valbenazine

section name header

Pronunciation ⬇

val-BEN-a-zeen

Classifications ⬆ ⬇

Therapeutic Classification: n/a

Pharmacologic Classification: reversible monoamine depleters

Indications ⬆ ⬇

REMS

Tardive dyskinesia.
Chorea associated with Huntington's disease.

Action ⬆ ⬇

Acts as a reversible inhibitor of the vesicular monoamine transporter 2, which inhibits the reuptake of serotonin, norepinephrine, and dopamine into vesicles in presynaptic neurons.

Therapeutic Effects:

Reduced severity of tardive dyskinesia.
Reduction in chorea.

Pharmacokinetics ⬆ ⬇

Absorption: 49% absorbed following oral administration.

Distribution: Well distributed to tissues.

Protein Binding: >99%.

Metabolism/Excretion: Rapidly and extensively metabolized by the liver via hydrolysis to the active metabolite, -dihydrotetrabenazine (-HTBZ); also metabolized via the CYP3A4 isoenzyme to form other minor metabolites. -HTBZ is further metabolized, in part, via the CYP2D6 isoenzyme. The CYP2D6 isoenzyme exhibits genetic polymorphism; 7% of population may be poor metabolizers and may have significantly ↑ concentrations and an ↑ risk of adverse effects. 60% eliminated in urine (<2% as unchanged drug) and 30% eliminated in feces (<2% as unchanged drug).

Half-life: 15–22 hr (valbenazine and -HTBZ).

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	0.5–1 hr	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity
Congenital long QT syndrome or history of torsades de pointes
Lactation: Lactation.

Use Cautiously in:

Patients with Huntington's disease with history of depression or suicidal thoughts/attempts
Poor CYP2D6 metabolizers or taking strong CYP2D6 inhibitor (may need to ↓ valbenazine dose)
Moderate or severe hepatic impairment (↓ dose)
OB: Safety not established in pregnancy
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

EENT: blurred vision.

GI: constipation, nausea, vomiting, xerostomia.

GU: urinary retention.

MS: arthralgia, bradykinesia.

Neuro: fatigue, sedation/somnolence, akathisia, balance difficulty, depression, dizziness, gait disturbances, headache, NEUROLEPTIC MALIGNANT SYNDROME (NMS), parkinsonism, restlessness, SUICIDAL THOUGHTS/BEHAVIORS, tremor, unsteady gait.
Misc: (INCLUDING ANGIOEDEMA)HYPERSENSITIVITY REACTIONS .

Interactions ⬆ ⬇

Drug-Drug:

MAO inhibitors may ↑ risk of serotonin syndrome and/or ↓ the effect of valbenazine; avoid concurrent use.
Strong CYP3A4 inhibitors, including itraconazole, ketoconazole, or clarithromycin may ↑ levels of valbenazine and its active metabolite (-HTBZ) and the risk of toxicity; ↓ valbenazine dose.
Strong CYP2D6 inhibitors, including fluoxetine, paroxetine, or quinidine may ↑ levels of the active metabolite (-HTBZ) and the risk of toxicity; may need to ↓ valbenazine dose.
Strong CYP3A4 inducers, including rifampin, carbamazepine, or phenytoin may ↓ levels and effectiveness; concurrent use not recommended.
May ↑ levels and the risk of toxicity of digoxin.

Drug-Natural Products:

St. John's wort may ↓ levels and effectiveness; concurrent use not recommended.

Route/Dosage ⬆ ⬇

Tardive Dyskinesia

PO (Adults): 40 mg once daily; after 1 wk, ↑ to 80 mg once daily. Known CYP2D6 poor metabolizer: 40 mg once daily (with no additional titration). Concurrent use of strong CYP3A4 inhibitors or strong CYP2D6 inhibitors: 40 mg once daily (with no additional titration).

Hepatic Impairment

PO (Adults): Moderate or severe hepatic impairment: 40 mg once daily (with no additional titration).

Chorea Associated with Huntington's Disease

PO (Adults): 40 mg once daily; ↑ by 20 mg/day every 2 wk until achieve recommended dose of 80 mg once daily. Known CYP2D6 poor metabolizer: 40 mg once daily (with no additional titration). Concurrent use of strong CYP3A4 inhibitors or strong CYP2D6 inhibitors: 40 mg once daily (with no additional titration).

Hepatic Impairment

PO (Adults): Moderate or severe hepatic impairment: 40 mg once daily (with no additional titration).

Availability ⬆ ⬇

Capsules: 40 mg; 60 mg; 80 mg;

Assessment ⬆ ⬇

Monitor for changes in signs and symptoms of tardive dyskinesia (uncontrolled rhythmic movement of mouth, face, and extremities; lip smacking or puckering; puffing of cheeks; uncontrolled chewing; rapid or worm-like movements of tongue, excessive eye blinking) periodically during therapy.
Monitor patients with Huntington's disease for new or worsening depression, and suicidal ideation or behaviors. If these reactions occur and do not resolve, consider discontinuing therapy.
Monitor for signs and symptoms of hypersensitivity (angioedema involving the larynx, glottis, lips, and eyelids). If signs and symptoms of hypersensitivity occur discontinue valbenazine.
Monitor for signs and symptoms of NMS (hyperpyrexia, muscle rigidity, altered mental status, evidence of autonomic instability [irregular pulse or blood pressure, tachycardia, diaphoresis, cardiac arrhythmia]). Immediately discontinue valbenazine if symptoms occur. Recurrence of NMS has been reported with resumption of therapy. If therapy with valbenazine is needed after recovery from NMS, patients should be monitored for signs of recurrence.

Implementation ⬆ ⬇

PO: Administer once daily without regard to food.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take valbenazine as directed. Do not stop taking valbenazine without consulting health care professional. Advise patient to read Patient Information before starting and with each Rx refill in case of changes.
May cause drowsiness. Caution patient to avoid driving and other activities requiring alertness until response to medication is known.
Advise patient to notify health care professional if symptoms of NMS, heart rhythm problems (fast, slow, or irregular heartbeat, shortness of breath, dizziness, fainting) or if a fast or irregular heartbeat occurs.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
May cause fetal harm. Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding during and for 5 days after last dose of therapy.

Evaluation/Desired Outcomes ⬆ ⬇

Decrease in severity of uncontrolled movements.
Reduction in chorea.

US Brand Names ⬆

Ingrezza