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Identification
NameTolvaptan
Accession NumberDB06212
TypeSmall Molecule
GroupsApproved
DescriptionTolvaptan is used to treat low blood sodium levels (hyponatremia) associated with various conditions like congestive heart failure, cirrhosis, and syndrome of inappropriate antidiuretic hormones (SIADH). FDA approved on May 19, 2009.
Structure
Thumb
Synonyms
Samsca
External Identifiers
  • OPC-41061
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
SamscaTablet30 mgOralOtsuka Pharmaceutical Co Ltd2011-09-22Not applicableCanada
SamscaTablet15 mg/1OralOtsuka America Pharmaceutical Inc.2009-05-19Not applicableUs
SamscaTablet30 mgOralOtsuka Pharmaceutical Europe Ltd.2009-08-03Not applicableEu
SamscaTablet60 mgOralOtsuka Pharmaceutical Co LtdNot applicableNot applicableCanada
SamscaTablet30 mg/1OralOtsuka America Pharmaceutical Inc.2009-05-19Not applicableUs
SamscaTablet30 mgOralOtsuka Pharmaceutical Europe Ltd.2009-08-03Not applicableEu
SamscaTablet15 mgOralOtsuka Pharmaceutical Europe Ltd.2009-08-03Not applicableEu
SamscaTablet15 mgOralOtsuka Pharmaceutical Co Ltd2011-09-22Not applicableCanada
SamscaTablet15 mgOralOtsuka Pharmaceutical Europe Ltd.2009-08-03Not applicableEu
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixtures
NameLabellerIngredients
JinarcOtsuka Pharmaceutical Co Ltd
SaltsNot Available
Categories
UNII21G72T1950
CAS number150683-30-0
WeightAverage: 448.941
Monoisotopic: 448.155370383
Chemical FormulaC26H25ClN2O3
InChI KeyGYHCTFXIZSNGJT-XMMPIXPASA-N
InChI
InChI=1S/C26H25ClN2O3/c1-16-6-3-4-7-20(16)25(31)28-19-10-11-21(17(2)14-19)26(32)29-13-5-8-24(30)22-15-18(27)9-12-23(22)29/h3-4,6-7,9-12,14-15,24,30H,5,8,13H2,1-2H3,(H,28,31)/t24-/m1/s1
IUPAC Name
N-{4-[(5R)-7-chloro-5-hydroxy-2,3,4,5-tetrahydro-1H-1-benzazepine-1-carbonyl]-3-methylphenyl}-2-methylbenzamide
SMILES
CC1=CC=CC=C1C(=O)NC1=CC(C)=C(C=C1)C(=O)N1CCC[C@@H](O)C2=C1C=CC(Cl)=C2
Pharmacology
IndicationTreatment of symptomatic and resistant to fluid restriction euvolemic or hypervolemic hyponatremia associated with congestive heart failure, SIADH, and cirrhosis.
Structured Indications
PharmacodynamicsUrine volume and fluid intake increase in a dose dependent manner which results in overall negative fluid balance in patients taking tolvaptan. Increases in serum sodium and osmolality can be observed 4-8 hours post-administration and is maintained for 24 hours. The magnitude of serum sodium and osmolality change increases with escalating doses. Furthermore, a decrease in urine osmolality and increase in free water clearance can be observed 4 hours after post-administration of tolvaptan. The affinity for V2 receptors is 29x greater than that of V1a receptors and does not have any appreciable affinity for V2 receptors.
Mechanism of actionTolvaptan is a selective and competitive arginine vasopressin receptor 2 antagonist. Vasopressin acts on the V2 receptors found in the walls of the vasculature and luminal membranes of renal collecting ducts. By blocking V2 receptors in the renal collecting ducts, aquaporins do not insert themselves into the walls thus preventing water absorption. This action ultimately results in an increase in urine volume, decrease urine osmolality, and increase electrolyte-free water clearance to reduce intravascular volume and an increase serum sodium levels. Tolvaptan is especially useful for heart failure patients as they have higher serum levels of vasopressin.
TargetKindPharmacological actionActionsOrganismUniProt ID
Vasopressin V2 receptorProteinyes
antagonist
HumanP30518 details
Vasopressin V1a receptorProteinno
antagonist
HumanP37288 details
Related Articles
AbsorptionTmax, Healthy subjects: 2 - 4 hours; Cmax, Healthy subjects, 30 mg: 374 ng/mL; Cmax, Healthy subjects, 90 mg: 418 ng/mL; Cmax, heart failure patients, 30 mg: 460 ng/mL; Cmax, heart failure patients, 90 mg: 723 ng/mL; AUC(0-24 hours), 60 mg: 3.71 μg·h/mL; AUC(∞), 60 mg: 4.55 μg·h/mL; The pharmacokinetic properties of tolvaptan are stereospecific, with a steady-state ratio of the S-(-) to the R-(+) enantiomer of about 3. The absolute bioavailability of tolvaptan is unknown. At least 40% of the dose is absorbed as tolvaptan or metabolites. Food does not impact the bioavailability of tolvaptan.
Volume of distribution

Healthy subjects: 3L/kg; slightly higher in heart failure patients.

Protein binding99% bound
Metabolism

Metabolism exclusively by CYP3A4 enzyme in the liver. Metabolites are inactive.

Route of eliminationFecal- very little renal elimination (<1% is excreted unchanged in the urine)
Half lifeTerminal half life, oral dose = 12 hours.
Clearance

4 mL/min/kg (post-oral dosing).

