Identification

Name
Tolvaptan
Accession Number
DB06212
Type
Small Molecule
Groups
Approved
Description

Tolvaptan 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
Not Available
External IDs
OPC-41061
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
SamscaTablet15 mgOralOtsuka Pharmaceutical Europe Ltd.2009-08-03Not applicableEu
SamscaTablet30 mg/1OralOtsuka Pharmaceutical Co., Ltd.2009-05-19Not applicableUs
SamscaTablet30 mgOralOtsuka Pharmaceutical Co., Ltd.2011-09-22Not applicableCanada
SamscaTablet30 mgOralOtsuka Pharmaceutical Europe Ltd.2009-08-03Not applicableEu
SamscaTablet15 mg/1OralOtsuka Pharmaceutical Co., Ltd.2009-05-19Not applicableUs
SamscaTablet15 mgOralOtsuka Pharmaceutical Co., Ltd.2011-09-22Not applicableCanada
SamscaTablet15 mgOralOtsuka Pharmaceutical Europe Ltd.2009-08-03Not applicableEu
SamscaTablet60 mgOralOtsuka Pharmaceutical Co., Ltd.Not applicableNot applicableCanada
SamscaTablet30 mgOralOtsuka Pharmaceutical Europe Ltd.2009-08-03Not applicableEu
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
JinarcTolvaptan (15 mg) + Tolvaptan (45 mg)TabletOralOtsuka Pharmaceutical Co., Ltd.2015-06-01Not applicableCanada
JinarcTolvaptan (30 mg) + Tolvaptan (90 mg)TabletOralOtsuka Pharmaceutical Co., Ltd.2015-06-01Not applicableCanada
JinarcTolvaptan (30 mg) + Tolvaptan (60 mg)TabletOralOtsuka Pharmaceutical Co., Ltd.2015-06-01Not applicableCanada
JinarcTolvaptan (30 mg) + Tolvaptan (90 mg)TabletOralOtsuka Pharmaceutical Co., Ltd.2015-06-01Not applicableCanada
JinarcTolvaptan (15 mg) + Tolvaptan (45 mg)TabletOralOtsuka Pharmaceutical Co., Ltd.2015-06-01Not applicableCanada
JinarcTolvaptan (30 mg) + Tolvaptan (60 mg)TabletOralOtsuka Pharmaceutical Co., Ltd.2015-06-01Not applicableCanada
International/Other Brands
Samsca
Categories
UNII
1E2497LPNY
CAS number
150683-30-0
Weight
Average: 448.941
Monoisotopic: 448.155370383
Chemical Formula
C26H25ClN2O3
InChI Key
GYHCTFXIZSNGJT-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[[email protected]@H](O)C2=C1C=CC(Cl)=C2

Pharmacology

Indication

Treatment of symptomatic and resistant to fluid restriction euvolemic or hypervolemic hyponatremia associated with congestive heart failure, SIADH, and cirrhosis.

Structured Indications
Pharmacodynamics

Urine 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 action

Tolvaptan 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.

TargetActionsOrganism
AVasopressin V2 receptor
antagonist
Human
NVasopressin V1a receptor
antagonist
Human
Absorption

Tmax, 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 binding

99% bound

Metabolism

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

Route of elimination

Fecal- very little renal elimination (<1% is excreted unchanged in the urine)

Half life

Terminal half life, oral dose = 12 hours.

