Identification

Name
Deutetrabenazine
Accession Number
DB12161
Type
Small Molecule
Groups
Approved, Investigational
Description

Deutetrabenazine is a novel, highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor indicated for the management of chorea associated with Huntington’s disease. It is a hexahydro-dimethoxybenzoquinolizine derivative and a deuterated Tetrabenazine [5]. The presence of deuterium in deutetrabenazine increases the half-lives of the active metabolite and prolongs their pharmacological activity by attenuating CYP2D6 metabolism of the compound [5]. This allows less frequent dosing and a lower daily dose with improvement in tolerability [2]. Decreased plasma fluctuations of deutetrabenazine due to attenuated metabolism may explain a lower incidence of adverse reactions associated with deutetrabenazine [1]. Deutetrabenazine is a racemic mixture containing RR-Deutetrabenazine and SS-Deutetrabenazine [Label].

Huntington's disease (HD) is a hereditary, progressive neurodegenerative disorder characterized by motor dysfunction, cognitive decline, and neuropsychiatric disturbances [2] that interfere with daily functioning and significantly reduce the quality of life. The most prominent physical symptom of HD that may increase the risk of injury is chorea, which is an involuntary, sudden movement that can affect any muscle and flow randomly across body regions [5]. Psychomotor symptoms of HD, such as chorea, are related to hyperactive dopaminergic neurotransmission [6]. Deutetrabenazine depletes the levels of presynaptic dopamine by blocking VMAT2, which is responsible for the uptake of dopamine into synaptic vesicles in monoaminergic neurons and exocytotic release [6]. As with other agents for the treatment of neurodegenerative diseases, deutetrabenazine is a drug to alleviate the motor symptoms of HD and is not proposed to halt the progression of the disease [7]. In clinical trials of patients with HD, 12 weeks of treatment of deutetrabenazine resulted in overall improvement in mean total maximal chorea scores and motor signs than placebo [5]. It was approved by FDA in April 2017 and is marketed under the trade name Austedo as oral tablets.

Structure
Thumb
Synonyms
Not Available
External IDs
SD-809
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AustedoTablet, coated6 mg/1OralTeva Neuroscience, Inc.2017-04-12Not applicableUs
AustedoTablet, coated12 mg/1OralTeva Neuroscience, Inc.2017-04-12Not applicableUs
AustedoTablet, coated9 mg/1OralTeva Neuroscience, Inc.2017-04-12Not applicableUs
Categories
UNII
P341G6W9NB
CAS number
1392826-25-3
Weight
Average: 323.466
Monoisotopic: 323.236754209
Chemical Formula
C19H27NO3
InChI Key
MKJIEFSOBYUXJB-WEZHFFAMSA-N
InChI
InChI=1S/C19H27NO3/c1-12(2)7-14-11-20-6-5-13-8-18(22-3)19(23-4)9-15(13)16(20)10-17(14)21/h8-9,12,14,16H,5-7,10-11H2,1-4H3/t14-,16-/m0/s1/i3D3,4D3
IUPAC Name
(3S,11bS)-9,10-di(2H3)methoxy-3-(2-methylpropyl)-1H,2H,3H,4H,6H,7H,11bH-pyrido[2,1-a]isoquinolin-2-one
SMILES
[2H]C([2H])([2H])OC1=CC2=C(C=C1OC([2H])([2H])[2H])[C@@H]1CC(=O)[C@@H](CC(C)C)CN1CC2

Pharmacology

Indication

Indicated for the treatment of chorea associated with Huntington’s disease [Label].

Associated Conditions
Pharmacodynamics

In clinical trials, there was an evidence of clinical effectiveness of deutetrabenazine in improving the symptoms of involuntary movements in patient with tardive dyskinesia by reducing the mean Abnormal Involuntary Movement Scale (AIMS) score [3, 4]. In a randomized, double-blind, placebo-controlled crossover study in healthy male and female subjects, single dose administration of 24 mg deutetrabenazine results in an approximately 4.5 msec mean increase in QTc [Label]. Effects at higher exposures to deutetrabenazine or its metabolites have not been evaluated [Label]. Deutetrabenazine and its metabolites were shown to bind to melanin-containing tissues including eyes, skin and fur in pigmented rats. After a single oral dose of radiolabeled deutetrabenazine, radioactivity was still detected in eye and fur at 35 days following dosing [Label].

Mechanism of action

The precise mechanism of action of deutetrabenazine in mediating its anti-chorea effects is not fully elucidated. Deutetrabenazine reversibly depletes the levels of monoamines, such as dopamine, serotonin, norepinephrine, and histamine, from nerve terminals via its active metabolites. The major circulating metabolites are α-dihydrotetrabenazine [HTBZ] and β-HTBZ that act as reversible inhibitors of VMAT2. Inhibition of VMAT2 results in decreased uptake of monoamines into synaptic terminal and depletion of monoamine stores from nerve terminals [Label].

Deutetrabenazine contains the molecule deuterium, which is a naturally-occurring, nontoxic hydrogen isotope but with an increased mass relative to hydrogen [5]. Placed at key positions, deuterium forms a stronger hydrogen bond with carbon that requires more energy for cleavage, thus attenuating CYP2D6-mediated metabolism without having any effect on the therapeutic target [5].

TargetActionsOrganism
ASynaptic vesicular amine transporter
inhibitor
Human
Absorption

The extent of absorption is 80% with oral deutetrabenazine. As deutetrabenazine is extensively metabolized to its main active metabolites following administration, linear dose dependence of peak plasma concentrations (Cmax) and AUC was observed for the metabolites after single or multiple doses of deutetrabenazine (6 mg to 24 mg and 7.5 mg twice daily to 22.5 mg twice daily) [Label]. Cmax of deuterated α-HTBZ and β-HTBZ are reached within 3-4 hours post-dosing [Label]. Food may increase the Cmax of α-HTBZ or β-HTBZ by approximately 50%, but is unlikely to have an effect on the AUC [Label].

Volume of distribution

The median volume of distribution (Vc/F) of the α-HTBZ, and the β-HTBZ metabolites of deutetrabenazine are approximately 500 L and 730 L, respectively [Label]. Human PET-scans of tetrabenazine indicate rapid distribution to the brain, with the highest binding in the striatum and lowest binding in the cortex [Label]. Similar distribution pattern is expected for deutetrabenazine.

Protein binding

At doses ranging from 50 to 200 ng/mL in vitro, tetrabenazine protein binding ranged from 82% to 85%, α-HTBZ binding ranged from 60% to 68%, and β-HTBZ binding ranged from 59% to 63% [Label]. Similar protein binding pattern is expected for deutetrabenazine and its metabolites.

Metabolism

Deutetrabenazine undergoes extensive hepatic biotransformation mediated by carbonyl reductase to form its major active metabolites, α-HTBZ and β­-HTBZ. These metabolites may subsequently metabolized to form several minor metabolites, with major contribution of CYP2D6 and minor contributions of CYP1A2 and CYP3A4/5 [Label].

Route of elimination

Deutetrabenazine is mainly excreted in the urine as metabolites. In healthy subjects, about 75% to 86% of the deutetrabenazine dose was excreted in the urine, and fecal recovery accounted for 8% to 11% of the dose [Label]. Sulfate and glucuronide conjugates of the α-HTBZ and β-HTBZ, as well as products of oxidative metabolism, accounted for the majority of metabolites in the urine [Label]. α-HTBZ and β-HTBZ metabolites accounted for less than 10% of the administered dose in the urine [Label].

