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Identification
NameConivaptan
Accession NumberDB00872  (APRD01302)
Typesmall molecule
Groupsapproved, investigational
Description

Conivaptan is a non-peptide inhibitor of antidiuretic hormone (vasopressin). It was approved in 2004 for hyponatremia (low blood sodium levels) caused by syndrome of inappropriate antidiuretic hormone (SIADH). Conivaptan inhibits both isotypes of the vasopressin receptor (V1a and V2).

Structure
Thumb
Synonyms
SynonymLanguageCode
4'-((4,5-dihydro-2-Methylimidazo(4,5-D)(1)benzazepin-6(1H)-yl)carbonyl)-2-biphenylcarboxanilideNot AvailableNot Available
ConivaptanNot AvailableNot Available
Salts
Name/CAS Structure Properties
Conivaptan hydrochloride
Thumb
  • InChI Key: BTYHAFSDANBVMJ-UHFFFAOYSA-N
  • Monoisotopic Mass: 534.182253835
  • Average Mass: 535.035
DBSALT000793
Brand names
NameCompany
VaprisolNot Available
Brand mixturesNot Available
CategoriesNot Available
CAS number210101-16-9
WeightAverage: 498.5744
Monoisotopic: 498.205576096
Chemical FormulaC32H26N4O2
InChI KeyIKENVDNFQMCRTR-UHFFFAOYSA-N
InChI
InChI=1S/C32H26N4O2/c1-21-33-28-19-20-36(29-14-8-7-13-27(29)30(28)34-21)32(38)23-15-17-24(18-16-23)35-31(37)26-12-6-5-11-25(26)22-9-3-2-4-10-22/h2-18H,19-20H2,1H3,(H,33,34)(H,35,37)
IUPAC Name
N-[4-({4-methyl-3,5,9-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(10),2(6),3,11,13-pentaen-9-yl}carbonyl)phenyl]-2-phenylbenzamide
SMILES
CC1=NC2=C(CCN(C(=O)C3=CC=C(NC(=O)C4=CC=CC=C4C4=CC=CC=C4)C=C3)C3=CC=CC=C23)N1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassBenzamides
Direct parentN-phenylbenzamides
Alternative parentsBiphenyls and Derivatives; Benzazepines; Anilides; Benzoyl Derivatives; Azepines; Tertiary Carboxylic Acid Amides; Imidazoles; Tertiary Amines; Secondary Carboxylic Acid Amides; Polyamines; Carboxylic Acids; Enolates
Substituentsbiphenyl; benzazepine; acetanilide; benzoyl; azepine; tertiary carboxylic acid amide; azole; imidazole; tertiary amine; secondary carboxylic acid amide; carboxamide group; polyamine; carboxylic acid; carboxylic acid derivative; enolate; amine; organonitrogen compound
Classification descriptionThis compound belongs to the n-phenylbenzamides.
Pharmacology
IndicationFor the treatment of euvolemic or hypervolemic hyponatremia (e.g. the syndrome of inappropriate secretion of antidiuretic hormone, or in the setting of hypothyroidism, adrenal insufficiency, pulmonary disorders, etc.) in hospitalized patients.
PharmacodynamicsConivaptan is a nonpeptide, dual antagonist of arginine vasopressin (AVP) V1A and V2 receptors. The level of AVP in circulating blood is critical for the regulation of water and electrolyte balance and is usually elevated in both euvolemic and hypervolemic hyponatremia. The AVP effect is mediated through V2 receptors, which are functionally coupled to aquaporin channels in the apical membrane of the collecting ducts of the kidney. These receptors help to maintain plasma osmolality within the normal range by increasing permeability of the renal collecting ducts to water. Vasopressin also causes vasoconstriction through its actions on vascular 1A receptors. The predominant pharmacodynamic effect of conivaptan in the treatment of hyponatremia is through its V2 antagonism of AVP in the renal collecting ducts, an effect that results in aquaresis, or excretion of free water. Conivaptan's antagonist activity on V1A receptors may also cause splanchnic vasodilation, resulting in possible hypotension or variceal bleeding in patients with cirrhosis. The pharmacodynamic effects of conivaptan include increased free water excretion (i.e., effective water clearance [EWC]) generally accompanied by increased net fluid loss, increased urine output, and decreased urine osmolality.
