Valbenazine

Valbenazine is an oral medication approved for adults across two conditions:

• Tardive dyskinesia — uncontrolled, repetitive movements (often of the face, lips, tongue, or limbs) typically caused by long-term use of certain psychiatric medications. Both Ingrezza and INGREZZA Sprinkle are approved for this use.
• Chorea associated with Huntington's disease — the involuntary, jerky movements that are a key feature of Huntington's disease. Both Ingrezza and INGREZZA Sprinkle are approved for this use.

Valbenazine works by blocking a protein in nerve cells called VMAT2 (vesicular monoamine transporter 2). This protein normally packages chemical messengers — particularly dopamine — into storage pouches inside nerve endings for release. By reversibly blocking VMAT2, valbenazine reduces the amount of these chemicals available at nerve junctions. The result is a calming of the overactive nerve signals that drive the abnormal, involuntary movements seen in tardive dyskinesia and Huntington's chorea. The precise details of why this helps aren't fully known, but the VMAT2 blockade is believed to be the key.

Importantly, valbenazine and its active form in the body do not significantly bind to dopamine, serotonin, or other common brain receptors — which may help explain its side-effect profile compared to some other movement-disorder medications.

Valbenazine is taken once daily by mouth, with or without food. Your prescriber will start you at a lower dose and increase it gradually — the schedule depends on whether you're being treated for tardive dyskinesia or Huntington's-related chorea. People with moderate or severe liver disease, those who are slow metabolizers of the drug (CYP2D6 poor metabolizers), or those taking certain interacting medications may need to stay at a lower dose.

• Ingrezza capsules are swallowed whole, once daily
• INGREZZA Sprinkle capsules can be sprinkled over soft food (like applesauce, yogurt, or pudding) or swallowed whole with water — but must not be crushed, chewed, or mixed into milk or water
• If using INGREZZA Sprinkle as a sprinkle, the mixture can sit for up to 2 hours at room temperature before being discarded

The most common side effect of valbenazine is drowsiness or sedation, which affects a meaningful number of people. Other frequently reported effects include:

• Somnolence (sleepiness), fatigue, or sedation
• Balance problems, dizziness, or falls
• Nausea or vomiting
• Anticholinergic effects such as dry mouth, blurred vision, constipation, or difficulty urinating
• Akathisia — a restless, can't-sit-still feeling
• Headache
• Joint pain (arthralgia)
• Skin rash or hives (more commonly reported in Huntington's patients)
• Trouble sleeping (insomnia), particularly in Huntington's patients

More serious reactions — including severe allergic reactions (angioedema), heart rhythm changes, Parkinson's-like symptoms, and a rare but dangerous condition called Neuroleptic Malignant Syndrome — require immediate medical attention if they occur.

• Depression and suicidal thinking in Huntington's disease (boxed warning): Valbenazine can increase the risk of depression and suicidal thoughts or behaviors in people with Huntington's disease. Caregivers and family members should watch closely for mood changes or talk of self-harm and report them to the doctor immediately. Extra caution is needed in anyone with a history of depression or prior suicide attempts.
• Serious allergic reactions (angioedema): Swelling of the face, throat, or airway has been reported and can be life-threatening. Stop the medication and get emergency care immediately if this happens.
• Drowsiness and sedation: Valbenazine can cause significant sleepiness. Avoid driving or operating dangerous machinery until you know how the drug affects you.
• QT prolongation (heart rhythm change): Valbenazine can lengthen a specific part of the heart's electrical cycle. This is most significant in people who process the drug slowly (CYP2D6 poor metabolizers) or who take certain interacting medications. People with congenital long QT syndrome or related arrhythmias should not use this medication.
• Neuroleptic Malignant Syndrome (NMS): A rare but potentially fatal reaction involving high fever, severe muscle stiffness, confusion, and unstable blood pressure or heart rate. Stop the medication and seek emergency care immediately.
• Parkinson-like symptoms: Tremors, slow movement, and muscle stiffness have been reported, some severely. Contact your doctor if these develop — a dose reduction or discontinuation may be needed.