Clearance

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

Toxicity

The 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcemetacinThe therapeutic efficacy of Tolvaptan can be decreased when used in combination with Acemetacin.Approved, Experimental, Investigational
AcetaminophenThe serum concentration of Tolvaptan can be increased when it is combined with Acetaminophen.Approved
AcetazolamideThe serum concentration of Tolvaptan can be increased when it is combined with Acetazolamide.Approved, Vet Approved
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Tolvaptan.Approved
AldesleukinThe serum concentration of Tolvaptan can be increased when it is combined with Aldesleukin.Approved
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Tolvaptan.Approved, Illicit
AlphacetylmethadolThe risk or severity of adverse effects can be increased when Alphacetylmethadol is combined with Tolvaptan.Experimental, Illicit
AlphaprodineThe risk or severity of adverse effects can be increased when Alphaprodine is combined with Tolvaptan.Illicit
AlprazolamThe serum concentration of Tolvaptan can be increased when it is combined with Alprazolam.Approved, Illicit, Investigational
AmbroxolThe serum concentration of Tolvaptan can be increased when it is combined with Ambroxol.Approved, Investigational
AmilorideTolvaptan may increase the hyperkalemic activities of Amiloride.Approved
AmiodaroneThe serum concentration of Tolvaptan can be increased when it is combined with Amiodarone.Approved, Investigational
AmlodipineThe serum concentration of Tolvaptan can be increased when it is combined with Amlodipine.Approved
AmprenavirThe serum concentration of Tolvaptan can be increased when it is combined with Amprenavir.Approved, Investigational
AnastrozoleThe serum concentration of Tolvaptan can be increased when it is combined with Anastrozole.Approved, Investigational
AntipyrineThe serum concentration of Tolvaptan can be increased when it is combined with Antipyrine.Approved, Investigational
AprepitantThe serum concentration of Tolvaptan can be increased when it is combined with Aprepitant.Approved, Investigational
Arsenic trioxideThe serum concentration of Tolvaptan can be increased when it is combined with Arsenic trioxide.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
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
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, Investigational
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
BetamethasoneThe serum concentration of Tolvaptan can be increased when it is combined with Betamethasone.Approved, Vet Approved
BezitramideThe risk or severity of adverse effects can be increased when Bezitramide is combined with Tolvaptan.Experimental, Illicit, Withdrawn
BicalutamideThe serum concentration of Tolvaptan can be increased when it is combined with Bicalutamide.Approved
BifonazoleThe serum concentration of Tolvaptan can be increased when it is combined with Bifonazole.Approved, Investigational
BoceprevirThe serum concentration of Tolvaptan can be increased when it is combined with Boceprevir.Approved, Withdrawn
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
BrigatinibThe serum concentration of Tolvaptan can be decreased when it is combined with Brigatinib.Approved, Investigational
BromocriptineThe serum concentration of Tolvaptan can be increased when it is combined with Bromocriptine.Approved, Investigational
BuprenorphineThe serum concentration of Tolvaptan can be increased when it is combined with Buprenorphine.Approved, Illicit, Investigational, Vet Approved
ButorphanolThe risk or severity of adverse effects can be increased when Butorphanol is combined with Tolvaptan.Approved, Illicit, Vet Approved
CabergolineThe serum concentration of Tolvaptan can be increased when it is combined with Cabergoline.Approved
CaffeineThe serum concentration of Tolvaptan can be increased when it is combined with Caffeine.Approved
CandesartanTolvaptan may increase the hyperkalemic activities of Candesartan.Experimental
Candesartan cilexetilThe risk or severity of hypotension can be increased when Candesartan cilexetil is combined with Tolvaptan.Approved
CandoxatrilTolvaptan may increase the hyperkalemic activities of Candoxatril.Experimental
CapsaicinThe serum concentration of Tolvaptan can be increased when it is combined with Capsaicin.Approved
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, Investigational, Vet Approved
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 Tolvaptan can be increased when it is combined with Cerivastatin.Approved, Withdrawn
ChloramphenicolThe serum concentration of Tolvaptan can be increased when it is combined with Chloramphenicol.Approved, Vet Approved
ChlorzoxazoneThe serum concentration of Tolvaptan can be increased when it is combined with Chlorzoxazone.Approved
CilazaprilTolvaptan may increase the hyperkalemic activities of Cilazapril.Approved
CilostazolThe serum concentration of Tolvaptan can be increased when it is combined with Cilostazol.Approved, Investigational
CimetidineThe serum concentration of Tolvaptan can be increased when it is combined with Cimetidine.Approved, Investigational
CiprofloxacinThe serum concentration of Tolvaptan can be increased when it is combined with Ciprofloxacin.Approved, Investigational
CisaprideThe serum concentration of Tolvaptan can be increased when it is combined with Cisapride.Approved, Investigational, Withdrawn
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, Investigational
ClindamycinThe serum concentration of Tolvaptan can be increased when it is combined with Clindamycin.Approved, Vet Approved