Mechanism of actionConivaptan is a dual AVP antagonist with nanomolar affinity for human arginine vasopressin V1A and V2 receptors in vitro. This antagonism occurs in the renal collecting ducts, resulting in aquaresis, or excretion of free water.
AbsorptionNot Available
Volume of distributionNot Available
Protein binding99%
Metabolism

CYP3A4 is the sole cytochrome P450 isozyme responsible for the metabolism of conivaptan. Four metabolites have been identified. The pharmacological activity of the metabolites at V1a and V2 receptors ranged from approximately 3-50% and 50-100% that of conivaptan, respectively.

Route of eliminationNot Available
Half life5 hours
ClearanceNot Available
ToxicityAlthough no data on overdosage in humans are available, conivaptan has been administered as a 20 mg loading dose on Day 1 followed by continuous infusion of 80 mg/day for 4 days in hyponatremia patients and up to 120 mg/day for 2 days in CHF patients. No new toxicities were identified at these higher doses, but adverse events related to the pharmacologic activity of conivaptan, e.g. hypotension and thirst, occurred more frequently at these higher doses.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.9522
Caco-2 permeable + 0.5291
P-glycoprotein substrate Substrate 0.5919
P-glycoprotein inhibitor I Inhibitor 0.6901
P-glycoprotein inhibitor II Inhibitor 0.8429
Renal organic cation transporter Non-inhibitor 0.6631
CYP450 2C9 substrate Non-substrate 0.7671
CYP450 2D6 substrate Non-substrate 0.7534
CYP450 3A4 substrate Substrate 0.6602
CYP450 1A2 substrate Inhibitor 0.7008
CYP450 2C9 substrate Inhibitor 0.5368
CYP450 2D6 substrate Non-inhibitor 0.6597
CYP450 2C19 substrate Inhibitor 0.8477
CYP450 3A4 substrate Inhibitor 0.9027
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.9043
Ames test Non AMES toxic 0.6672
Carcinogenicity Non-carcinogens 0.8831
Biodegradation Not ready biodegradable 0.9584
Rat acute toxicity 2.5446 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9885
hERG inhibition (predictor II) Inhibitor 0.8456
Pharmacoeconomics
Manufacturers
  • Astellas pharma us inc
Packagers
Dosage formsNot Available
Prices
Unit descriptionCostUnit
Vaprisol 20 mg/100 ml bag6.3USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States57236061999-12-152019-12-15
Properties
Statesolid
Experimental Properties
PropertyValueSource
water solubilityVery slightly soluble (0.15 mg/mL at 23 °C)Not Available
logP6.3Not Available
Predicted Properties
PropertyValueSource
water solubility1.75e-03 g/lALOGPS
logP5.23ALOGPS
logP5.44ChemAxon
logS-5.5ALOGPS
pKa (strongest acidic)11.14ChemAxon
pKa (strongest basic)6.23ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count3ChemAxon
hydrogen donor count2ChemAxon
polar surface area78.09ChemAxon
rotatable bond count4ChemAxon
refractivity150.83ChemAxon
polarizability55.51ChemAxon
number of rings6ChemAxon
bioavailability1ChemAxon
rule of fiveNoChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Ali F, Raufi MA, Washington B, Ghali JK: Conivaptan: a dual vasopressin receptor v1a/v2 antagonist [corrected]. Cardiovasc Drug Rev. 2007 Fall;25(3):261-79. Pubmed
  2. Mao ZL, Stalker D, Keirns J: Pharmacokinetics of conivaptan hydrochloride, a vasopressin V(1A)/V(2)-receptor antagonist, in patients with euvolemic or hypervolemic hyponatremia and with or without congestive heart failure from a prospective, 4-day open-label study. Clin Ther. 2009 Jul;31(7):1542-50. Pubmed
  3. Ghali JK, Farah JO, Daifallah S, Zabalawi HA, Zmily HD: Conivaptan and its role in the treatment of hyponatremia. Drug Des Devel Ther. 2009 Dec 29;3:253-68. Pubmed
External Links
ResourceLink
KEGG DrugD01236
PubChem Compound151171
PubChem Substance46504533
ChemSpider133239
ChEBI681850
ChEMBLCHEMBL1755
Therapeutic Targets DatabaseDNC001525
PharmGKBPA164742939
IUPHAR2203
Guide to Pharmacology2203
Drugs.comhttp://www.drugs.com/cdi/conivaptan.html
WikipediaConivaptan
ATC CodesC03XA02
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelshow(145 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AlfuzosinCYP3A4 Inhibitors (Strong) may increase the serum concentration of Alfuzosin. Concomitant use of alfuzosin with a strong CYP3A4 inhibitor is a listed contraindication according to alfuzosin prescribing information.
