valbenazine (Rx)

Brand and Other Names:Ingrezza
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule

  • 40mg
  • 80mg

Tardive Dyskinesia

Indicated for treatment of tardive dyskinesia in adults

40 mg PO qDay x1 week, then increase to the recommended dose of 80 mg PO qDay

Continuation of 40 mg once daily may be considered for some patients

Also see Administration

Dosage Modifications

Strong CYP3A4 inducers: Coadministration not recommended

Strong CYP3A4 inhibitors: If coadministered, reduce valbenazine dose to 40 mg/day

Strong CYP2D6 inhibitors or known CYP2D6 poor metabolizers: If coadministered, consider reducing dose

Hepatic impairment

  • Mild: No dose adjustment required
  • Moderate-to-severe (Child-Pugh 7-15): Not to exceed 40 mg/day

Renal impairment

  • Mild-to-moderate (CrCl 30-90 mL/min): No dose adjustment required
  • Severe (CrCl <30 mL/min): Use not recommended

Tardive dyskinesia: Safety and efficacy not established

Tourette Syndrome (Orphan)

Orphan designation for treatment of Tourette syndrome

Sponsor

  • Neurocrine Biosciences, Inc; 12780 El Camino Real; San Diego, California 92130
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Interactions

Interaction Checker

and valbenazine

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10%

            Somnolence (10.9%)

            1-10%

            Anticholinergic effects (5.4%)

            Balance disorders/fall (4.1%)

            Headache (3.4%)

            Akathisia (2.7%)

            Vomiting (2.6%)

            Nausea (2.3%)

            Arthralgia (2.3%)

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            Warnings

            Contraindications

            None

            Cautions

            Can cause somnolence; warn patients not to perform activities requiring mental alertness (eg, driving or operating hazardous machinery) until they know how they will be affected

            QT prolongation

            • May prolong the QT interval, although the degree of QT prolongation is not clinically significant at concentrations expected with recommended dosing
            • If coadministered with a strong CYP2D6 or CYP3A4 inhibitor, or patients who are CYP2D6 poor metabolizers, valbenazine concentrations may increase and cause clinically significant QT prolongation (see Dosage Modifications)
            • Avoid in patients with congenital long QT syndrome or with arrhythmias associated with a prolonged QT interval
            • For patients at increased risk of a prolonged QT interval, assess the QT interval before increasing the dosage

            Drug interaction overview

            • MAOIs
              • Avoid coadministration
              • Concomitant use may increase concentration of monoamine neurotransmitters in synapses, potentially leading to increased risk of adverse reactions (eg, serotonin syndrome) or attenuated treatment effect of valbenazine
            • Strong CYP3A4 inhibitors
              • Reduce valbenazine dose (see Dosage Modifications)
              • Coadministration increases exposure (Cmax and AUC) to valbenazine and its active metabolite compared with the use of valbenazine alone
            • Strong CYP2D6 inhibitors
              • Consider reducing valbenazine dose based on tolerability
              • Coadministration increases exposure (Cmax and AUC) to valbenazine’s active metabolite compared with the use of valbenazine alone
            • Strong CYP3A4 inducers
              • Concomitant use not recommended
              • Coadministration decreases systemic exposure of valbenazine and its active metabolite, thereby decreasing efficacy
            • Digoxin
              • Coadministration increases digoxin levels owing to P-gp inhibition
              • Monitor digoxin levels if coadministered; dosage adjustment of digoxin may be necessary
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            Pregnancy

            Pregnancy

            Data are limited on use in pregnant women

            Based on animal studies, may cause fetal harm; advise pregnant women of the potential risk

            Animal studies

            • Administration to pregnant rats during organogenesis through lactation produced an increase in the number of stillborn pups and postnatal pup mortalities at doses <1 times the maximum recommended human dose (MRHD) of 80 mg/day based on mg/m² body surface area
            • However, no malformations were observed when administered orally to rats and rabbits during the period of organogenesis at doses up to 1.8 or 24 times, respectively, the MRHD

            Lactation

            Unknown if distributed in human breast milk

            Valbenazine and its metabolites have been detected in rat milk at concentrations higher than in plasma following oral administration at doses 0.1-1.2 times the MRHD based on mg/m²

            Based on animal findings of increased perinatal mortality in exposed fetuses and pups, advise a woman not to breastfeed during treatment and for 5 days after the final dose

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

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            Pharmacology

            Mechanism of Action

            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

            Absorption

            Bioavailability: ~49%

            Peak plasma time: 0.5-1 hr (parent); 4-8 hr (active metabolite)

            Steady-state: 1 week

            Distribution

            Protein bound: >99% (parent); ~64% (active metabolite)

            Vd: 92 L

            Metabolism

            Extensively metabolized after oral administration by hydrolysis of the valine ester to form the active metabolite ([+]-alpha-HTBZ) and by oxidative metabolism, primarily by CYP3A4/5, to form mono-oxidized valbenazine and other minor metabolites

            [+]-alpha-HTBZ appears to be further metabolized in part by CYP2D6

            Elimination

            Half-life: 15-22 hr (parent drug and active metabolite)

            Total plasma clearance: 7.2 L/hr

            Excretion: 60% urine; 30% feces; <2% excreted as unchanged valbenazine or [+]-alpha-HTBZ

            Pharmacogenomics

            CYP2D6 poor metabolizers

            • Consider reducing valbenazine dose based on tolerability for known CYP2D6 poor metabolizers
            • Increased exposure (Cmax and AUC) to the active metabolite is anticipated in CYP2D6 poor metabolizers, which may increase risk for exposure-related adverse effects
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            Administration

            Oral Administration

            May take with or without food

            Also see Dosage Modifications

            Storage

            Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F)

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

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            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
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            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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