Ingrezza: 7 things you should know

Medically reviewed by Carmen Pope, BPharm. Last updated on May 15, 2024.

1. How it works

• Ingrezza is a brand (trade) name for valbenazine which may be used to treat adults with tardive dyskinesia or those with chorea associated with Huntington's disease (HD).
• Experts aren’t sure how Ingrezza works but suspect it blocks a protein transporter called vesicular monoamine transporter 2 (VMAT2), which is responsible for regulating the uptake of monoamine neurotransmitters such as dopamine, noradrenaline, and serotonin from the cytoplasm of the cell into the synaptic vessels. Synaptic vessels store neurotransmitters for release into the synapse (the space between two nerves). These neurotransmitters have various functions within the body but dopamine, in particular, plays a role in movement as well as pleasure, motivation, and learning. The abnormal functioning of dopamine is thought to be a cause of tardive dyskinesia (TD) and chorea associated with HD. By blocking VMAT2, Ingrezza reduces the uptake of monamines, such as dopamine, causing a decrease in symptoms of TD and chorea.
• Older-generation (typical) antipsychotic medications, such as haloperidol, trifluoperazine, or fluphenazine are the most likely to cause TD. The condition may be reversible if recognized in the earliest stages and the causative agent is stopped but can be permanent. Huntington's disease (HD) is an inherited disorder that usually starts in middle age.
• Ingrezza belongs to the class of medicines known as VMAT2 inhibitors.

2. Upsides

• Taken once a day orally (by mouth).
• Available in 40mg and 80mg capsules or sprinkle capsules. The sprinkle capsules can be easily opened and the contents sprinkled on soft food for those who have difficulty swallowing. The initial dosage for TD is 40mg once a day which may be increased after one week to 80mg. For chorea associated with HD, the initial dosage is 40mg which may be increased by 20mg every two weeks to a maximum of 80mg once a day.
• May be taken with or without food.
• A highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor.
• Was the first product approved for adults with tardive dyskinesia (TD).
• 53% of patients and 43% of health professionals reported that overall, HD chorea symptoms were "very much improved" or "much improved" after 12 weeks of Ingrezza. It is well tolerated in people with HD with the most common side effects reported as somnolence/lethargy/sedation, urticaria, rash, and insomnia.
• Ingrezza is not an antipsychotic agent. By inhibiting VMAT2 it slows the uptake of dopamine by the brain.
• Reduces unwanted body movements associated with tardive dyskinesia (TD) such as tongue-thrusting, repetitive chewing, jaw swinging, lip-smacking, and/or facial grimacing. For chorea associated with HD, it demonstrated a three-times greater improvement in chorea severity compared with a placebo (an inactive pill).
• Ingrezza is also available as a one-month free trial for new patients, through the Ingrezza Start program. For more information, call 84-INGREZZA (844-647-3992) 8 am to 8 pm EST, Monday through Friday.
• No dosage reduction is required for those with mild, moderate, or severe renal impairment.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Fatigue, sleepiness, constipation, dry mouth, headache, a rash, nausea, or vomiting are the most common side effects reported. Other side effects include an increased risk of falls and symptoms similar to Parkinson's disease, such as feelings of restlessness, gait disturbances, tremors, and drooling.
• Hypersensitivity reactions have occurred with Ingrezza with symptoms such as a rash and swelling reported.
• Carries a boxed warning for a risk of depression and suicidal thoughts.
• May take up to 32 weeks to work for TD although some improvement may be noticed within 1 to 2 weeks. Symptoms of TD return within four weeks of discontinuing Ingrezza.
• May take up to 12 weeks to work for chorea associated with Huntington's disease (HD), although some improvement in symptoms is noticed within 2 weeks.
• Does not cure TD or chorea associated with HD.
• Safety and effectiveness in children has not been established.
• The maximum dosage in patients with moderate to severe liver disease and known CYP2D6-poor metabolizers is 40mg/day.
• There is not enough data to know the effect Ingrezza has during pregnancy on the unborn child. Women should not breastfeed while taking Ingrezza and for five days after the last dose.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

Ingrezza may be used to treat adults with tardive dyskinesia or chorea associated with Huntington's disease. It works by blocking VMAT2, which reduces the uptake of dopamine by the brain. Although some reduction in symptoms may be noticed within a week or two, it can take up to 32 weeks (for TD) or up to 12 weeks (for chorea associated with HD) to have an effect. Side effects include fatigue, sleepiness, changes in balance, a rash, and a dry mouth.

5. Tips

• Your doctor will tell you how much Ingrezza to take and when to take it. Do not stop taking this medicine without first speaking to your doctor.
• If you or someone you care for has difficulty swallowing the capsules, ask your healthcare provider for the Ingrezza Sprinkle capsules. These are easily opened and the contents sprinkled on food.
• Contact the INBRACE Support Program to see if you qualify for copay assistance and also for other support and advice at 1-84-INGREZZA (1-844-647-3992) 8 am to 8 pm EST, Monday through Friday.
• Ingrezza can make you sleepy and affect your ability to drive or operate a vehicle or perform other hazardous tasks.
• Report any worrying side effects to your doctor, such as heart palpitations, feeling faint, changes in your mood, or loss of consciousness. Ingrezza may cause symptoms similar to Parkinson's disease, such as gait disturbances, tremors, drooling, and an increase in the risk of falls.
• Tell your doctor or other health care provider about all the medicines you take, including prescription and over-the-counter (OTC) medicines, vitamins, and herbal supplements. Let them know if you eat grapefruit or drink grapefruit juice. Ingrezza interacts with several medicines and it may not be safe to take them together.
• Always tell your doctor about other underlying conditions you may have, such as heart rhythm disturbances.
• See your doctor immediately if you develop any signs of an allergic reaction after taking Ingrezza, such as facial swelling or a rash.
• There is no data on the use of Ingrezza during pregnancy. Tell your doctor immediately if you become pregnant. Do not breastfeed while taking Ingrezza.