AlmotriptanCYP3A4 Inhibitors (Strong) may increase the serum concentration of Almotriptan. Use an initial almotriptan dose of 6.25mg when using almotriptan with a strong CYP3A4 inhibitor, and do not exceed 12.5mg of almotriptan in any 24-hour period. Avoid concurrent use of almotriptan with a strong CYP3A4 inhibitor in patients with impaired hepatic or renal function.
ArtemetherConivaptan, a strong CYP3A inhibitor, may increase the toxicity of artemether by inhibiting its metabolism. Consider alternate therapy or allow at least 7 days to elapse between conivaptan and artemether therapy.
BexaroteneConivaptan may increase the serum concentration of CYP3A4 substrates such as bexarotene. Upon completion/discontinuation of conivaptan, allow at least 7 days before initiating therapy with drugs that are CYP3A4 substrates. Consider therapy modification.
BezafibrateConivaptan may increase the serum concentration of CYP3A4 substrates like bezafibrates. Consider therapy modification. Conivaptan may increase the serum concentration of CYP3A4 substrates.
BoceprevirBoceprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
BromazepamConivaptan, a strong CYP3A4 inhibitor, may increase the serum concentration of bromazepam by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of bromazepam if conivaptan is initiated, discontinued or dose changed. Dosage adjustments may be required.
BudesonideCYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Systemic, Oral Inhalation). onsider reducing the oral budesonide dose when used together with a strong CYP3A4 inhibitor. This interaction is likely less severe with orally inhaled budesonide. Any patient receiving both budesonide and a strong CYP3A4 inhibitor should be monitored closely for signs/symptoms of corticosteroid excess.
BupivacaineConivaptan may increase the serum concentration of CYP3A4 Substrates such as bupivacaine. Upon completion/discontinuation of conivaptan, allow at least 7 days before initiating therapy with drugs that are CYP3A4 substrates.
BuprenorphineConivaptan may increase the serum concentration of CYP3A4 Substrates like buprenorphine. Upon completion/discontinuation of conivaptan, allow at least 7 days before initiating therapy with drugs that are CYP3A4 substrates.
CaffeineConivaptan may increase the serum concentration of CYP3A4 substrates such as caffeine. Upon completion/discontinuation of conivaptan, allow at least 7 days before initiating therapy with drugs that are CYP3A4 substrates.
CevimelineConivaptan may increase the serum concentration of CYP3A4 substrates such as cevimeline. Upon completion/discontinuation of conivaptan, allow at least 7 days before initiating therapy with drugs that are CYP3A4 substrates.
ColchicineCYP3A4 Inhibitors (Strong) may increase the serum concentration of Colchicine. In patients with normal renal and hepatic function, reduce colchicine dose (for gout flares: to 0.6 mg x 1 dose, followed by 0.3 mg 1 hour later, with next dose no sooner than 3 days later; for gout flare prophylaxis: if target dose would otherwise be 0.6 mg daily, change to 0.3 mg every other day, and if target dose would otherwise be 0.6 mg twice daily, change to 0.3 mg daily; for Familial Mediterranean Fever: to no more than 0.6 mg/day) when using in combination with a strong CYP3A4 inhibitor such as clarithromycin or ritonavir. Increase monitoring for colchicine-related toxicity when using such combinations. Colchicine use is contraindicated in patients with impaired renal and/or hepatic function who are also receiving a strong CYP3A4 inhibitor.
DantroleneConivaptan may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if conivaptan is initiated, discontinued or dose changed.
