Ingrezza 60mg 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
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 is a medication used to treat uncontrolled, involuntary movements of the face and body (tardive dyskinesia) and involuntary movements associated with Huntington's disease (chorea). It works by affecting a chemical messenger in the brain that controls movement.
How to Use This Medicine
Taking Your Medication Correctly
To ensure you get the most benefit from your medication, follow these steps:
Take your medication exactly as directed by your doctor. Read all the information provided and follow the instructions carefully.
You can take your medication with or without food.
Continue taking your medication as prescribed by your doctor or healthcare provider, even if you start to feel better.
Swallowing Your Medication
You can swallow your medication whole with a glass of water. Do not crush or chew the medication. Alternatively, you can open the capsule and sprinkle the contents into a small amount (1 tablespoon; 15 mL) of soft food, such as applesauce, yogurt, or pudding. Avoid mixing the medication with milk or water. Stir the mixture well and swallow it immediately. Then, drink a full glass of water (8 ounces; 240 mL).
Preparing and Storing the Mixture
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 after 2 hours if it has not been taken.
Important Administration Instructions
Do not administer this medication through a feeding tube.
Storing and Disposing of Your Medication
To maintain the quality and safety of your medication:
Store it 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 and secure 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 ensure you get the most benefit from your medication, follow these steps:
Take your medication exactly as directed by your doctor. Read all the information provided and follow the instructions carefully.
You can take your medication with or without food.
Continue taking your medication as prescribed by your doctor or healthcare provider, even if you start to feel better.
Swallowing Your Medication
You can swallow your medication whole with a glass of water. Do not crush or chew the medication. Alternatively, you can open the capsule and sprinkle the contents into a small amount (1 tablespoon; 15 mL) of soft food, such as applesauce, yogurt, or pudding. Avoid mixing the medication with milk or water. Stir the mixture well and swallow it immediately. Then, drink a full glass of water (8 ounces; 240 mL).
Preparing and Storing the Mixture
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 after 2 hours if it has not been taken.
Important Administration Instructions
Do not administer this medication through a feeding tube.
Storing and Disposing of Your Medication
To maintain the quality and safety of your medication:
Store it 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 and secure 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.
Lifestyle & Tips
- Take exactly as prescribed, once daily, with or without food.
- If using sprinkle capsules, open and sprinkle contents on 1 tablespoon of soft food (e.g., applesauce, yogurt). Consume immediately. Do not chew the contents.
- Do not crush or chew the capsule itself.
- Do not take a double dose if you miss a dose. Take the next dose at your regular time.
- Avoid driving or operating heavy machinery until you know how this medication affects you, as it may cause drowsiness or dizziness.
- Inform your doctor about all medications, supplements, and herbal products you are taking, especially strong CYP3A4 or CYP2D6 inhibitors, or other drugs that can affect heart rhythm.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
Initial 40 mg once daily for 1 week, then increase to 80 mg once daily. For sprinkle capsules, open capsule and sprinkle contents on 1 tablespoon of soft food (e.g., applesauce, yogurt). Consume immediately. Do not chew contents.
Dose Range:
40 - 80 mg
Condition-Specific Dosing:
Tardive Dyskinesia:
Initial 40 mg once daily for 1 week, then increase to 80 mg once daily. Max 80 mg/day.
Huntington's Disease Chorea:
Initial 40 mg once daily for 1 week, then increase to 60 mg once daily for 1 week, then 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 dosage adjustment needed.
Moderate:
No dosage adjustment needed.
Severe:
Initial 40 mg once daily. Max 40 mg/day. Consider 60 mg/day for Huntington's disease chorea if tolerated.
Dialysis:
Not studied. Avoid use.
Hepatic Impairment:
Mild:
No dosage adjustment needed.
Moderate:
Initial 40 mg once daily. Max 40 mg/day. Consider 60 mg/day for Huntington's disease chorea if tolerated.
Severe:
Initial 40 mg once daily. Max 40 mg/day. Consider 60 mg/day for Huntington's disease chorea if tolerated.
Pharmacology
Mechanism of Action
Valbenazine is a selective and reversible inhibitor of vesicular monoamine transporter 2 (VMAT2). The precise mechanism by which valbenazine exerts its therapeutic effects in tardive dyskinesia and Huntington's disease chorea is unknown, but it is thought to be mediated through the reduction of dopamine release from nerve terminals by inhibiting VMAT2.
Pharmacokinetics
Absorption:
Bioavailability:
Not available (extensive first-pass metabolism)
Tmax:
0.5 to 4 hours (valbenazine); 3 to 8 hours (active metabolite, [+]-Îą-dihydrotetrabenazine (DTBZ))
FoodEffect:
High-fat meal decreases Cmax by 27% and AUC by 16% for valbenazine, but increases Cmax by 29% and AUC by 20% for DTBZ. Can be taken with or without food.
