INGREZZA Dosage & Rx Info | Uses, Side Effects

Ingrezza Generic Name & Formulations

Legal Class

General Description

Valbenazine 40mg, 60mg, 80mg; caps.

Pharmacological Class

Vesicular monoamine transporter 2 (VMAT2) inhibitor.

How Supplied

Caps—30; Initiation pack for tardive dyskinesia (4-week)—28 (7×40mg + 21×80mg); Initiation pack for Huntington’s chorea (4-week)—28 (14×40mg + 14×60mg)

Manufacturer

Neurocrine Biosciences, Inc.

Generic Availability

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.

Ingrezza Indications

Indications

Tardive dyskinesia. Huntington’s chorea.

Ingrezza Dosage and Administration

Adult

Take with or without food. Tardive dyskinesia: Initially 40mg once daily, then increase to 80mg once daily after 1 week. Huntington’s chorea: Initially 40mg once daily, then increase in 20mg increments every 2 weeks up to 80mg once daily. Both: may consider 40mg or 60mg once daily based on response and tolerability. Moderate or severe hepatic impairment: 40mg once daily. Concomitant with strong CYP3A4 inducers: not recommended. Concomitant with strong CYP3A4 or CYP2D6 inhibitors, or CYP2D6 poor metabolizers: 40mg once daily.

Children

Not established.

Ingrezza Contraindications

Not Applicable

Ingrezza Boxed Warnings

Boxed Warning

Depression and suicidal ideation and behavior in patients with Huntington’s disease.

Ingrezza Warnings/Precautions

Warnings/Precautions

Increased risk for depression, suicidal ideation or behaviors in Huntington’s patients; monitor for emergence or worsening of these reactions; consider discontinuing if not resolved. History of depression. Prior suicidal ideation or attempts. Discontinue if hypersensitivity reactions occur (eg, angioedema). Somnolence. Risk for QT prolongation. Avoid in congenital long QT syndrome or arrhythmias associated with a prolonged QT interval. Monitor for neuroleptic malignant syndrome (NMS); discontinue and treat if occurs. Known CYP2D6 poor metabolizers. Parkinsonism: reduce dose or discontinue if significant signs/symptoms develop. Moderate or severe hepatic impairment: reduce dose (see Adults). Pregnancy. Nursing mothers: not recommended (during and for 5 days after the last dose).

Ingrezza Pharmacokinetics

Absorption

Time to reach maximum plasma concentration: 0.5–1 hour. Steady state plasma concentrations are reached within 1 week. Absolute oral bioavailability: ~49%.

Distribution

Plasma protein bound: >99%. Mean steady state volume of distribution: 92 L.

Metabolism

CYP3A4/5 (primarily), CYP2D6.

Elimination

Renal (60%), fecal (30%). Half-life: 15–22 hours. Mean total plasma systemic clearance: 7.2 L/hr.

Ingrezza Interactions

Interactions

See Adults. Avoid concomitant with MAOIs (eg, isocarboxazid, phenelzine, selegiline). Potentiated by strong CYP3A4 inhibitors (eg, itraconazole, ketoconazole, clarithromycin). May be potentiated by strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine, quinidine). Antagonized by strong CYP3A4 inducers (eg, rifampin, carbamazepine, phenytoin, St. John's wort). Monitor digoxin levels; dose adjustment may be needed.

Ingrezza Adverse Reactions

Adverse Reactions

Tardive dyskinesia: somnolence, anticholinergic effects, balance disorders/fall, headache, akathisia, vomiting, nausea, arthralgia. Huntington's chorea: somnolence/lethargy/sedation, fatigue, urticaria, rash, akathisia, insomnia, back pain, diarrhea, nausea.

Ingrezza Clinical Trials

See Literature

Ingrezza Note