Valbenazine

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Valbenazine
Clinical data
Trade namesIngrezza
Other namesNBI-98854
AHFS/Drugs.comMonograph
MedlinePlusa617023
License data
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding>99%
MetabolismActivation by hydrolysis, deactivation by CYP3A, CYP2D6
Metabolites[+]-α-Dihydrotetrabenazine (active metabolite)
Elimination half-life15–22 hrs
Excretion60% urine, 30% faeces
Identifiers
  • (2R,3R,11bR)-3-Isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl L-valinate
JSmol)
  • CC(C)C[C@@H]1CN2CCc3cc(c(cc3[C@H]2C[C@H]1OC(=O)[C@H](C(C)C)N)OC)OC
  • InChI=InChI=1S/C24H38N2O4/c1-14(2)9-17-13-26-8-7-16-10-21(28-5)22(29-6)11-18(16)19(26)12-20(17)30-24(27)23(25)15(3)4/h10-11,14-15,17,19-20,23H,7-9,12-13,25H2,1-6H3/t17-,19-,20-,23+/m1/s1
  • Key:GEJDGVNQKABXKG-CFKGEZKQSA-N

Valbenazine, sold under the brand name Ingrezza, is a medication used to treat tardive dyskinesia.[1] It acts as a vesicular monoamine transporter 2 (VMAT2) inhibitor.[2]

Medical use

Valbenazine is used to treat tardive dyskinesia in adults.[1] Tardive dyskinesia is a drug-induced neurological injury characterized by involuntary movements.[3] The clinical trials that led to the approval of valbenazine by the US Food and Drug Administration (FDA) were six weeks in duration.[1] An industry-sponsored study has studied the use of valbenazine for up to 48 weeks, in which it was found to be safe and effective for maintaining short-term (6 week) improvements in tardive dyskinesia.[4]

Contraindications

There are no contraindications for the use of valbenazine according to the prescribing information.[1]

Adverse effects

Side effects may include sleepiness or QT prolongation.[5] Significant prolongation has not yet been observed at recommended dosage levels, however, those taking inhibitors of the liver enzymes CYP2D6 or CYP3A4 – or who are poor CYP2D6 metabolizers – may be at risk for significant prolongation.[5]

Valbenazine has not been effectively studied in pregnancy, and it is recommended that women who are pregnant or breastfeeding avoid use of valbenazine.[5]

Pharmacology

Mechanism of action

See also: Monoamine-depleting agent

Valbenazine is known to cause reversible reduction of

upstream inhibition of these other monoamines.[9]

Pharmacokinetics

Valbenazine is a

hydrolyzed to the active metabolite DTBZ. Plasma protein binding of valbenazine is over 99%, and that of DTBZ is about 64%. The biological half-life of both valbenazine and DTBZ is 15 to 22 hours. Liver enzymes involved in inactivation are CYP3A4, CYP3A5 and CYP2D6. The drug is excreted, mostly in form of inactive metabolites, via the urine (60%) and the feces (30%).[10]

Society and culture

Legal status

Valbenazine is produced by Neurocrine Biosciences. Valbenazine is the first medication approved by the FDA for the treatment of tardive dyskinesia, in April 2017.[11]

Economics

While Neurocrine Biosciences does not hold a final patent for valbenazine or elagolix, they do hold a patent for the VMAT2 inhibitor [9,10-dimethoxy-3-(2-methylpropyl)-1H,2H,3H,4H,6H,7H,11bH-pyrido-[2,1-a]isoquinolin-2-yl]methanol and related compounds, which includes valbenazine.[12]

Names

The

International Nonproprietary Name (INN) is valbenazine.[13]
: 114 

Research

Valbenazine is being studied for the treatment of Tourette's syndrome.[14][15]

References

  1. ^ a b c d e "Ingrezza- valbenazine capsule; Ingrezza- valbenazine kit". DailyMed. 18 August 2023. Retrieved 17 November 2023.
  2. PMID 26346941
    .
  3. ^ "Tardive dyskinesia". rarediseases.info.nih.gov. 1 June 2017. Archived from the original on 18 June 2017. Retrieved 21 February 2018.
  4. ^ Janeczko L. "Long-term Valbenazine Appears Safe for Patients With Tardive Dyskinesia". www.medscape.com. Reuters Health Information. Retrieved 21 February 2018.[permanent dead link]
  5. ^ a b c "Valbenazine: Drug Information". UpToDate. Retrieved 14 July 2017.
  6. ^ "NBI-98854 – VMAT2 Inhibitor | Tics in Children Treatment | Neurocrine Biosciences". www.neurocrine.com. Archived from the original on 30 January 2015. Retrieved 13 November 2016.
  7. ^ "tardive-dyskinesia". www.priory.com. Retrieved 13 November 2016.
  8. ISBN 978-1-60535-380-7
    .
  9. ^ "NBIX: NDA for Valbenazine in Tardive Dyskinesia to be Filed in 2016…". Retrieved 13 November 2016.
  10. ^ Valbenazine Professional Drug Facts.
  11. ^ Office of the Commissioner. "Press Announcements - FDA approves first drug to treat tardive dyskinesia". www.fda.gov. Retrieved 12 April 2017.
  12. ^ US 20160289226, Ashweek N, Harriott N, "[9,10-dimethoxy-3-(2-methylpropyl)-1h,2h,3h,4h,6h,7h,11bh-pyrido-[2,1-a]isoquinolin-2-yl]methanol And Compounds, Compositions And Methods Relating Thereto", published 6 October 2016, assigned to Neurocrine Biosciences, Inc. [permanent dead link]
  13. ^ "International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names: List 71" (PDF). World Health Organization. Retrieved 18 November 2016.
  14. ^ "Tourette Syndrome Clinical Trials". Neurocrine Biosciences. Archived from the original on 14 November 2016. Retrieved 13 November 2016.
  15. ^ Clinical trial number NCT02581865 for "Safety and Efficacy Study of NBI-98854 in Adults With Tourette Syndrome" at ClinicalTrials.gov

Further reading
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