Ingrezza 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 medication used to help control involuntary movements, such as those seen in tardive dyskinesia (uncontrolled movements of the face, tongue, or other body parts) or chorea associated with Huntington's disease (jerky, uncontrolled movements). It works by affecting how a natural chemical called dopamine is handled in the brain.
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, and continue taking it even if you feel well. It's essential to follow your doctor's or healthcare provider's advice on dosage and duration of treatment.
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. When disposing of unused or expired medications, do not flush them down the toilet or pour them down the drain unless instructed to do so. Instead, consult your pharmacist for guidance on proper disposal methods. You may also want to explore 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 scheduled dose, skip the missed dose and resume your regular dosing 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, and continue taking it even if you feel well. It's essential to follow your doctor's or healthcare provider's advice on dosage and duration of treatment.
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. When disposing of unused or expired medications, do not flush them down the toilet or pour them down the drain unless instructed to do so. Instead, consult your pharmacist for guidance on proper disposal methods. You may also want to explore 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 scheduled dose, skip the missed dose and resume your regular dosing schedule. Do not take two doses at the same time or take extra doses to make up for the missed one.
Lifestyle & Tips
- Take with or without food.
- Avoid alcohol, as it may worsen drowsiness.
- Be cautious when driving or operating machinery until you know how this medication affects you, as it can cause drowsiness or dizziness.
- Do not stop taking this medication suddenly without consulting your doctor, as it may worsen your symptoms.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
For Tardive Dyskinesia: Initial 40 mg orally once daily; after 1 week, increase to 80 mg orally once daily. For Chorea associated with Huntington's Disease: Initial 40 mg orally once daily; may increase by 20 mg increments weekly to 80 mg orally once daily.
Dose Range:
40 - 80 mg
Condition-Specific Dosing:
Tardive Dyskinesia:
Initial 40 mg once daily for 1 week, then 80 mg once daily. Max 80 mg/day.
Chorea associated with Huntington's Disease:
Initial 40 mg once daily, may increase by 20 mg increments weekly to 80 mg once daily. Max 80 mg/day.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
No dose adjustment needed.
Moderate:
No dose adjustment needed.
Severe:
No dose adjustment needed.
Dialysis:
Not studied; use with caution.
Hepatic Impairment:
Mild:
No dose adjustment needed.
Moderate:
Initial 40 mg orally once daily. Max 40 mg/day.
Severe:
Initial 40 mg orally once daily. Max 40 mg/day.
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 and chorea associated with Huntington's disease is unknown, but it is thought to be mediated through the reversible inhibition of VMAT2, leading to a reduction in the amount of dopamine released from presynaptic neurons.
Pharmacokinetics
Absorption:
Bioavailability:
Not explicitly quantified, well absorbed.
Tmax:
Valbenazine: 0.5-2 hours; Îą-dihydrotetrabenazine (active metabolite): 4-8 hours.
FoodEffect:
High-fat meal decreases Cmax by 27% and AUC by 10% for valbenazine, but increases Cmax by 29% and AUC by 12% for Îą-dihydrotetrabenazine. Can be taken with or without food.
Distribution:
Vd:
Valbenazine: 92 L; Îą-dihydrotetrabenazine: 120 L.
ProteinBinding:
Valbenazine: >99%; Îą-dihydrotetrabenazine: 60%.
CnssPenetration:
Yes
Elimination:
HalfLife:
Valbenazine: 15-22 hours; Îą-dihydrotetrabenazine: 15-22 hours.
Clearance:
Primarily hepatic.
ExcretionRoute:
Urine (60%), Feces (30%).
Unchanged:
<1% in urine.
Pharmacodynamics
OnsetOfAction:
Within 1-2 weeks (clinical effect).
PeakEffect:
Not precisely defined, but steady state reached within 1 week.
DurationOfAction:
Not precisely defined, but consistent with once-daily dosing and half-life.
