Ingrezza

The FDA has approved Ingrezza capsules (valbenazine, Neurocrine Biosciences, Inc) for the treatment of adults with tardive dyskinesia (TD).¹ TD results when medications such as antipsychotics are used to block dopamine receptors in the brain, resulting in uncontrollable, abnormal, and repetitive movements of the trunk, extremities, or face. The symptoms can be severe and persistent and are sometimes irreversible. TD affects an estimated 500,000 or more Americans.²

Pharmacology and Pharmacokinetics

Ingrezza is a vesicular monoamine transporter 2 (VMAT2) inhibitor. Its exact mechanism in the treatment of TD is unknown.

Ingrezza reaches maximal plasma concentration 30 to 60 minutes after oral administration. Steady-state plasma concentrations are achieved within 1 week of beginning treatment. The medication is converted to an active metabolite and extensively metabolized by CYP3A4/5; its metabolite is further metabolized, in part, by CYP2D6.¹

Dosage and Administration

The initial dose of Ingrezza is 40 mg by mouth once daily, with or without food. After 1 week, the dose should be increased to 80 mg once daily. However, patients with moderate or severe hepatic impairment should continue with 40 mg daily, and a dose reduction may be required in patients who are known CYP2D6 poor metabolizers.¹

Clinical Trials

Ingrezza was evaluated in a randomized, double-blind, placebo-controlled trial of 234 patients with moderate to severe TD and underlying schizophrenia, schizoaffective disorder, or mood disorder. Of the patients enrolled, 70% were receiving atypical antipsychotics, 14% were receiving typical or combination antipsychotics, and 16% were not receiving antipsychotics. Patients received either Ingrezza 80 mg daily, Ingrezza 40 mg daily, or placebo. After 6 weeks, patients receiving placebo were re-randomized to receive either 80 or 40 mg of Ingrezza daily until week 48. The medication met the primary end point of the study, with a mean change from baseline to week 6 in the Abnormal Involuntary Movement Scale (AIMS) dyskinesia total score of —3.2 for the Ingrezza 80-mg group, compared with –0.1 in the placebo group. Additionally, 40% of the 80-mg group experienced at least a 50% reduction in AIMS, compared with 8.7% in the placebo group.^1,2

Contraindications, Warnings, and Precautions

There are no contraindications to treatment with Ingrezza.

Ingrezza can cause somnolence and may impair the ability to drive or operate hazardous machinery. Patients should not perform activities requiring mental alertness until they know how Ingrezza will affect them.

Ingrezza may cause an increase in the QT interval and should not be used in patients with congenital long QT syndrome or arrhythmias associated with a prolonged QT interval.

The medication should not be used concomitantly with monoamine oxidase inhibitors or strong CYP3A4 inducers. If Ingrezza is used in combination with strong CYP3A4 inhibitors, the dose should be decreased to 40 mg daily. When used concomitantly with strong CYP2D6 inhibitors, a dose reduction based on tolerability should be considered.

Ingrezza should not be used in patients who are pregnant or breast-feeding or who have severe renal impairment. Patients with mild to moderate renal impairment require no dose adjustment.

The most common adverse reaction (≥5% and twice the rate of placebo) is somnolence.¹

Dr. Holmberg earned her PharmD from the University of Connecticut and completed an ambulatory care residency at the Phoenix VA Healthcare System. Her practice has also included pediatrics and inpatient mental health. She lives in Phoenix, Arizona.

References

• Ingrezza [prescribing information]. San Diego, CA: Neurocrine Biosciences, Inc; 2017.
• Neurocrine announces FDA approval of Ingrezza (valbenazine) capsules as the first and only approved treatment for adults with tardive dyskinesia (TD) [press release]. San Diego, CA: Neurocrine Biosciences, Inc; April 11, 2017. http://phoenix.corporate-ir.net/phoenix.zhtml?c=68817&p=irol-newsArticle&ID=2261452. Accessed August 30, 2017.