ToxicityThe oral LD50 of tolvaptan in rats and dogs is >2000 mg/kg. Most common adverse reactions (≥5% placebo) are thirst, dry mouth, asthenia, constipation, pollakiuria or polyuria, and hyperglycemia.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
AcebutololThe serum concentration of Acebutolol can be increased when it is combined with Tolvaptan.Approved
AcetaminophenThe serum concentration of Tolvaptan can be increased when it is combined with Acetaminophen.Approved
Acetylsalicylic acidThe serum concentration of Acetylsalicylic acid can be increased when it is combined with Tolvaptan.Approved, Vet Approved
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Tolvaptan.Approved
AlbendazoleThe serum concentration of Tolvaptan can be increased when it is combined with Albendazole.Approved, Vet Approved
AldosteroneThe serum concentration of Tolvaptan can be decreased when it is combined with Aldosterone.Experimental
AlectinibThe serum concentration of Tolvaptan can be increased when it is combined with Alectinib.Approved
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Tolvaptan.Approved, Illicit
AlitretinoinThe serum concentration of Alitretinoin can be increased when it is combined with Tolvaptan.Approved, Investigational
AlphacetylmethadolThe risk or severity of adverse effects can be increased when Alphacetylmethadol is combined with Tolvaptan.Experimental, Illicit
AmantadineThe serum concentration of Tolvaptan can be increased when it is combined with Amantadine.Approved
AmbrisentanThe serum concentration of Ambrisentan can be increased when it is combined with Tolvaptan.Approved, Investigational
AmilorideTolvaptan may increase the hyperkalemic activities of Amiloride.Approved
Aminohippuric acidThe serum concentration of Tolvaptan can be increased when it is combined with Aminohippuric acid.Approved
AmiodaroneThe serum concentration of Tolvaptan can be increased when it is combined with Amiodarone.Approved, Investigational
AmitriptylineThe serum concentration of Tolvaptan can be increased when it is combined with Amitriptyline.Approved
AmlodipineThe serum concentration of Tolvaptan can be increased when it is combined with Amlodipine.Approved
AmprenavirThe serum concentration of Tolvaptan can be decreased when it is combined with Amprenavir.Approved
AmsacrineThe serum concentration of Tolvaptan can be increased when it is combined with Amsacrine.Approved
ApixabanThe serum concentration of Apixaban can be increased when it is combined with Tolvaptan.Approved
AprepitantThe serum concentration of Tolvaptan can be increased when it is combined with Aprepitant.Approved, Investigational
Arsenic trioxideThe serum concentration of Arsenic trioxide can be increased when it is combined with Tolvaptan.Approved, Investigational
AstemizoleThe serum concentration of Tolvaptan can be increased when it is combined with Astemizole.Approved, Withdrawn
AtazanavirThe serum concentration of Tolvaptan can be increased when it is combined with Atazanavir.Approved, Investigational
AtenololThe serum concentration of Tolvaptan can be increased when it is combined with Atenolol.Approved
AtomoxetineThe serum concentration of Tolvaptan can be increased when it is combined with Atomoxetine.Approved
AtorvastatinThe serum concentration of Tolvaptan can be increased when it is combined with Atorvastatin.Approved
AxitinibThe serum concentration of Axitinib can be increased when it is combined with Tolvaptan.Approved, Investigational
AzelastineThe serum concentration of Tolvaptan can be increased when it is combined with Azelastine.Approved
Azilsartan medoxomilTolvaptan may increase the hyperkalemic activities of Azilsartan medoxomil.Approved
AzithromycinThe serum concentration of Tolvaptan can be increased when it is combined with Azithromycin.Approved
BenazeprilTolvaptan may increase the hyperkalemic activities of Benazepril.Approved, Investigational
BenzocaineThe serum concentration of Tolvaptan can be increased when it is combined with Benzocaine.Approved
BepridilThe serum concentration of Tolvaptan can be increased when it is combined with Bepridil.Approved, Withdrawn
BetamethasoneThe serum concentration of Betamethasone can be increased when it is combined with Tolvaptan.Approved, Vet Approved
BexaroteneThe serum concentration of Tolvaptan can be decreased when it is combined with Bexarotene.Approved, Investigational
BezitramideThe risk or severity of adverse effects can be increased when Bezitramide is combined with Tolvaptan.Experimental, Illicit, Withdrawn
BiperidenThe serum concentration of Tolvaptan can be increased when it is combined with Biperiden.Approved
BoceprevirThe serum concentration of Tolvaptan can be increased when it is combined with Boceprevir.Approved
BortezomibThe serum concentration of Tolvaptan can be increased when it is combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Tolvaptan can be decreased when it is combined with Bosentan.Approved, Investigational
BosutinibThe serum concentration of Bosutinib can be increased when it is combined with Tolvaptan.Approved
Brentuximab vedotinThe serum concentration of Brentuximab vedotin can be increased when it is combined with Tolvaptan.Approved
BromocriptineThe serum concentration of Tolvaptan can be increased when it is combined with Bromocriptine.Approved, Investigational
BuprenorphineThe risk or severity of adverse effects can be increased when Buprenorphine is combined with Tolvaptan.Approved, Illicit, Investigational, Vet Approved
BuspironeThe serum concentration of Tolvaptan can be increased when it is combined with Buspirone.Approved, Investigational
ButorphanolThe risk or severity of adverse effects can be increased when Butorphanol is combined with Tolvaptan.Approved, Illicit, Vet Approved
CabazitaxelThe serum concentration of Tolvaptan can be increased when it is combined with Cabazitaxel.Approved
CaffeineThe serum concentration of Tolvaptan can be increased when it is combined with Caffeine.Approved
CamptothecinThe serum concentration of Camptothecin can be increased when it is combined with Tolvaptan.Experimental
CanagliflozinThe serum concentration of Canagliflozin can be increased when it is combined with Tolvaptan.Approved
CandesartanTolvaptan may increase the hyperkalemic activities of Candesartan.Approved
CandoxatrilTolvaptan may increase the hyperkalemic activities of Candoxatril.Experimental
CaptoprilTolvaptan may increase the hyperkalemic activities of Captopril.Approved
CarbamazepineThe serum concentration of Tolvaptan can be decreased when it is combined with Carbamazepine.Approved, Investigational
CarfentanilThe risk or severity of adverse effects can be increased when Carfentanil is combined with Tolvaptan.Illicit, Vet Approved
CarfilzomibThe serum concentration of Carfilzomib can be increased when it is combined with Tolvaptan.Approved
CarvedilolThe serum concentration of Tolvaptan can be increased when it is combined with Carvedilol.Approved, Investigational
CaspofunginThe serum concentration of Tolvaptan can be increased when it is combined with Caspofungin.Approved
CeritinibThe serum concentration of Tolvaptan can be increased when it is combined with Ceritinib.Approved
CerivastatinThe serum concentration of Cerivastatin can be increased when it is combined with Tolvaptan.Withdrawn
ChloroquineThe serum concentration of Tolvaptan can be increased when it is combined with Chloroquine.Approved, Vet Approved
ChlorpromazineThe serum concentration of Tolvaptan can be increased when it is combined with Chlorpromazine.Approved, Vet Approved
ChlorpropamideThe serum concentration of Tolvaptan can be increased when it is combined with Chlorpropamide.Approved
ChlorprothixeneThe serum concentration of Tolvaptan can be increased when it is combined with Chlorprothixene.Approved, Withdrawn
CholesterolThe serum concentration of Tolvaptan can be increased when it is combined with Cholesterol.Experimental
Cholic AcidThe serum concentration of Tolvaptan can be decreased when it is combined with Cholic Acid.Approved
CilazaprilTolvaptan may increase the hyperkalemic activities of Cilazapril.Approved
CimetidineThe serum concentration of Tolvaptan can be decreased when it is combined with Cimetidine.Approved
CiprofloxacinThe serum concentration of Tolvaptan can be increased when it is combined with Ciprofloxacin.Approved, Investigational
