Ingrezza 60mg 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, known as tardive dyskinesia, and also the involuntary movements associated with Huntington's disease, called chorea. It works by affecting certain chemicals in the brain to help reduce these movements.
How to Use This Medicine
Taking Your Medication Correctly
To get the most benefit from your medication, it's essential to take it exactly as directed by your doctor. Carefully read all the information provided with your prescription, and follow the instructions closely. You can take this medication with or without food. Continue taking your medication as prescribed by your doctor or healthcare provider, even if you start feeling well.
Storing and Disposing of Your Medication
To maintain the quality and safety of your medication, store it at room temperature in a dry place, avoiding bathrooms. Keep all medications in a secure location, out of the 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 with your pharmacist for guidance on the best disposal method. You may also want to explore local drug take-back programs in your area.
What to Do If You Miss 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 get the most benefit from your medication, it's essential to take it exactly as directed by your doctor. Carefully read all the information provided with your prescription, and follow the instructions closely. You can take this medication with or without food. Continue taking your medication as prescribed by your doctor or healthcare provider, even if you start feeling well.
Storing and Disposing of Your Medication
To maintain the quality and safety of your medication, store it at room temperature in a dry place, avoiding bathrooms. Keep all medications in a secure location, out of the 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 with your pharmacist for guidance on the best disposal method. You may also want to explore local drug take-back programs in your area.
What to Do If You Miss 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 exactly as prescribed by your doctor, usually once daily.
- Can be taken with or without food.
- Do not stop taking Ingrezza suddenly without talking to your doctor, as this could worsen your symptoms.
- Avoid alcohol or other sedating medications, as Ingrezza can cause drowsiness.
- Be cautious when driving or operating machinery until you know how Ingrezza affects you.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
For Tardive Dyskinesia: Initial 40 mg once daily; after 1 week, increase to 80 mg once daily. For Chorea associated with Huntington's Disease: Initial 40 mg once daily; after 2 weeks, increase to 60 mg once daily; after another 2 weeks, may increase to 80 mg once daily if needed.
Dose Range:
40 - 80 mg
Condition-Specific Dosing:
Tardive Dyskinesia:
Initial 40 mg once daily, increase to 80 mg once daily after 1 week.
Chorea associated with Huntington's Disease:
Initial 40 mg once daily, increase to 60 mg after 2 weeks, then 80 mg after 2 weeks if needed.
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:
Maximum recommended dose is 40 mg once daily (CrCl <30 mL/min, including ESRD).
Dialysis:
Maximum recommended dose is 40 mg once daily for patients with ESRD on dialysis.
Hepatic Impairment:
Mild:
Maximum recommended dose is 40 mg once daily (Child-Pugh A).
Moderate:
Maximum recommended dose is 40 mg once daily (Child-Pugh B).
Severe:
Not recommended (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 and chorea associated with Huntington's disease is unknown, but it is thought to be mediated through the reversible inhibition of VMAT2, leading to reduced dopamine release from presynaptic terminals.
Pharmacokinetics
Absorption:
Bioavailability:
Not explicitly quantified, but well absorbed.
Tmax:
0.5-4 hours (valbenazine); 4-5 hours (alpha-dihydrotetrabenazine [a-HTBZ], active metabolite)
FoodEffect:
Food (high-fat meal) decreases Cmax and AUC of valbenazine and a-HTBZ slightly, but not considered clinically significant. Can be taken with or without food.
Distribution:
Vd:
Approximately 92 L (valbenazine); Approximately 120 L (a-HTBZ)
ProteinBinding:
Approximately 99% (valbenazine); Approximately 60% (a-HTBZ)
CnssPenetration:
Yes
Elimination:
HalfLife:
Approximately 15-22 hours (valbenazine and a-HTBZ)
Clearance:
Not explicitly quantified, but primarily hepatic metabolism.
ExcretionRoute:
Urine (approximately 60%), Feces (approximately 30%)
Unchanged:
<2% (in urine)
Pharmacodynamics
OnsetOfAction:
Clinical improvement typically observed within weeks.
PeakEffect:
Steady-state concentrations are reached within 1 week.
DurationOfAction:
Sustained effect with once-daily dosing due to long half-life of parent drug and active metabolite.
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 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 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 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 deadly 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 or your child experience any of the following:
Drowsiness
Fatigue or weakness
Dry mouth
Constipation
Restlessness
* Trouble sleeping
These are not all the possible side effects that may occur. 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 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 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 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 deadly 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 or your child experience any of the following:
Drowsiness
Fatigue or weakness
Dry mouth
Constipation
Restlessness
* Trouble sleeping
These are not all the possible side effects that may occur. 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:
- New or worsening depression, anxiety, or agitation
- Thoughts about self-harm or suicide
- Unusual changes in behavior or mood
- Restlessness or feeling unable to sit still (akathisia)
- New or worsening tremors, stiffness, or slow movements (parkinsonism)
- Severe dizziness or fainting spells
- Fast or irregular heartbeat
- Signs of an allergic reaction (rash, hives, swelling of face/lips/tongue/throat, difficulty 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 of certain medications for depression or Parkinson's disease within the last 14 days, 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. Specifically, inform your doctor about rifampin, St. John's Wort, or certain antiseizure medications, as these may interact with this drug.
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 your healthcare team determine whether it is safe for you 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 of certain medications for depression or Parkinson's disease within the last 14 days, 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. Specifically, inform your doctor about rifampin, St. John's Wort, or certain antiseizure medications, as these may interact with this drug.