6. Response and effectiveness

• Takes approximately 6 to 8 weeks to start working, although some improvements in symptoms of tardive dyskinesia (TD) may be noticed in one to two weeks. Maximal effects take up to 32 weeks to develop.
• Symptoms of TD return within four weeks of discontinuing Ingrezza.
• KINECT study: Although the change in symptoms from baseline with valbenazine was not significantly different than placebo after 4 weeks of treatment, 61% of participants who continued with valbenazine 50mg were assessed to be “much improved” or “very much improved” according to their CGI-TD score (-5.8 change from baseline with AIMS).
• KINECT 2 study: 67% of patients were assessed as very much improved or much improved according to CGI-TD score after 6 weeks of treatment with valbenazine (25mg to 75mg). The AIMS change from baseline was statistically significant at -2.4.
• KINECT 3 study: Participants received either a placebo, valbenazine 40mg daily or valbenazine 80mg daily for six weeks. Although symptoms of TD were reduced in both treatment groups only the 80mg treatment group was statistically significant (change in AIMS scores of valbenazine vs. placebo: -3.2 vs. -0.1). There were no statistically significant differences among groups according to the CGI-TD score. Those who continued treatment for a further 42 weeks reported statistically significant reductions in their mean AIMS score (-3.0 in the 40mg group and -4.8 in the 80mg group) as well as reductions in the CGI-TD.
• For chorea associated with HD, Ingrezza demonstrated a three-times greater improvement in chorea severity compared with a placebo (an inactive pill) in a study that spanned 12 weeks. There was a 4.6-point improvement in chorea severity score with Ingrezza compared with a 1.4-point improvement with placebo by the end of 12 weeks (mean difference –3.2, 95% CI, –4.4 to –2.0; P < 0.0001).
• Nearly half of all patients with chorea saw a greater than 40% reduction in their chorea symptoms. 53% of patients and 43% of health professionals reported that overall, HD chorea symptoms were "very much improved" or "much improved" at Week 12.
• Two weeks after discontinuing Ingrezza, symptoms of chorea associated with HD returned to baseline (what they were before the medication was started).

7. Interactions

Medicines that interact with Ingrezza may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with Ingrezza. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Ingrezza interacts with over 455 drugs and most of these interactions are considered moderate or major. Common medications that may interact with Ingrezza include:

• albuterol
• anti-anxiety medications such as diazepam and oxazepam
• antibiotics, such as clarithromycin or cotrimoxazole
• anticonvulsants, such as phenytoin
• antidepressants, such as amitriptyline, imipramine, nortriptyline, or SSRIs (eg, citalopram, fluoxetine, or paroxetine), or MAOIs (such as selegiline, isocarboxazid, phenelzine, or tranylcypromine)
• antifungals, such as itraconazole or ketoconazole
• antihistamines that cause sedation, such as diphenhydramine
• azelastine
• bisacodyl
• cannabis
• chloroquine and hydroxychloroquine
• cisapride
• CYP2D6 strong inhibitors (such as bupropion, fluoxetine, paroxetine, quinidine, or terbinafine. The maximum dosage is 40mg/day
• CYP3A4 strong inhibitors (such as clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, verapamil, goldenseal, or grapefruit). The maximum dosage is 40mg/day
• CYP3A4 strong or moderate inducers (such as phenobarbital, phenytoin, rifampicin, rifabutin, St. John's Wort, or glucocorticoids [eg, dexamethasone]). Avoid coadministration
• bupropion
• digoxin
• duloxetine
• herbals, such as echinacea
• HIV medications such as indinavir and ritonavir
• ketamine
• lithium
• loperamide
• mifepristone
• monoamine oxidase inhibitors, such as selegiline, isocarboxazid, or phenelzine
• multiple sclerosis treatments such as fingolimod
• muscle relaxants such as baclofen and cyclobenzaprine
• opioid analgesics such as oxycodone and morphine
• quinidine
• rifampin and rifabutin
• serotonin modulators, such as nefazodone and trazodone
• sleeping pills, such as Zolpidem or Zaleplon
• some chemotherapy treatments
• some heart medications, such as amiodarone
• other medications used to treat mental illness, such as clozapine and thioridazine
• any other medication that inhibits or induces CYP2D6 or CYP3A4.

Grapefruit juice and grapefruit products may increase the blood levels of Ingrezza and increase side effects such as drowsiness and QT prolongation.

Alcohol may worsen the side effects of Ingrezza such as drowsiness and dizziness.

Note that this list is not all-inclusive and includes only common medications that may interact with Ingrezza. You should refer to the prescribing information for Ingrezza for a complete list of interactions.

References

• Ingrezza Support Program https://inbracesupportprogram.com/ingrezzahcp/
• Ingrezza Sprinkle Package Insert. Revised 04/2024. Neurocrine Biosciences, Inc. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/218390s000lbl.pdf
• Ingrezza Package Insert. Revised 08/2023. Neurocrine Biosciences, Inc. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/209241s026lbl.pdf

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Ingrezza only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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