CisplatinThe serum concentration of Cisplatin can be increased when it is combined with Tolvaptan.Approved
CitalopramThe serum concentration of Tolvaptan can be increased when it is combined with Citalopram.Approved
ClarithromycinThe serum concentration of Tolvaptan can be increased when it is combined with Clarithromycin.Approved
ClemastineThe serum concentration of Tolvaptan can be increased when it is combined with Clemastine.Approved
ClobazamThe serum concentration of Clobazam can be increased when it is combined with Tolvaptan.Approved, Illicit
ClofazimineThe serum concentration of Tolvaptan can be increased when it is combined with Clofazimine.Approved, Investigational
ClomifeneThe serum concentration of Clomifene can be increased when it is combined with Tolvaptan.Approved, Investigational
ClomipramineThe serum concentration of Tolvaptan can be increased when it is combined with Clomipramine.Approved, Vet Approved
ClonidineThe serum concentration of Clonidine can be increased when it is combined with Tolvaptan.Approved
ClopidogrelThe serum concentration of Clopidogrel can be increased when it is combined with Tolvaptan.Approved, Nutraceutical
ClotrimazoleThe serum concentration of Tolvaptan can be increased when it is combined with Clotrimazole.Approved, Vet Approved
ClozapineThe serum concentration of Clozapine can be increased when it is combined with Tolvaptan.Approved
CobicistatThe serum concentration of Tolvaptan can be increased when it is combined with Cobicistat.Approved
CobimetinibThe serum concentration of Cobimetinib can be increased when it is combined with Tolvaptan.Approved
CodeineThe risk or severity of adverse effects can be increased when Codeine is combined with Tolvaptan.Approved, Illicit
ColchicineThe serum concentration of Colchicine can be increased when it is combined with Tolvaptan.Approved
ColforsinThe serum concentration of Tolvaptan can be increased when it is combined with Colforsin.Experimental
ConivaptanThe serum concentration of Tolvaptan can be increased when it is combined with Conivaptan.Approved, Investigational
Conjugated Equine EstrogensThe serum concentration of Conjugated Equine Estrogens can be increased when it is combined with Tolvaptan.Approved
CrizotinibThe serum concentration of Tolvaptan can be increased when it is combined with Crizotinib.Approved
CyclophosphamideThe serum concentration of Tolvaptan can be increased when it is combined with Cyclophosphamide.Approved, Investigational
CyclosporineThe serum concentration of Tolvaptan can be increased when it is combined with Cyclosporine.Approved, Investigational, Vet Approved
Dabigatran etexilateThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Tolvaptan.Approved
DabrafenibThe serum concentration of Tolvaptan can be decreased when it is combined with Dabrafenib.Approved
DaclatasvirThe serum concentration of Tolvaptan can be increased when it is combined with Daclatasvir.Approved
DactinomycinThe serum concentration of Tolvaptan can be increased when it is combined with Dactinomycin.Approved
DapagliflozinThe serum concentration of Dapagliflozin can be increased when it is combined with Tolvaptan.Approved
DarunavirThe serum concentration of Tolvaptan can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Tolvaptan can be increased when it is combined with Dasatinib.Approved, Investigational
DaunorubicinThe serum concentration of Tolvaptan can be decreased when it is combined with Daunorubicin.Approved
DebrisoquinThe serum concentration of Debrisoquin can be increased when it is combined with Tolvaptan.Approved
DeferasiroxThe serum concentration of Tolvaptan can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe serum concentration of Tolvaptan can be increased when it is combined with Delavirdine.Approved
DesipramineThe serum concentration of Tolvaptan can be increased when it is combined with Desipramine.Approved
DesloratadineThe serum concentration of Tolvaptan can be increased when it is combined with Desloratadine.Approved, Investigational
DesmopressinThe therapeutic efficacy of Desmopressin can be decreased when used in combination with Tolvaptan.Approved
DexamethasoneThe serum concentration of Tolvaptan can be decreased when it is combined with Dexamethasone.Approved, Investigational, Vet Approved
DextromethorphanThe serum concentration of Tolvaptan can be increased when it is combined with Dextromethorphan.Approved
DextromoramideThe risk or severity of adverse effects can be increased when Dextromoramide is combined with Tolvaptan.Experimental, Illicit
DextropropoxypheneThe risk or severity of adverse effects can be increased when Dextropropoxyphene is combined with Tolvaptan.Approved, Illicit, Withdrawn
DezocineThe risk or severity of adverse effects can be increased when Dezocine is combined with Tolvaptan.Approved
DiazepamThe serum concentration of Diazepam can be increased when it is combined with Tolvaptan.Approved, Illicit, Vet Approved
DiclofenacThe serum concentration of Tolvaptan can be increased when it is combined with Diclofenac.Approved, Vet Approved
DiethylstilbestrolThe serum concentration of Diethylstilbestrol can be increased when it is combined with Tolvaptan.Approved
DigitoxinThe serum concentration of Digitoxin can be increased when it is combined with Tolvaptan.Approved
DigoxinThe serum concentration of Digoxin can be increased when it is combined with Tolvaptan.Approved
DihydrocodeineThe risk or severity of adverse effects can be increased when Dihydrocodeine is combined with Tolvaptan.Approved, Illicit
DihydroergotamineThe serum concentration of Tolvaptan can be increased when it is combined with Dihydroergotamine.Approved
DihydroetorphineThe risk or severity of adverse effects can be increased when Dihydroetorphine is combined with Tolvaptan.Experimental, Illicit
DihydromorphineThe risk or severity of adverse effects can be increased when Dihydromorphine is combined with Tolvaptan.Experimental, Illicit
DihydrotestosteroneThe serum concentration of Dihydrotestosterone can be increased when it is combined with Tolvaptan.Illicit
DiltiazemThe serum concentration of Tolvaptan can be increased when it is combined with Diltiazem.Approved
DiphenoxylateThe risk or severity of adverse effects can be increased when Diphenoxylate is combined with Tolvaptan.Approved, Illicit
DipyridamoleThe serum concentration of Tolvaptan can be increased when it is combined with Dipyridamole.Approved
DocetaxelThe serum concentration of Docetaxel can be increased when it is combined with Tolvaptan.Approved, Investigational
DomperidoneThe serum concentration of Domperidone can be increased when it is combined with Tolvaptan.Approved, Investigational, Vet Approved
DoxazosinThe serum concentration of Tolvaptan can be increased when it is combined with Doxazosin.Approved
DoxepinThe serum concentration of Tolvaptan can be increased when it is combined with Doxepin.Approved
DoxorubicinThe serum concentration of Doxorubicin can be increased when it is combined with Tolvaptan.Approved, Investigational
DoxorubicinThe serum concentration of Tolvaptan can be decreased when it is combined with Doxorubicin.Approved, Investigational
DoxycyclineThe serum concentration of Tolvaptan can be increased when it is combined with Doxycycline.Approved, Investigational, Vet Approved
DPDPEThe risk or severity of adverse effects can be increased when DPDPE is combined with Tolvaptan.Investigational
DronabinolThe serum concentration of Tolvaptan can be increased when it is combined with Dronabinol.Approved, Illicit
DronedaroneThe serum concentration of Tolvaptan can be increased when it is combined with Dronedarone.Approved
EdoxabanThe serum concentration of Edoxaban can be increased when it is combined with Tolvaptan.Approved
EfavirenzThe serum concentration of Tolvaptan can be decreased when it is combined with Efavirenz.Approved, Investigational
ElbasvirThe serum concentration of Tolvaptan can be increased when it is combined with Elbasvir.Approved
EletriptanThe serum concentration of Eletriptan can be increased when it is combined with Tolvaptan.Approved, Investigational
EnalaprilTolvaptan may increase the hyperkalemic activities of Enalapril.Approved, Vet Approved
EnalaprilatTolvaptan may increase the hyperkalemic activities of Enalaprilat.Approved
