(val BEN a zeen)
- Valbenazine Tosylate
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Ingrezza: 40 mg [contains brilliant blue fcf (fd&c blue #1), fd&c red #40]
Brand Names: U.S.
- Central Monoamine-Depleting Agent
- Vesicular Monoamine Transporter 2 (VMAT2) Inhibitor
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. Valbenazine and its active metabolite have no appreciable binding affinity for VMAT1 or dopaminergic, serotonergic, adrenergic, histaminergic or muscarinic receptors.
High-fat meals decrease Cmax by 47% and AUC by 13%.
Vd: 92 L
Metabolism: Extensively 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.
Urine (~60%, primarily as inactive metabolites); feces (~30%, primarily as inactive metabolites)
Time to Peak
Valbenazine: 0.5 to 1 hours; Active metabolite: 4 to 8 hours
15 to 22 hours (valbenazine and active metabolite)
Valbenazine: >99%; Active metabolite: ~64%
Use: Labeled Indications
Tardive dyskinesia: Treatment of adults with tardive dyskinesia
There are no contraindications listed in the manufacturer's labeling.
Tardive dyskinesia: Oral: Initial: 40 mg once daily; after 1 week, increase to 80 mg once daily. Continuation of 40 mg once daily may be considered for some patients based on response and tolerability.
Dosage adjustment for concomitant CYP3A4 and CYP2D6 inhibitors/inducers:
Concomitant administration with a strong CYP3A4 inducer (eg, carbamazepine, phenytoin, rifampin, St John's wort): Use is not recommended.
Concomitant administration with a strong CYP3A4 inhibitor (eg, clarithromycin, itraconazole, ketoconazole): Maximum dose: 40 mg once daily
Concomitant administration with a strong CYP2D6 inhibitor (eg, fluoxetine, paroxetine, quinidine): Dosage adjustment is not provided in the manufacturer's labeling, however, a dose reduction may be necessary based on tolerability.
Refer to adult dosing.
Dosing: Renal Impairment
Mild to moderate impairment (CrCl 30 to 90 mL/minute): No dosage adjustment necessary.
Severe impairment (CrCl <30 mL/minute): Use is not recommended.
Dosing: Hepatic Impairment
Mild impairment (Child-Pugh class A): There are no dosage adjustments provided in the manufacturer's labeling.
Moderate to severe impairment (Child-Pugh class B or C): 40 mg once daily
Administer with or without food.
Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
CYP2D6 Inhibitors (Strong): May increase serum concentrations of the active metabolite(s) of Valbenazine. Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Valbenazine. Avoid combination
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Valbenazine. Management: Reduce the valbenazine dose to 40 mg daily when combined with strong CYP3A4 inhibitors. Consider therapy modification
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Digoxin: Valbenazine may increase the serum concentration of Digoxin. Monitor therapy
Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
MAO Inhibitors: Valbenazine may enhance the adverse/toxic effect of MAO Inhibitors. Avoid combination
MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification
Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
St John's Wort: May decrease the serum concentration of Valbenazine. Avoid combination
Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
>10%: Central nervous system: Drowsiness (≤11%), fatigue (≤11%), sedation (≤11%)
1% to 10%:
Central nervous system: Abnormal gait (≤4%), dizziness (≤4%), equilibrium disturbance (≤4%), falling (≤4%), akathisia (≤3%), restlessness (≤3%), anxiety (≥1% to <2%), drooling (≥1% to <2%), extrapyramidal reaction (≥1% to <2%), insomnia (≥1% to <2%)
Endocrine & metabolic: Increased serum glucose (≥1% to <2%), weight gain (≥1% to <2%)
Gastrointestinal: Vomiting (3%)
Neuromuscular & skeletal: Arthralgia (2%), dyskinesia (≥1% to <2%)
Respiratory: Respiratory tract infection (≥1% to <2%)
Frequency not defined:
Endocrine & metabolic: Increased serum prolactin (dose-related)
Hepatic: Increased serum alkaline phosphatase (dose-related), increased serum bilirubin (dose-related)
Concerns related to adverse effects:
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).
• Depression/suicidal ideation: VMAT inhibitors have been associated with depression and suicidal thoughts and behavior; although short-term studies with valbenazine have not detected this adverse effect, longer studies have not yet been published (O'Brien 2015).
• QT prolongation: May prolong the QT interval; use caution when used concomitantly with a strong CYP2D6 or CYP3A4 inhibitor or in a poor CYP2D6 metabolizer, dose reduction may be necessary. Avoid use in patients with congenital long QT syndrome or arrhythmias associated with prolonged QT interval. For patients at risk of prolonged QT interval, perform EKG before increasing the dosage.
• Hepatic impairment: Use with caution in patients with moderate or severe hepatic impairment; use reduced dose.
• Renal impairment: Use is not recommended in patients with severe renal impairment.
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
• CYP2D6 poor metabolizers: CYP2D6 poor metabolizes may have increased levels of primary drug metabolites which may increase the risk of adverse effects; consider dose reduction based on tolerability.
Abnormal Involuntary Movement Scale (AIMS) or Dyskinesia Identification System Condensed User Scale (DISCUS); EKG (for patients at risk for QT prolongation)
Adverse events were observed in some animal reproduction studies
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience fatigue, loss of strength or energy, dry mouth, or constipation. Have patient report immediately to prescriber difficulty focusing, blurred vision, difficult urination, tachycardia, abnormal heartbeat, or passing out (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.