Half life

The half-life of total (α+β)-HTBZ from deutetrabenazine is approximately 9 to 10 hours [Label].

Clearance

In patients with Huntington's disease, the median clearance values (CL/F) of the α-HTBZ, and the β-HTBZ metabolites of deutetrabenazine are approximately 47 L/hour and 70 L/hour, respectively [Label].

Toxicity

Adverse reactions associated with overdosage include acute dystonia, oculogyric crisis, nausea and vomiting, sweating, sedation, hypotension, confusion, diarrhea, hallucinations, rubor, and tremor [Label]. In case of an overdose, general supportive and symptomatic measures are recommended while monitoring cardiac rhythm and vital signs. In managing overdosage, the possibility of multiple drug involvement should always be considered [Label].

No carcinogenicity studies were performed with deutetrabenazine. In p53+/– transgenic mice, there were no detectable tumors following oral administration of deutetrabenazine at doses of 0, 5, 15, and 30 mg/kg/day for 26 weeks [Label]. Findings from in vitro assays and in vivo mice micronucleus assay suggest that deutetrabenazine and its metabolites are unlikely to be mutagenic [Label]. The effects of deutetrabenazine on fertility have not been evaluated. Oral administration of tetrabenazine had no effects on mating and reproductive systems of male and female rats [Label].

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline is combined with Deutetrabenazine.Experimental
AbirateroneThe serum concentration of Deutetrabenazine can be increased when it is combined with Abiraterone.Approved
AcepromazineThe risk or severity of adverse effects can be increased when Acepromazine is combined with Deutetrabenazine.Approved, Vet Approved
AceprometazineThe risk or severity of adverse effects can be increased when Aceprometazine is combined with Deutetrabenazine.Approved
AcetophenazineThe risk or severity of adverse effects can be increased when Acetophenazine is combined with Deutetrabenazine.Approved
Acetyl sulfisoxazoleThe metabolism of Deutetrabenazine can be decreased when combined with Acetyl sulfisoxazole.Approved, Vet Approved
Acetylglycinamide chloral hydrateThe risk or severity of sedation and somnolence can be increased when Acetylglycinamide chloral hydrate is combined with Deutetrabenazine.Experimental
AgomelatineThe risk or severity of sedation and somnolence can be increased when Agomelatine is combined with Deutetrabenazine.Approved, Investigational
AlizaprideThe risk or severity of adverse effects can be increased when Alizapride is combined with Deutetrabenazine.Approved
AllobarbitalThe risk or severity of sedation and somnolence can be increased when Allobarbital is combined with Deutetrabenazine.Experimental
AlprazolamThe risk or severity of sedation and somnolence can be increased when Alprazolam is combined with Deutetrabenazine.Approved, Illicit, Investigational
AmiodaroneAmiodarone may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Investigational
AmisulprideThe risk or severity of adverse effects can be increased when Amisulpride is combined with Deutetrabenazine.Approved, Investigational
AmobarbitalThe risk or severity of sedation and somnolence can be increased when Amobarbital is combined with Deutetrabenazine.Approved, Illicit
AmoxapineThe risk or severity of adverse effects can be increased when Amoxapine is combined with Deutetrabenazine.Approved
AmperozideThe risk or severity of adverse effects can be increased when Amperozide is combined with Deutetrabenazine.Experimental
AmphetamineThe risk or severity of adverse effects can be increased when Amphetamine is combined with Deutetrabenazine.Approved, Illicit, Investigational
AnagrelideAnagrelide may increase the QTc-prolonging activities of Deutetrabenazine.Approved
ApalutamideThe serum concentration of Deutetrabenazine can be decreased when it is combined with Apalutamide.Approved, Investigational
AprepitantThe serum concentration of Deutetrabenazine can be increased when it is combined with Aprepitant.Approved, Investigational
AprobarbitalThe risk or severity of sedation and somnolence can be increased when Aprobarbital is combined with Deutetrabenazine.Approved, Illicit
ApronalideThe risk or severity of sedation and somnolence can be increased when Apronalide is combined with Deutetrabenazine.Experimental
AripiprazoleThe risk or severity of adverse effects can be increased when Aripiprazole is combined with Deutetrabenazine.Approved, Investigational
Arsenic trioxideArsenic trioxide may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Investigational
ArtemetherThe metabolism of Deutetrabenazine can be decreased when combined with Artemether.Approved
AS-8112The risk or severity of adverse effects can be increased when AS-8112 is combined with Deutetrabenazine.Experimental
AsenapineThe risk or severity of adverse effects can be increased when Asenapine is combined with Deutetrabenazine.Approved
AstemizoleAstemizole may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Withdrawn
AtazanavirThe metabolism of Deutetrabenazine can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Deutetrabenazine can be decreased when combined with Atomoxetine.Approved
AzaperoneThe risk or severity of adverse effects can be increased when Azaperone is combined with Deutetrabenazine.Investigational, Vet Approved
AZD-3043The risk or severity of sedation and somnolence can be increased when AZD-3043 is combined with Deutetrabenazine.Investigational
AzithromycinAzithromycin may increase the QTc-prolonging activities of Deutetrabenazine.Approved
BarbitalThe risk or severity of sedation and somnolence can be increased when Barbital is combined with Deutetrabenazine.Illicit
BenmoxinThe risk or severity of adverse effects can be increased when Benmoxin is combined with Deutetrabenazine.Withdrawn
BenperidolThe risk or severity of adverse effects can be increased when Benperidol is combined with Deutetrabenazine.Approved, Investigational
BepridilBepridil may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Withdrawn
BetaxololThe metabolism of Deutetrabenazine can be decreased when combined with Betaxolol.Approved, Investigational
BifeprunoxThe risk or severity of adverse effects can be increased when Bifeprunox is combined with Deutetrabenazine.Investigational
BlonanserinThe risk or severity of adverse effects can be increased when Blonanserin is combined with Deutetrabenazine.Approved, Investigational
BoceprevirThe metabolism of Deutetrabenazine can be decreased when combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Deutetrabenazine can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Deutetrabenazine can be decreased when it is combined with Bosentan.Approved, Investigational
BrexpiprazoleThe risk or severity of adverse effects can be increased when Brexpiprazole is combined with Deutetrabenazine.Approved, Investigational
BrofaromineThe risk or severity of adverse effects can be increased when Brofaromine is combined with Deutetrabenazine.Experimental
BromisovalThe risk or severity of sedation and somnolence can be increased when Bromisoval is combined with Deutetrabenazine.Experimental
BromocriptineThe risk or severity of adverse effects can be increased when Bromocriptine is combined with Deutetrabenazine.Approved, Investigational
BromoprideThe risk or severity of adverse effects can be increased when Bromopride is combined with Deutetrabenazine.Approved, Investigational
BromperidolThe risk or severity of adverse effects can be increased when Bromperidol is combined with Deutetrabenazine.Approved, Investigational
BrotizolamThe risk or severity of sedation and somnolence can be increased when Brotizolam is combined with Deutetrabenazine.Approved, Investigational, Withdrawn
BupropionThe serum concentration of the active metabolites of Deutetrabenazine can be increased when Deutetrabenazine is used in combination with Bupropion.Approved
BuspironeThe risk or severity of adverse effects can be increased when Buspirone is combined with Deutetrabenazine.Approved, Investigational
ButabarbitalThe risk or severity of sedation and somnolence can be increased when Butabarbital is combined with Deutetrabenazine.Approved, Illicit
ButalbitalThe risk or severity of sedation and somnolence can be increased when Butalbital is combined with Deutetrabenazine.Approved, Illicit
ButaperazineThe risk or severity of adverse effects can be increased when Butaperazine is combined with Deutetrabenazine.Experimental
ButethalThe risk or severity of sedation and somnolence can be increased when Butethal is combined with Deutetrabenazine.Approved, Illicit
CaffeineThe metabolism of Deutetrabenazine can be decreased when combined with Caffeine.Approved
CarbamazepineThe metabolism of Deutetrabenazine can be increased when combined with Carbamazepine.Approved, Investigational
CarbromalThe risk or severity of sedation and somnolence can be increased when Carbromal is combined with Deutetrabenazine.Experimental
CariprazineThe risk or severity of adverse effects can be increased when Cariprazine is combined with Deutetrabenazine.Approved, Investigational
CaroxazoneThe risk or severity of adverse effects can be increased when Caroxazone is combined with Deutetrabenazine.Withdrawn
CarphenazineThe risk or severity of adverse effects can be increased when Carphenazine is combined with Deutetrabenazine.Withdrawn
CelecoxibThe metabolism of Deutetrabenazine can be decreased when combined with Celecoxib.Approved, Investigational
CeritinibThe serum concentration of Deutetrabenazine can be increased when it is combined with Ceritinib.Approved
Chloral hydrateThe risk or severity of sedation and somnolence can be increased when Chloral hydrate is combined with Deutetrabenazine.Approved, Illicit, Investigational, Vet Approved
ChlordiazepoxideThe risk or severity of sedation and somnolence can be increased when Chlordiazepoxide is combined with Deutetrabenazine.Approved, Illicit, Investigational
ChloroquineChloroquine may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Investigational, Vet Approved
ChlorproethazineThe risk or severity of adverse effects can be increased when Chlorproethazine is combined with Deutetrabenazine.Experimental
ChlorpromazineChlorpromazine may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Investigational, Vet Approved
ChlorprothixeneThe risk or severity of adverse effects can be increased when Chlorprothixene is combined with Deutetrabenazine.Approved, Investigational, Withdrawn
CholecalciferolThe metabolism of Deutetrabenazine can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
CilostazolCilostazol may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Investigational
CimetidineThe metabolism of Deutetrabenazine can be decreased when combined with Cimetidine.Approved, Investigational
CinacalcetThe serum concentration of the active metabolites of Deutetrabenazine can be increased when Deutetrabenazine is used in combination with Cinacalcet.Approved
CinolazepamThe risk or severity of sedation and somnolence can be increased when Cinolazepam is combined with Deutetrabenazine.Approved
CiprofloxacinCiprofloxacin may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Investigational