EnzalutamideThe serum concentration of Tolvaptan can be decreased when it is combined with Enzalutamide.Approved
EpinastineThe serum concentration of Epinastine can be increased when it is combined with Tolvaptan.Approved, Investigational
EplerenoneTolvaptan may increase the hyperkalemic activities of Eplerenone.Approved
EprosartanTolvaptan may increase the hyperkalemic activities of Eprosartan.Approved
ErgonovineThe serum concentration of Tolvaptan can be increased when it is combined with Ergonovine.Approved
ErgotamineThe serum concentration of Tolvaptan can be increased when it is combined with Ergotamine.Approved
ErlotinibThe serum concentration of Erlotinib can be increased when it is combined with Tolvaptan.Approved, Investigational
ErythromycinThe serum concentration of Tolvaptan can be increased when it is combined with Erythromycin.Approved, Vet Approved
Eslicarbazepine acetateThe serum concentration of Tolvaptan can be decreased when it is combined with Eslicarbazepine acetate.Approved
EstradiolThe serum concentration of Estradiol can be increased when it is combined with Tolvaptan.Approved, Investigational, Vet Approved
EstramustineThe serum concentration of Tolvaptan can be increased when it is combined with Estramustine.Approved
EstriolThe serum concentration of Tolvaptan can be decreased when it is combined with Estriol.Approved, Vet Approved
EstroneThe serum concentration of Tolvaptan can be decreased when it is combined with Estrone.Approved
Ethinyl EstradiolThe serum concentration of Ethinyl Estradiol can be increased when it is combined with Tolvaptan.Approved
EthylmorphineThe risk or severity of adverse effects can be increased when Ethylmorphine is combined with Tolvaptan.Approved, Illicit
EtoposideThe serum concentration of Tolvaptan can be increased when it is combined with Etoposide.Approved
EtorphineThe risk or severity of adverse effects can be increased when Etorphine is combined with Tolvaptan.Illicit, Vet Approved
EtravirineThe serum concentration of Tolvaptan can be decreased when it is combined with Etravirine.Approved
EverolimusThe serum concentration of Everolimus can be increased when it is combined with Tolvaptan.Approved
EzetimibeThe serum concentration of Ezetimibe can be increased when it is combined with Tolvaptan.Approved
FelodipineThe serum concentration of Tolvaptan can be increased when it is combined with Felodipine.Approved, Investigational
FentanylThe risk or severity of adverse effects can be increased when Fentanyl is combined with Tolvaptan.Approved, Illicit, Investigational, Vet Approved
FesoterodineThe serum concentration of Fesoterodine can be increased when it is combined with Tolvaptan.Approved
FexofenadineThe serum concentration of Tolvaptan can be increased when it is combined with Fexofenadine.Approved
FidaxomicinThe serum concentration of Fidaxomicin can be increased when it is combined with Tolvaptan.Approved
FluconazoleThe serum concentration of Tolvaptan can be increased when it is combined with Fluconazole.Approved
FluoxetineThe serum concentration of Tolvaptan can be increased when it is combined with Fluoxetine.Approved, Vet Approved
FlupentixolThe serum concentration of Tolvaptan can be increased when it is combined with Flupentixol.Approved, Withdrawn
FluphenazineThe serum concentration of Tolvaptan can be increased when it is combined with Fluphenazine.Approved
FlurazepamThe serum concentration of Tolvaptan can be increased when it is combined with Flurazepam.Approved, Illicit
Fluticasone furoateThe serum concentration of Fluticasone furoate can be increased when it is combined with Tolvaptan.Approved
FluvoxamineThe serum concentration of Tolvaptan can be increased when it is combined with Fluvoxamine.Approved, Investigational
ForasartanTolvaptan may increase the hyperkalemic activities of Forasartan.Experimental
FosamprenavirThe serum concentration of Tolvaptan can be increased when it is combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Tolvaptan can be increased when it is combined with Fosaprepitant.Approved
FosinoprilTolvaptan may increase the hyperkalemic activities of Fosinopril.Approved
FosphenytoinThe serum concentration of Tolvaptan can be decreased when it is combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Tolvaptan can be increased when it is combined with Fusidic Acid.Approved
GefitinibThe serum concentration of Tolvaptan can be increased when it is combined with Gefitinib.Approved, Investigational
GemcitabineThe serum concentration of Gemcitabine can be increased when it is combined with Tolvaptan.Approved
GenisteinThe serum concentration of Tolvaptan can be increased when it is combined with Genistein.Investigational
GlyburideThe serum concentration of Tolvaptan can be increased when it is combined with Glyburide.Approved
GlycerolThe serum concentration of Tolvaptan can be increased when it is combined with Glycerol.Experimental
Gramicidin DThe serum concentration of Tolvaptan can be increased when it is combined with Gramicidin D.Approved
GrazoprevirThe serum concentration of Grazoprevir can be increased when it is combined with Tolvaptan.Approved
GrepafloxacinThe serum concentration of Tolvaptan can be increased when it is combined with Grepafloxacin.Withdrawn
HaloperidolThe serum concentration of Tolvaptan can be increased when it is combined with Haloperidol.Approved
HeroinThe risk or severity of adverse effects can be increased when Heroin is combined with Tolvaptan.Approved, Illicit
HydrocodoneThe risk or severity of adverse effects can be increased when Hydrocodone is combined with Tolvaptan.Approved, Illicit
HydrocortisoneThe serum concentration of Tolvaptan can be increased when it is combined with Hydrocortisone.Approved, Vet Approved
HydromorphoneThe risk or severity of adverse effects can be increased when Hydromorphone is combined with Tolvaptan.Approved, Illicit
IbuprofenThe serum concentration of Ibuprofen can be increased when it is combined with Tolvaptan.Approved
IdelalisibThe serum concentration of Tolvaptan can be increased when it is combined with Idelalisib.Approved
ImatinibThe serum concentration of Tolvaptan can be increased when it is combined with Imatinib.Approved
ImidaprilTolvaptan may increase the hyperkalemic activities of Imidapril.Investigational
ImipramineThe serum concentration of Tolvaptan can be increased when it is combined with Imipramine.Approved
IndacaterolThe serum concentration of Indacaterol can be increased when it is combined with Tolvaptan.Approved
IndinavirThe serum concentration of Tolvaptan can be increased when it is combined with Indinavir.Approved
IndomethacinThe serum concentration of Tolvaptan can be increased when it is combined with Indomethacin.Approved, Investigational
IrbesartanTolvaptan may increase the hyperkalemic activities of Irbesartan.Approved, Investigational
IrinotecanThe serum concentration of Irinotecan can be increased when it is combined with Tolvaptan.Approved, Investigational
IsavuconazoniumThe serum concentration of Tolvaptan can be increased when it is combined with Isavuconazonium.Approved, Investigational
IsradipineThe serum concentration of Tolvaptan can be increased when it is combined with Isradipine.Approved
ItraconazoleThe serum concentration of Tolvaptan can be increased when it is combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Tolvaptan can be increased when it is combined with Ivacaftor.Approved
IvermectinThe serum concentration of Tolvaptan can be increased when it is combined with Ivermectin.Approved, Vet Approved
KetamineThe serum concentration of Tolvaptan can be increased when it is combined with Ketamine.Approved, Vet Approved
KetazolamThe serum concentration of Ketazolam can be increased when it is combined with Tolvaptan.Approved
KetobemidoneThe risk or severity of adverse effects can be increased when Ketobemidone is combined with Tolvaptan.Approved
KetoconazoleThe serum concentration of Tolvaptan can be increased when it is combined with Ketoconazole.Approved, Investigational
LamivudineThe serum concentration of Lamivudine can be increased when it is combined with Tolvaptan.Approved, Investigational
LamotrigineThe serum concentration of Lamotrigine can be increased when it is combined with Tolvaptan.Approved, Investigational
LansoprazoleThe serum concentration of Tolvaptan can be increased when it is combined with Lansoprazole.Approved, Investigational