DronedaroneCYP3A4 Inhibitors (Strong) may increase the serum concentration of Dronedarone. Concurrent use of strong CYP3A4 inhibitors with dronedarone is contraindicated according to dronedarone prescribing information.
EplerenoneCYP3A4 Inhibitors (Strong) may increase the serum concentration of Eplerenone. The combination of eplerenone with any strong CYP3A4 inhibitor is contraindicated.
EverolimusCYP3A4 Inhibitors (Strong) may increase the serum concentration of Everolimus. Everolimus prescribing information recommends avoiding concurrent use with strong CYP3A4 inhbitors.
FentanylCYP3A4 Inhibitors (Strong) may increase the serum concentration of Fentanyl. Concurrent use of fentanyl with any CYP3A4 inhibitor may result in increased fentanyl concentrations and could increase or prolong adverse effects, including potentially fatal respiratory depression. Patients receiving fentanyl and any CYP3A4 inhibitor should be closely monitored for several days following initiation of the combination, and fentanyl dosage reductions should be made as appropriate.
FesoterodineCYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Fesoterodine. Avoid fesoterodine doses greater than 4mg daily in patients who are also receiving strong CYP3A4 inhibitors.
FluconazoleAntifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Conivaptan. Concomitant use of conivaptan with strong CYP3A4 inhibitors (e.g., azole antifungals) is contraindicated.
Fluticasone PropionateCYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Oral Inhalation). Concurrent use of orally inhaled fluticasone with strong CYP3A4 inhibitors is not recommended.
HalofantrineCYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Oral Inhalation). Concurrent use of orally inhaled fluticasone with strong CYP3A4 inhibitors is not recommended.
IloperidoneCYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolites P88 and P95 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Iloperidone. Reduce iloperidone dose by half when administered with a strong CYP3A4 inhibitor.
ItraconazoleAntifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Conivaptan. Concomitant use of conivaptan with strong CYP3A4 inhibitors (e.g., azole antifungals) is contraindicated.
IxabepiloneCYP3A4 Inhibitors (Strong) may increase the serum concentration of Ixabepilone. The dose of ixabepilone must be reduced when used with strong inhibitors of CYP3A.1 In one published abstract, ixabepilone 20mg/m2 was the maximum tolerated dose in patients who were also receiving the CYP3A-inhibitor ketoconazole (400mg).
KetoconazoleAntifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Conivaptan. Concomitant use of conivaptan with strong CYP3A4 inhibitors (e.g., azole antifungals) is contraindicated.
LurasidoneCYP3A4 Inhibitors (Strong) may increase the serum concentration of Lurasidone. Avoid use of lurasidone in patients receiving strong CYP3A4 inhibitors.
MaravirocCYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc. When used with a strong CYP3A4 inhibitor, the adult dose of maraviroc should be decreased to 150 mg twice daily. Maraviroc is contraindicated in patients with severe renal impairment (creatinine clearance less than 30 mL/min) receiving a strong CYP3A4 inhibitor. Maraviroc may be administered at a dose of 300 mg twice daily with concomitant tipranavir/ritonavir but not with other ritonavir combinations.
MethylprednisoloneCYP3A4 Inhibitors (Strong) may increase the serum concentration of Methylprednisolone. Consider methylprednisolone dose titration and/or adjustments in patients receiving strong CYP3A4 inhibitors (eg, azole antifungals, protease inhibitors) and monitor for increased steroid related adverse effects.
NilotinibCYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib. Nilotinib prescribing information recommends avoiding concurrent use of nilotinib with strong inhibitors of CYP3A4.
NisoldipineCYP3A4 Inhibitors (Strong) may increase the serum concentration of Nisoldipine. Avoid concurrent use of nisoldipine with strong inhibitors of CYP3A4, as the combination may lead to substantial increases in nisoldipine concentrations.
PaclitaxelAvoid combination because it will likely increase the serum concentration of CYP3A4 substrates.
PazopanibCYP3A4 Inhibitors (Strong) may increase the serum concentration of Pazopanib. Avoid concurrent use of pazopanib with strong inhibitors of CYP3A4 whenever possible. If it is not possible to avoid such a combination, reduce pazopanib dose to 400 mg. Further dose reductions may also be required.
PonatinibStrong CYP3A4 inhibitors may increase levels of ponatinib. Monitor concomitant therapy closely.
PosaconazoleAntifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Conivaptan. Concomitant use of conivaptan with strong CYP3A4 inhibitors (e.g., azole antifungals) is contraindicated.
RanolazineCYP3A4 Inhibitors (Strong) may increase the serum concentration of Ranolazine. The manufacturer contraindicates the use of ranolazine and strong CYP3A4 inhibitors (such as the azole antifungals).1 Monitor for increased effects/toxicity of ranolazine during concomitant use.
RivaroxabanCYP3A4 Inhibitors (Strong) may increase the serum concentration of Rivaroxaban. Consider avoiding use of rivaroxaban with any strong CYP3A4 inhibitors as many such agents are inhibitors of both CYP3A4 and P-glycoprotein. Use of rivaroxaban concomitantly with drugs that are strong inhibitors of both CYP3A4 and P-glycoprotein is specifically contraindicated.
RomidepsinCYP3A4 Inhibitors (Strong) may increase the serum concentration of Romidepsin. Avoid concurrent use of strong CYP3A4 inhibitors with romidepsin when possible.
SalmeterolCYP3A4 Inhibitors (Strong) may increase the serum concentration of Salmeterol. Concurrent use of salmeterol with strong inhibitors of CYP3A4 is not recommended according to salmeterol prescribing information.
SaxagliptinCYP3A4 Inhibitors (Strong) may increase the serum concentration of Saxagliptin. Limit saxagliptin dose to 2.5 mg/day and monitor for increased saxagliptin levels/effects (e.g., hypoglycemia) with concomitant administration of a strong CYP3A4 inhibitor (e.g., ketoconazole). Monitor for decreased saxagliptin levels/effects with discontinuation of concomitant CYP3A4 inhibitor.
SildenafilCYP3A4 Inhibitors (Strong) such as conivaptan may increase the serum concentration of Sildenafil. When sildenanfil is used for treatment of pulmonary arterial hypertension, concurrent use with strong CYP3A4 inhibitors is not recommended. When sildenafil is used for treatment of erectile dysfunction, consider using a lower starting dose of 25 mg in patients who are also taking a strong CYP3A4 inhibitor. Due to the particularly strong effects of ritonavir, sildenafil (for erectile dysfunction) doses greater than 25 mg per 48 hours are not recommended. Of note, the interaction between CYP3A4 inhibitors and sildenafil is predicted to be greater with orally administered than with injected sildenafil.
SilodosinCYP3A4 Inhibitors (Strong) such as conivaptan may increase the serum concentration of Silodosin. Use of silodosin concomitantly with a strong CYP3A4 inhibitor is contraindicated.
TacrolimusThe strong CYP3A4 inhibitor, Conivaptan, may decrease the metabolism and clearance of Tacrolimus, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Tacrolimus if Conivaptan is initiated, discontinued or dose changed.
TadalafilConivaptan may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
TamoxifenConivaptan may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen.
TamsulosinConivaptan, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Conivaptan is initiated, discontinued, or dose changed.
TelaprevirTelaprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
TelithromycinCo-administration may result in altered plasma concentrations of Conivaptan and/or Telithromycin. Consider alternate therapy or monitor the therapeutic/adverse effects of both agents.
TemsirolimusConivaptan may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
TeniposideThe strong CYP3A4 inhibitor, Conivaptan, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Conivaptan is initiated, discontinued or dose changed.
TiagabineThe strong CYP3A4 inhibitor, Conivaptan, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Conivaptan is initiated, discontinued or dose changed.
TicagrelorCYP3A4 Inhibitors (Strong) such as conivaptan may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ticagrelor. Avoid use of ticagrelor in combination with strong CYP3A4 inhibitors.
TolterodineConivaptan may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
TolvaptanCYP3A4 Inhibitors (Strong) such as conivaptan may increase the serum concentration of Tolvaptan. Coadministration of a strong CYP3A4 inhibitor with tolvaptan is contraindicated.
ToremifeneCYP3A4 Inhibitors (Strong) such as conivaptan may enhance the adverse/toxic effect of Toremifene. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Toremifene. Concurrent use of toremifene with strong CYP3A4 inhibitors should be avoided.
