FDA Approved INGREZZA™ (Valbenazine)

 

This is the first and only FDA-approved product indicated for the treatment of adults with tardive dyskinesia. This post will summarize basic details regarding this medication.

Mechanism of Action:

  • Selective Vesicular Monoamine Transporter 2 (VMAT2) Inhibitor.

 

Q: Where is this transporter located?

  • In the membrane of synaptic vesicles of presynaptic neurons.

 

Q: What is the function of this transporter?

  • Transports monoamine neurotransmitters into vesicles, which prevents their degradation from monoamine oxidase (MAO) enzymes. This enzymes works at Step D in figure below.

 

Recommended Dosages:

  • Initiate Dose at 40 mg daily.
  • Increase dose in one week to 80 mg daily (which is recommended dosage).

 

Dosage Recommendation for Hepatic Impairment:

  • Moderate or Severe Hepatic Impairment (Child-Pugh score 7 to 15): 40 mg once daily. 

 

Dosage Recommendation for Renal Impairment: 

  • No dosage reduction in mild-moderate renal impairment.
  • Not recommended in severe renal impairment (creatinine clearance <30 mL/min).

 

Patients taking strong CYP2D6 or CYP3A4 inhibitor

  • Higher INGREZZA concentration and resultant QTc prolongation. Dose reduction to 40 mg daily is recommended. 

Adverse Reactions:

  • Well tolerated
  • Somnolence is the most common adverse event (≥5% and twice the rate of placebo)

Warnings and Precautions:

(1) Somnolence: May impair patient’s ability to drive or operate hazardous machinery.

(2) QT Prolongation: Avoid use in patients with congenital long QT syndrome or with arrhythmias associated with a prolonged QT interval.

Important Drug Interactions:

 

MEDICATIONS CLINICAL IMPLICATIONS
Monoamine Oxidase Inhibitors (MAOIs)
    • May increase the concentration of monoamine neurotransmitters in synapses- leading to increased risk of serotonin syndrome.

 

  • Avoid concomitant use of INGREZZA with MAOIs.
Strong CYP3A4 Inhibitors (itraconazole, ketoconazole, clarithromycin)
  • Higher INGREZZA concentration and resultant QTc prolongation
  • Reduce INGREZZA dose to 40 mg daily.
Strong CYP2D6 Inhibitors (paroxetine, fluoxetine, quinidine)
  • Higher INGREZZA concentration and resultant QTc prolongation
  • Reduce INGREZZA dose to 40 mg daily.
Strong CYP3A4 Inducers (rifampin, carbamazepine, phenytoin, St. John’s wort)
  • Reduce the exposure of valbenazine and its active metabolite.
  • Concomitant use of strong CYP3A4 inducers with INGREZZA is not recommended.
Digoxin
  • Increased digoxin levels because of inhibition of intestinal P-glycoprotein.
  • Digoxin concentrations should be monitored and Dosage adjustment of digoxin may be necessary. 

Response Time:

INGREZZA provides significant, rapid and meaningful improvement in tardive dyskinesia signs and symptoms compared to placebo through 6 weeks, with continued reductions in tardive dyskinesia observed through 48 weeks of treatment.

Source: INGREZZATM (valbenazine) Package insert. 

 

Please do post your questions or comments below. 


Dr. Harvinder Singh, M.D. (Admin)


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