CisaprideCisapride may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Investigational, Withdrawn
CitalopramCitalopram may increase the QTc-prolonging activities of Deutetrabenazine.Approved
ClarithromycinClarithromycin may increase the QTc-prolonging activities of Deutetrabenazine.Approved
CleboprideThe risk or severity of adverse effects can be increased when Clebopride is combined with Deutetrabenazine.Experimental
ClemastineThe metabolism of Deutetrabenazine can be decreased when combined with Clemastine.Approved, Investigational
ClobazamThe metabolism of Deutetrabenazine can be decreased when combined with Clobazam.Approved, Illicit
clomethiazoleThe risk or severity of sedation and somnolence can be increased when clomethiazole is combined with Deutetrabenazine.Investigational
ClomipramineThe metabolism of Deutetrabenazine can be decreased when combined with Clomipramine.Approved, Investigational, Vet Approved
ClopenthixolThe risk or severity of adverse effects can be increased when Clopenthixol is combined with Deutetrabenazine.Experimental
ClothiapineThe risk or severity of adverse effects can be increased when Clothiapine is combined with Deutetrabenazine.Experimental
ClotrimazoleThe metabolism of Deutetrabenazine can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe risk or severity of adverse effects can be increased when Clozapine is combined with Deutetrabenazine.Approved
CobicistatThe serum concentration of Deutetrabenazine can be increased when it is combined with Cobicistat.Approved
CocaineCocaine may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Illicit
ConivaptanThe serum concentration of Conivaptan can be increased when it is combined with Deutetrabenazine.Approved, Investigational
CrizotinibThe metabolism of Deutetrabenazine can be decreased when combined with Crizotinib.Approved
CurcuminThe metabolism of Deutetrabenazine can be decreased when combined with Curcumin.Approved, Investigational
CyamemazineThe risk or severity of adverse effects can be increased when Cyamemazine is combined with Deutetrabenazine.Approved
CyclobarbitalThe risk or severity of sedation and somnolence can be increased when Cyclobarbital is combined with Deutetrabenazine.Experimental
CyclosporineThe metabolism of Deutetrabenazine can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
Cyproterone acetateThe serum concentration of Deutetrabenazine can be decreased when it is combined with Cyproterone acetate.Approved, Investigational
DabrafenibThe serum concentration of Deutetrabenazine can be decreased when it is combined with Dabrafenib.Approved, Investigational
DapiprazoleThe risk or severity of adverse effects can be increased when Dapiprazole is combined with Deutetrabenazine.Approved
DarifenacinThe metabolism of Deutetrabenazine can be decreased when combined with Darifenacin.Approved, Investigational
DarunavirThe serum concentration of Deutetrabenazine can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Deutetrabenazine can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Deutetrabenazine can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe serum concentration of the active metabolites of Deutetrabenazine can be increased when Deutetrabenazine is used in combination with Delavirdine.Approved
DesipramineThe metabolism of Deutetrabenazine can be decreased when combined with Desipramine.Approved, Investigational
DetomidineThe risk or severity of sedation and somnolence can be increased when Detomidine is combined with Deutetrabenazine.Vet Approved
DexmedetomidineThe risk or severity of sedation and somnolence can be increased when Dexmedetomidine is combined with Deutetrabenazine.Approved, Vet Approved
DiazepamThe risk or severity of sedation and somnolence can be increased when Diazepam is combined with Deutetrabenazine.Approved, Illicit, Investigational, Vet Approved
DichloralphenazoneThe risk or severity of sedation and somnolence can be increased when Dichloralphenazone is combined with Deutetrabenazine.Approved, Illicit
DihydroergotamineThe metabolism of Deutetrabenazine can be decreased when combined with Dihydroergotamine.Approved, Investigational
DiltiazemThe metabolism of Deutetrabenazine can be decreased when combined with Diltiazem.Approved, Investigational
DiphenhydramineThe risk or severity of sedation and somnolence can be increased when Diphenhydramine is combined with Deutetrabenazine.Approved, Investigational
DisopyramideDisopyramide may increase the QTc-prolonging activities of Deutetrabenazine.Approved
DixyrazineThe risk or severity of adverse effects can be increased when Dixyrazine is combined with Deutetrabenazine.Experimental
DofetilideDofetilide may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Investigational
DomperidoneDomperidone may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Investigational, Vet Approved
DonepezilDonepezil may increase the QTc-prolonging activities of Deutetrabenazine.Approved
DosulepinThe serum concentration of the active metabolites of Deutetrabenazine can be increased when Deutetrabenazine is used in combination with Dosulepin.Approved
DoxefazepamThe risk or severity of sedation and somnolence can be increased when Doxefazepam is combined with Deutetrabenazine.Experimental
DoxepinThe risk or severity of adverse effects can be increased when Doxepin is combined with Deutetrabenazine.Approved, Investigational
DoxycyclineThe metabolism of Deutetrabenazine can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneDronedarone may increase the QTc-prolonging activities of Deutetrabenazine.Approved
DroperidolDroperidol may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Vet Approved
DuloxetineThe metabolism of Deutetrabenazine can be decreased when combined with Duloxetine.Approved
EcopipamThe risk or severity of adverse effects can be increased when Ecopipam is combined with Deutetrabenazine.Investigational
EliglustatThe metabolism of Deutetrabenazine can be decreased when combined with Eliglustat.Approved
EmeproniumThe risk or severity of sedation and somnolence can be increased when Emepronium is combined with Deutetrabenazine.Experimental
EnzalutamideThe serum concentration of Deutetrabenazine can be decreased when it is combined with Enzalutamide.Approved
ErythromycinErythromycin may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Investigational, Vet Approved
EscitalopramEscitalopram may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Investigational
EstazolamThe risk or severity of sedation and somnolence can be increased when Estazolam is combined with Deutetrabenazine.Approved, Illicit
EszopicloneThe risk or severity of sedation and somnolence can be increased when Eszopiclone is combined with Deutetrabenazine.Approved, Investigational
EthanolThe risk or severity of sedation and somnolence can be increased when Ethanol is combined with Deutetrabenazine.Approved
EthchlorvynolThe risk or severity of sedation and somnolence can be increased when Ethchlorvynol is combined with Deutetrabenazine.Approved, Illicit, Withdrawn
EtomidateThe risk or severity of sedation and somnolence can be increased when Etomidate is combined with Deutetrabenazine.Approved
EtoperidoneThe risk or severity of adverse effects can be increased when Etoperidone is combined with Deutetrabenazine.Withdrawn
EtorphineThe risk or severity of sedation and somnolence can be increased when Etorphine is combined with Deutetrabenazine.Illicit, Vet Approved
FencamfamineThe risk or severity of adverse effects can be increased when Fencamfamine is combined with Deutetrabenazine.Approved, Illicit, Withdrawn
FlecainideFlecainide may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Withdrawn
FlibanserinThe risk or severity of adverse effects can be increased when Flibanserin is combined with Deutetrabenazine.Approved, Investigational
FluanisoneThe risk or severity of adverse effects can be increased when Fluanisone is combined with Deutetrabenazine.Experimental
FluconazoleFluconazole may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Investigational
FlunitrazepamThe risk or severity of sedation and somnolence can be increased when Flunitrazepam is combined with Deutetrabenazine.Approved, Illicit
FluoxetineThe serum concentration of the active metabolites of Deutetrabenazine can be increased when Deutetrabenazine is used in combination with Fluoxetine.Approved, Vet Approved
FlupentixolThe risk or severity of adverse effects can be increased when Flupentixol is combined with Deutetrabenazine.Approved, Investigational, Withdrawn
FluphenazineThe risk or severity of adverse effects can be increased when Fluphenazine is combined with Deutetrabenazine.Approved
FlurazepamThe risk or severity of sedation and somnolence can be increased when Flurazepam is combined with Deutetrabenazine.Approved, Illicit, Investigational
FluspirileneThe risk or severity of adverse effects can be increased when Fluspirilene is combined with Deutetrabenazine.Approved, Investigational
FluvoxamineThe metabolism of Deutetrabenazine can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Deutetrabenazine can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Deutetrabenazine can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Deutetrabenazine can be increased when combined with Fosphenytoin.Approved, Investigational
FospropofolThe risk or severity of sedation and somnolence can be increased when Fospropofol is combined with Deutetrabenazine.Approved, Illicit, Investigational
FurazolidoneThe risk or severity of adverse effects can be increased when Furazolidone is combined with Deutetrabenazine.Approved, Investigational, Vet Approved
Fusidic AcidThe serum concentration of Deutetrabenazine can be increased when it is combined with Fusidic Acid.Approved, Investigational