LapatinibThe serum concentration of Tolvaptan can be increased when it is combined with Lapatinib.Approved, Investigational
LedipasvirThe serum concentration of Ledipasvir can be increased when it is combined with Tolvaptan.Approved
LenalidomideThe serum concentration of Lenalidomide can be increased when it is combined with Tolvaptan.Approved
LenvatinibThe serum concentration of Lenvatinib can be increased when it is combined with Tolvaptan.Approved
LevetiracetamThe serum concentration of Levetiracetam can be increased when it is combined with Tolvaptan.Approved, Investigational
LevofloxacinThe serum concentration of Tolvaptan can be increased when it is combined with Levofloxacin.Approved, Investigational
Levomethadyl AcetateThe risk or severity of adverse effects can be increased when Levomethadyl Acetate is combined with Tolvaptan.Approved
LevomilnacipranThe serum concentration of Levomilnacipran can be increased when it is combined with Tolvaptan.Approved
LevorphanolThe risk or severity of adverse effects can be increased when Levorphanol is combined with Tolvaptan.Approved
LevothyroxineThe serum concentration of Tolvaptan can be decreased when it is combined with Levothyroxine.Approved
LidocaineThe serum concentration of Tolvaptan can be increased when it is combined with Lidocaine.Approved, Vet Approved
LinagliptinThe serum concentration of Linagliptin can be increased when it is combined with Tolvaptan.Approved
LiothyronineThe serum concentration of Tolvaptan can be decreased when it is combined with Liothyronine.Approved, Vet Approved
LiotrixThe serum concentration of Tolvaptan can be decreased when it is combined with Liotrix.Approved
LisinoprilTolvaptan may increase the hyperkalemic activities of Lisinopril.Approved, Investigational
LofentanilThe risk or severity of adverse effects can be increased when Lofentanil is combined with Tolvaptan.Illicit
LomitapideThe serum concentration of Tolvaptan can be increased when it is combined with Lomitapide.Approved
LoperamideThe serum concentration of Tolvaptan can be increased when it is combined with Loperamide.Approved
LopinavirThe serum concentration of Tolvaptan can be increased when it is combined with Lopinavir.Approved
LoratadineThe serum concentration of Tolvaptan can be increased when it is combined with Loratadine.Approved
LosartanTolvaptan may increase the hyperkalemic activities of Losartan.Approved
LovastatinThe serum concentration of Tolvaptan can be increased when it is combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Tolvaptan can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Tolvaptan can be decreased when it is combined with Lumacaftor.Approved
MannitolThe serum concentration of Mannitol can be increased when it is combined with Tolvaptan.Approved, Investigational
MaprotilineThe serum concentration of Tolvaptan can be increased when it is combined with Maprotiline.Approved
MebendazoleThe serum concentration of Tolvaptan can be increased when it is combined with Mebendazole.Approved, Vet Approved
MefloquineThe serum concentration of Tolvaptan can be increased when it is combined with Mefloquine.Approved
Megestrol acetateThe serum concentration of Tolvaptan can be increased when it is combined with Megestrol acetate.Approved, Vet Approved
MeprobamateThe serum concentration of Tolvaptan can be increased when it is combined with Meprobamate.Approved, Illicit
MethadoneThe risk or severity of adverse effects can be increased when Methadone is combined with Tolvaptan.Approved
Methadyl AcetateThe risk or severity of adverse effects can be increased when Methadyl Acetate is combined with Tolvaptan.Approved, Illicit
MethotrexateThe serum concentration of Methotrexate can be increased when it is combined with Tolvaptan.Approved
MethylprednisoloneThe serum concentration of Methylprednisolone can be increased when it is combined with Tolvaptan.Approved, Vet Approved
MetoprololThe serum concentration of Tolvaptan can be increased when it is combined with Metoprolol.Approved, Investigational
MibefradilThe serum concentration of Tolvaptan can be increased when it is combined with Mibefradil.Withdrawn
MiconazoleThe serum concentration of Tolvaptan can be increased when it is combined with Miconazole.Approved, Investigational, Vet Approved
MidazolamThe serum concentration of Tolvaptan can be decreased when it is combined with Midazolam.Approved, Illicit
MifepristoneThe serum concentration of Tolvaptan can be increased when it is combined with Mifepristone.Approved, Investigational
MirabegronThe serum concentration of Mirabegron can be increased when it is combined with Tolvaptan.Approved
MitomycinThe serum concentration of Tolvaptan can be increased when it is combined with Mitomycin.Approved
MitotaneThe serum concentration of Tolvaptan can be decreased when it is combined with Mitotane.Approved
MitoxantroneThe serum concentration of Tolvaptan can be decreased when it is combined with Mitoxantrone.Approved, Investigational
ModafinilThe serum concentration of Tolvaptan can be decreased when it is combined with Modafinil.Approved, Investigational
MoexiprilTolvaptan may increase the hyperkalemic activities of Moexipril.Approved
MorphineThe risk or severity of adverse effects can be increased when Morphine is combined with Tolvaptan.Approved, Investigational
Mycophenolate mofetilThe serum concentration of Mycophenolate mofetil can be increased when it is combined with Tolvaptan.Approved, Investigational
NadololThe serum concentration of Nadolol can be increased when it is combined with Tolvaptan.Approved
NafcillinThe serum concentration of Tolvaptan can be decreased when it is combined with Nafcillin.Approved
NalbuphineThe risk or severity of adverse effects can be increased when Nalbuphine is combined with Tolvaptan.Approved
NaloxegolThe serum concentration of Naloxegol can be increased when it is combined with Tolvaptan.Approved
NaloxoneThe serum concentration of Naloxone can be increased when it is combined with Tolvaptan.Approved, Vet Approved
NaltrexoneThe serum concentration of Tolvaptan can be increased when it is combined with Naltrexone.Approved, Investigational, Vet Approved
NaringeninThe serum concentration of Tolvaptan can be increased when it is combined with Naringenin.Experimental
NefazodoneThe serum concentration of Tolvaptan can be increased when it is combined with Nefazodone.Approved, Withdrawn
NelfinavirThe serum concentration of Tolvaptan can be increased when it is combined with Nelfinavir.Approved
NeostigmineThe serum concentration of Tolvaptan can be increased when it is combined with Neostigmine.Approved, Vet Approved
NetupitantThe serum concentration of Tolvaptan can be increased when it is combined with Netupitant.Approved
NevirapineThe serum concentration of Tolvaptan can be decreased when it is combined with Nevirapine.Approved
NicardipineThe serum concentration of Tolvaptan can be increased when it is combined with Nicardipine.Approved
NifedipineThe serum concentration of Tolvaptan can be decreased when it is combined with Nifedipine.Approved
NilotinibThe serum concentration of Tolvaptan can be increased when it is combined with Nilotinib.Approved, Investigational
NintedanibThe serum concentration of Nintedanib can be increased when it is combined with Tolvaptan.Approved
NisoldipineThe serum concentration of Tolvaptan can be increased when it is combined with Nisoldipine.Approved
NitrazepamThe serum concentration of Tolvaptan can be increased when it is combined with Nitrazepam.Approved
NitrendipineThe serum concentration of Tolvaptan can be increased when it is combined with Nitrendipine.Approved
NizatidineThe serum concentration of Nizatidine can be increased when it is combined with Tolvaptan.Approved
NorethisteroneThe serum concentration of Tolvaptan can be decreased when it is combined with Norethisterone.Approved
NormethadoneThe risk or severity of adverse effects can be increased when Normethadone is combined with Tolvaptan.Approved, Illicit
OlanzapineThe serum concentration of Olanzapine can be increased when it is combined with Tolvaptan.Approved, Investigational
OlaparibThe serum concentration of Tolvaptan can be increased when it is combined with Olaparib.Approved
OlmesartanTolvaptan may increase the hyperkalemic activities of Olmesartan.Approved, Investigational
