Ingrezza 40mg Sprinkle 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
Agent for tardive dyskinesia
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 (valbenazine) is a medication used to treat uncontrolled body movements, often in the face, arms, or legs, called tardive dyskinesia. This condition can be a side effect of certain medicines used for mental health conditions. Ingrezza works by helping to balance certain chemicals in the brain that control movement.
How to Use This Medicine
Taking Your Medication
To take this medication correctly, follow your doctor's instructions and read all the information provided. Take your medication with or without food, as directed by your healthcare provider. Continue taking your medication as prescribed, even if you start to feel better.
You can swallow your medication whole with a glass of water. Alternatively, you can open the capsule and mix the contents with a small amount of soft food, such as applesauce, yogurt, or pudding (about 1 tablespoon or 15 mL). Do not mix the medication with milk or water. Stir the mixture well and swallow it immediately. Then, drink a full glass of water (8 ounces or 240 mL). Be sure not to crush or chew the medication.
If you need to prepare the mixture in advance, you can store it at room temperature for up to 2 hours. However, discard the mixture if it has not been taken within 2 hours. Do not administer this medication through a feeding tube.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, away from the bathroom. Keep the medication in its original container with the lid tightly closed. Store all medications in a safe location, out of the reach of children and pets.
Missing a Dose
If you miss a dose, take it as soon as you remember. However, if it is 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 a missed dose.
To take this medication correctly, follow your doctor's instructions and read all the information provided. Take your medication with or without food, as directed by your healthcare provider. Continue taking your medication as prescribed, even if you start to feel better.
You can swallow your medication whole with a glass of water. Alternatively, you can open the capsule and mix the contents with a small amount of soft food, such as applesauce, yogurt, or pudding (about 1 tablespoon or 15 mL). Do not mix the medication with milk or water. Stir the mixture well and swallow it immediately. Then, drink a full glass of water (8 ounces or 240 mL). Be sure not to crush or chew the medication.
If you need to prepare the mixture in advance, you can store it at room temperature for up to 2 hours. However, discard the mixture if it has not been taken within 2 hours. Do not administer this medication through a feeding tube.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, away from the bathroom. Keep the medication in its original container with the lid tightly closed. Store all medications in a safe location, out of the reach of children and pets.
Missing a Dose
If you miss a dose, take it as soon as you remember. However, if it is 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 a missed dose.
Lifestyle & Tips
- Avoid alcohol and other medications that cause drowsiness, as Ingrezza can increase these effects.
- Use caution when driving or operating machinery until you know how Ingrezza affects you, due to potential for somnolence.
- Take the capsule whole or open and sprinkle the contents on a small amount (e.g., 1 tablespoon) of soft food (e.g., applesauce, yogurt). Consume immediately without chewing. Do not store for later use.
- Do not crush or chew the capsule contents if sprinkled.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
Initial 40 mg orally once daily; after 1 week, increase to 80 mg orally once daily.
Dose Range:
40 - 80 mg
Condition-Specific Dosing:
Tardive Dyskinesia:
Initial 40 mg orally once daily; after 1 week, increase to 80 mg orally 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 adjustment needed
Moderate:
No adjustment needed
Severe:
No adjustment needed
Dialysis:
Not studied; avoid use in patients with end-stage renal disease (ESRD).
Hepatic Impairment:
Mild:
No adjustment needed
Moderate:
No adjustment needed
Severe:
Max 40 mg orally once daily.
Pharmacology
Mechanism of Action
Valbenazine is a prodrug that is converted to the active metabolite, dihydrotetrabenazine (DTBZ). DTBZ is a highly selective, reversible inhibitor of vesicular monoamine transporter 2 (VMAT2). The inhibition of VMAT2 leads to a reduction in the uptake of monoamines (like dopamine) into synaptic vesicles and a subsequent decrease in their release into the synaptic cleft. This mechanism is thought to reduce the involuntary movements associated with tardive dyskinesia.
Pharmacokinetics
Absorption:
Bioavailability:
Not available (prodrug)
Tmax:
0.5-4 hours (valbenazine); 4-8 hours (DTBZ)
FoodEffect:
High-fat meal decreases Cmax and AUC of valbenazine and DTBZ by approximately 10-20%, but this is not considered clinically significant. Can be taken with or without food.
Distribution:
Vd:
92-102 L (valbenazine); 120 L (DTBZ)
ProteinBinding:
>99% (valbenazine); 60-64% (DTBZ)
CnssPenetration:
Yes
Elimination:
HalfLife:
15-22 hours (valbenazine); 9-10 hours (DTBZ)
Clearance:
Not available
ExcretionRoute:
Primarily urine (60%), feces (30%)
Unchanged:
<2% (in urine)
Pharmacodynamics
OnsetOfAction:
Clinical improvement may be observed within 1-2 weeks.
PeakEffect:
Maximal effect typically seen within 2-8 weeks of stable dosing.
DurationOfAction:
Related to half-life; effects persist for approximately 24 hours 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 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:
+ Difficulty moving or walking
+ Trouble 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 experience minimal 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 persist:
Drowsiness
Fatigue or weakness
Dry mouth
Constipation
Restlessness
* Trouble sleeping
Reporting Side Effects
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 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:
+ Difficulty moving or walking
+ Trouble 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 experience minimal 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 persist:
Drowsiness
Fatigue or weakness
Dry mouth
Constipation
Restlessness
* Trouble sleeping
Reporting Side Effects
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 onset of uncontrolled movements.
- Symptoms of Parkinson's disease (e.g., shaking, stiffness, difficulty moving).
