Tardive dyskinesia and INGREZZA mechanism of action (MOA)

INGREZZA is a selective VMAT2 inhibitor with once-daily dosing1,2

1

Selective VMAT2 inhibition

Key showing a vesicle, VMAT2, Dopamine, D2 receptor, Ingrezza

While the MOA of INGREZZA® (valbenazine) capsules is not fully understood, it is believed that it may be mediated through selective inhibition of VMAT2 in presynaptic neurons, with no appreciable binding affinity for VMAT1, dopaminergic receptors, or serotonergic receptors2

VMAT1, vesicular monoamine transporter 1; VMAT2, vesicular monoamine transporter 2.

2

Reduction of dopamine release

INGREZZA® (valbenazine) capsules is believed to provide reversible reductions of dopamine release into the synaptic cleft2

VMAT1, vesicular monoamine transporter 1; VMAT2, vesicular monoamine transporter 2.

3

Less dopamine available to receptors

INGREZZA® (valbenazine) capsules is believed to reduce the amount of dopamine available to hypersensitive postsynaptic dopamine D2 receptors1,2

VMAT1, vesicular monoamine transporter 1; VMAT2, vesicular monoamine transporter 2.

Tardive dyskinesia (TD)—an often persistent movement disorder
induced by prolonged DRBA exposure3

1

VMAT2 packages dopamine

2

DRBA exposure causes hypersensitivity

3

Hypersensitive dopamine receptors may trigger uncontrolled movements

1

VMAT2 packages dopamine

INGREZZA

VMAT2 plays a key role in dopamine signaling2

  • VMAT2 is a transporter protein found in presynaptic neurons of the CNS
  • VMAT2 packages monoamines (eg, dopamine) for release into the synaptic cleft

CNS, central nervous system; DRBA, dopamine receptor blocking agent; VMAT2, vesicular monoamine transporter 2.

2

DRBA exposure causes hypersensitivity

TD is associated with prolonged exposure to DRBAs, including antipsychotics3

CNS, central nervous system; DRBA, dopamine receptor blocking agent; VMAT2, vesicular monoamine transporter 2.

3

Hypersensitive dopamine receptors may trigger uncontrolled movements

Prolonged exposure to DRBAs is believed to cause hypersensitivity in postsynaptic dopamine D2 receptors in one of the areas of the brain that controls motor function2

CNS, central nervous system; DRBA, dopamine receptor blocking agent; VMAT2, vesicular monoamine transporter 2.

Watch the INGREZZA MOA video

See how INGREZZA® (valbenazine) capsules is thought to work.

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THE ONLY ONCE-DAILY
VMAT2 INHIBITOR

One-capsule, once-daily dosing with three effective dosing options sets INGREZZA apart from other VMAT2 inhibitors1

EXPLORE DOSING

TREAT FIRST LINE WITH
VMAT2 INHIBITORS

VMAT2 inhibitors, like INGREZZA, are recommended as first-line treatment for TD4-6

TD GUIDELINES

REFERENCES: 1. INGREZZA [package insert]. San Diego, CA: Neurocrine Biosciences, Inc. 2. Harriott ND, Williams JP, Smith EB, Bozigian HP, Grigoriadis DE. VMAT2 inhibitors and the path to INGREZZA (valbenazine). Prog Med Chem. 2018;57(1):87-111. 3. Hauser RA, Factor SA, Marder SR, et al. KINECT 3: a phase 3 randomized, double-blind, placebo-controlled trial of valbenazine for tardive dyskinesia. Am J Psychiatry. 2017;174(5):476-484. 4. Keepers GA, Fochtmann LJ, Anzia JM, et al. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia. 3rd ed. American Psychiatric Association Publishing, 2020. 5. Bhidayasiri R, Jitkritsadakul O, Friedman JH, Fahn S. Updating the recommendations for treatment of tardive syndromes: a systematic review of new evidence and practical treatment algorithm. J Neurol Sci. 2018;389:67-75. 6. Caroff SN, Citrome L, Meyer J, et al. A modified Delphi consensus study of the screening, diagnosis, and treatment of tardive dyskinesia. J Clin Psychiatry. 2020;81(2):19cs12983.