TramadolConivaptan may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
TrazodoneThe CYP3A4 inhibitor, Conivaptan, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Consider alternate therapy or monitor for changes in Trazodone efficacy/toxicity if Conivaptan is initiated, discontinued or dose changed.
VardenafilConivaptan, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.
VenlafaxineConivaptan, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Conivaptan is initiated, discontinued, or dose changed.
VerapamilConivaptan, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Conivaptan is initiated, discontinued or dose changed.
VilazodoneCYP3A4 Inhibitors (Strong) such as conivaptan may increase the serum concentration of Vilazodone. Limit maximum adult vilazodone dose to 20 mg/day in patients receiving strong CYP3A4 inhibitors.
VinblastineConivaptan, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Conivaptan is initiated, discontinued or dose changed.
VincristineConivaptan, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Conivaptan is initiated, discontinued or dose changed.
VinorelbineConivaptan, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Conivaptan is initiated, discontinued or dose changed.
VoriconazoleVoriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of conivaptan by inhibiting its metabolism. Concomitant therapy is contraindicated.
ZolpidemConivaptan, a strong CYP3A4 inhibitor, may increase the serum concentration of zolpidem by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zolpidem if conivaptan is initiated, discontinued or dose changed.
ZonisamideConivaptan, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if conivaptan is initiated, discontinued or dose changed.
ZopicloneConivaptan, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if conivaptan is initiated, discontinued or dose changed.
Food InteractionsNot Available

Targets

1. Vasopressin V1a receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Vasopressin V1a receptor P37288 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Ali F, Raufi MA, Washington B, Ghali JK: Conivaptan: a dual vasopressin receptor v1a/v2 antagonist [corrected]. Cardiovasc Drug Rev. 2007 Fall;25(3):261-79. Pubmed
  3. Wada K, Matsukawa U, Fujimori A, Arai Y, Sudoh K, Sasamata M, Miyata K: A novel vasopressin dual V1A/V2 receptor antagonist, conivaptan hydrochloride, improves hyponatremia in rats with syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Biol Pharm Bull. 2007 Jan;30(1):91-5. Pubmed
  4. Walter KA: Conivaptan: new treatment for hyponatremia. Am J Health Syst Pharm. 2007 Jul 1;64(13):1385-95. Pubmed
  5. Mao ZL, Stalker D, Keirns J: Pharmacokinetics of conivaptan hydrochloride, a vasopressin V(1A)/V(2)-receptor antagonist, in patients with euvolemic or hypervolemic hyponatremia and with or without congestive heart failure from a prospective, 4-day open-label study. Clin Ther. 2009 Jul;31(7):1542-50. Pubmed
  6. Ghali JK, Koren MJ, Taylor JR, Brooks-Asplund E, Fan K, Long WA, Smith N: Efficacy and safety of oral conivaptan: a V1A/V2 vasopressin receptor antagonist, assessed in a randomized, placebo-controlled trial in patients with euvolemic or hypervolemic hyponatremia. J Clin Endocrinol Metab. 2006 Jun;91(6):2145-52. Epub 2006 Mar 7. Pubmed
  7. Annane D, Decaux G, Smith N: Efficacy and safety of oral conivaptan, a vasopressin-receptor antagonist, evaluated in a randomized, controlled trial in patients with euvolemic or hypervolemic hyponatremia. Am J Med Sci. 2009 Jan;337(1):28-36. Pubmed
  8. Ghali JK, Farah JO, Daifallah S, Zabalawi HA, Zmily HD: Conivaptan and its role in the treatment of hyponatremia. Drug Des Devel Ther. 2009 Dec 29;3:253-68. Pubmed
  9. Ali F, Guglin M, Vaitkevicius P, Ghali JK: Therapeutic potential of vasopressin receptor antagonists. Drugs. 2007;67(6):847-58. Pubmed
  10. Hoque MZ, Arumugham P, Huda N, Verma N, Afiniwala M, Karia DH: Conivaptan: promise of treatment in heart failure. Expert Opin Pharmacother. 2009 Sep;10(13):2161-9. Pubmed

2. Vasopressin V2 receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Vasopressin V2 receptor P30518 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Wada K, Fujimori A, Matsukawa U, