Ingrezza 40-80mg Capsules
WARNING: This drug may raise the chance of depression and suicidal thoughts or actions in people with Huntington's disease. If you have ever had depression or suicidal thoughts or actions, talk with your doctor. This drug may not be right for you. People who take this drug must be watched closely. Call your doctor right away if you have signs like depression, nervousness, restlessness, grouchiness, panic attacks, or any other changes in feelings, mood, or behavior. Call your doctor right away if you have any thoughts or actions of suicide. @ COMMON USES: It is used to treat tardive dyskinesia. It is used to treat disabling involuntary movements in Huntington's chorea.
Drug Class
VMAT2 Inhibitor
Pharmacologic Class
Vesicular Monoamine Transporter 2 (VMAT2) Inhibitor
Pregnancy Category
Not available
FDA Approved
Apr 2017
DEA Schedule
Not Controlled
Overview
What is this medicine?
Ingrezza is a prescription medication used to treat uncontrolled, involuntary movements of the face, tongue, or other body parts, a condition called tardive dyskinesia. It works by affecting certain chemicals in the brain that control movement.
How to Use This Medicine
Taking Your Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. Take your medication as directed, with or without food. Continue taking it even if you feel well, unless your doctor or healthcare provider advises you to stop.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, avoiding bathrooms. Keep all medications in a safe location, out of reach of children and pets. Dispose of unused or expired medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so. If you have questions about disposal, consult your pharmacist. You may also want to check if there are drug take-back programs in your area.
Missing a Dose
If you miss a dose, take it as soon as you remember. However, if it's close to the time for your next dose, skip the missed dose and resume your regular schedule. Do not take two doses at the same time or take extra doses to make up for the missed one.
To use this medication correctly, follow your doctor's instructions and read all the information provided. Take your medication as directed, with or without food. Continue taking it even if you feel well, unless your doctor or healthcare provider advises you to stop.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, avoiding bathrooms. Keep all medications in a safe location, out of reach of children and pets. Dispose of unused or expired medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so. If you have questions about disposal, consult your pharmacist. You may also want to check if there are drug take-back programs in your area.
Missing a Dose
If you miss a dose, take it as soon as you remember. However, if it's close to the time for your next dose, skip the missed dose and resume your regular schedule. Do not take two doses at the same time or take extra doses to make up for the missed one.
Lifestyle & Tips
- Avoid driving or operating heavy machinery until you know how Ingrezza affects you, as it can cause drowsiness or dizziness.
- Avoid alcohol or other central nervous system (CNS) depressants (e.g., benzodiazepines, opioids) as they can increase drowsiness and sedation.
- Do not stop taking Ingrezza suddenly without consulting your doctor, as this may worsen your tardive dyskinesia symptoms.
- Inform your doctor about all other medications, over-the-counter drugs, supplements, and herbal products you are taking to avoid potential drug interactions.
- Take Ingrezza exactly as prescribed by your doctor, with or without food.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
Initial 40 mg orally once daily. After 2 weeks, may increase to 80 mg orally once daily.
Dose Range:
40 - 80 mg
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
No dose adjustment needed (CrCl 50-89 mL/min).
Moderate:
No dose adjustment needed (CrCl 30-49 mL/min).
Severe:
Initial 40 mg once daily. May increase to 60 mg once daily after 2 weeks if tolerated and needed (CrCl <30 mL/min).
Dialysis:
Initial 40 mg once daily. May increase to 60 mg once daily after 2 weeks if tolerated and needed (ESRD requiring dialysis).
Hepatic Impairment:
Mild:
No dose adjustment needed (Child-Pugh A).
Moderate:
Initial 40 mg once daily. May increase to 60 mg once daily after 2 weeks if tolerated and needed (Child-Pugh B).
Severe:
Initial 40 mg once daily. May increase to 60 mg once daily after 2 weeks if tolerated and needed (Child-Pugh C).
Pharmacology
Mechanism of Action
Valbenazine is a selective vesicular monoamine transporter 2 (VMAT2) inhibitor. The precise mechanism by which valbenazine exerts its therapeutic effects in tardive dyskinesia is unknown, but it is thought to involve the reversible inhibition of VMAT2, leading to reduced dopamine release from presynaptic terminals.
Pharmacokinetics
Absorption:
Bioavailability:
Not explicitly quantified, but well absorbed.
