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Valbenazine: Drug information

Valbenazine: Drug information
(For additional information see "Valbenazine: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Ingrezza
Pharmacologic Category
  • Central Monoamine-Depleting Agent;
  • Vesicular Monoamine Transporter 2 (VMAT2) Inhibitor
Dosing: Adult
Tardive dyskinesia

Tardive dyskinesia: Oral: Initial: 40 mg once daily; after 1 week, increase to 80 mg once daily. Continuation of 40 or 60 mg once daily may be considered for some patients based on response and tolerability.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

Mild to severe impairment: No dosage adjustment necessary.

Dosing: Hepatic Impairment: Adult

Mild impairment (Child-Pugh class A): There are no dosage adjustments provided in the manufacturer's labeling.

Moderate to severe impairment (Child-Pugh class B or C): 40 mg once daily

Dosing: Older Adult

Refer to adult dosing.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral, as tosylate:

Ingrezza: 40 mg, 60 mg [contains fd&c blue #1 (brilliant blue), fd&c red #40 (allura red ac dye)]

Ingrezza: 80 mg [contains corn starch, fd&c blue #1 (brilliant blue), fd&c red #40 (allura red ac dye)]

Capsule Therapy Pack, Oral, as tosylate:

Ingrezza: Valbenazine 40 mg (7s) and valbenazine 80 mg (21s) [28 day therapy pack] (28 ea) [contains fd&c blue #1 (brilliant blue), fd&c red #40 (allura red ac dye)]

Generic Equivalent Available: US

No

Administration: Adult

Administer with or without food.

Use: Labeled Indications

Tardive dyskinesia: Treatment of adults with tardive dyskinesia

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%: Central nervous system: Drowsiness (≤11%), fatigue (≤11%), sedation (≤11%)

1% to 10%:

Central nervous system: Abnormal gait (≤4%), dizziness (≤4%), equilibrium disturbance (≤4%), falling (≤4%), akathisia (≤3%), restlessness (≤3%), anxiety (1% to <2%), drooling (1% to <2%), extrapyramidal reaction (1% to <2%), insomnia (1% to <2%)

Endocrine & metabolic: Increased serum glucose (1% to <2%), weight gain (1% to <2%)

Gastrointestinal: Vomiting (3%)

Neuromuscular & skeletal: Arthralgia (2%), dyskinesia (1% to <2%)

Respiratory: Respiratory tract infection (1% to <2%)

Frequency not defined:

Endocrine & metabolic: Increased serum prolactin

Hepatic: Increased serum alkaline phosphatase, increased serum bilirubin

<1%, postmarketing and/or case reports: Hypersensitivity reaction, skin rash

Contraindications

Hypersensitivity to valbenazine or any component of the formulation

Warnings/Precautions

Concerns related to adverse effects:

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).

• Depression/Suicidal ideation: Vesicular monoamine transport inhibitors have been associated with depression and suicidal thoughts and behavior. In a pooled analysis of two 6-week trials and a 42-week extension trial, 96.5% (N=113) of patients who reported no suicidal ideation at baseline continued to have no suicidal ideation at any time during the study; however, 4 patients (2 on placebo, 2 on valbenazine) reported a shift in their Columbia-Suicide Severity Rating Scale score to suicidal thoughts/ideation (McIntyre 2019).

• Parkinsonism: Cases of parkinson-like symptoms (eg, falls, gait disturbances, tremor, drooling, hypokinesia), some severe requiring hospitalization, have been reported. Onset of severe symptoms occurs most commonly within 2 weeks of the start of therapy or a dose increase; may resolve with discontinuation of therapy. Reduce dose or discontinue treatment in patients who develop clinically significant parkinson-like signs or symptoms.

• QT prolongation: May prolong the QT interval; use caution when used concomitantly with a strong CYP2D6 or CYP3A4 inhibitor or in a poor CYP2D6 metabolizer, dose reduction may be necessary. Avoid use in patients with congenital long QT syndrome or arrhythmias associated with prolonged QT interval. For patients at risk of prolonged QT interval, perform EKG before increasing the dosage.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with moderate or severe hepatic impairment; use reduced dose.

Special populations:

• CYP2D6 poor metabolizers: CYP2D6 poor metabolizes may have increased levels of primary drug metabolites, which may increase the risk of adverse effects; dosage reduction is recommended.