OmapatrilatTolvaptan may increase the hyperkalemic activities of Omapatrilat.Investigational
OmbitasvirThe serum concentration of Ombitasvir can be increased when it is combined with Tolvaptan.Approved
OmeprazoleThe serum concentration of Tolvaptan can be increased when it is combined with Omeprazole.Approved, Investigational, Vet Approved
OpiumThe risk or severity of adverse effects can be increased when Opium is combined with Tolvaptan.Approved, Illicit
OsimertinibThe serum concentration of Tolvaptan can be increased when it is combined with Osimertinib.Approved
OxycodoneThe risk or severity of adverse effects can be increased when Oxycodone is combined with Tolvaptan.Approved, Illicit, Investigational
OxymorphoneThe risk or severity of adverse effects can be increased when Oxymorphone is combined with Tolvaptan.Approved, Investigational, Vet Approved
P-NitrophenolThe serum concentration of Tolvaptan can be increased when it is combined with P-Nitrophenol.Experimental
PaclitaxelThe serum concentration of Tolvaptan can be increased when it is combined with Paclitaxel.Approved, Vet Approved
PalbociclibThe serum concentration of Tolvaptan can be increased when it is combined with Palbociclib.Approved
Palmitic AcidThe serum concentration of Tolvaptan can be increased when it is combined with Palmitic Acid.Experimental
PanobinostatThe serum concentration of Panobinostat can be increased when it is combined with Tolvaptan.Approved, Investigational
PantoprazoleThe serum concentration of Tolvaptan can be increased when it is combined with Pantoprazole.Approved
ParoxetineThe serum concentration of Tolvaptan can be increased when it is combined with Paroxetine.Approved, Investigational
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Tolvaptan.Approved
PentazocineThe risk or severity of adverse effects can be increased when Pentazocine is combined with Tolvaptan.Approved, Vet Approved
PentobarbitalThe serum concentration of Tolvaptan can be decreased when it is combined with Pentobarbital.Approved, Vet Approved
PerindoprilTolvaptan may increase the hyperkalemic activities of Perindopril.Approved
PethidineThe risk or severity of adverse effects can be increased when Pethidine is combined with Tolvaptan.Approved
PhenobarbitalThe serum concentration of Tolvaptan can be decreased when it is combined with Phenobarbital.Approved
PhenytoinThe serum concentration of Tolvaptan can be decreased when it is combined with Phenytoin.Approved, Vet Approved
PimozideThe serum concentration of Tolvaptan can be increased when it is combined with Pimozide.Approved
PiritramideThe risk or severity of adverse effects can be increased when Piritramide is combined with Tolvaptan.Investigational
PitavastatinThe serum concentration of Pitavastatin can be increased when it is combined with Tolvaptan.Approved
Platelet Activating FactorThe serum concentration of Tolvaptan can be decreased when it is combined with Platelet Activating Factor.Experimental
PomalidomideThe serum concentration of Pomalidomide can be increased when it is combined with Tolvaptan.Approved
PonatinibThe serum concentration of Ponatinib can be increased when it is combined with Tolvaptan.Approved
PosaconazoleThe serum concentration of Tolvaptan can be increased when it is combined with Posaconazole.Approved, Investigational, Vet Approved
PravastatinThe serum concentration of Tolvaptan can be increased when it is combined with Pravastatin.Approved
PrazosinThe serum concentration of Tolvaptan can be increased when it is combined with Prazosin.Approved
PrednisoloneThe serum concentration of Prednisolone can be increased when it is combined with Tolvaptan.Approved, Vet Approved
PrednisoneThe serum concentration of Tolvaptan can be increased when it is combined with Prednisone.Approved, Vet Approved
PrimidoneThe serum concentration of Tolvaptan can be decreased when it is combined with Primidone.Approved, Vet Approved
ProbenecidThe serum concentration of Tolvaptan can be increased when it is combined with Probenecid.Approved
ProgesteroneThe serum concentration of Tolvaptan can be decreased when it is combined with Progesterone.Approved, Vet Approved
PromethazineThe serum concentration of Tolvaptan can be increased when it is combined with Promethazine.Approved
PropafenoneThe serum concentration of Tolvaptan can be increased when it is combined with Propafenone.Approved
PropranololThe serum concentration of Tolvaptan can be increased when it is combined with Propranolol.Approved, Investigational
ProtriptylineThe serum concentration of Tolvaptan can be increased when it is combined with Protriptyline.Approved
PrucaloprideThe serum concentration of Prucalopride can be increased when it is combined with Tolvaptan.Approved
QuercetinThe serum concentration of Tolvaptan can be increased when it is combined with Quercetin.Experimental
QuetiapineThe serum concentration of Quetiapine can be increased when it is combined with Tolvaptan.Approved
QuinacrineThe serum concentration of Tolvaptan can be increased when it is combined with Quinacrine.Approved
QuinaprilTolvaptan may increase the hyperkalemic activities of Quinapril.Approved, Investigational
QuinidineThe serum concentration of Tolvaptan can be increased when it is combined with Quinidine.Approved
QuinineThe serum concentration of Tolvaptan can be increased when it is combined with Quinine.Approved
RamiprilTolvaptan may increase the hyperkalemic activities of Ramipril.Approved
RanitidineThe serum concentration of Tolvaptan can be increased when it is combined with Ranitidine.Approved
RanolazineThe serum concentration of Tolvaptan can be increased when it is combined with Ranolazine.Approved, Investigational
ReboxetineThe serum concentration of Tolvaptan can be increased when it is combined with Reboxetine.Approved, Investigational
RegorafenibThe serum concentration of Tolvaptan can be increased when it is combined with Regorafenib.Approved
RemifentanilThe risk or severity of adverse effects can be increased when Remifentanil is combined with Tolvaptan.Approved
RescinnamineTolvaptan may increase the hyperkalemic activities of Rescinnamine.Approved
ReserpineThe serum concentration of Tolvaptan can be decreased when it is combined with Reserpine.Approved
RifabutinThe serum concentration of Tolvaptan can be decreased when it is combined with Rifabutin.Approved
RifampicinThe serum concentration of Tolvaptan can be decreased when it is combined with Rifampicin.Approved
RifapentineThe serum concentration of Tolvaptan can be decreased when it is combined with Rifapentine.Approved
RifaximinThe serum concentration of Rifaximin can be increased when it is combined with Tolvaptan.Approved, Investigational
RilpivirineThe serum concentration of Tolvaptan can be increased when it is combined with Rilpivirine.Approved
RisperidoneThe serum concentration of Risperidone can be increased when it is combined with Tolvaptan.Approved, Investigational
RitonavirThe serum concentration of Tolvaptan can be increased when it is combined with Ritonavir.Approved, Investigational
RivaroxabanThe serum concentration of Rivaroxaban can be increased when it is combined with Tolvaptan.Approved
RolapitantThe serum concentration of Tolvaptan can be increased when it is combined with Rolapitant.Approved
RomidepsinThe serum concentration of Romidepsin can be increased when it is combined with Tolvaptan.Approved, Investigational
SacubitrilTolvaptan may increase the hyperkalemic activities of Sacubitril.Approved
Salicylic acidThe serum concentration of Salicylic acid can be increased when it is combined with Tolvaptan.Approved, Vet Approved
SaprisartanTolvaptan may increase the hyperkalemic activities of Saprisartan.Experimental
SaquinavirThe serum concentration of Tolvaptan can be increased when it is combined with Saquinavir.Approved, Investigational
SaralasinTolvaptan may increase the hyperkalemic activities of Saralasin.Investigational
ScopolamineThe serum concentration of Tolvaptan can be increased when it is combined with Scopolamine.Approved
SelegilineThe serum concentration of Tolvaptan can be increased when it is combined with Selegiline.Approved, Investigational, Vet Approved
SelexipagThe serum concentration of Selexipag can be increased when it is combined with Tolvaptan.Approved
SertralineThe serum concentration of Tolvaptan can be increased when it is combined with Sertraline.Approved