GatifloxacinGatifloxacin may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Investigational
GlutethimideThe risk or severity of sedation and somnolence can be increased when Glutethimide is combined with Deutetrabenazine.Approved, Illicit
GrepafloxacinGrepafloxacin may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Investigational, Withdrawn
HalofantrineHalofantrine may increase the QTc-prolonging activities of Deutetrabenazine.Approved
HaloperidolHaloperidol may increase the QTc-prolonging activities of Deutetrabenazine.Approved
HarmalineThe risk or severity of adverse effects can be increased when Harmaline is combined with Deutetrabenazine.Experimental
HeptabarbitalThe risk or severity of sedation and somnolence can be increased when Heptabarbital is combined with Deutetrabenazine.Approved
HexapropymateThe risk or severity of sedation and somnolence can be increased when Hexapropymate is combined with Deutetrabenazine.Experimental
HexobarbitalThe risk or severity of sedation and somnolence can be increased when Hexobarbital is combined with Deutetrabenazine.Approved
HydracarbazineThe risk or severity of adverse effects can be increased when Hydracarbazine is combined with Deutetrabenazine.Experimental
IbutilideIbutilide may increase the QTc-prolonging activities of Deutetrabenazine.Approved
IdelalisibThe metabolism of Deutetrabenazine can be decreased when combined with Idelalisib.Approved
IloperidoneThe risk or severity of adverse effects can be increased when Iloperidone is combined with Deutetrabenazine.Approved
ImatinibThe metabolism of Deutetrabenazine can be decreased when combined with Imatinib.Approved
ImipramineThe metabolism of Deutetrabenazine can be decreased when combined with Imipramine.Approved
IndinavirThe metabolism of Deutetrabenazine can be decreased when combined with Indinavir.Approved
IndiplonThe risk or severity of sedation and somnolence can be increased when Indiplon is combined with Deutetrabenazine.Investigational
IproclozideThe risk or severity of adverse effects can be increased when Iproclozide is combined with Deutetrabenazine.Withdrawn
IproniazidThe risk or severity of adverse effects can be increased when Iproniazid is combined with Deutetrabenazine.Withdrawn
IsavuconazoleThe serum concentration of Deutetrabenazine can be increased when it is combined with Isavuconazole.Approved, Investigational
IsavuconazoniumThe metabolism of Deutetrabenazine can be decreased when combined with Isavuconazonium.Approved, Investigational
IsocarboxazidThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Deutetrabenazine.Approved
IsoniazidThe metabolism of Deutetrabenazine can be decreased when combined with Isoniazid.Approved, Investigational
IsradipineThe metabolism of Deutetrabenazine can be decreased when combined with Isradipine.Approved, Investigational
ItraconazoleThe metabolism of Deutetrabenazine can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Deutetrabenazine can be increased when it is combined with Ivacaftor.Approved
JNJ-37822681The risk or severity of adverse effects can be increased when JNJ-37822681 is combined with Deutetrabenazine.Investigational
KetoconazoleThe metabolism of Deutetrabenazine can be decreased when combined with Ketoconazole.Approved, Investigational
LevofloxacinLevofloxacin may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Investigational
Levomethadyl AcetateLevomethadyl Acetate may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Investigational
LidocaineThe metabolism of Deutetrabenazine can be decreased when combined with Lidocaine.Approved, Vet Approved
LisurideThe risk or severity of adverse effects can be increased when Lisuride is combined with Deutetrabenazine.Approved, Investigational
Lithium cationThe risk or severity of adverse effects can be increased when Lithium is combined with Deutetrabenazine.Experimental
LobeglitazoneThe metabolism of Deutetrabenazine can be decreased when combined with Lobeglitazone.Approved, Investigational
LopinavirThe serum concentration of the active metabolites of Deutetrabenazine can be increased when Deutetrabenazine is used in combination with Lopinavir.Approved
LoprazolamThe risk or severity of sedation and somnolence can be increased when Loprazolam is combined with Deutetrabenazine.Experimental
LorazepamThe risk or severity of sedation and somnolence can be increased when Lorazepam is combined with Deutetrabenazine.Approved
LorcaserinThe metabolism of Deutetrabenazine can be decreased when combined with Lorcaserin.Approved
LormetazepamThe risk or severity of sedation and somnolence can be increased when Lormetazepam is combined with Deutetrabenazine.Approved
LorpiprazoleThe serum concentration of Deutetrabenazine can be increased when it is combined with Lorpiprazole.Approved
LovastatinThe metabolism of Deutetrabenazine can be decreased when combined with Lovastatin.Approved, Investigational
LoxapineThe risk or severity of adverse effects can be increased when Loxapine is combined with Deutetrabenazine.Approved
LuliconazoleThe serum concentration of Deutetrabenazine can be increased when it is combined with Luliconazole.Approved
LumacaftorThe metabolism of Deutetrabenazine can be increased when combined with Lumacaftor.Approved
LumefantrineThe metabolism of Deutetrabenazine can be decreased when combined with Lumefantrine.Approved
LurasidoneThe risk or severity of adverse effects can be increased when Lurasidone is combined with Deutetrabenazine.Approved, Investigational
ManidipineThe metabolism of Deutetrabenazine can be decreased when combined with Manidipine.Approved, Investigational
MebanazineThe risk or severity of adverse effects can be increased when Mebanazine is combined with Deutetrabenazine.Withdrawn
MedazepamThe risk or severity of sedation and somnolence can be increased when Medazepam is combined with Deutetrabenazine.Experimental
MedetomidineThe risk or severity of sedation and somnolence can be increased when Medetomidine is combined with Deutetrabenazine.Vet Approved
MelatoninThe risk or severity of sedation and somnolence can be increased when Melatonin is combined with Deutetrabenazine.Approved, Nutraceutical, Vet Approved
MelperoneThe risk or severity of adverse effects can be increased when Melperone is combined with Deutetrabenazine.Approved, Investigational
MeprobamateThe risk or severity of sedation and somnolence can be increased when Meprobamate is combined with Deutetrabenazine.Approved, Illicit
MesoridazineMesoridazine may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Investigational
MethadoneMethadone may increase the QTc-prolonging activities of Deutetrabenazine.Approved
MethapyrileneThe risk or severity of sedation and somnolence can be increased when Methapyrilene is combined with Deutetrabenazine.Withdrawn
MethaqualoneThe risk or severity of sedation and somnolence can be increased when Methaqualone is combined with Deutetrabenazine.Illicit, Withdrawn
MethohexitalThe risk or severity of sedation and somnolence can be increased when Methohexital is combined with Deutetrabenazine.Approved
MethotrimeprazineMethotrimeprazine may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Investigational
Methylene blueThe risk or severity of adverse effects can be increased when Methylene blue is combined with Deutetrabenazine.Approved, Investigational
MethylergometrineThe risk or severity of adverse effects can be increased when Methylergometrine is combined with Deutetrabenazine.Approved
MethylpentynolThe risk or severity of sedation and somnolence can be increased when Methylpentynol is combined with Deutetrabenazine.Experimental
MethylphenobarbitalThe risk or severity of sedation and somnolence can be increased when Methylphenobarbital is combined with Deutetrabenazine.Approved
MethyprylonThe risk or severity of sedation and somnolence can be increased when Methyprylon is combined with Deutetrabenazine.Approved, Illicit, Withdrawn
MetoclopramideThe risk or severity of adverse effects can be increased when Metoclopramide is combined with Deutetrabenazine.Approved, Investigational
MetoprololThe metabolism of Deutetrabenazine can be decreased when combined with Metoprolol.Approved, Investigational
MexiletineThe metabolism of Deutetrabenazine can be decreased when combined with Mexiletine.Approved, Investigational
MianserinThe risk or severity of adverse effects can be increased when Mianserin is combined with Deutetrabenazine.Approved, Investigational
MidazolamThe risk or severity of sedation and somnolence can be increased when Midazolam is combined with Deutetrabenazine.Approved, Illicit
MidostaurinThe serum concentration of the active metabolites of Deutetrabenazine can be increased when Deutetrabenazine is used in combination with Midostaurin.Approved, Investigational
MifepristoneThe serum concentration of Deutetrabenazine can be increased when it is combined with Mifepristone.Approved, Investigational
MinaprineThe risk or severity of adverse effects can be increased when Minaprine is combined with Deutetrabenazine.Approved
MirabegronThe metabolism of Deutetrabenazine can be decreased when combined with Mirabegron.Approved
MitotaneThe serum concentration of Deutetrabenazine can be decreased when it is combined with Mitotane.Approved
MoclobemideThe risk or severity of adverse effects can be increased when Moclobemide is combined with Deutetrabenazine.Approved, Investigational
MolindoneThe risk or severity of adverse effects can be increased when Molindone is combined with Deutetrabenazine.Approved
MoperoneThe risk or severity of adverse effects can be increased when Moperone is combined with Deutetrabenazine.Experimental
MosapramineThe risk or severity of adverse effects can be increased when Mosapramine is combined with Deutetrabenazine.Experimental