ClofazimineThe serum concentration of Tolvaptan can be increased when it is combined with Clofazimine.Approved, Investigational
ClomifeneThe serum concentration of Tolvaptan can be increased when it is combined with Clomifene.Approved, Investigational
ClotiazepamThe serum concentration of Tolvaptan can be increased when it is combined with Clotiazepam.Approved, Illicit
ClotrimazoleThe serum concentration of Tolvaptan can be increased when it is combined with Clotrimazole.Approved, Vet Approved
ClozapineThe serum concentration of Tolvaptan can be increased when it is combined with Clozapine.Approved
CobicistatThe serum concentration of Tolvaptan can be increased when it is combined with Cobicistat.Approved
CocaineThe serum concentration of Tolvaptan can be increased when it is combined with Cocaine.Approved, Illicit
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
ConivaptanThe serum concentration of Tolvaptan can be increased when it is combined with Conivaptan.Approved, Investigational
Cortisone acetateThe serum concentration of Tolvaptan can be increased when it is combined with Cortisone acetate.Approved, Investigational
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, Investigational
DalfopristinThe serum concentration of Tolvaptan can be increased when it is combined with Dalfopristin.Approved
DanazolThe serum concentration of Tolvaptan can be increased when it is combined with Danazol.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 increased when it is combined with Daunorubicin.Approved
DeferasiroxThe serum concentration of Tolvaptan can be decreased when it is combined with Deferasirox.Approved, Investigational
DelaprilTolvaptan may increase the hyperkalemic activities of Delapril.Experimental
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, Investigational
DesmopressinThe therapeutic efficacy of Desmopressin can be decreased when used in combination with Tolvaptan.Approved
DexamethasoneThe serum concentration of Tolvaptan can be increased when it is combined with Dexamethasone.Approved, Investigational, Vet Approved
DextromoramideThe risk or severity of adverse effects can be increased when Dextromoramide is combined with Tolvaptan.Experimental, Illicit
DextropropoxypheneThe serum concentration of Tolvaptan can be increased when it is combined with Dextropropoxyphene.Approved, Illicit, Investigational, Withdrawn
DezocineThe risk or severity of adverse effects can be increased when Dezocine is combined with Tolvaptan.Approved, Investigational
DiacereinThe serum concentration of Tolvaptan can be increased when it is combined with Diacerein.Approved, Investigational
DiazepamThe serum concentration of Tolvaptan can be increased when it is combined with Diazepam.Approved, Illicit, Investigational, Vet Approved
DiethylstilbestrolThe serum concentration of Tolvaptan can be increased when it is combined with Diethylstilbestrol.Approved, Investigational
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, Investigational
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
DiltiazemThe serum concentration of Tolvaptan can be increased when it is combined with Diltiazem.Approved, Investigational
Dimethyl sulfoxideThe serum concentration of Tolvaptan can be increased when it is combined with Dimethyl sulfoxide.Approved, Vet Approved
DiphenoxylateThe risk or severity of adverse effects can be increased when Diphenoxylate is combined with Tolvaptan.Approved, Illicit
DocetaxelThe serum concentration of Tolvaptan can be increased when it is combined with Docetaxel.Approved, Investigational
DoxorubicinThe serum concentration of Tolvaptan can be increased 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.Experimental
DronedaroneThe serum concentration of Tolvaptan can be increased when it is combined with Dronedarone.Approved
EconazoleThe serum concentration of Tolvaptan can be increased when it is combined with Econazole.Approved
EdoxabanThe serum concentration of Edoxaban can be increased when it is combined with Tolvaptan.Approved
EfavirenzThe serum concentration of Tolvaptan can be increased when it is combined with Efavirenz.Approved, Investigational
ElbasvirThe serum concentration of Tolvaptan can be increased when it is combined with Elbasvir.Approved
EnalaprilTolvaptan may increase the hyperkalemic activities of Enalapril.Approved, Vet Approved
EnalaprilatTolvaptan may increase the hyperkalemic activities of Enalaprilat.Approved
EnasidenibThe serum concentration of Tolvaptan can be increased when it is combined with Enasidenib.Approved, Investigational
EnzalutamideThe serum concentration of Tolvaptan can be decreased when it is combined with Enzalutamide.Approved
EpinephrineThe serum concentration of Tolvaptan can be increased when it is combined with Epinephrine.Approved, Vet Approved
EplerenoneTolvaptan may increase the hyperkalemic activities of Eplerenone.Approved
EprosartanTolvaptan may increase the hyperkalemic activities of Eprosartan.Approved
Ergoloid mesylateThe serum concentration of Tolvaptan can be increased when it is combined with Ergoloid mesylate.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
ErythromycinThe serum concentration of Tolvaptan can be increased when it is combined with Erythromycin.Approved, Investigational, Vet Approved
EthanolThe serum concentration of Tolvaptan can be increased when it is combined with Ethanol.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
EtoricoxibThe serum concentration of Tolvaptan can be increased when it is combined with Etoricoxib.Approved, Investigational
EtorphineThe risk or severity of adverse effects can be increased when Etorphine is combined with Tolvaptan.Illicit, Vet Approved
EverolimusThe serum concentration of Everolimus can be increased when it is combined with Tolvaptan.Approved
