Ingrezza 40mg 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
Vesicular Monoamine Transporter 2 (VMAT2) Inhibitor
Pharmacologic Class
VMAT2 Inhibitor
Pregnancy Category
Not available
FDA Approved
Apr 2017
DEA Schedule
Not Controlled
Overview
What is this medicine?
Ingrezza (valbenazine) is a medication used to treat uncontrolled, involuntary movements of the face and body, a condition called tardive dyskinesia. It works by affecting certain chemical messengers in the brain to help reduce these movements.
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 the bathroom. 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 the bathroom. 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
- Take exactly as prescribed, with or without food.
- Do not stop taking without consulting your doctor, as symptoms may worsen.
- Avoid driving or operating heavy machinery until you know how Ingrezza affects you, as it can cause drowsiness or dizziness.
- Inform your doctor about all other medications you are taking, including over-the-counter drugs, supplements, and herbal products, especially those that can affect heart rhythm.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
40 mg orally once daily for 1 week, then increase to 80 mg orally once daily
Dose Range:
40 - 80 mg
Condition-Specific Dosing:
initial:
40 mg once daily for 1 week
maintenance:
80 mg once daily
reduced_dose_with_strong_CYP3A4_inhibitors:
40 mg once daily
reduced_dose_with_strong_CYP2D6_inhibitors:
Not required, but monitor for adverse reactions
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:
No dose adjustment needed
Hepatic Impairment:
Mild:
No dose adjustment needed
Moderate:
Initial dose 40 mg once daily, then consider increasing to 60 mg once daily after 1 week based on response and tolerability.
Severe:
Initial dose 40 mg once daily, then consider increasing to 60 mg once daily after 1 week based on response and tolerability.
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 a reduction in the amount of dopamine released from presynaptic terminals.
Pharmacokinetics
Absorption:
Bioavailability:
Not available (extensive first-pass metabolism)
Tmax:
0.5 to 2 hours (valbenazine); 4 to 8 hours (active metabolite, Îą-dihydrotetrabenazine)
FoodEffect:
High-fat meal decreases Cmax by 16% and AUC by 6% for valbenazine, and decreases Cmax by 28% and AUC by 17% for Îą-dihydrotetrabenazine. Can be taken with or without food.
Distribution:
Vd:
92 L (valbenazine); 120 L (Îą-dihydrotetrabenazine)
ProteinBinding:
99% (valbenazine); 60% (Îą-dihydrotetrabenazine)
CnssPenetration:
Yes
Elimination:
HalfLife:
15 to 22 hours (valbenazine); 15 to 22 hours (Îą-dihydrotetrabenazine)
Clearance:
Not available
ExcretionRoute:
Primarily urine (60%), feces (30%)
Unchanged:
<2% (valbenazine); <1% (Îą-dihydrotetrabenazine)
Pharmacodynamics
OnsetOfAction:
Within 2 weeks (clinical trials)
PeakEffect:
Not precisely defined, sustained effect with continued dosing
DurationOfAction:
24 hours (due to long half-life of active metabolite)
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 immediately or seek emergency 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 similar to 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 rare but 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 taking this medication do not experience severe side effects. However, some may occur. If you experience any of the following side effects, contact your doctor 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, this medication can cause severe and potentially life-threatening side effects. If you experience any of the following symptoms, contact your doctor immediately or seek emergency 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 similar to 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 rare but 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 taking this medication do not experience severe side effects. However, some may occur. If you experience any of the following side effects, contact your doctor 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:
- Severe dizziness or fainting spells (may indicate heart rhythm problems)
- New or worsening involuntary movements
- Severe drowsiness or sedation
- Restlessness or feeling like you need to move (akathisia)
- Symptoms of Parkinson's disease (e.g., tremor, stiffness, slow movement)
- 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 conditions to ensure safe treatment:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Describe the allergic reaction and its symptoms.
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, or vitamins, that may interact with this medication. Specifically, inform your doctor about rifampin, St. John's Wort, or certain antiseizure medications, as these may have significant interactions.
Breastfeeding status: Do not breastfeed while taking this medication and for 5 days after the last dose.
To ensure your safety, 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 treatments. Never start, stop, or change the dose of any medication without consulting your doctor first.
It is essential to inform your doctor about the following conditions to ensure safe treatment:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Describe the allergic reaction and its symptoms.
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, or vitamins, that may interact with this medication. Specifically, inform your doctor about rifampin, St. John's Wort, or certain antiseizure medications, as these may have significant interactions.
Breastfeeding status: Do not breastfeed while taking this medication and for 5 days after the last dose.
To ensure your safety, 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 treatments. Never start, stop, or change the dose of any medication without consulting your doctor first.
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 activities that require alertness. Before consuming alcohol, using marijuana or other cannabis products, or taking prescription or over-the-counter medications that may impair your reactions, consult with your doctor. If you have Huntington's disease, be aware that your symptoms may still worsen while using this medication. Immediately contact your doctor if you experience new or worsening symptoms. Additionally, this drug may pose a risk to the unborn baby if taken during pregnancy. If you are pregnant or become pregnant while taking this medication, notify your doctor promptly.