MoxifloxacinMoxifloxacin may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Investigational
NefazodoneThe metabolism of Deutetrabenazine can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Deutetrabenazine can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Deutetrabenazine can be increased when it is combined with Netupitant.Approved, Investigational
NevirapineThe metabolism of Deutetrabenazine can be increased when combined with Nevirapine.Approved
NialamideThe risk or severity of adverse effects can be increased when Nialamide is combined with Deutetrabenazine.Withdrawn
NiaprazineThe risk or severity of sedation and somnolence can be increased when Niaprazine is combined with Deutetrabenazine.Experimental
NicardipineThe metabolism of Deutetrabenazine can be decreased when combined with Nicardipine.Approved, Investigational
NilotinibThe metabolism of Deutetrabenazine can be decreased when combined with Nilotinib.Approved, Investigational
NitrazepamThe risk or severity of sedation and somnolence can be increased when Nitrazepam is combined with Deutetrabenazine.Approved
NortriptylineThe risk or severity of adverse effects can be increased when Nortriptyline is combined with Deutetrabenazine.Approved
OctamoxinThe risk or severity of adverse effects can be increased when Octamoxin is combined with Deutetrabenazine.Withdrawn
OlanzapineThe risk or severity of adverse effects can be increased when Olanzapine is combined with Deutetrabenazine.Approved, Investigational
OlaparibThe metabolism of Deutetrabenazine can be decreased when combined with Olaparib.Approved
OndansetronOndansetron may increase the QTc-prolonging activities of Deutetrabenazine.Approved
OsanetantThe risk or severity of adverse effects can be increased when Osanetant is combined with Deutetrabenazine.Investigational
OsimertinibThe serum concentration of Deutetrabenazine can be increased when it is combined with Osimertinib.Approved
OxaliplatinOxaliplatin may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Investigational
OxazepamThe risk or severity of sedation and somnolence can be increased when Oxazepam is combined with Deutetrabenazine.Approved
OxypertineThe risk or severity of adverse effects can be increased when Oxypertine is combined with Deutetrabenazine.Experimental
PalbociclibThe serum concentration of Deutetrabenazine can be increased when it is combined with Palbociclib.Approved, Investigational
PaliperidoneThe risk or severity of adverse effects can be increased when Paliperidone is combined with Deutetrabenazine.Approved
PanobinostatThe serum concentration of Deutetrabenazine can be increased when it is combined with Panobinostat.Approved, Investigational
PapaverinePapaverine may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Investigational
ParaldehydeThe risk or severity of sedation and somnolence can be increased when Paraldehyde is combined with Deutetrabenazine.Approved, Investigational
PargylineThe risk or severity of adverse effects can be increased when Pargyline is combined with Deutetrabenazine.Approved
ParoxetineThe serum concentration of the active metabolites of Deutetrabenazine can be increased when Deutetrabenazine is used in combination with Paroxetine.Approved, Investigational
Peginterferon alfa-2bThe serum concentration of Deutetrabenazine can be decreased when it is combined with Peginterferon alfa-2b.Approved
PenfluridolThe risk or severity of adverse effects can be increased when Penfluridol is combined with Deutetrabenazine.Experimental
PentamidinePentamidine may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Investigational
PentobarbitalThe risk or severity of sedation and somnolence can be increased when Pentobarbital is combined with Deutetrabenazine.Approved, Investigational, Vet Approved
PerazineThe risk or severity of adverse effects can be increased when Perazine is combined with Deutetrabenazine.Approved, Investigational
PerospironeThe risk or severity of adverse effects can be increased when Perospirone is combined with Deutetrabenazine.Approved
PerphenazineThe risk or severity of adverse effects can be increased when Perphenazine is combined with Deutetrabenazine.Approved
PhenelzineThe risk or severity of adverse effects can be increased when Phenelzine is combined with Deutetrabenazine.Approved
PhenibutThe risk or severity of sedation and somnolence can be increased when Phenibut is combined with Deutetrabenazine.Experimental
PheniprazineThe risk or severity of adverse effects can be increased when Pheniprazine is combined with Deutetrabenazine.Withdrawn
PhenobarbitalThe risk or severity of sedation and somnolence can be increased when Phenobarbital is combined with Deutetrabenazine.Approved, Investigational
PhenoxypropazineThe risk or severity of adverse effects can be increased when Phenoxypropazine is combined with Deutetrabenazine.Withdrawn
PhenytoinThe metabolism of Deutetrabenazine can be increased when combined with Phenytoin.Approved, Vet Approved
PimozidePimozide may increase the QTc-prolonging activities of Deutetrabenazine.Approved
PipamperoneThe risk or severity of adverse effects can be increased when Pipamperone is combined with Deutetrabenazine.Approved, Investigational
PipotiazineThe risk or severity of adverse effects can be increased when Pipotiazine is combined with Deutetrabenazine.Approved, Investigational
PirlindoleThe risk or severity of adverse effects can be increased when Pirlindole is combined with Deutetrabenazine.Approved
PitolisantThe serum concentration of Deutetrabenazine can be decreased when it is combined with Pitolisant.Approved, Investigational
PivhydrazineThe risk or severity of adverse effects can be increased when Pivhydrazine is combined with Deutetrabenazine.Withdrawn
PosaconazoleThe metabolism of Deutetrabenazine can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PrimidoneThe risk or severity of sedation and somnolence can be increased when Primidone is combined with Deutetrabenazine.Approved, Vet Approved
ProbucolProbucol may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Investigational
ProcainamideProcainamide may increase the QTc-prolonging activities of Deutetrabenazine.Approved
ProcaineThe risk or severity of adverse effects can be increased when Procaine is combined with Deutetrabenazine.Approved, Investigational, Vet Approved
ProcarbazineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Deutetrabenazine.Approved, Investigational
ProchlorperazineThe risk or severity of adverse effects can be increased when Prochlorperazine is combined with Deutetrabenazine.Approved, Vet Approved
PromazineThe risk or severity of adverse effects can be increased when Promazine is combined with Deutetrabenazine.Approved, Vet Approved
PromethazineThe risk or severity of adverse effects can be increased when Promethazine is combined with Deutetrabenazine.Approved, Investigational
PropericiazineThe risk or severity of adverse effects can be increased when Propericiazine is combined with Deutetrabenazine.Approved, Investigational
PropiomazineThe risk or severity of adverse effects can be increased when Propiomazine is combined with Deutetrabenazine.Approved
PropofolPropofol may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Investigational, Vet Approved
ProthipendylThe risk or severity of adverse effects can be increased when Prothipendyl is combined with Deutetrabenazine.Investigational
ProxibarbalThe risk or severity of sedation and somnolence can be increased when Proxibarbal is combined with Deutetrabenazine.Experimental
PyrithyldioneThe risk or severity of sedation and somnolence can be increased when Pyrithyldione is combined with Deutetrabenazine.Experimental
QuazepamThe risk or severity of sedation and somnolence can be increased when Quazepam is combined with Deutetrabenazine.Approved, Illicit
QuetiapineThe risk or severity of adverse effects can be increased when Quetiapine is combined with Deutetrabenazine.Approved
QuinidineQuinidine may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Investigational
QuinineThe metabolism of Deutetrabenazine can be decreased when combined with Quinine.Approved
RacloprideThe risk or severity of adverse effects can be increased when Raclopride is combined with Deutetrabenazine.Investigational
RamelteonThe risk or severity of sedation and somnolence can be increased when Ramelteon is combined with Deutetrabenazine.Approved, Investigational
RanolazineThe metabolism of Deutetrabenazine can be decreased when combined with Ranolazine.Approved, Investigational
RasagilineThe risk or severity of adverse effects can be increased when Rasagiline is combined with Deutetrabenazine.Approved
RemifentanilThe risk or severity of sedation and somnolence can be increased when Remifentanil is combined with Deutetrabenazine.Approved
RemoxiprideThe risk or severity of adverse effects can be increased when Remoxipride is combined with Deutetrabenazine.Approved, Withdrawn
ReposalThe risk or severity of sedation and somnolence can be increased when Reposal is combined with Deutetrabenazine.Approved
ReserpineThe therapeutic efficacy of Deutetrabenazine can be increased when used in combination with Reserpine.Approved, Investigational
RifabutinThe metabolism of Deutetrabenazine can be increased when combined with Rifabutin.Approved, Investigational
RifampicinThe metabolism of Deutetrabenazine can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Deutetrabenazine can be increased when combined with Rifapentine.Approved, Investigational
RisperidoneThe risk or severity of adverse effects can be increased when Risperidone is combined with Deutetrabenazine.Approved, Investigational
RitanserinThe risk or severity of adverse effects can be increased when Ritanserin is combined with Deutetrabenazine.Investigational