Several medications can significantly affect how valbenazine works in your body — or be affected by it:

• MAOIs (monoamine oxidase inhibitors): Do not use together or within 14 days of stopping an MAOI — risk of serious nervous system reactions, including serotonin syndrome.
• Strong CYP3A4 inhibitors (e.g., certain antifungals, HIV medications): Raise valbenazine levels, increasing the risk of side effects including heart rhythm changes. A lower dose is required.
• Strong CYP2D6 inhibitors (e.g., certain antidepressants like paroxetine): Increase levels of valbenazine's active metabolite, raising the risk of side effects. A lower dose is required.
• Strong CYP3A4 inducers (e.g., rifampin, certain anti-seizure drugs): Lower valbenazine levels, potentially making it less effective. This combination is not recommended.
• Digoxin: Valbenazine can raise digoxin levels in the blood by blocking its absorption pathway. Digoxin levels should be monitored closely, and the digoxin dose may need adjustment.

This is not a complete list of interactions. Always talk with your doctor or pharmacist before starting, stopping, or changing any medication.

• Tell your doctor if you have a personal or family history of depression or suicidal thoughts — this is especially critical if you have Huntington's disease.
• Tell your doctor if you have moderate or severe liver disease — a lower dose is recommended.
• Tell your doctor if you have a heart rhythm disorder, particularly congenital long QT syndrome or arrhythmias tied to a prolonged QT interval — valbenazine may not be appropriate.
• If you are a known CYP2D6 poor metabolizer (a genetic variation that slows drug processing), tell your doctor — a lower dose is needed.
• Tell your doctor about all medications you take, especially antidepressants, antifungals, HIV drugs, anti-seizure medications, and heart medications like digoxin.
• Pregnancy: This medication may cause harm to an unborn baby. Discuss the risks with your doctor if you are pregnant or planning to become pregnant.
• Breastfeeding: You should not breastfeed while taking this medication.
• Safety and effectiveness have only been established in adults; this medication is not indicated for children.

There is limited information about what an overdose of valbenazine looks like in humans. There is no specific antidote. If you suspect an overdose, call the Poison Help line at 1-800-222-1222 or go to an emergency room right away. Medical staff will provide supportive care and close monitoring, and will check whether other medications may also be involved.

Valbenazine selectively blocks the VMAT2 transporter in the brain, reducing the packaging and release of dopamine and related chemical messengers at nerve connections. It also converts in the body to an active metabolite that also binds VMAT2 very strongly. Neither valbenazine nor its active metabolite meaningfully bind to dopamine (D2), serotonin, adrenaline, histamine, or muscarinic receptors at relevant levels. At recommended doses, the effect on heart rhythm (QT interval) is generally mild, but can become more significant at higher drug exposures — particularly in people who are slow metabolizers or who take certain interacting medications.

After taking Ingrezza by mouth, valbenazine is absorbed quickly, reaching peak levels in as little as 30 minutes to 1 hour, and steady levels in the blood within about one week. The drug is extensively broken down in the body, primarily by liver enzymes (CYP3A4/5 and CYP2D6), into an active metabolite that peaks about 4 to 8 hours after a dose. Both valbenazine and its active metabolite have half-lives of 15 to 22 hours — meaning they stay in the body for a meaningful amount of time after each dose. The drug is eliminated mainly through the urine, with some in the stool.

Food can slow how quickly Ingrezza is absorbed (lower peak level), though the overall amount absorbed is not greatly affected. INGREZZA Sprinkle sprinkled on applesauce is absorbed somewhat more slowly than the standard Ingrezza capsule, but the total drug exposure is similar. People with moderate or severe liver disease have higher drug levels, which is why a lower dose is recommended for them.

INGREZZA: Store at 15°C to 30°C (59°F to 86°F). Store at 20°C to 25°C (68°F to 77°F). Protect from moisture.