Tmax:
Valbenazine: 0.5-2 hours; Active metabolite (Îą-dihydrotetrabenazine [Îą-HTBZ]): 4-8 hours.
FoodEffect:
High-fat meal decreases Cmax by 27% and AUC by 16% for valbenazine, but increases Cmax by 29% and AUC by 24% for Îą-HTBZ. Can be taken with or without food.
Distribution:
Vd:
Valbenazine: 92 L; Îą-HTBZ: 120 L.
ProteinBinding:
Valbenazine: >99%; Îą-HTBZ: >99%.
CnssPenetration:
Yes
Elimination:
HalfLife:
Valbenazine: 15-22 hours; Îą-HTBZ: 15-22 hours.
Clearance:
Primarily hepatic metabolism and renal excretion.
ExcretionRoute:
Urine (60%) and feces (30%).
Unchanged:
<2% excreted unchanged in urine.
Pharmacodynamics
OnsetOfAction:
Clinical improvement observed within 2 weeks.
PeakEffect:
Maximal effect typically seen by 6-12 weeks.
DurationOfAction:
Sustained effect with once-daily dosing.
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you or your child experience any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Difficulty focusing
Blurred vision
Trouble urinating
Slow heartbeat
Shortness of breath
Dizziness
Abnormal heartbeat (prolonged QT interval), which can cause:
+ Fast heartbeat
+ Irregular heartbeat
+ Fainting
Symptoms resembling Parkinson's disease, such as:
+ Trouble moving or walking
+ Difficulty controlling body movements
+ Shakiness
+ Changes in balance or falls
+ Drooling
Neuroleptic malignant syndrome (NMS), a potentially life-threatening condition, which can cause:
+ Fever
+ Muscle cramps or stiffness
+ Dizziness
+ Severe headache
+ Confusion
+ Changes in thinking
+ Fast heartbeat
+ Irregular heartbeat
+ Excessive sweating
Angioedema, a severe and potentially life-threatening reaction, which can cause:
+ Swelling of the hands, face, lips, eyes, tongue, or throat
+ Trouble breathing
+ Trouble swallowing
+ Unusual hoarseness
Other Possible Side Effects
Most people experience few or no side effects while taking this medication. However, if you or your child experience any of the following side effects, contact your doctor or seek medical attention if they bother you or do not go away:
Drowsiness
Fatigue or weakness
Dry mouth
Constipation
Restlessness
* Trouble sleeping
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you or your child experience any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Difficulty focusing
Blurred vision
Trouble urinating
Slow heartbeat
Shortness of breath
Dizziness
Abnormal heartbeat (prolonged QT interval), which can cause:
+ Fast heartbeat
+ Irregular heartbeat
+ Fainting
Symptoms resembling Parkinson's disease, such as:
+ Trouble moving or walking
+ Difficulty controlling body movements
+ Shakiness
+ Changes in balance or falls
+ Drooling
Neuroleptic malignant syndrome (NMS), a potentially life-threatening condition, which can cause:
+ Fever
+ Muscle cramps or stiffness
+ Dizziness
+ Severe headache
+ Confusion
+ Changes in thinking
+ Fast heartbeat
+ Irregular heartbeat
+ Excessive sweating
Angioedema, a severe and potentially life-threatening reaction, which can cause:
+ Swelling of the hands, face, lips, eyes, tongue, or throat
+ Trouble breathing
+ Trouble swallowing
+ Unusual hoarseness
Other Possible Side Effects
Most people experience few or no side effects while taking this medication. However, if you or your child experience any of the following side effects, contact your doctor or seek medical attention if they bother you or do not go away:
Drowsiness
Fatigue or weakness
Dry mouth
Constipation
Restlessness
* Trouble sleeping
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Worsening or new involuntary movements (tardive dyskinesia)
- New or worsening tremors, stiffness, slow movements, or difficulty walking (signs of parkinsonism)
- Feeling restless or unable to sit still (akathisia)
- Severe drowsiness or sedation
- Dizziness, lightheadedness, fainting, or a fast/irregular heartbeat (signs of QTc prolongation)
- Signs of an allergic reaction (e.g., rash, itching, swelling, severe dizziness, trouble breathing)
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced.
A history of abnormal heart rhythms, including a prolonged QT interval on an electrocardiogram (ECG).
Recent use (within the last 14 days) of certain medications for depression or Parkinson's disease, such as isocarboxazid, phenelzine, tranylcypromine, selegiline, or rasagiline.