EzetimibeThe serum concentration of Tolvaptan can be increased when it is combined with Ezetimibe.Approved
FelodipineThe serum concentration of Tolvaptan can be increased when it is combined with Felodipine.Approved, Investigational
FentanylThe serum concentration of Tolvaptan can be increased when it is combined with Fentanyl.Approved, Illicit, Investigational, Vet Approved
FimasartanTolvaptan may increase the hyperkalemic activities of Fimasartan.Approved, Investigational
FluconazoleThe serum concentration of Tolvaptan can be increased when it is combined with Fluconazole.Approved, Investigational
FluoxetineThe serum concentration of Tolvaptan can be increased when it is combined with Fluoxetine.Approved, Vet Approved
Fluticasone propionateThe serum concentration of Tolvaptan can be increased when it is combined with Fluticasone propionate.Approved
FluvastatinThe serum concentration of Tolvaptan can be increased when it is combined with Fluvastatin.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, Investigational
Fusidic AcidThe serum concentration of Tolvaptan can be increased when it is combined with Fusidic Acid.Approved, Investigational
GemfibrozilThe serum concentration of Tolvaptan can be increased when it is combined with Gemfibrozil.Approved
GestodeneThe serum concentration of Tolvaptan can be increased when it is combined with Gestodene.Approved, Investigational
GlecaprevirThe serum concentration of Tolvaptan can be increased when it is combined with Glecaprevir.Approved, Investigational
GlyburideThe serum concentration of Tolvaptan can be increased when it is combined with Glyburide.Approved
Glycerol PhenylbutyrateThe serum concentration of Tolvaptan can be increased when it is combined with Glycerol Phenylbutyrate.Approved
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, Investigational
HistamineThe serum concentration of Tolvaptan can be increased when it is combined with Histamine.Approved, Investigational
HydralazineThe serum concentration of Tolvaptan can be increased when it is combined with Hydralazine.Approved
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
IdelalisibThe serum concentration of Tolvaptan can be increased when it is combined with Idelalisib.Approved
IfosfamideThe serum concentration of Tolvaptan can be increased when it is combined with Ifosfamide.Approved
IloperidoneThe serum concentration of Tolvaptan can be increased when it is combined with Iloperidone.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
IndinavirThe serum concentration of Tolvaptan can be increased when it is combined with Indinavir.Approved
IndisulamThe serum concentration of Tolvaptan can be increased when it is combined with Indisulam.Investigational
IrbesartanTolvaptan may increase the hyperkalemic activities of Irbesartan.Approved, Investigational
IrinotecanThe serum concentration of Tolvaptan can be increased when it is combined with Irinotecan.Approved, Investigational
IsavuconazoniumThe serum concentration of Tolvaptan can be increased when it is combined with Isavuconazonium.Approved, Investigational
IsoniazidThe serum concentration of Tolvaptan can be increased when it is combined with Isoniazid.Approved, Investigational
IsradipineThe serum concentration of Tolvaptan can be increased when it is combined with Isradipine.Approved, Investigational
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
JosamycinThe serum concentration of Tolvaptan can be increased when it is combined with Josamycin.Approved, Investigational
KetazolamThe serum concentration of Tolvaptan can be increased when it is combined with Ketazolam.Approved
KetobemidoneThe risk or severity of adverse effects can be increased when Ketobemidone is combined with Tolvaptan.Approved, Investigational
KetoconazoleThe serum concentration of Tolvaptan can be increased when it is combined with Ketoconazole.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
LercanidipineThe serum concentration of Tolvaptan can be increased when it is combined with Lercanidipine.Approved, Investigational
LetermovirThe serum concentration of Tolvaptan can be increased when it is combined with Letermovir.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, Investigational
LevorphanolThe risk or severity of adverse effects can be increased when Levorphanol is combined with Tolvaptan.Approved
LevosalbutamolThe serum concentration of Tolvaptan can be increased when it is combined with Levosalbutamol.Approved, Investigational
LidocaineThe serum concentration of Tolvaptan can be increased when it is combined with Lidocaine.Approved, Vet Approved
LinagliptinThe serum concentration of Tolvaptan can be increased when it is combined with Linagliptin.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, Investigational
LomustineThe serum concentration of Tolvaptan can be increased when it is combined with Lomustine.Approved, Investigational
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, Investigational
LorpiprazoleThe serum concentration of Tolvaptan can be increased when it is combined with Lorpiprazole.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
LurasidoneThe serum concentration of Tolvaptan can be increased when it is combined with Lurasidone.Approved, Investigational
ManidipineThe serum concentration of Tolvaptan can be increased when it is combined with Manidipine.Approved, Investigational
MefloquineThe serum concentration of Tolvaptan can be increased when it is combined with Mefloquine.Approved, Investigational
MeptazinolThe risk or severity of adverse effects can be increased when Meptazinol is combined with Tolvaptan.Experimental