RitonavirThe serum concentration of the active metabolites of Deutetrabenazine can be increased when Deutetrabenazine is used in combination with Ritonavir.Approved, Investigational
RolapitantThe metabolism of Deutetrabenazine can be decreased when combined with Rolapitant.Approved, Investigational
RopiniroleThe metabolism of Deutetrabenazine can be decreased when combined with Ropinirole.Approved, Investigational
RoxithromycinRoxithromycin may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Investigational, Withdrawn
RucaparibThe metabolism of Deutetrabenazine can be decreased when combined with Rucaparib.Approved, Investigational
SafrazineThe risk or severity of adverse effects can be increased when Safrazine is combined with Deutetrabenazine.Withdrawn
SaquinavirThe metabolism of Deutetrabenazine can be decreased when combined with Saquinavir.Approved, Investigational
SarilumabThe therapeutic efficacy of Deutetrabenazine can be decreased when used in combination with Sarilumab.Approved, Investigational
ScopolamineThe risk or severity of sedation and somnolence can be increased when Scopolamine is combined with Deutetrabenazine.Approved, Investigational
SecobarbitalThe risk or severity of sedation and somnolence can be increased when Secobarbital is combined with Deutetrabenazine.Approved, Vet Approved
SelegilineThe risk or severity of adverse effects can be increased when Selegiline is combined with Deutetrabenazine.Approved, Investigational, Vet Approved
SertindoleThe risk or severity of adverse effects can be increased when Sertindole is combined with Deutetrabenazine.Approved, Investigational, Withdrawn
SertralineThe metabolism of Deutetrabenazine can be decreased when combined with Sertraline.Approved
SevofluraneSevoflurane may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Vet Approved
SildenafilThe metabolism of Deutetrabenazine can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Deutetrabenazine can be decreased when it is combined with Siltuximab.Approved, Investigational
SimeprevirThe serum concentration of Deutetrabenazine can be increased when it is combined with Simeprevir.Approved
SotalolSotalol may increase the QTc-prolonging activities of Deutetrabenazine.Approved
SparfloxacinSparfloxacin may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Investigational
St. John's WortThe serum concentration of Deutetrabenazine can be decreased when it is combined with St. John's Wort.Approved, Investigational, Nutraceutical
StiripentolThe serum concentration of Deutetrabenazine can be increased when it is combined with Stiripentol.Approved
SulfisoxazoleThe metabolism of Deutetrabenazine can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
SulpirideSulpiride may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Investigational
SultoprideSultopride may increase the QTc-prolonging activities of Deutetrabenazine.Experimental
TalbutalThe risk or severity of sedation and somnolence can be increased when Talbutal is combined with Deutetrabenazine.Approved, Illicit
TasimelteonThe risk or severity of sedation and somnolence can be increased when Tasimelteon is combined with Deutetrabenazine.Approved, Investigational
TelaprevirThe metabolism of Deutetrabenazine can be decreased when combined with Telaprevir.Approved, Withdrawn
TelithromycinThe metabolism of Deutetrabenazine can be decreased when combined with Telithromycin.Approved
TemazepamThe risk or severity of sedation and somnolence can be increased when Temazepam is combined with Deutetrabenazine.Approved, Investigational
Tenofovir disoproxilThe metabolism of Deutetrabenazine can be decreased when combined with Tenofovir disoproxil.Approved, Investigational
TerbinafineThe serum concentration of the active metabolites of Deutetrabenazine can be increased when Deutetrabenazine is used in combination with Terbinafine.Approved, Investigational, Vet Approved
TerfenadineTerfenadine may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Withdrawn
TeriflunomideThe serum concentration of Deutetrabenazine can be decreased when it is combined with Teriflunomide.Approved
TerlipressinTerlipressin may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Investigational
TerodilineTerodiline may increase the QTc-prolonging activities of Deutetrabenazine.Experimental
TetrabenazineThe therapeutic efficacy of Deutetrabenazine can be increased when used in combination with Tetrabenazine.Approved, Investigational
TetrahydropalmatineThe risk or severity of adverse effects can be increased when Tetrahydropalmatine is combined with Deutetrabenazine.Investigational
TheophyllineThe metabolism of Deutetrabenazine can be decreased when combined with Theophylline.Approved
ThiamylalThe risk or severity of sedation and somnolence can be increased when Thiamylal is combined with Deutetrabenazine.Approved, Vet Approved
ThiethylperazineThe risk or severity of adverse effects can be increased when Thiethylperazine is combined with Deutetrabenazine.Withdrawn
ThiopentalThe risk or severity of sedation and somnolence can be increased when Thiopental is combined with Deutetrabenazine.Approved, Vet Approved
ThiopropazateThe risk or severity of adverse effects can be increased when Thiopropazate is combined with Deutetrabenazine.Experimental
ThioproperazineThe risk or severity of adverse effects can be increased when Thioproperazine is combined with Deutetrabenazine.Approved
ThioridazineThioridazine may increase the QTc-prolonging activities of Deutetrabenazine.Approved, Withdrawn
ThiothixeneThe risk or severity of adverse effects can be increased when Thiothixene is combined with Deutetrabenazine.Approved
TiaprideThe risk or severity of adverse effects can be increased when Tiapride is combined with Deutetrabenazine.Approved, Investigational
TiclopidineThe metabolism of Deutetrabenazine can be decreased when combined with Ticlopidine.Approved
TipranavirThe serum concentration of the active metabolites of Deutetrabenazine can be increased when Deutetrabenazine is used in combination with Tipranavir.Approved, Investigational
TocilizumabThe serum concentration of Deutetrabenazine can be decreased when it is combined with Tocilizumab.Approved
ToloxatoneThe risk or severity of adverse effects can be increased when Toloxatone is combined with Deutetrabenazine.Approved
TranylcypromineThe risk or severity of adverse effects can be increased when Tranylcypromine is combined with Deutetrabenazine.Approved, Investigational
TriazolamThe risk or severity of sedation and somnolence can be increased when Triazolam is combined with Deutetrabenazine.Approved, Investigational
TriclofosThe risk or severity of sedation and somnolence can be increased when Triclofos is combined with Deutetrabenazine.Withdrawn
TrifluoperazineThe risk or severity of adverse effects can be increased when Trifluoperazine is combined with Deutetrabenazine.Approved, Investigational
TrifluperidolThe risk or severity of adverse effects can be increased when Trifluperidol is combined with Deutetrabenazine.Experimental
TriflupromazineThe risk or severity of adverse effects can be increased when Triflupromazine is combined with Deutetrabenazine.Approved, Vet Approved
ValerianThe risk or severity of sedation and somnolence can be increased when Valerian is combined with Deutetrabenazine.Approved, Experimental, Investigational
ValnoctamideThe risk or severity of sedation and somnolence can be increased when Valnoctamide is combined with Deutetrabenazine.Investigational
VandetanibVandetanib may increase the QTc-prolonging activities of Deutetrabenazine.Approved
VemurafenibThe serum concentration of Deutetrabenazine can be increased when it is combined with Vemurafenib.Approved
VenlafaxineThe metabolism of Deutetrabenazine can be decreased when combined with Venlafaxine.Approved
VeraliprideThe risk or severity of adverse effects can be increased when Veralipride is combined with Deutetrabenazine.Experimental
VerapamilThe metabolism of Deutetrabenazine can be decreased when combined with Verapamil.Approved
VinbarbitalThe risk or severity of sedation and somnolence can be increased when Vinbarbital is combined with Deutetrabenazine.Experimental
VinylbitalThe risk or severity of sedation and somnolence can be increased when Vinylbital is combined with Deutetrabenazine.Experimental
VoriconazoleThe metabolism of Deutetrabenazine can be decreased when combined with Voriconazole.Approved, Investigational
XylazineThe risk or severity of sedation and somnolence can be increased when Xylazine is combined with Deutetrabenazine.Vet Approved
YKP-1358The risk or severity of adverse effects can be increased when YKP-1358 is combined with Deutetrabenazine.Investigational
YohimbineThe risk or severity of adverse effects can be increased when Yohimbine is combined with Deutetrabenazine.Approved, Investigational, Vet Approved
ZaleplonThe risk or severity of sedation and somnolence can be increased when Zaleplon is combined with Deutetrabenazine.Approved, Illicit, Investigational
ZiprasidoneThe risk or severity of adverse effects can be increased when Ziprasidone is combined with Deutetrabenazine.Approved
ZolpidemThe risk or severity of sedation and somnolence can be increased when Zolpidem is combined with Deutetrabenazine.Approved
ZopicloneThe risk or severity of sedation and somnolence can be increased when Zopiclone is combined with Deutetrabenazine.Approved
ZotepineThe risk or severity of adverse effects can be increased when Zotepine is combined with Deutetrabenazine.Approved, Investigational, Withdrawn
ZucapsaicinThe metabolism of Deutetrabenazine can be decreased when combined with Zucapsaicin.Approved, Investigational
ZuclopenthixolThe risk or severity of adverse effects can be increased when Zuclopenthixol is combined with Deutetrabenazine.Approved, Investigational
Food Interactions
Not Available

