Ingrezza (valbenazine) is generally well tolerated, but its most common side effect is drowsiness, which affects roughly 11% of people taking it compared to about 4% on placebo. The medication works by reducing the amount of dopamine and other signaling chemicals available in certain parts of the brain, which is how it treats the involuntary movements of tardive dyskinesia. That same mechanism, though, is what drives most of its side effects.
The Most Common Side Effects
The FDA evaluated Ingrezza’s safety across three placebo-controlled studies involving 445 patients over six-week treatment periods. Two side effect categories stood out as occurring more often than placebo.
Somnolence was the most frequently reported issue. About 10.9% of patients taking Ingrezza experienced drowsiness, fatigue, or sedation, compared to 4.2% on placebo. This is a direct consequence of how the drug works: by lowering the availability of certain brain chemicals involved in alertness and movement. If you’re starting Ingrezza, this is the side effect you’re most likely to notice, and it can affect your ability to drive or operate machinery.
A smaller group, about 5.4%, experienced what the prescribing information groups as anticholinergic effects: dry mouth, constipation, difficulty concentrating, blurred vision, or trouble urinating. That rate was only slightly above the 4.9% seen with placebo, so these effects are mild and relatively uncommon.
What the Long-Term Data Shows
Short trials don’t tell the whole story for a medication many people take indefinitely. A long-term extension study followed 430 adults with tardive dyskinesia for up to 48 weeks. About two-thirds of participants reported at least one side effect during that time, and 14.7% eventually stopped treatment because of side effects.
The pattern of side effects shifted slightly with longer use. Headache, urinary tract infections, and somnolence were the three most common issues. Among people with schizophrenia, urinary tract infections affected 6.1%, headache 5.8%, and somnolence 5.2%. People with mood disorders reported higher rates across the board: headache at 12.4%, urinary tract infections at 10.7%, and somnolence at 9.1%.
The reassuring finding from this study was that changes in lab work, vital signs, heart rhythm tracings, and movement disorder scales were minimal and not considered clinically significant over the full 48 weeks. Psychiatric symptoms also remained stable during treatment, an important detail since most people taking Ingrezza are also managing schizophrenia or a mood disorder.
The Boxed Warning for Huntington’s Disease
Ingrezza carries the FDA’s most serious safety warning, but it applies to a specific group: people with Huntington’s disease. VMAT2 inhibitors, the drug class Ingrezza belongs to, can increase the risk of depression and suicidal thoughts and behavior in this population. This boxed warning exists because a related drug in the same class, tetrabenazine, was originally approved for Huntington’s chorea and showed these risks. If you’re taking Ingrezza for tardive dyskinesia and don’t have Huntington’s disease, this particular warning is less directly relevant to you, though any new mood changes while on the medication are still worth discussing with your prescriber.
How the Drug’s Mechanism Creates Side Effects
Ingrezza works by blocking a protein called VMAT2, which is responsible for packaging dopamine and other signaling molecules so nerve cells can release them. By partially blocking this process, the drug reduces the excess dopamine signaling that causes the involuntary facial and body movements of tardive dyskinesia. But dopamine isn’t only involved in movement. It also plays roles in wakefulness, motivation, and mood, which explains why drowsiness and fatigue are the drug’s primary side effects.
Animal studies during development confirmed that the central nervous system was the main area affected by the drug. Animals showed signs consistent with reduced brain signaling chemicals, including decreased activity, unsteady movement, and trembling. In humans, these effects are much milder at approved doses, but they explain why some people feel sluggish or sedated, especially early in treatment.
Drug Interactions That Can Worsen Side Effects
Certain medications can increase the amount of Ingrezza in your bloodstream, which raises the likelihood of side effects. The biggest concern is drugs that strongly inhibit a liver enzyme responsible for breaking down Ingrezza. Common examples include the antifungals itraconazole and ketoconazole, and the antibiotic clarithromycin. When someone needs to take one of these medications alongside Ingrezza, the prescribing information recommends the lower 40 mg dose rather than the standard 80 mg to compensate for the higher drug levels.
If you’re prescribed a new medication while taking Ingrezza and notice a sudden increase in drowsiness or other side effects, a drug interaction could be the reason. Your pharmacist can check whether any of your medications affect how Ingrezza is processed.
Liver Function and Dose Adjustments
Because the liver is responsible for breaking down Ingrezza, people with moderate to severe liver impairment may process the drug more slowly, leading to higher levels in the body and a greater chance of side effects. Dose adjustments are typically made for these patients to keep the drug at safe and effective levels. If you have known liver disease, your prescriber will likely factor that into your dosing.