MequitazineThe serum concentration of Tolvaptan can be increased when it is combined with Mequitazine.Approved
MethadoneThe serum concentration of Tolvaptan can be increased when it is combined with Methadone.Approved
Methadyl AcetateThe risk or severity of adverse effects can be increased when Methadyl Acetate is combined with Tolvaptan.Approved, Illicit
MethazolamideThe serum concentration of Tolvaptan can be increased when it is combined with Methazolamide.Approved
MethimazoleThe serum concentration of Tolvaptan can be increased when it is combined with Methimazole.Approved
MethylergometrineThe serum concentration of Tolvaptan can be increased when it is combined with Methylergometrine.Approved
MethylprednisoloneThe serum concentration of Tolvaptan can be increased when it is combined with Methylprednisolone.Approved, Vet Approved
MetronidazoleThe serum concentration of Tolvaptan can be increased when it is combined with Metronidazole.Approved
MetyraponeThe serum concentration of Tolvaptan can be increased when it is combined with Metyrapone.Approved, Investigational
MibefradilThe serum concentration of Tolvaptan can be increased when it is combined with Mibefradil.Investigational, 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 increased when it is combined with Midazolam.Approved, Illicit
MidostaurinThe serum concentration of Tolvaptan can be increased when it is combined with Midostaurin.Approved, Investigational
MifepristoneThe serum concentration of Tolvaptan can be increased when it is combined with Mifepristone.Approved, Investigational
MirtazapineThe serum concentration of Tolvaptan can be increased when it is combined with Mirtazapine.Approved
MitotaneThe serum concentration of Tolvaptan can be decreased when it is combined with Mitotane.Approved
MitoxantroneThe serum concentration of Tolvaptan can be increased when it is combined with Mitoxantrone.Approved, Investigational
ModafinilThe serum concentration of Tolvaptan can be increased 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
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
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
NetupitantThe serum concentration of Tolvaptan can be increased when it is combined with Netupitant.Approved, Investigational
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, Investigational
NicomorphineThe risk or severity of adverse effects can be increased when Nicomorphine is combined with Tolvaptan.Experimental
NicotinamideThe serum concentration of Tolvaptan can be increased when it is combined with Nicotinamide.Approved, Investigational
NifedipineThe serum concentration of Tolvaptan can be increased when it is combined with Nifedipine.Approved
NilotinibThe serum concentration of Tolvaptan can be increased when it is combined with Nilotinib.Approved, Investigational
NilvadipineThe serum concentration of Tolvaptan can be increased when it is combined with Nilvadipine.Approved, Investigational
NisoldipineThe serum concentration of Tolvaptan can be increased when it is combined with Nisoldipine.Approved
NitrendipineThe serum concentration of Tolvaptan can be increased when it is combined with Nitrendipine.Approved, Investigational
Nitric OxideThe serum concentration of Tolvaptan can be increased when it is combined with Nitric Oxide.Approved
NorfloxacinThe serum concentration of Tolvaptan can be increased when it is combined with Norfloxacin.Approved
NormethadoneThe risk or severity of adverse effects can be increased when Normethadone is combined with Tolvaptan.Approved, Illicit
NoscapineThe serum concentration of Tolvaptan can be increased when it is combined with Noscapine.Investigational
OlanzapineThe serum concentration of Tolvaptan can be increased when it is combined with Olanzapine.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
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
OxybutyninThe serum concentration of Tolvaptan can be increased when it is combined with Oxybutynin.Approved, Investigational
OxycodoneThe risk or severity of adverse effects can be increased when Oxycodone is combined with Tolvaptan.Approved, Illicit, Investigational
OxymetholoneThe serum concentration of Tolvaptan can be increased when it is combined with Oxymetholone.Approved, Illicit
OxymorphoneThe risk or severity of adverse effects can be increased when Oxymorphone is combined with Tolvaptan.Approved, Investigational, Vet Approved
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, Investigational
ParamethasoneThe serum concentration of Tolvaptan can be increased when it is combined with Paramethasone.Approved
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, Investigational, Vet Approved
PergolideThe serum concentration of Tolvaptan can be increased when it is combined with Pergolide.Approved, Investigational, Vet Approved, Withdrawn
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
PhenazocineThe risk or severity of adverse effects can be increased when Phenazocine is combined with Tolvaptan.Experimental
PhenelzineThe serum concentration of Tolvaptan can be increased when it is combined with Phenelzine.Approved
PhenobarbitalThe serum concentration of Tolvaptan can be decreased when it is combined with Phenobarbital.Approved, Investigational
PhenoperidineThe risk or severity of adverse effects can be increased when Phenoperidine is combined with Tolvaptan.Experimental
PhenytoinThe serum concentration of Tolvaptan can be decreased when it is combined with Phenytoin.Approved, Vet Approved
PibrentasvirThe serum concentration of Tolvaptan can be increased when it is combined with Pibrentasvir.Approved, Investigational
PilocarpineThe serum concentration of Tolvaptan can be increased when it is combined with Pilocarpine.Approved, Investigational