References

General References
  1. Paton DM: Deutetrabenazine: Treatment of hyperkinetic aspects of Huntington's disease, tardive dyskinesia and Tourette syndrome. Drugs Today (Barc). 2017 Feb;53(2):89-102. doi: 10.1358/dot.2017.53.2.2589164. [PubMed:28387387]
  2. Rodrigues FB, Duarte GS, Costa J, Ferreira JJ, Wild EJ: Tetrabenazine Versus Deutetrabenazine for Huntington's Disease: Twins or Distant Cousins? Mov Disord Clin Pract. 2017 Jul-Aug;4(4):582-585. doi: 10.1002/mdc3.12483. Epub 2017 Mar 29. [PubMed:28920068]
  3. Anderson KE, Stamler D, Davis MD, Factor SA, Hauser RA, Isojarvi J, Jarskog LF, Jimenez-Shahed J, Kumar R, McEvoy JP, Ochudlo S, Ondo WG, Fernandez HH: Deutetrabenazine for treatment of involuntary movements in patients with tardive dyskinesia (AIM-TD): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Psychiatry. 2017 Aug;4(8):595-604. doi: 10.1016/S2215-0366(17)30236-5. Epub 2017 Jun 28. [PubMed:28668671]
  4. Fernandez HH, Factor SA, Hauser RA, Jimenez-Shahed J, Ondo WG, Jarskog LF, Meltzer HY, Woods SW, Bega D, LeDoux MS, Shprecher DR, Davis C, Davis MD, Stamler D, Anderson KE: Randomized controlled trial of deutetrabenazine for tardive dyskinesia: The ARM-TD study. Neurology. 2017 May 23;88(21):2003-2010. doi: 10.1212/WNL.0000000000003960. Epub 2017 Apr 26. [PubMed:28446646]
  5. Frank S, Testa CM, Stamler D, Kayson E, Davis C, Edmondson MC, Kinel S, Leavitt B, Oakes D, O'Neill C, Vaughan C, Goldstein J, Herzog M, Snively V, Whaley J, Wong C, Suter G, Jankovic J, Jimenez-Shahed J, Hunter C, Claassen DO, Roman OC, Sung V, Smith J, Janicki S, Clouse R, Saint-Hilaire M, Hohler A, Turpin D, James RC, Rodriguez R, Rizer K, Anderson KE, Heller H, Carlson A, Criswell S, Racette BA, Revilla FJ, Nucifora F Jr, Margolis RL, Ong M, Mendis T, Mendis N, Singer C, Quesada M, Paulsen JS, Brashers-Krug T, Miller A, Kerr J, Dubinsky RM, Gray C, Factor SA, Sperin E, Molho E, Eglow M, Evans S, Kumar R, Reeves C, Samii A, Chouinard S, Beland M, Scott BL, Hickey PT, Esmail S, Fung WL, Gibbons C, Qi L, Colcher A, Hackmyer C, McGarry A, Klos K, Gudesblatt M, Fafard L, Graffitti L, Schneider DP, Dhall R, Wojcieszek JM, LaFaver K, Duker A, Neefus E, Wilson-Perez H, Shprecher D, Wall P, Blindauer KA, Wheeler L, Boyd JT, Houston E, Farbman ES, Agarwal P, Eberly SW, Watts A, Tariot PN, Feigin A, Evans S, Beck C, Orme C, Edicola J, Christopher E: Effect of Deutetrabenazine on Chorea Among Patients With Huntington Disease: A Randomized Clinical Trial. JAMA. 2016 Jul 5;316(1):40-50. doi: 10.1001/jama.2016.8655. [PubMed:27380342]
  6. Wimalasena K: Vesicular monoamine transporters: structure-function, pharmacology, and medicinal chemistry. Med Res Rev. 2011 Jul;31(4):483-519. doi: 10.1002/med.20187. Epub 2010 Feb 4. [PubMed:20135628]
  7. 39. (2012). In Rang and Dale's Pharmacology (7th ed., pp. 489-490). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8]
External Links
PubChem Compound
73442840
PubChem Substance
347828453
ChemSpider
32700662
Wikipedia
Deutetrabenazine
FDA label
Download (754 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentGilles de la Tourette's Syndrome1
2, 3CompletedTreatmentTardive Dyskinesia1
2, 3RecruitingTreatmentGilles de la Tourette's Syndrome1
3Active Not RecruitingTreatmentTardive Dyskinesia1
3CompletedTreatmentChorea1
3CompletedTreatmentChorea Associated With Huntington Disease1
3CompletedTreatmentTardive Dyskinesia1
3Not Yet RecruitingTreatmentGilles de la Tourette's Syndrome1
3RecruitingTreatmentGilles de la Tourette's Syndrome1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Tablet, coatedOral12 mg/1
Tablet, coatedOral6 mg/1
Tablet, coatedOral9 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8524733No2011-03-272031-03-27Us
US9296739No2013-09-182033-09-18Us
US9233959No2013-09-182033-09-18Us
US9550780No2013-09-182033-09-18Us
US9814708No2013-09-182033-09-18Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.361 mg/mLALOGPS
logP3.23ALOGPS
logP3.4ChemAxon
logS-2.9ALOGPS
pKa (Strongest Acidic)18.26ChemAxon
pKa (Strongest Basic)7.33ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area38.77 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity91.31 m3·mol-1ChemAxon
Polarizability36.83 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as tetrahydroisoquinolines. These are tetrahydrogenated isoquinoline derivatives.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Tetrahydroisoquinolines
Sub Class
Not Available
Direct Parent
Tetrahydroisoquinolines
Alternative Parents
Anisoles / Piperidinones / Aralkylamines / Alkyl aryl ethers / Trialkylamines / Cyclic ketones / Azacyclic compounds / Organic oxides / Hydrocarbon derivatives
Substituents
Tetrahydroisoquinoline / Anisole / Phenol ether / Alkyl aryl ether / Piperidinone / Aralkylamine / Piperidine / Benzenoid / Tertiary aliphatic amine / Tertiary amine
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Monoamine transmembrane transporter activity
Specific Function
Involved in the ATP-dependent vesicular transport of biogenic amine neurotransmitters. Pumps cytosolic monoamines including dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles...
Gene Name
SLC18A2
Uniprot ID
Q05940
Uniprot Name
Synaptic vesicular amine transporter
Molecular Weight
55712.075 Da

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Prostaglandin-e2 9-reductase activity
Specific Function
NADPH-dependent reductase with broad substrate specificity. Catalyzes the reduction of a wide variety of carbonyl compounds including quinones, prostaglandins, menadione, plus various xenobiotics. ...
Gene Name
CBR1
Uniprot ID
P16152
Uniprot Name
Carbonyl reductase [NADPH] 1
Molecular Weight
30374.73 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Nadph binding
Specific Function
Has low NADPH-dependent oxidoreductase activity towards 4-benzoylpyridine and menadione (in vitro).
Gene Name
CBR3
Uniprot ID
O75828
Uniprot Name
Carbonyl reductase [NADPH] 3
Molecular Weight
30849.97 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da

Drug created on October 20, 2016 15:30 / Updated on July 02, 2018 19:33