SildenafilThe serum concentration of Tolvaptan can be increased when it is combined with Sildenafil.Approved, Investigational
SilodosinThe serum concentration of Silodosin can be increased when it is combined with Tolvaptan.Approved
SiltuximabThe serum concentration of Tolvaptan can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Tolvaptan can be increased when it is combined with Simeprevir.Approved
SimvastatinThe serum concentration of Tolvaptan can be increased when it is combined with Simvastatin.Approved
SirolimusThe serum concentration of Tolvaptan can be decreased when it is combined with Sirolimus.Approved, Investigational
SitagliptinThe serum concentration of Sitagliptin can be increased when it is combined with Tolvaptan.Approved, Investigational
Sodium ChlorideThe risk or severity of adverse effects can be increased when Sodium Chloride is combined with Tolvaptan.Approved, Vet Approved
SofosbuvirThe serum concentration of Sofosbuvir can be increased when it is combined with Tolvaptan.Approved
SorafenibThe serum concentration of Tolvaptan can be increased when it is combined with Sorafenib.Approved, Investigational
SparfloxacinThe serum concentration of Sparfloxacin can be increased when it is combined with Tolvaptan.Approved
SphingosineThe serum concentration of Sphingosine can be increased when it is combined with Tolvaptan.Experimental
SpiraprilTolvaptan may increase the hyperkalemic activities of Spirapril.Approved
SpironolactoneTolvaptan may increase the hyperkalemic activities of Spironolactone.Approved
St. John's WortThe serum concentration of Tolvaptan can be decreased when it is combined with St. John&#39;s Wort.Nutraceutical
StaurosporineThe serum concentration of Tolvaptan can be increased when it is combined with Staurosporine.Experimental
StiripentolThe serum concentration of Tolvaptan can be increased when it is combined with Stiripentol.Approved
StreptozocinThe serum concentration of Tolvaptan can be decreased when it is combined with Streptozocin.Approved
SufentanilThe risk or severity of adverse effects can be increased when Sufentanil is combined with Tolvaptan.Approved, Investigational
SulfinpyrazoneThe serum concentration of Tolvaptan can be increased when it is combined with Sulfinpyrazone.Approved
SulfisoxazoleThe serum concentration of Tolvaptan can be increased when it is combined with Sulfisoxazole.Approved, Vet Approved
SumatriptanThe serum concentration of Tolvaptan can be increased when it is combined with Sumatriptan.Approved, Investigational
SunitinibThe serum concentration of Tolvaptan can be increased when it is combined with Sunitinib.Approved, Investigational
TacrineThe serum concentration of Tolvaptan can be increased when it is combined with Tacrine.Withdrawn
TacrolimusThe serum concentration of Tolvaptan can be decreased when it is combined with Tacrolimus.Approved, Investigational
TamoxifenThe serum concentration of Tolvaptan can be decreased when it is combined with Tamoxifen.Approved
TapentadolThe risk or severity of adverse effects can be increased when Tapentadol is combined with Tolvaptan.Approved
TasosartanTolvaptan may increase the hyperkalemic activities of Tasosartan.Approved
Taurocholic AcidThe serum concentration of Tolvaptan can be increased when it is combined with Taurocholic Acid.Experimental
Technetium Tc-99m sestamibiThe serum concentration of Technetium Tc-99m sestamibi can be increased when it is combined with Tolvaptan.Approved
TelaprevirThe serum concentration of Tolvaptan can be increased when it is combined with Telaprevir.Approved
TelithromycinThe serum concentration of Tolvaptan can be increased when it is combined with Telithromycin.Approved
TelmisartanTolvaptan may increase the hyperkalemic activities of Telmisartan.Approved, Investigational
TemocaprilTolvaptan may increase the hyperkalemic activities of Temocapril.Experimental, Investigational
TemsirolimusThe serum concentration of Tolvaptan can be increased when it is combined with Temsirolimus.Approved
TerazosinThe serum concentration of Tolvaptan can be increased when it is combined with Terazosin.Approved
TerfenadineThe serum concentration of Tolvaptan can be increased when it is combined with Terfenadine.Withdrawn
TesmilifeneThe serum concentration of Tolvaptan can be decreased when it is combined with Tesmilifene.Investigational
TestosteroneThe serum concentration of Tolvaptan can be increased when it is combined with Testosterone.Approved, Investigational
TicagrelorThe serum concentration of Ticagrelor can be increased when it is combined with Tolvaptan.Approved
TiclopidineThe serum concentration of Tolvaptan can be increased when it is combined with Ticlopidine.Approved
TimololThe serum concentration of Timolol can be increased when it is combined with Tolvaptan.Approved
TocilizumabThe serum concentration of Tolvaptan can be decreased when it is combined with Tocilizumab.Approved
TopotecanThe serum concentration of Topotecan can be increased when it is combined with Tolvaptan.Approved, Investigational
ToremifeneThe serum concentration of Toremifene can be increased when it is combined with Tolvaptan.Approved, Investigational
TramadolThe risk or severity of adverse effects can be increased when Tramadol is combined with Tolvaptan.Approved, Investigational
TrandolaprilTolvaptan may increase the hyperkalemic activities of Trandolapril.Approved
Trastuzumab emtansineThe serum concentration of Trastuzumab emtansine can be increased when it is combined with Tolvaptan.Approved
TrazodoneThe serum concentration of Tolvaptan can be decreased when it is combined with Trazodone.Approved, Investigational
TriamtereneTolvaptan may increase the hyperkalemic activities of Triamterene.Approved
TrifluoperazineThe serum concentration of Tolvaptan can be increased when it is combined with Trifluoperazine.Approved
TriflupromazineThe serum concentration of Tolvaptan can be increased when it is combined with Triflupromazine.Approved, Vet Approved
TrimethoprimThe serum concentration of Tolvaptan can be decreased when it is combined with Trimethoprim.Approved, Vet Approved
TrimipramineThe serum concentration of Tolvaptan can be increased when it is combined with Trimipramine.Approved
TroleandomycinThe serum concentration of Tolvaptan can be increased when it is combined with Troleandomycin.Approved
UlipristalThe serum concentration of Ulipristal can be increased when it is combined with Tolvaptan.Approved
UmeclidiniumThe serum concentration of Umeclidinium can be increased when it is combined with Tolvaptan.Approved
ValsartanTolvaptan may increase the hyperkalemic activities of Valsartan.Approved, Investigational
VecuroniumThe serum concentration of Vecuronium can be increased when it is combined with Tolvaptan.Approved
VenetoclaxThe serum concentration of Venetoclax can be increased when it is combined with Tolvaptan.Approved
VenlafaxineThe serum concentration of Tolvaptan can be increased when it is combined with Venlafaxine.Approved
VerapamilThe serum concentration of Tolvaptan can be increased when it is combined with Verapamil.Approved
VinblastineThe serum concentration of Tolvaptan can be decreased when it is combined with Vinblastine.Approved
VincristineThe serum concentration of Vincristine can be increased when it is combined with Tolvaptan.Approved, Investigational
VincristineThe serum concentration of Tolvaptan can be decreased when it is combined with Vincristine.Approved, Investigational
VinorelbineThe serum concentration of Tolvaptan can be increased when it is combined with Vinorelbine.Approved, Investigational
VismodegibThe serum concentration of Vismodegib can be increased when it is combined with Tolvaptan.Approved
VoriconazoleThe serum concentration of Tolvaptan can be increased when it is combined with Voriconazole.Approved, Investigational
ZidovudineThe serum concentration of Zidovudine can be increased when it is combined with Tolvaptan.Approved
ZimelidineThe serum concentration of Tolvaptan can be increased when it is combined with Zimelidine.Withdrawn
ZiprasidoneThe serum concentration of Tolvaptan can be increased when it is combined with Ziprasidone.Approved
Food InteractionsNot Available
References
Synthesis Reference

Bandi Parthasaradhi Reddy, “PROCESS FOR PREPARING TOLVAPTAN INTERMEDIATES.” U.S. Patent US20130190490, issued July 25, 2013.