Overdose Information
Overdose Symptoms:
- Severe drowsiness
- Dizziness
- Confusion
- Nausea
- Vomiting
- Diarrhea
- Hypotension
- QT prolongation
What to Do:
Seek immediate medical attention or call Poison Control at 1-800-222-1222. Treatment is supportive and symptomatic. Monitor cardiac rhythm (ECG) and vital signs.
Drug Interactions
Major Interactions
- Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir): Reduce valbenazine dose.
- Drugs that prolong QT interval (e.g., quinidine, procainamide, amiodarone, sotalol, ziprasidone, chlorpromazine, thioridazine, moxifloxacin): Concomitant use may increase risk of QT prolongation. Avoid if possible or use with caution.
Moderate Interactions
- Strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine, quinidine): No dose adjustment for valbenazine, but monitor for adverse reactions.
- Digoxin: Valbenazine may increase digoxin exposure; monitor digoxin levels.
Monitoring
Baseline Monitoring
Electrocardiogram (ECG)
Rationale: To assess baseline QTc interval, as valbenazine can prolong the QT interval.
Timing: Prior to initiation, especially in patients at risk for QT prolongation.
Liver function tests (LFTs)
Rationale: To assess hepatic impairment, which may require dose adjustment.
Timing: Prior to initiation in patients with suspected hepatic impairment.
Routine Monitoring
Clinical response to tardive dyskinesia
Frequency: Regularly, e.g., monthly or as clinically indicated
Target: Reduction in AIMS (Abnormal Involuntary Movement Scale) score
Action Threshold: Lack of efficacy or worsening symptoms may require dose adjustment or re-evaluation.
Adverse reactions (e.g., somnolence, fatigue, akathisia, parkinsonism)
Frequency: Regularly, especially during dose titration and maintenance
Target: Absence or minimal severity of adverse effects
Action Threshold: Significant or bothersome adverse effects may require dose reduction or discontinuation.
QTc interval (ECG)
Frequency: As clinically indicated, especially if new cardiac symptoms or concomitant QT-prolonging drugs are initiated.
Target: Normal QTc interval (e.g., <450 ms for males, <470 ms for females)
Action Threshold: QTc >500 ms or increase of >60 ms from baseline; consider dose reduction or discontinuation.
Symptom Monitoring
- Worsening of tardive dyskinesia
- Somnolence/sedation
- Fatigue
- Akathisia (restlessness)
- Parkinsonism (tremor, rigidity, bradykinesia)
- Dizziness
- Nausea
- Cardiac symptoms (palpitations, syncope, dizziness) suggestive of QT prolongation
Special Patient Groups
Pregnancy
Limited data on valbenazine use in pregnant women are insufficient to inform a drug-associated risk for major birth defects or miscarriage. Consider the potential for fetal harm.
Trimester-Specific Risks:
First Trimester:
Risk unknown, animal studies showed developmental toxicity at high doses.
Second Trimester:
Risk unknown.
Third Trimester:
Risk unknown.
Lactation
It is not known if valbenazine or its metabolites are excreted in human milk. Because of the potential for serious adverse reactions in breastfed infants, including somnolence and effects on central nervous system, advise women not to breastfeed during treatment with valbenazine and for 5 days after the final dose.
Infant Risk:
Potential for somnolence, central nervous system effects.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established. Not indicated for use 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 of valbenazine, particularly somnolence and QT prolongation. Monitor closely.
Clinical Information
Clinical Pearls
- Valbenazine is a once-daily oral medication for tardive dyskinesia.
- Initial dose is 40 mg for one week, then typically increased to 80 mg daily, but individual response and tolerability should guide titration.
- Can be taken with or without food.
- Patients should be monitored for somnolence, fatigue, and QT prolongation, especially during initiation and dose adjustments.
- No dose adjustment needed for renal impairment, but dose adjustment is recommended for moderate to severe hepatic impairment.
- Avoid concomitant use with other drugs that prolong the QT interval if possible.
- Not indicated for drug-induced parkinsonism or other movement disorders.
Alternative Therapies
- Deutetrabenazine (Austedo) - another VMAT2 inhibitor for tardive dyskinesia and Huntington's disease chorea.
Cost & Coverage
Average Cost:
$7,000 - $8,000 per 30 capsules (40mg or 80mg)
Insurance Coverage:
Specialty Tier (requires prior authorization)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe use, never share your medication with others, and do not take medication prescribed to someone else. This medication is accompanied by a Medication Guide, which is a crucial patient fact sheet. Please read it carefully and review it again whenever you receive a refill. If you have any questions or concerns about this medication, consult 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 seeking help, be prepared to provide information about the medication taken, the amount, and the time it occurred.