red#40, and gelatin.

Ingrezza Sprinkle capsules: silicified microcrystalline cellulose, isomalt, pregelatinized maize starch, hypromellose, magnesium stearate, polyvinyl alcohol, titanium dioxide, polyethylene glycol, and talc. The hard gelatin capsule shells contain gelatin and candurin silver fine.