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 your healthcare team determine whether it is safe for you 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.
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:
- Severe drowsiness
- Dizziness
- Confusion
- Hypotension (low blood pressure)
- QTc prolongation
- Extrapyramidal symptoms (e.g., dystonia, parkinsonism)
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 inducers (e.g., rifampin, carbamazepine, phenytoin): Avoid coadministration as they can significantly decrease valbenazine exposure and efficacy.
Moderate Interactions
- Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, itraconazole): Reduce valbenazine dose to 40 mg once daily.
- QT-prolonging drugs (e.g., quinidine, procainamide, amiodarone, sotalol, antipsychotics, antidepressants): Use with caution, as valbenazine can prolong the QTc interval.
Minor Interactions
- Strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine, quinidine): No dose adjustment needed for valbenazine, but exposure to the active metabolite a-HTBZ may increase.
- Digoxin: Valbenazine is a weak P-gp inhibitor and may increase digoxin levels. Monitor digoxin levels if coadministered.
Monitoring
Baseline Monitoring
Electrocardiogram (ECG)
Rationale: To assess baseline QTc interval, especially in patients with pre-existing cardiac conditions or those on other QT-prolonging medications.
Timing: Prior to initiation of therapy.
Liver Function Tests (LFTs)
Rationale: To assess hepatic function, as dose adjustments are required for hepatic impairment.
Timing: Prior to initiation of therapy.
Renal Function Tests (e.g., CrCl)
Rationale: To assess renal function, as dose adjustments are required for severe renal impairment.
Timing: Prior to initiation of therapy.
Routine Monitoring
Clinical assessment of tardive dyskinesia/chorea symptoms
Frequency: Regularly, as clinically indicated (e.g., at follow-up visits)
Target: Reduction in abnormal involuntary movements (e.g., lower AIMS score)
Action Threshold: Lack of improvement or worsening symptoms may warrant dose adjustment or re-evaluation.
Adverse effects monitoring (e.g., somnolence, fatigue, akathisia, parkinsonism, QT prolongation)
Frequency: Regularly, especially during dose titration and at follow-up visits.
Target: Absence or tolerability of side effects.
Action Threshold: Intolerable side effects may require dose reduction or discontinuation.
QTc interval (if risk factors present)
Frequency: As clinically indicated, especially if new QT-prolonging drugs are added or cardiac symptoms develop.
Target: Within normal limits or acceptable for patient's baseline.
Action Threshold: Significant QTc prolongation (>500 ms or >60 ms increase from baseline) may require dose reduction or discontinuation.
Symptom Monitoring
- Worsening of tardive dyskinesia or chorea symptoms
- New or worsening depression, suicidal thoughts or behavior
- Akathisia (inner restlessness, inability to sit still)
- Parkinsonism (tremor, rigidity, bradykinesia)
- Somnolence (drowsiness)
- Fatigue
- Signs of hypersensitivity reactions (rash, itching, swelling)
- Symptoms of QT prolongation (dizziness, palpitations, syncope)
Special Patient Groups
Pregnancy
Limited human data on valbenazine use in pregnant women are insufficient to inform a drug-associated risk for major birth defects or miscarriage. Animal studies have shown developmental toxicity (e.g., increased 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 developmental toxicity observed in animal studies at high doses.
Second Trimester:
Potential for developmental toxicity observed in animal studies at high doses.
Third Trimester:
Potential for developmental toxicity observed in animal studies at high doses.
Lactation
It is not known whether valbenazine or its metabolites are excreted in human milk. Valbenazine and its metabolites are excreted in the milk of lactating rats. Because of the potential for serious adverse reactions in breastfed infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Infant Risk:
Unknown; potential for serious adverse reactions based on animal data.
Pediatric Use
Safety and effectiveness of valbenazine have not been established in pediatric patients.
Geriatric Use
No overall differences in safety or effectiveness were observed between older and younger patients. However, greater sensitivity of some older individuals cannot be ruled out. Dose adjustments for renal or hepatic impairment should be followed.
Clinical Information
Clinical Pearls
- Valbenazine is a highly selective VMAT2 inhibitor, which contributes to its favorable side effect profile compared to older dopamine-blocking agents.
- The dose titration schedule is important for managing potential side effects and optimizing efficacy.
- Patients should be monitored for new or worsening psychiatric symptoms, including depression and suicidality, especially in the context of Huntington's disease.
- Ingrezza can be taken with or without food, offering flexibility for patients.
- It is crucial to educate patients not to abruptly discontinue the medication, as this can lead to worsening of dyskinesia or chorea.
Alternative Therapies
- Deutetrabenazine (Austedo, another VMAT2 inhibitor)
- Tetrabenazine (Xenazine, an older VMAT2 inhibitor, less selective)
- For Tardive Dyskinesia: Off-label use of atypical antipsychotics (e.g., clozapine, quetiapine) in some cases, or benzodiazepines, though these are not primary treatments for TD itself.
- For Chorea associated with Huntington's Disease: Other symptomatic treatments for HD (e.g., antipsychotics for behavioral symptoms).
Cost & Coverage
Average Cost:
Highly variable, typically several thousand USD per 30 capsules
Insurance Coverage:
Specialty Tier (requires prior authorization, step therapy)
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 or take someone else's medication. This medication is accompanied by a Medication Guide, which provides crucial information for patients. Please read this guide carefully and review it again whenever you receive a refill of this medication. 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 reporting the incident, be prepared to provide details about the medication taken, the quantity, and the time it occurred.