PimozideThe serum concentration of Tolvaptan can be increased when it is combined with Pimozide.Approved
PiperaquineThe serum concentration of Tolvaptan can be increased when it is combined with Piperaquine.Approved, Investigational
PiritramideThe risk or severity of adverse effects can be increased when Piritramide is combined with Tolvaptan.Approved, Investigational
PosaconazoleThe serum concentration of Tolvaptan can be increased when it is combined with Posaconazole.Approved, Investigational, Vet Approved
PrasteroneThe serum concentration of Tolvaptan can be increased when it is combined with Prasterone.Approved, Investigational, Nutraceutical
PravastatinThe serum concentration of Tolvaptan can be increased when it is combined with Pravastatin.Approved
PrednisoloneThe serum concentration of Tolvaptan can be increased when it is combined with Prednisolone.Approved, Vet Approved
PrednisoneThe serum concentration of Tolvaptan can be increased when it is combined with Prednisone.Approved, Vet Approved
PrimaquineThe serum concentration of Tolvaptan can be increased when it is combined with Primaquine.Approved
PrimidoneThe serum concentration of Tolvaptan can be decreased when it is combined with Primidone.Approved, Vet Approved
ProgesteroneThe serum concentration of Tolvaptan can be increased when it is combined with Progesterone.Approved, Vet Approved
PropofolThe serum concentration of Tolvaptan can be increased when it is combined with Propofol.Approved, Investigational, Vet Approved
Propoxyphene napsylateThe serum concentration of Tolvaptan can be increased when it is combined with Propoxyphene napsylate.Approved
PrucaloprideThe serum concentration of Prucalopride can be increased when it is combined with Tolvaptan.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, Investigational
QuinineThe serum concentration of Tolvaptan can be increased when it is combined with Quinine.Approved
QuinupristinThe serum concentration of Tolvaptan can be increased when it is combined with Quinupristin.Approved
RabeprazoleThe serum concentration of Tolvaptan can be increased when it is combined with Rabeprazole.Approved, Investigational
RaloxifeneThe serum concentration of Tolvaptan can be increased when it is combined with Raloxifene.Approved, Investigational
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 Ranolazine can be increased when it is combined with Tolvaptan.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
RepaglinideThe serum concentration of Tolvaptan can be increased when it is combined with Repaglinide.Approved, Investigational
RescinnamineTolvaptan may increase the hyperkalemic activities of Rescinnamine.Approved
ResveratrolThe serum concentration of Tolvaptan can be increased when it is combined with Resveratrol.Approved, Experimental, Investigational
RheinThe serum concentration of Tolvaptan can be increased when it is combined with Rhein.Experimental
RibociclibThe serum concentration of Tolvaptan can be increased when it is combined with Ribociclib.Approved, Investigational
RifabutinThe serum concentration of Tolvaptan can be decreased when it is combined with Rifabutin.Approved, Investigational
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, Investigational
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 Tolvaptan can be increased when it is combined with Risperidone.Approved, Investigational
RitonavirThe serum concentration of Tolvaptan can be increased when it is combined with Ritonavir.Approved, Investigational
RivastigmineThe serum concentration of Tolvaptan can be increased when it is combined with Rivastigmine.Approved, Investigational
RolitetracyclineThe serum concentration of Tolvaptan can be increased when it is combined with Rolitetracycline.Approved
RosuvastatinThe serum concentration of Tolvaptan can be increased when it is combined with Rosuvastatin.Approved
RoxithromycinThe serum concentration of Tolvaptan can be increased when it is combined with Roxithromycin.Approved, Investigational, Withdrawn
RucaparibThe serum concentration of Tolvaptan can be increased when it is combined with Rucaparib.Approved, Investigational
RutinThe serum concentration of Tolvaptan can be increased when it is combined with Rutin.Experimental, Investigational
SacubitrilTolvaptan may increase the hyperkalemic activities of Sacubitril.Approved
SalbutamolThe serum concentration of Tolvaptan can be increased when it is combined with Salbutamol.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
SarilumabThe therapeutic efficacy of Tolvaptan can be decreased when used in combination with Sarilumab.Approved, Investigational
SeproxetineThe serum concentration of Tolvaptan can be increased when it is combined with Seproxetine.Investigational
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, Investigational
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 increased when it is combined with Sirolimus.Approved, Investigational
SitaxentanThe serum concentration of Tolvaptan can be increased when it is combined with Sitaxentan.Approved, Investigational, Withdrawn
Sodium ChlorideThe risk or severity of adverse effects can be increased when Sodium Chloride is combined with Tolvaptan.Approved, Vet Approved
Sodium phosphateTolvaptan may increase the nephrotoxic activities of Sodium phosphate.Approved
SorafenibThe serum concentration of Tolvaptan can be increased when it is combined with Sorafenib.Approved, Investigational
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's Wort.Approved, Investigational, Nutraceutical
StiripentolThe serum concentration of Tolvaptan can be increased when it is combined with Stiripentol.Approved
