valbenazine

Contraindicated in:

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

Use Cautiously in:

Patients with Huntington 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: HYPERSENSITIVITY REACTIONS (INCLUDING ANGIOEDEMA)

Interactions ⬆ ⬇

Drug-drug:

MAO inhibitors may ↑ risk of serotonin syndrome and/or ↓ the effectiveness of valbenazine; avoid concurrent use.
Strong CYP3A4 inhibitors, including itraconazole, ketoconazole, or clarithromycin, may ↑ levels of valbenazine and its active metabolite (α-HTBZ) and the risk of toxicity; ↓ valbenazine dose.
Strong CYP2D6 inhibitors, including fluoxetine, paroxetine, or quinidine, may ↑ levels of the active metabolite (α-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 risk of toxicity of digoxin.

Drug-Natural Products:

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

Availability ⬆ ⬇

(Generic available)

Capsules: 40 mg; 60 mg; 80 mg
Sprinkle capsules: 40 mg; 60 mg; 80 mg

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 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).

US Brand Names ⬆ ⬇

Ingrezza, Ingrezza Sprinkle

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.

Classifications ⬆ ⬇

Therapeutic Classification: none assigned

Pharmacologic Classification: reversible monoamine depleters

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, α-dihydrotetrabenazine (α-HTBZ); also metabolized via the CYP3A4 isoenzyme to form other minor metabolites. α-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); 30% eliminated in feces (<2% as unchanged drug).

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

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	0.5–1 hr	unknown

Patient/Family Teaching ⬆ ⬇

Explain the purpose and side effects of valbenazine to patient. Instruct patient to take valbenazine as directed. Do not stop taking valbenazine without consulting health care provider. Advise patient to read Patient Information before starting and with each Rx refill in case of changes.
Advise patient and family to monitor for changes, especially sudden changes, in mood, behaviors, thoughts, or feelings. If new or worse feelings of sadness or crying spells; lack of interest in friends or activities; sleeping a lot more or less; feelings of unimportance, guilt, hopelessness, or helplessness; irritability or aggression; feeling more or less hungry; having difficulty paying attention; or thoughts of hurting self or ending life occur, notify health care provider promptly.
Explain need for continued medical follow-up to assess effectiveness and possible side effects of medication.
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 provider if symptoms of NMS or heart rhythm problems (fast, slow, or irregular heartbeat; shortness of breath; fever; dizziness; fainting; severe muscle rigidity) occur.
Instruct patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care provider before taking any new medications.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected and to avoid breastfeeding during therapy and for 5 days after last dose.

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Indications ⬇

Contraind./Precautions ⬆ ⬇