Important Information

INDICATION & USAGE

INGREZZA® (valbenazine) capsules is indicated for the treatment of adults with tardive dyskinesia.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

INGREZZA is contraindicated in patients with a history of hypersensitivity to valbenazine or any components of INGREZZA. Rash, urticaria, and reactions consistent with angioedema (e.g., swelling of the face, lips, and mouth) have been reported.

WARNINGS & PRECAUTIONS

Somnolence

INGREZZA can cause somnolence. Patients should not perform activities requiring mental alertness such as operating a motor vehicle or operating hazardous machinery until they know how they will be affected by INGREZZA.

QT Prolongation

INGREZZA may prolong the QT interval, although the degree of QT prolongation is not clinically significant at concentrations expected with recommended dosing. INGREZZA should be avoided in patients with congenital long QT syndrome or with arrhythmias associated with a prolonged QT interval. For patients at increased risk of a prolonged QT interval, assess the QT interval before increasing the dosage.

Parkinsonism

INGREZZA may cause parkinsonism in patients with tardive dyskinesia. Parkinsonism has also been observed with other VMAT2 inhibitors. Reduce the dose or discontinue INGREZZA treatment in patients who develop clinically significant parkinson-like signs or symptoms.

ADVERSE REACTIONS

The most common adverse reaction (≥5% and twice the rate of placebo) is somnolence. Other adverse reactions (≥2% and >Placebo) include: anticholinergic effects, balance disorders/falls, headache, akathisia, vomiting, nausea, and arthralgia.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit MedWatch at www.fda.gov/medwatch or call 1-800-FDA-1088.

Please see INGREZZA full Prescribing Information

Indication and Important Safety Information

INGREZZA is contraindicated in patients with a history of hypersensitivity to valbenazine or any components of INGREZZA.

+Expand-Collapse

Rash, urticaria, and reactions consistent with angioedema (e.g., swelling of the face, lips, and mouth) have been reported.

INDICATION & USAGE

INGREZZA® (valbenazine) capsules is indicated for the treatment of adults with tardive dyskinesia.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

INGREZZA is contraindicated in patients with a history of hypersensitivity to valbenazine or any components of INGREZZA. Rash, urticaria, and reactions consistent with angioedema (e.g., swelling of the face, lips, and mouth) have been reported.

Important Information

INDICATION & USAGE

INGREZZA® (valbenazine) capsules is indicated for the treatment of adults with tardive dyskinesia.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

INGREZZA is contraindicated in patients with a history of hypersensitivity to valbenazine or any components of INGREZZA. Rash, urticaria, and reactions consistent with angioedema (e.g., swelling of the face, lips, and mouth) have been reported.

WARNINGS & PRECAUTIONS

Somnolence

INGREZZA can cause somnolence. Patients should not perform activities requiring mental alertness such as operating a motor vehicle or operating hazardous machinery until they know how they will be affected by INGREZZA.

QT Prolongation

INGREZZA may prolong the QT interval, although the degree of QT prolongation is not clinically significant at concentrations expected with recommended dosing. INGREZZA should be avoided in patients with congenital long QT syndrome or with arrhythmias associated with a prolonged QT interval. For patients at increased risk of a prolonged QT interval, assess the QT interval before increasing the dosage.

Parkinsonism

INGREZZA may cause parkinsonism in patients with tardive dyskinesia. Parkinsonism has also been observed with other VMAT2 inhibitors. Reduce the dose or discontinue INGREZZA treatment in patients who develop clinically significant parkinson-like signs or symptoms.

ADVERSE REACTIONS

The most common adverse reaction (≥5% and twice the rate of placebo) is somnolence. Other adverse reactions (≥2% and >Placebo) include: anticholinergic effects, balance disorders/falls, headache, akathisia, vomiting, nausea, and arthralgia.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit MedWatch at www.fda.gov/medwatch or call 1-800-FDA-1088.

Please see INGREZZA full Prescribing Information

EXPAND FOR
GUIDELINES

INGREZZA is a recommended first-line TD treatment option.

See guidelines and recommendations