- Restlessness or feeling like you can't sit still (akathisia).
- Excessive drowsiness or feeling very sleepy.
- Signs of a serious reaction called Neuroleptic Malignant Syndrome (NMS), such as high fever, stiff muscles, confusion, sweating, or fast/irregular heartbeat.
- Signs of heart rhythm problems (QT prolongation), such as dizziness, lightheadedness, fainting, or a fast/pounding heartbeat.
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 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 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. Many drugs cannot be taken with this medication, 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 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 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 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. Many drugs cannot be taken with this medication, 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 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:
- Somnolence (excessive sleepiness)
- Dystonia (sustained muscle contractions)
- Dyskinesia (involuntary movements)
What to Do:
There is no specific antidote for valbenazine overdose. Management should be supportive, including general supportive measures and symptomatic treatment. Contact a poison control center (1-800-222-1222) or seek emergency medical attention immediately.
Drug Interactions
Major Interactions
- Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, itraconazole, ritonavir): Reduce valbenazine dose to 40 mg once daily.
- QT-prolonging drugs: Use with caution; may have additive effect on QTc interval.
- Drugs causing somnolence (e.g., alcohol, benzodiazepines, hypnotics, antipsychotics): May increase somnolence.
Moderate Interactions
- Moderate CYP3A4 inhibitors (e.g., erythromycin, diltiazem, verapamil, fluconazole): Consider reducing valbenazine dose to 40 mg once daily if adverse reactions occur.
- Strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine, quinidine): No dose adjustment for valbenazine, but valbenazine may increase exposure of CYP2D6 substrates.
Monitoring
Baseline Monitoring
Neurological assessment (e.g., AIMS scale)
Rationale: To establish baseline severity of tardive dyskinesia and monitor treatment response.
Timing: Prior to initiation of therapy.
Electrocardiogram (ECG) for QTc interval
Rationale: To assess baseline cardiac conduction, especially in patients with pre-existing cardiac conditions or those on other QT-prolonging medications.
Timing: Prior to initiation of therapy, particularly in patients at risk for QT prolongation.
Routine Monitoring
Neurological assessment (e.g., AIMS scale)
Frequency: Periodically (e.g., every 4-8 weeks during titration, then every 3-6 months)
Target: Reduction in AIMS score indicating improvement in TD symptoms.
Action Threshold: Worsening or lack of improvement may warrant dose adjustment or re-evaluation of therapy.
QTc interval
Frequency: As clinically indicated, especially if new cardiac symptoms develop or if co-administered with other QT-prolonging drugs.
Target: Normal QTc interval (e.g., <450 ms for males, <470 ms for females).
Action Threshold: Significant QTc prolongation (>500 ms or increase of >60 ms from baseline) may require dose reduction or discontinuation.
Mental status/CNS effects
Frequency: Regularly
Target: Absence of excessive somnolence, sedation, or parkinsonism.
Action Threshold: Significant somnolence, sedation, or emergence/worsening of parkinsonism may require dose reduction.
Symptom Monitoring
- Worsening or new onset of tardive dyskinesia symptoms
- Symptoms of parkinsonism (e.g., tremor, rigidity, bradykinesia)
- Akathisia (restlessness, inability to sit still)
- Excessive somnolence or sedation
- Signs of neuroleptic malignant syndrome (NMS) such as high fever, muscle rigidity, altered mental status, autonomic instability
- Symptoms of QT prolongation (e.g., dizziness, palpitations, syncope, seizures)
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, reduced fetal weight, skeletal abnormalities) at exposures higher than clinical exposures. Use 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 not known whether valbenazine or its metabolites are excreted in human milk. Valbenazine and its metabolites are excreted in the milk of lactating rats. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Ingrezza and any potential adverse effects on the breastfed infant from Ingrezza or from the underlying maternal condition. A decision should be made whether to discontinue breastfeeding or to discontinue the drug.
Infant Risk:
Risk unknown; potential for somnolence or other adverse effects in the infant.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established. Tardive dyskinesia is rare in pediatric patients.
Geriatric Use
No overall differences in safety or effectiveness were observed between older and younger adult patients. However, greater sensitivity of some older individuals cannot be ruled out. Dose adjustments for renal or hepatic impairment should follow specific guidelines regardless of age.
Clinical Information
Clinical Pearls
- Ingrezza Sprinkle Capsules can be opened and sprinkled on a small amount of soft food (e.g., applesauce, yogurt) for patients who have difficulty swallowing capsules whole. The mixture should be consumed immediately.
- Patients should be monitored for worsening or new onset of parkinsonism or akathisia, which are potential side effects.
- Valbenazine is a prodrug; its active metabolite (DTBZ) is responsible for the therapeutic effect.
- QTc prolongation risk is generally low at recommended doses but should be considered in patients with pre-existing cardiac conditions or on other QT-prolonging medications.
- Therapeutic effects may not be fully apparent for several weeks after starting treatment or dose titration.
Alternative Therapies
- Deutetrabenazine (Austedo) - another VMAT2 inhibitor approved for tardive dyskinesia and Huntington's chorea.
- Tetrabenazine (Xenazine) - approved for Huntington's chorea, sometimes used off-label for severe tardive dyskinesia, but has a less favorable side effect profile than valbenazine or deutetrabenazine.
Cost & Coverage
Average Cost:
$7,000 - $8,000+ per 30 capsules (40mg or 80mg)
Insurance Coverage:
Specialty Tier (requires prior authorization, step therapy, and/or quantity limits)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. 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, 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 for guidance. 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.