US20130190490
General References
  1. Gheorghiade M, Teerlink JR, Mebazaa A: Pharmacology of new agents for acute heart failure syndromes. Am J Cardiol. 2005 Sep 19;96(6A):68G-73G. [PubMed:16181825 ]
  2. Ambrosy A, Goldsmith SR, Gheorghiade M: Tolvaptan for the treatment of heart failure: a review of the literature. Expert Opin Pharmacother. 2011 Apr;12(6):961-76. doi: 10.1517/14656566.2011.567267. Epub 2011 Mar 15. [PubMed:21401442 ]
  3. Yi S, Jeon H, Yoon SH, Cho JY, Shin SG, Jang IJ, Yu KS: Pharmacokinetics and pharmacodynamics of oral tolvaptan administered in 15- to 60-mg single doses to healthy Korean men. J Cardiovasc Pharmacol. 2012 Apr;59(4):315-22. doi: 10.1097/FJC.0b013e318241e89c. [PubMed:22130104 ]
  4. Nemerovski C, Hutchinson DJ: Treatment of hypervolemic or euvolemic hyponatremia associated with heart failure, cirrhosis, or the syndrome of inappropriate antidiuretic hormone with tolvaptan: a clinical review. Clin Ther. 2010 Jun;32(6):1015-32. doi: 10.1016/j.clinthera.2010.06.015. [PubMed:20637957 ]
External Links
ATC CodesC03XA01
AHFS Codes
  • 40:28.28
PDB EntriesNot Available
FDA labelDownload (468 KB)
MSDSDownload (103 KB)
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.961
Blood Brain Barrier+0.8429
Caco-2 permeable-0.5116
P-glycoprotein substrateSubstrate0.6765
P-glycoprotein inhibitor IInhibitor0.5241
P-glycoprotein inhibitor IINon-inhibitor0.5525
Renal organic cation transporterNon-inhibitor0.767
CYP450 2C9 substrateNon-substrate0.7217
CYP450 2D6 substrateNon-substrate0.7662
CYP450 3A4 substrateSubstrate0.7372
CYP450 1A2 substrateNon-inhibitor0.7512
CYP450 2C9 inhibitorNon-inhibitor0.7214
CYP450 2D6 inhibitorNon-inhibitor0.7887
CYP450 2C19 inhibitorNon-inhibitor0.5308
CYP450 3A4 inhibitorInhibitor0.8545
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5874
Ames testNon AMES toxic0.7247
CarcinogenicityNon-carcinogens0.8623
BiodegradationNot ready biodegradable0.9939
Rat acute toxicity2.2269 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9807
hERG inhibition (predictor II)Inhibitor0.682
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
TabletOral
TabletOral15 mg/1
TabletOral15 mg
TabletOral30 mg/1
TabletOral30 mg
TabletOral60 mg
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5258510 No1993-11-022010-11-02Us
US5753677 No2000-05-192020-05-19Us
US8501730 No2006-09-012026-09-01Us
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.00124 mg/mLALOGPS
logP4.14ALOGPS
logP5.35ChemAxon
logS-5.6ALOGPS
pKa (Strongest Acidic)11.76ChemAxon
pKa (Strongest Basic)-2.1ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area69.64 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity129.16 m3·mol-1ChemAxon
Polarizability48.16 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as n-phenylbenzamides. These are benzamides that are N-linked to a phenyl group via the carboxamide group.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzamides
Direct ParentN-phenylbenzamides
Alternative Parents
Substituents
  • N-phenylbenzamide
  • Benzazepine
  • N-arylamide
  • Aminobenzoic acid or derivatives
  • Benzoic acid or derivatives
  • Aminotoluene
  • Benzoyl
  • Toluene
  • Chlorobenzene
  • Azepine
  • Aryl halide
  • Aryl chloride
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Secondary alcohol
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Vasopressin receptor activity
Specific Function:
Receptor for arginine vasopressin. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Involved in renal water reabsorption.
Gene Name:
AVPR2
Uniprot ID:
P30518
Molecular Weight:
40278.57 Da
References
  1. Aperis G, Alivanis P: Tolvaptan: a new therapeutic agent. Rev Recent Clin Trials. 2011 May;6(2):177-88. [PubMed:20868352 ]
  2. Dixon MB, Lien YH: Tolvaptan and its potential in the treatment of hyponatremia. Ther Clin Risk Manag. 2008 Dec;4(6):1149-55. [PubMed:19337422 ]
Kind
Protein
Organism
Human
Pharmacological action
no
Actions
antagonist
General Function:
Vasopressin receptor activity
Specific Function:
Receptor for arginine vasopressin. The activity of this receptor is mediated by G proteins which activate a phosphatidyl-inositol-calcium second messenger system. Has been involved in social behaviors, including affiliation and attachment.
Gene Name:
AVPR1A
Uniprot ID:
P37288
Molecular Weight:
46799.105 Da
References
  1. Nemerovski C, Hutchinson DJ: Treatment of hypervolemic or euvolemic hyponatremia associated with heart failure, cirrhosis, or the syndrome of inappropriate antidiuretic hormone with tolvaptan: a clinical review. Clin Ther. 2010 Jun;32(6):1015-32. doi: 10.1016/j.clinthera.2010.06.015. [PubMed:20637957 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Aperis G, Alivanis P: Tolvaptan: a new therapeutic agent. Rev Recent Clin Trials. 2011 May;6(2):177-88. [PubMed:20868352 ]
  2. Dixon MB, Lien YH: Tolvaptan and its potential in the treatment of hyponatremia. Ther Clin Risk Manag. 2008 Dec;4(6):1149-55. [PubMed:19337422 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
no
Actions
substrateinhibitor
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
References
  1. Shoaf SE, Ohzone Y, Ninomiya S, Furukawa M, Bricmont P, Kashiyama E, Mallikaarjun S: In vitro P-glycoprotein interactions and steady-state pharmacokinetic interactions between tolvaptan and digoxin in healthy subjects. J Clin Pharmacol. 2011 May;51(5):761-9. doi: 10.1177/0091270010376193. Epub 2010 Aug 2. [PubMed:20679500 ]
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Drug created on March 19, 2008 10:17 / Updated on December 10, 2016 02:40