Current use of linezolid or methylene blue, as these medications should not be taken with this drug.
Use of any other medications, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins, that may interact with this medication. This includes rifampin, St. John's Wort, and certain antiseizure medications. There are many medications that should not be taken with this drug, so it is crucial to disclose all medications you are taking.
If you are breastfeeding, as you should not breastfeed while taking this medication and for 5 days after your last dose.
To ensure your safety, it is crucial to inform your doctor and pharmacist about all your medications (prescription and OTC), natural products, vitamins, and health problems. This will help determine if it is safe to take this medication with your other medications and health conditions. Never start, stop, or change the dose of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced.
A history of abnormal heart rhythms, including a prolonged QT interval on an electrocardiogram (ECG).
Recent use (within the last 14 days) of certain medications for depression or Parkinson's disease, such as isocarboxazid, phenelzine, tranylcypromine, selegiline, or rasagiline.
Current use of linezolid or methylene blue, as these medications should not be taken with this drug.
Use of any other medications, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins, that may interact with this medication. This includes rifampin, St. John's Wort, and certain antiseizure medications. There are many medications that should not be taken with this drug, so it is crucial to disclose all medications you are taking.
If you are breastfeeding, as you should not breastfeed while taking this medication and for 5 days after your last dose.
To ensure your safety, it is crucial to inform your doctor and pharmacist about all your medications (prescription and OTC), natural products, vitamins, and health problems. This will help determine if it is safe to take this medication with your other medications and health conditions. Never start, stop, or change the dose of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
Before operating a vehicle or engaging in any activity that requires your full attention, wait until you understand how this medication affects you. It is also crucial to discuss the use of alcohol, marijuana, or other forms of cannabis, as well as prescription or over-the-counter (OTC) drugs that may cause drowsiness, with your doctor beforehand.
If you have Huntington's disease, be aware that your symptoms may still worsen while taking this medication. Immediately contact your doctor if you experience any new or worsening symptoms.
Additionally, if you are pregnant or become pregnant while taking this medication, there is a risk of harm to the unborn baby. If you are pregnant or suspect you may be pregnant, notify your doctor right away.
Before operating a vehicle or engaging in any activity that requires your full attention, wait until you understand how this medication affects you. It is also crucial to discuss the use of alcohol, marijuana, or other forms of cannabis, as well as prescription or over-the-counter (OTC) drugs that may cause drowsiness, with your doctor beforehand.
If you have Huntington's disease, be aware that your symptoms may still worsen while taking this medication. Immediately contact your doctor if you experience any new or worsening symptoms.
Additionally, if you are pregnant or become pregnant while taking this medication, there is a risk of harm to the unborn baby. If you are pregnant or suspect you may be pregnant, notify your doctor right away.
Overdose Information
Overdose Symptoms:
- Exaggerated known adverse effects, including severe somnolence, dizziness, nausea, vomiting, and potentially QTc prolongation.
What to Do:
Seek immediate medical attention or call Poison Control (1-800-222-1222). Supportive care and symptomatic treatment are recommended. There is no specific antidote for valbenazine overdose.
Drug Interactions
Major Interactions
- Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) - requires dose reduction of valbenazine.
- Strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine, quinidine) - requires dose reduction of valbenazine.
- Strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's Wort) - avoid coadministration.
Monitoring
Baseline Monitoring
Abnormal Involuntary Movement Scale (AIMS) score
Rationale: To assess the severity of tardive dyskinesia before treatment and monitor response.
Timing: Prior to initiation of therapy.
Electrocardiogram (ECG) for QTc interval
Rationale: Valbenazine can cause QTc prolongation; baseline assessment is important, especially in patients with risk factors (e.g., congenital long QT syndrome, history of cardiac arrhythmias, concomitant use of QT-prolonging drugs, electrolyte imbalances).
Timing: Prior to initiation, especially if risk factors for QTc prolongation are present.
Routine Monitoring
AIMS score
Frequency: Periodically (e.g., every 4-8 weeks initially, then every 3-6 months) to assess treatment response.
Target: Reduction in score indicating improvement.
Action Threshold: Worsening or lack of improvement may warrant dose adjustment or re-evaluation of therapy.
Clinical assessment for adverse effects (e.g., somnolence, QTc prolongation symptoms, parkinsonism, akathisia)
Frequency: At each visit, especially during dose titration and initial treatment phase.
