Valbenazine
Valbenazine Uses, Dosage, Side Effects, Food Interaction and all others data.
Valbenazine (development name NBI-98854) has been used in trials studying the treatment and basic science of Tourette Syndrome and Tardive Dyskinesia. In April, 2017, valbenazine was approved by the FDA (as Ingrezza) as the first and only approved treatment for adults with Tardive Dyskinesia (TD).
Valbenazine decreases the availability of monoamine neurotransmitters by preventing their storage in synaptic vesicles . This is believed to be the reason behind its therapeutic effect in tardive dyskinesia although the exact mechanism is unknown.
| Trade Name | Valbenazine |
| Availability | Prescription only |
| Generic | Valbenazine |
| Valbenazine Other Names | Valbenazine |
| Related Drugs | Ingrezza, Austedo, vitamin e, deutetrabenazine, Alpha E |
| Weight | 40mg, 40mg + 80mg, 80mg |
| Type | Oral capsule |
| Formula | C24H38N2O4 |
| Weight | Average: 418.578 Monoisotopic: 418.283157712 |
| Protein binding | Valbenazine is >99% bound to plasma proteins . Its active metabolite [+]-α-HTBZ is 64% bound to plasma proteins. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Valbenazine is a vesicular monoamine transporter 2 inhibitor used to treat tardive dyskinesia.
For the treatment of tardive dyskinesia in adults .
Valbenazine is also used to associated treatment for these conditions: Tardive Dyskinesia (TD)
How Valbenazine works
Valbenazine and its active meabolites bind to and inhibit vesicular monoamine transporter 2 (VMAT2)with high selectivity (valbenazine Ki = 150nM, [+]-α-HTBZ Ki = 1.98nM, NBI136110 Ki = 160nM) with no significant binding to VMAT1 (Ki 2. This prevents the reuptake and storage of monoamine neurotransmitters noradrenaline, dopamine, and serotonin in synaptic vesicles making them vulnerable to metabolism by cytosolic enzymes. The presynaptic release of monoamine neurotransmitters is decreased due to the lack of vesicles with packaged neurotransmitter ready for release into the synapse. Neither valbenazine nor its active metabolite exhibit significant off target binding at dopamine, serotonin, or adrenaline receptors or uptake transporters at 10microM concentrations.
Toxicity
No carcinogenicity, mutagenicity, or impairment of fertility has been observed . QT prolongation may occur with strong CYP2D6 or CYP3A4 inhibitors, or in people who are poor CYP2D6 metabolizers. No overdose information is currently available.
Food Interaction
- Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of valbenazine.
- Take with or without food.
[Major] ADJUST DOSE: Coadministration with grapefruit juice may increase the plasma concentration of valbenazine.
The mechanism is inhibition of CYP450 3A4-mediated first-metabolism in the gut wall by certain compounds present in grapefruits.
The use of valbenazine has been associated with modest prolongation of the QT interval.
However, clinically significant QT prolongation may occur in patients taking a strong CYP450 3A4 inhibitor due to increased concentrations of valbenazine and its active metabolite (+)-alfa-dihydrotetrabenazine.
In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia).
The extent of drug-induced QT prolongation is dependent on the particular drugs involved and dosages of the drugs.
MANAGEMENT: Pharmacologic response to valbenazine should be monitored more closely whenever a strong inhibitor of CYP450 3A4 is added to or withdrawn from therapy.
Assessment of baseline QT interval and periodic monitoring during therapy may be considered.
The manufacturer recommends reducing the dose of valbenazine to 40 mg once daily during concomitant administration with strong CYP450 3A4 inhibitors.
Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.
In addition, patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol.
Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.
Valbenazine Drug Interaction
Major: ziprasidoneModerate: aripiprazole, deutetrabenazine, diphenhydramine, benztropine, duloxetine, famotidineUnknown: amphetamine / dextroamphetamine, aspirin, olmesartan, docusate, hydrocortisone topical, cholecalciferol, docusate, abobotulinumtoxinA, apixaban, omega-3 polyunsaturated fatty acids, tamsulosin, thiamine, ascorbic acid
Valbenazine Disease Interaction
Major: hepatic dysfunction, QT prolongation, renal dysfunctionModerate: parkinson
Volume of Distribution
92 Liters .
Elimination Route
Oral bioavailability of 49% . Tmax of 0.5-1h.
Half Life
Both valbenazine and its active metabolite [+]-α-HTBZ have a half life of 15-22 hours .
Clearance
7.2 Liters/hour .
Elimination Route
Roughly 60% is excreted in urine and 30% in feces . Less than 2% if the parent compound or active metabolite was excreted unchanged.
Innovators Monograph
You find simplified version here Valbenazine