SufentanilThe risk or severity of adverse effects can be increased when Sufentanil is combined with Tolvaptan.Approved, Investigational
SulfamethoxazoleThe serum concentration of Tolvaptan can be increased when it is combined with Sulfamethoxazole.Approved
SulfanilamideThe serum concentration of Tolvaptan can be increased when it is combined with Sulfanilamide.Approved
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
TacrolimusThe serum concentration of Tolvaptan can be increased when it is combined with Tacrolimus.Approved, Investigational
TadalafilThe serum concentration of Tolvaptan can be increased when it is combined with Tadalafil.Approved, Investigational
TamoxifenThe serum concentration of Tolvaptan can be increased 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
TelaprevirThe serum concentration of Tolvaptan can be increased when it is combined with Telaprevir.Approved, Withdrawn
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
TeniposideThe serum concentration of Tolvaptan can be increased when it is combined with Teniposide.Approved
TerfenadineThe serum concentration of Tolvaptan can be increased when it is combined with Terfenadine.Approved, Withdrawn
TesmilifeneThe serum concentration of Tolvaptan can be increased when it is combined with Tesmilifene.Investigational
TestosteroneThe serum concentration of Tolvaptan can be increased when it is combined with Testosterone.Approved, Investigational
Testosterone cypionateThe serum concentration of Tolvaptan can be increased when it is combined with Testosterone cypionate.Approved
Testosterone enanthateThe serum concentration of Tolvaptan can be increased when it is combined with Testosterone enanthate.Approved
Testosterone undecanoateThe serum concentration of Tolvaptan can be increased when it is combined with Testosterone undecanoate.Approved, Investigational
TetracyclineThe serum concentration of Tolvaptan can be increased when it is combined with Tetracycline.Approved, Vet Approved
ThiopentalThe serum concentration of Tolvaptan can be increased when it is combined with Thiopental.Approved, Vet Approved
TicagrelorThe serum concentration of Tolvaptan can be increased when it is combined with Ticagrelor.Approved
TiclopidineThe serum concentration of Tolvaptan can be increased when it is combined with Ticlopidine.Approved
TilidineThe risk or severity of adverse effects can be increased when Tilidine is combined with Tolvaptan.Experimental
TioconazoleThe serum concentration of Tolvaptan can be increased when it is combined with Tioconazole.Approved
TipranavirThe serum concentration of Tolvaptan can be increased when it is combined with Tipranavir.Approved, Investigational
TocilizumabThe serum concentration of Tolvaptan can be decreased when it is combined with Tocilizumab.Approved
TofisopamThe serum concentration of Tolvaptan can be increased when it is combined with Tofisopam.Approved
TopiroxostatThe serum concentration of Tolvaptan can be increased when it is combined with Topiroxostat.Approved, Investigational
TopotecanThe serum concentration of Topotecan can be increased when it is combined with Tolvaptan.Approved, Investigational
TramadolThe serum concentration of Tolvaptan can be increased when it is combined with Tramadol.Approved, Investigational
TrandolaprilTolvaptan may increase the hyperkalemic activities of Trandolapril.Approved
TranylcypromineThe serum concentration of Tolvaptan can be increased when it is combined with Tranylcypromine.Approved, Investigational
TriamtereneTolvaptan may increase the hyperkalemic activities of Triamterene.Approved
TroglitazoneThe serum concentration of Tolvaptan can be increased when it is combined with Troglitazone.Investigational, Withdrawn
TroleandomycinThe serum concentration of Tolvaptan can be increased when it is combined with Troleandomycin.Approved
Valproic AcidThe serum concentration of Tolvaptan can be increased when it is combined with Valproic Acid.Approved, Investigational
ValsartanTolvaptan may increase the hyperkalemic activities of Valsartan.Approved, Investigational
VemurafenibThe serum concentration of Tolvaptan can be increased when it is combined with Vemurafenib.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 increased when it is combined with Vinblastine.Approved
VincristineThe serum concentration of Tolvaptan can be increased when it is combined with Vincristine.Approved, Investigational
VincristineThe excretion of Vincristine can be decreased when combined with Tolvaptan.Approved, Investigational
VinorelbineThe serum concentration of Tolvaptan can be increased when it is combined with Vinorelbine.Approved, Investigational
VoriconazoleThe serum concentration of Tolvaptan can be increased when it is combined with Voriconazole.Approved, Investigational
ZafirlukastThe serum concentration of Tolvaptan can be increased when it is combined with Zafirlukast.Approved, Investigational
ZiprasidoneThe serum concentration of Tolvaptan can be increased when it is combined with Ziprasidone.Approved
ZofenoprilTolvaptan may increase the hyperkalemic activities of Zofenopril.Experimental
ZucapsaicinThe serum concentration of Tolvaptan can be increased when it is combined with Zucapsaicin.Approved, Investigational
Food Interactions
Not 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
KEGG Drug
D01213
PubChem Compound
443894
PubChem Substance
175427060
ChemSpider
391976
ChEMBL
CHEMBL344159
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Tolvaptan
ATC Codes
C03XA01 — Tolvaptan
AHFS Codes
  • 40:28.28 — Vasopressin Antagonists
FDA label
Download (468 KB)
MSDS
Download (103 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceNephrolithiasis, Calcium Oxalate / Nephrolithiasis, Calcium Phosphate1
