The FDA has approved the use of valbenazine (ingrezza), a monoamine transporter inhibitor, to treat tardive dyskinesia. Involuntary movements of the face, neck, jaw, and other body parts are known as tardive dyskinesias, and they typically develop after antipsychotic medication use.

Ingrezza (valbenazine) dose in Adults

Ingrezza (valbenazine) dose in the treatment of Tardive dyskinesia:

• • 40 mg orally once a day
  • after one week, increase to 80 mg once a day.
  • Based on response and tolerability, it may be possible for certain individuals to continue taking 40 mg once a day.

• Dosage adjustment for concomitant CYP3A4 and CYP2D6 inhibitors/inducers:

  • It is not advised to administer a powerful CYP3A4 inducer (such as carbamazepine, phenytoin, rifampin, or St. John's wort) concurrently.

  • Simultaneous delivery of a potent CYP3A4 inhibitor (eg, clarithromycin, itraconazole, ketoconazole):

    • The maximum dose of ingrezza (valbenazine) is  40 mg daily.

  • Concomitant administration with a strong CYP2D6 inhibitor (eg, fluoxetine, paroxetine, quinidine):

    • The manufacturer's labelling does not mention dosage adjustment, although depending on tolerability, a dose reduction can be required.

Ingrezza (valbenazine) dose in Children

Safety and efficacy in children not established. 

Ingrezza (valbenazine) pregnancy Risk Factor: C

• In some studies on animal reproduction, adverse events were observed

Use of valbenazine while breastfeeding

• It is unknown if valbenazine can be found in breast milk.
• According to animal studies, the manufacturer doesn't recommend breastfeeding during therapy or for more than 5 days following the last dose.

Ingrezza (valbenazine) dose in renal disease:

• Mild to moderate impairment (CrCl 30 - 90 mL/minute).

  • There is no need to adjust the dosage.

• Severe impairment (CrCl >30 mL/minute).

  • It is not recommended.

Ingrezza (valbenazine) dose in liver disease:

• Mild impairment (Child Puugh class A)

  • The manufacturer's labeling does not include any dosage adjustments.

• Moderate to severe impairment (Child Puugh class B orC):

  • 40 mg daily

Common Side Effects of Ingrezza (Valbenazine) Include:

• Central nervous system:

  • Drowsiness
  • Fatigue
  • Sedation

Less Common Side Effects of Ingrezza (Valbenazine) Include:

• Central Nervous System:

  • Abnormal gait
  • Dizziness
  • Equilibrium Disturbance
  • Falling
  • Akathisia
  • Restlessness
  • Anxiety
  • Drooling
  • Extrapyramidal Reaction
  • Insomnia

• Endocrine & Metabolic:

  • Increased Serum Glucose
  • Weight Gain

• Gastrointestinal:

  • Vomiting

• Neuromuscular & Skeletal:

  • Arthralgia
  • Dyskinesia

• Respiratory:

  • Respiratory tract infection

valbenazine side effects (rare)

• Endocrine & metabolic:

  • Increased serum prolactin

• Hepatic:

  • Increased serum alkaline phosphatase
  • Increased serum bilirubin

Contraindication to Ingrezza (Valbenazine) Include:

Hypersensitivity to valbenazine and any part of this formulation

Warnings and precautions

• Depression in the CNS:
  • It can cause CNS depression that may lead to mental or physical impairments.
  • The risks of taking this medication should be discussed with patients before they engage in activities like driving or operating machinery that call for mental awareness.
• Depression and suicidal ideation
  • VMAT inhibitors are also associated with depression, suicidal thoughts, and behavior.
• Extension of QT
  • It could prolong the QT interval
  • Use caution when taking CYP2D6 inhibitors or CYP3A4 metabolizers. Dose reduction may be required.
  • This medication should not be used by people who have congenital long-QT syndrome, arrhythmias, or prolonged QT intervals.
  • Before increasing the dosage, an EKG should be done on patients who are at high risk for a prolonged QT interval.
• Hepatic impairment:
  • Patients with severe or moderate hepatic impairment should be cautious; they may need to take a lower dose.
• Renal impairment
  • Patients with severe renal impairment should not use this medication.

Valbenazine: Drug Interaction

Monitor:

• Abnormal Involuntary Movement Scale (AIMS), also known as the Condensed User Scales for Dyskinesia Identification Systems (DISCUS).
• ECG (for those with high risk of QT prolongation) (for patients at high risk of QT prolongation).

How to administer Valbenazine?

• Administer with or without food.

Valbenazine Mechanism of action (Ingrezza MOA):

• Although its mechanism of action remains unknown, it is believed to reverse the effects of the vesicular monamine transporter 2, (VMAT2)
• A monoamine transporter called VMAT2 controls how much monoamine is stored and released from the cytoplasm.
• A significant binding affinity for VMAT1 or any dopaminergic, serotonergic, muscarinic, or dopaminergic receptors is not present in valbenazine or its active metabolite.

Absorption:

• High-fat meals decrease C by 47% and AUC by 13%.

Distribution: V :

• 92 L

Protein binding:

• Valbenazine: >99%; Active metabolite: ~64%

Metabolism:

• It is mainly metabolized by hydrolysis to form active metabolite ([+]-α-HTBZ) (and by oxidative metabolism, primarily by CYP3A4/5, to form monooxidized valbenazine and other minor metabolites).
• The active metabolite is further metabolized in part by CYP2D6.

Bioavailability:

• ~49%

Half-life elimination:

• 15 to 22 hours (valbenazine and active metabolite)

Time to peak:

• 0.5 - 1 hour for the main drug and 4 - 8 hours for the active metabolites.

Excretion:

• Via Urine (~60%, primarily as inactive metabolites); feces (~30%, primarily as inactive metabolites 

International Brands of Valbenazine:

• Ingrezza

Ingrezza (valbenazine) Brands in Pakistan:

 No Brands Available in Pakistan.