Distribution:
Vd:
92 L (valbenazine); 120 L (DTBZ)
ProteinBinding:
>99% (valbenazine); >99% (DTBZ)
CnssPenetration:
Yes
Elimination:
HalfLife:
15 to 22 hours (valbenazine); 9 to 10 hours (DTBZ)
Clearance:
Not available
ExcretionRoute:
Primarily urine (60%), feces (30%)
Unchanged:
<2% (valbenazine); <1% (DTBZ)
Pharmacodynamics
OnsetOfAction:
Within 1-2 weeks (clinical improvement)
PeakEffect:
Typically within 6-8 weeks of reaching target dose
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 immediately or seek emergency medical attention:
Signs of an allergic reaction, such as:
+ Rash or 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 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 or your child experience any of the following:
Feeling sleepy or tired
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 immediately or seek emergency medical attention:
Signs of an allergic reaction, such as:
+ Rash or 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 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 or your child experience any of the following:
Feeling sleepy or tired
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:
- Worsening or new involuntary movements
- New or worsening symptoms of Parkinson's disease (e.g., tremor, stiffness, slow movement)
- Feeling restless or unable to sit still (akathisia)
- Excessive sleepiness or drowsiness
- Signs of an allergic reaction (e.g., rash, itching, swelling, severe dizziness, trouble breathing)
- Signs of a heart rhythm problem (e.g., fast/irregular heartbeat, severe dizziness, fainting)
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 and situations 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, 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 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 whether 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 conditions and situations 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, 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 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 whether 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 cannabis products, as well as prescription or over-the-counter medications 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, taking this medication during pregnancy may pose a risk to the unborn baby. If you are pregnant or become pregnant while taking this medication, 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 cannabis products, as well as prescription or over-the-counter medications 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, taking this medication during pregnancy may pose a risk to the unborn baby. If you are pregnant or become pregnant while taking this medication, notify your doctor right away.
Overdose Information
Overdose Symptoms:
- Sedation
- Dizziness
- Confusion
- Hypotension
- QTc 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 and vital signs.
Drug Interactions
Major Interactions
- Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, itraconazole, ritonavir): May increase valbenazine and DTBZ exposure, increasing risk of adverse reactions. Reduce valbenazine dose.
- Strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine, quinidine): May increase DTBZ exposure. Reduce valbenazine dose.
- QT-prolonging drugs (e.g., Class IA and Class III antiarrhythmics, antipsychotics, macrolide antibiotics): May increase risk of QTc prolongation. Use with caution.
Moderate Interactions
- Moderate CYP3A4 inhibitors (e.g., diltiazem, erythromycin, grapefruit juice): May increase valbenazine and DTBZ exposure. Monitor for adverse reactions.
- CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's Wort): May decrease valbenazine and DTBZ exposure, reducing efficacy. Avoid coadministration.
Confidence Interactions
Monitoring
Baseline Monitoring
Electrocardiogram (ECG)
Rationale: To assess QTc interval, especially in patients with cardiac disease or on other QTc-prolonging medications.
Timing: Prior to initiation
Routine Monitoring
Abnormal Involuntary Movement Scale (AIMS)
Frequency: Periodically (e.g., every 3-6 months or as clinically indicated)
Target: Reduction in score indicating improvement
Action Threshold: Worsening or new dyskinesia may require dose adjustment or discontinuation.
Clinical assessment for parkinsonism, akathisia, somnolence
Frequency: Regularly, especially during dose titration
Target: Absence or minimal symptoms
Action Threshold: Development or worsening of symptoms may require dose adjustment or discontinuation.
QTc interval (if risk factors present or on interacting drugs)
Frequency: As clinically indicated
Target: <450 ms (men), <470 ms (women)
Action Threshold: Significant QTc prolongation (>500 ms or >60 ms increase from baseline) requires re-evaluation and potential discontinuation.
Symptom Monitoring
- Worsening or new involuntary movements (e.g., lip smacking, tongue protrusion, grimacing, blinking, limb movements)
- Symptoms of parkinsonism (e.g., tremor, rigidity, bradykinesia)
- Symptoms of akathisia (e.g., inner restlessness, inability to sit still)
- Excessive somnolence or sedation
- Signs of QTc prolongation (e.g., dizziness, palpitations, syncope)
Special Patient Groups
Pregnancy
There are no adequate and well-controlled studies of valbenazine in pregnant women. Based on animal studies, valbenazine may cause fetal harm. 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 (e.g., increased fetal loss, reduced fetal weight, skeletal abnormalities).
Second Trimester:
Potential for developmental toxicity observed in animal studies.
Third Trimester:
Potential for developmental toxicity observed in animal studies.
Lactation
It is not known if valbenazine or its metabolites are excreted in human milk. Valbenazine and its metabolites were present in the milk of lactating rats. Because of the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment with valbenazine and for 5 days after the final dose.
Infant Risk:
Risk of serious adverse reactions (e.g., somnolence, movement disorders) in breastfed infants. Avoid breastfeeding.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established for tardive dyskinesia or Huntington's disease chorea.
Geriatric Use
No dosage adjustment is generally recommended based on age alone. However, elderly patients may be more sensitive to the adverse effects (e.g., somnolence, QTc prolongation) and should be monitored closely.
Clinical Information
Clinical Pearls
- Valbenazine is a highly selective VMAT2 inhibitor, leading to fewer off-target effects compared to older agents like tetrabenazine.
- The sprinkle capsule formulation provides flexibility for patients who have difficulty swallowing capsules whole.
- Clinical improvement in tardive dyskinesia may take several weeks to become apparent, and full effect may not be seen until 6-8 weeks at the target dose.
- Patients should be monitored for new or worsening parkinsonism or akathisia, which can occur with VMAT2 inhibitors.
- While QTc prolongation risk is generally low at recommended doses, caution is advised in patients with pre-existing cardiac conditions or on other QTc-prolonging medications.
- Educate patients on the importance of consistent daily dosing and proper administration of sprinkle capsules.
Alternative Therapies
- Deutetrabenazine (Austedo) - another VMAT2 inhibitor for tardive dyskinesia and Huntington's disease chorea.
- Tetrabenazine (Xenazine) - older VMAT2 inhibitor, higher risk of side effects.
- Off-label antipsychotics (e.g., clozapine) for refractory tardive dyskinesia (with significant side effect burden).
- Botulinum toxin injections (for focal dyskinesias).
Cost & Coverage
Average Cost:
Varies, typically $7,000 - $8,000+ per 30 capsules
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 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 your prescription is refilled. 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.