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, this medication can cause severe and potentially life-threatening side effects. If you experience any of the following symptoms, contact your doctor or seek medical attention immediately:
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 similar to Parkinson's disease, such as:
+ Difficulty moving or walking
+ Trouble controlling body movements
+ Shakiness
+ Balance problems or falls
+ Drooling
Neuroleptic malignant syndrome (NMS), a rare but potentially life-threatening condition, which can cause:
+ Fever
+ Muscle cramps or stiffness
+ Dizziness
+ Severe headache
+ Confusion
+ Changes in thinking
+ Fast or 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
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to contact your doctor if you're bothered by any of the following:
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, this medication can cause severe and potentially life-threatening side effects. If you experience any of the following symptoms, contact your doctor or seek medical attention immediately:
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 similar to Parkinson's disease, such as:
+ Difficulty moving or walking
+ Trouble controlling body movements
+ Shakiness
+ Balance problems or falls
+ Drooling
Neuroleptic malignant syndrome (NMS), a rare but potentially life-threatening condition, which can cause:
+ Fever
+ Muscle cramps or stiffness
+ Dizziness
+ Severe headache
+ Confusion
+ Changes in thinking
+ Fast or 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
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to contact your doctor if you're bothered by any of the following:
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 of your involuntary movements or new types of movements.
- New or worsening depression, anxiety, or agitation.
- Thoughts of harming yourself or others (suicidal ideation).
- Unusual changes in behavior or mood.
- Severe dizziness or fainting spells.
- Fast, pounding, or irregular heartbeat.
- Difficulty breathing or swallowing.
- Signs of an allergic reaction (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. Describe the allergic reaction you experienced, including the symptoms that occurred.
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 medications, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins, that may interact with this medication. This includes, but is not limited to, rifampin, St. John's Wort, and certain antiseizure medications.
If you are breastfeeding, as you should not breastfeed while taking this medication and for 5 days after your last dose.
To ensure safe use, it is crucial to provide your doctor and pharmacist with a comprehensive list of all your medications, including prescription and OTC drugs, natural products, and vitamins, as well as any health problems you have. This will help determine if it is safe to take this medication with your other medications and health conditions. Do not 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. Describe the allergic reaction you experienced, including the symptoms that occurred.
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 medications, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins, that may interact with this medication. This includes, but is not limited to, rifampin, St. John's Wort, and certain antiseizure medications.
If you are breastfeeding, as you should not breastfeed while taking this medication and for 5 days after your last dose.
To ensure safe use, it is crucial to provide your doctor and pharmacist with a comprehensive list of all your medications, including prescription and OTC drugs, natural products, and vitamins, as well as any health problems you have. This will help determine if it is safe to take this medication with your other medications and health conditions. Do not 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.
Until you understand how this drug affects you, avoid operating a vehicle or engaging in any activities that require your full attention. Before consuming alcohol, using marijuana or other cannabis products, or taking any prescription or over-the-counter medications that may cause drowsiness, consult with your doctor.
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.
This medication may pose a risk to an unborn baby if taken during pregnancy. If you are pregnant or become pregnant while taking this drug, notify your doctor right away.
Until you understand how this drug affects you, avoid operating a vehicle or engaging in any activities that require your full attention. Before consuming alcohol, using marijuana or other cannabis products, or taking any prescription or over-the-counter medications that may cause drowsiness, consult with your doctor.
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.
This medication may pose a risk to an unborn baby if taken during pregnancy. If you are pregnant or become pregnant while taking this drug, notify your doctor right away.
Overdose Information
Overdose Symptoms:
- Severe somnolence (extreme drowsiness)
- Dizziness
- Confusion
- Dyskinetic movements (uncontrolled movements)
- Hypotension (low blood pressure)
- QT prolongation (abnormal heart rhythm)
What to Do:
Seek immediate medical attention. Call 911 or Poison Control at 1-800-222-1222. Treatment is supportive, including monitoring of vital signs and ECG.
Drug Interactions
Major Interactions
- Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin): Reduce valbenazine dose to 40 mg/day.
- Strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine, quinidine): Reduce valbenazine dose to 40 mg/day.
- Drugs that prolong QT interval: Use with caution, monitor ECG.
- Monoamine Oxidase Inhibitors (MAOIs): Concomitant use not recommended due to theoretical risk of hypertensive crisis (though mechanism differs from MAOIs).
Moderate Interactions
- Moderate CYP3A4 inhibitors: Consider dose reduction.
- Moderate CYP2D6 inhibitors: Consider dose reduction.
Monitoring
Baseline Monitoring
ECG
Rationale: To assess baseline QT interval, especially in patients with cardiac disease or on other QT-prolonging drugs.
Timing: Prior to initiation of therapy.
Liver function tests (LFTs)
Rationale: To assess hepatic function, as dose adjustments are needed for moderate to severe hepatic impairment.
Timing: Prior to initiation of therapy, especially if hepatic impairment is suspected.
Routine Monitoring
Clinical response (e.g., AIMS scale for TD, UHDRS for HD chorea)
Frequency: Regularly during dose titration and maintenance.
Target: Reduction in involuntary movements.
Action Threshold: Lack of improvement or worsening of symptoms may require dose adjustment or re-evaluation.
Adverse effects (e.g., somnolence, fatigue, anticholinergic effects, parkinsonism, akathisia, QT prolongation)
Frequency: Regularly, especially during dose titration.
Target: Minimization of side effects.
Action Threshold: Significant or bothersome side effects may require dose reduction or discontinuation.
ECG
Frequency: Periodically, especially if dose is increased, or if concomitant QT-prolonging drugs are initiated.
Target: Normal QT interval.
Action Threshold: Significant QT prolongation (e.g., QTc >500 ms or increase >60 ms from baseline) may require dose reduction or discontinuation.
Mental status/mood
Frequency: Regularly.
Target: Stable mood, absence of suicidal ideation.
Action Threshold: New or worsening depression, suicidal thoughts, or unusual behavioral changes require immediate evaluation.
Symptom Monitoring
- Somnolence
- Fatigue
- Dry mouth
- Constipation
- Blurred vision
- Urinary retention
- Akathisia (inner restlessness)
- Parkinsonism (tremor, rigidity, bradykinesia)
- Restlessness
- Agitation
- Depression
- Suicidal ideation
- Irregular heartbeat
- Dizziness
- Fainting
Special Patient Groups
Pregnancy
Limited human data on valbenazine use in pregnant women. Animal studies have shown developmental toxicity (e.g., increased fetal mortality, reduced fetal weight, skeletal abnormalities) at exposures similar to or greater than clinical exposures. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Trimester-Specific Risks:
First Trimester:
Potential for developmental toxicity 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 unknown if valbenazine or its metabolites are excreted in human milk. Valbenazine and its metabolites are excreted in rat milk. Due to the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment with valbenazine and for 5 days after the last dose.
Infant Risk:
Potential for serious adverse reactions (e.g., somnolence, effects on central nervous system).
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
Geriatric Use
No overall differences in safety or effectiveness were observed between elderly patients (65 years and older) and younger patients. No dose adjustment is generally needed based on age alone.
Clinical Information
Clinical Pearls
- Valbenazine is the first and only FDA-approved VMAT2 inhibitor specifically for tardive dyskinesia.
- It can be taken with or without food, offering dosing flexibility.
- Patients should be monitored for somnolence and advised to use caution when driving or operating machinery.
- While not carrying a Black Box Warning for suicidality like tetrabenazine, patients should still be monitored for new or worsening depression and suicidal ideation.
- Dose titration is important to optimize efficacy while managing potential side effects.
Alternative Therapies
- Deutetrabenazine (Austedo) - another VMAT2 inhibitor for TD and HD chorea.
- Tetrabenazine (Xenazine) - a VMAT2 inhibitor for HD chorea (off-label for TD).
- For TD: Off-label use of benzodiazepines, botulinum toxin injections, or switching/reducing dose of causative antipsychotics.
- For HD chorea: Symptomatic treatments for other HD symptoms.
Cost & Coverage
Average Cost:
Highly variable, typically $7,000 - $10,000+ per 30 capsules
Insurance Coverage:
Specialty Tier (requires prior authorization)
General Drug Facts
If your symptoms or health problems do not improve or worsen over time, it is essential to contact your doctor for further evaluation and guidance. To ensure safe and effective treatment, never share your medication with others or take someone else's medication.
This medication is accompanied by a Medication Guide, a patient fact sheet that provides crucial information about its use. It is vital to read this guide carefully and review it again whenever your prescription is refilled. If you have any questions or concerns about this medication, consult your doctor, pharmacist, or other healthcare provider for clarification.
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 detailed information, including the name of the medication taken, the amount consumed, and the time it occurred.
This medication is accompanied by a Medication Guide, a patient fact sheet that provides crucial information about its use. It is vital to read this guide carefully and review it again whenever your prescription is refilled. If you have any questions or concerns about this medication, consult your doctor, pharmacist, or other healthcare provider for clarification.
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 detailed information, including the name of the medication taken, the amount consumed, and the time it occurred.