1CompletedTreatmentAscites / Hepatic Cirrhosis1
1CompletedTreatmentHealthy Adult Males1
1CompletedTreatmentHealthy Volunteers1
1RecruitingTreatmentCongestive Heart Failure (CHF) / Prophylaxis of cardiomyopathy1
1, 2CompletedBasic ScienceSyndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)1
2CompletedTreatmentAscites / Hepatic Cirrhosis1
2CompletedTreatmentAutosomal Dominant Polycystic Kidney Disease (ADPKD)6
2CompletedTreatmentCarcinomatous Edema1
2CompletedTreatmentCardiovascular Disease (CVD) / Renal Dysfunction1
2CompletedTreatmentChronic Renal Failure (CRF)3
2CompletedTreatmentCongestive Heart Failure (CHF)3
2CompletedTreatmentCongestive Heart Failure (CHF) / Edema1
2CompletedTreatmentHypovolemic Hyponatremia1
2CompletedTreatmentLiver Cirrhosis1
2CompletedTreatmentRenal Dysfunction1
2TerminatedTreatmentHyponatremias1
2, 3Active Not RecruitingTreatmentLiver Cirrhosis / Refractory/Recurrent Ascites1
2, 3Unknown StatusTreatmentNon-hypovolemic Non-acute Hyponatremia1
3Active Not RecruitingTreatmentAutosomal Dominant Polycystic Kidney Disease (ADPKD)1
3CompletedNot AvailableHyponatremias / Liver Cirrhosis1
3CompletedTreatmentAscites / Hepatic Cirrhosis1
3CompletedTreatmentAutosomal Dominant Polycystic Kidney Disease (ADPKD)4
3CompletedTreatmentAutosomal Dominant Polycystic Kidney Disease (ADPKD) / Chronic Kidney Disease (CKD)1
3CompletedTreatmentCardiac-induced Edema1
3CompletedTreatmentCongestive Heart Failure (CHF)1
3CompletedTreatmentDyspnea / Heart Failure, Unspecified1
3CompletedTreatmentEdema, Cardiac3
3CompletedTreatmentHeart Failure, Unspecified1
3CompletedTreatmentHepatic Encephalopathy / Hyponatremias / Liver Cirrhosis1
3CompletedTreatmentHyponatremias2
3CompletedTreatmentHyponatremias / Inappropriate ADH Syndrome / Water Intoxication / Water-Electrolyte Imbalance1
3CompletedTreatmentHyponatremias / Inappropriate ADH Syndrome / Water Intoxication / Water-Electrolyte Imbalances1
3CompletedTreatmentLiver Cirrhosis3
3RecruitingTreatmentAutosomal Dominant Polycystic Kidney Disease (ADPKD)1
3RecruitingTreatmentSyndrome of Inappropriate Antidiuretic Hormone Secretion1
3TerminatedTreatmentDilutional Hyponatremia / Hyponatremias / Inappropriate ADH Syndrome1
3TerminatedTreatmentHyponatremias2
3Unknown StatusTreatmentAcute Heart Failure (AHF)1
3WithdrawnTreatmentHyponatremias1
4CompletedNot AvailableHealthy Volunteers1
4CompletedTreatmentAcute Decompensated Heart Failure (ADHF)1
4CompletedTreatmentAdvanced Cancers1
4CompletedTreatmentAscites / Liver Cirrhosis1
4CompletedTreatmentCardiovascular Disease (CVD) / Heart Diseases / Heart Failure, Unspecified1
4CompletedTreatmentHeart Failure, Unspecified1
4CompletedTreatmentRight Heart Failure / Tricuspid valve incompetence1
4Enrolling by InvitationTreatmentHeart Failure, Unspecified1
4RecruitingTreatmentCongestive Heart Failure (CHF)1
4RecruitingTreatmentDecompensated Heart Failure / Hyponatremias1
4RecruitingTreatmentHeart Failure, Unspecified1
4RecruitingTreatmentHeart Failure, Unspecified / Hyponatremias1
4TerminatedTreatmentHeart Failure With Hyponatremia1
4TerminatedTreatmentHyponatremias1
4Unknown StatusTreatmentAscites / Hyponatremias1
4Unknown StatusTreatmentHyponatremia and Extracellular Fluid in Cirrhotic1
4WithdrawnPreventionHeart Failure, Unspecified1
Not AvailableRecruitingNot AvailableAutosomal Dominant Polycystic Kidney Disease (ADPKD)1
Not AvailableRecruitingNot AvailableSafety1
Not AvailableRecruitingTreatmentAutosomal Dominant Polycystic Kidney Disease (ADPKD)1
Not AvailableRecruitingTreatmentCongestive Heart Failure (CHF)1
Not AvailableRecruitingTreatmentCystine renal calculi1
Not AvailableTerminatedNot AvailableBrain Injury / Hyponatremias1
Not AvailableUnknown StatusNot AvailableNon-Hyponatremia / Non-SIADH Hyponatremia / SIADH1
Not AvailableWithdrawnTreatmentHyponatremias / SIADH1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral
TabletOral15 mg
TabletOral15 mg/1
TabletOral30 mg/1
TabletOral30 mg
TabletOral60 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5258510No1993-11-022010-11-02Us
US5753677No2000-05-192020-05-19Us
US8501730No2006-09-012026-09-01Us

Properties

State
Solid
Experimental Properties
Not 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 FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

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 benzanilides. These are aromatic compounds containing an anilide group in which the carboxamide group is substituted with a benzene ring. They have the general structure RNC(=O)R', where R,R'= benzene.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Anilides
Direct Parent
Benzanilides
Alternative Parents
Benzazepines / o-Toluamides / Benzamides / Benzoyl derivatives / Azepines / Aryl chlorides / Tertiary carboxylic acid amides / Secondary carboxylic acid amides / Secondary alcohols / Azacyclic compounds
show 5 more
Substituents
Benzanilide / Benzazepine / Benzamide / O-toluamide / Toluamide / Benzoic acid or derivatives / Benzoyl / Azepine / Toluene / Aryl chloride
show 19 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not 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
Uniprot Name
Vasopressin V2 receptor
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 behavi...
Gene Name
AVPR1A
Uniprot ID
P37288
Uniprot Name
Vasopressin V1a receptor
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
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
Substrate
Inhibitor
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
Uniprot Name
Multidrug resistance protein 1
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]

Drug created on March 19, 2008 10:17 / Updated on February 13, 2018 09:48