Metabolism/Transport Effects

Substrate of CYP2D6 (major), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Ajmaline: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Artemether and Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CYP2D6 Inhibitors (Moderate): May increase serum concentrations of the active metabolite(s) of Valbenazine. Risk C: Monitor therapy

CYP2D6 Inhibitors (Strong): May increase serum concentrations of the active metabolite(s) of Valbenazine. Management: Reduce valbenazine dose to 40 mg once daily when combined with a strong CYP2D6 inhibitor. Monitor for increased valbenazine effects/toxicities. Risk D: Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease serum concentrations of the active metabolite(s) of Valbenazine. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Valbenazine. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease serum concentrations of the active metabolite(s) of Valbenazine. CYP3A4 Inducers (Strong) may decrease the serum concentration of Valbenazine. Risk X: Avoid combination

CYP3A4 Inhibitors (Moderate): May increase serum concentrations of the active metabolite(s) of Valbenazine. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Valbenazine. Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May increase serum concentrations of the active metabolite(s) of Valbenazine. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Valbenazine. Management: Reduce the valbenazine dose to 40 mg daily when combined with strong CYP3A4 inhibitors. Risk D: Consider therapy modification

Deutetrabenazine: May enhance the adverse/toxic effect of Valbenazine. Risk X: Avoid combination

Digoxin: Valbenazine may increase the serum concentration of Digoxin. Risk C: Monitor therapy

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Monoamine Oxidase Inhibitors: Valbenazine may enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

St John's Wort: May decrease the serum concentration of Valbenazine. Risk X: Avoid combination

Tetrabenazine: May enhance the adverse/toxic effect of Valbenazine. Risk X: Avoid combination

Pregnancy Considerations

Adverse events were observed in some animal reproduction studies

Breastfeeding Considerations

It is not known if valbenazine is present in breast milk. Based on data from animal studies, the manufacturer does not recommend breastfeeding during therapy or until 5 days after the last dose.

Monitoring Parameters

Abnormal Involuntary Movement Scale (AIMS) or Dyskinesia Identification System Condensed User Scale (DISCUS); EKG (for patients at risk for QT prolongation)

Mechanism of Action

The mechanism of action of valbenazine in the treatment of tardive dyskinesia is unknown, but is thought to be mediated through the reversible inhibition of vesicular monoamine transporter 2 (VMAT2), a transporter that regulates monoamine uptake from the cytoplasm to the synaptic vesicle for storage and release. Valbenazine and its active metabolite have no appreciable binding affinity for VMAT1 or dopaminergic, serotonergic, adrenergic, histaminergic or muscarinic receptors.

Pharmacokinetics

Absorption: High-fat meals decrease Cmax by 47% and AUC by 13%.

Distribution: Vd: 92 L

Protein binding: Valbenazine: >99%; Active metabolite: ~64%

Metabolism: Extensively metabolized by hydrolysis to form active metabolite ([+]-α-HTBZ) and by oxidative metabolism, primarily by CYP3A4/5, to form monooxidized valbenazine and other minor metabolites. The active metabolite is further metabolized in part by CYP2D6.

Bioavailability: ~49%

Half-life elimination: 15 to 22 hours (valbenazine and active metabolite)

Time to peak: Valbenazine: 0.5 to 1 hours; Active metabolite: 4 to 8 hours

Excretion: Urine (~60%, primarily as inactive metabolites); feces (~30%, primarily as inactive metabolites)

Pricing: US

Capsule Therapy Pack (Ingrezza Oral)

40 & 80 mg (per each): $343.80

Capsules (Ingrezza Oral)

40 mg (per each): $292.08

60 mg (per each): $320.88

80 mg (per each): $320.88

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Ingrezza (IN)


For country code abbreviations (show table)
  1. Ingrezza (valbenazine) [prescribing information]. San Diego, CA: Neurocrine Biosciences Inc; August 2022.
  2. McIntyre RS, Calabrese JR, Nierenberg AA, et al. The effects of valbenazine on tardive dyskinesia in patients with a primary mood disorder. J Affect Disord. 2019;246:217-223. doi: 10.1016/j.jad.2018.12.023. [PubMed 30583148]
Topic 112668 Version 102.0