Target: Absence or minimal, tolerable adverse effects.
Action Threshold: Significant or bothersome adverse effects may require dose reduction or discontinuation.
ECG for QTc interval
Frequency: As clinically indicated, especially if risk factors for QTc prolongation develop or symptoms (e.g., dizziness, palpitations, syncope) arise.
Target: QTc <450 ms (men), <470 ms (women).
Action Threshold: QTc >500 ms or increase of >60 ms from baseline warrants re-evaluation, dose reduction, or discontinuation.
Symptom Monitoring
- Worsening or new onset of tardive dyskinesia (involuntary movements)
- New or worsening parkinsonism (tremor, rigidity, bradykinesia, gait instability)
- Akathisia (restlessness, inability to sit still)
- Somnolence (drowsiness, sedation)
- Signs of QTc prolongation (e.g., dizziness, lightheadedness, fainting, palpitations, irregular heartbeat)
- Rash or other signs of allergic reaction
Special Patient Groups
Pregnancy
Limited human data on valbenazine use in pregnant women. Animal studies show developmental toxicity (embryo-fetal mortality, skeletal abnormalities) at doses higher than clinical exposure. Use only if the potential benefit justifies the potential risk to the fetus.
Trimester-Specific Risks:
First Trimester:
Potential for embryo-fetal mortality and skeletal abnormalities based on animal data.
Second Trimester:
Potential for developmental toxicity based on animal data.
Third Trimester:
Potential for developmental toxicity based on animal data.
Lactation
It is not known if valbenazine or its metabolites are excreted in human milk. Valbenazine and its metabolites are present in the milk of lactating rats. Due to the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment with Ingrezza and for 5 days after the last dose.
Infant Risk:
Potential for serious adverse reactions (e.g., somnolence, effects on CNS) in breastfed infants.
Pediatric Use
Safety and effectiveness have not been established in pediatric patients.
Geriatric Use
No specific dose adjustment is required based on age. However, elderly patients may be more sensitive to the adverse effects, particularly somnolence and QTc prolongation. Monitor closely for adverse reactions.
Clinical Information
Clinical Pearls
- Ingrezza (valbenazine) is the first FDA-approved medication specifically for the treatment of tardive dyskinesia in adults.
- It is generally well-tolerated, with somnolence and QTc prolongation being key adverse effects to monitor.
- Dose titration is recommended, starting at 40 mg and increasing to 80 mg after 2 weeks based on individual response and tolerability.
- Patients should be educated on the importance of adherence and not abruptly stopping the medication, as this can lead to worsening of symptoms.
- Improvement in tardive dyskinesia symptoms may take several weeks to become apparent, and continued treatment is often necessary for sustained benefit.
- Can be taken with or without food, offering flexibility for patients.
Alternative Therapies
- Deutetrabenazine (Austedo, VMAT2 inhibitor)
- Off-label treatments for TD (e.g., clonazepam, amantadine, ginkgo biloba, botulinum toxin for focal TD)
- Dose reduction or discontinuation of the causative antipsychotic or dopamine receptor blocking agent (if clinically appropriate).
- Management of the underlying psychiatric condition.
Cost & Coverage
Average Cost:
Highly variable, typically $6,000 - $8,000+ per 30 capsules
Insurance Coverage:
Specialty Tier (often requires prior authorization, may have high co-pay or co-insurance).
General Drug Facts
If your symptoms or health issues persist or worsen, it's essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication.
This medication is accompanied by a Medication Guide, which provides crucial information about its use. Please read this guide carefully and review it again whenever you receive a refill of your medication. If you have any questions or concerns about this medication, don't hesitate to discuss them with your doctor, pharmacist, or other healthcare provider.
In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When reporting the incident, be prepared to provide details about the medication taken, the amount consumed, and the time it occurred. This information will help healthcare professionals provide you with the most effective treatment.
This medication is accompanied by a Medication Guide, which provides crucial information about its use. Please read this guide carefully and review it again whenever you receive a refill of your medication. If you have any questions or concerns about this medication, don't hesitate to discuss them with your doctor, pharmacist, or other healthcare provider.
In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When reporting the incident, be prepared to provide details about the medication taken, the amount consumed, and the time it occurred. This information will help healthcare professionals provide you with the most effective treatment.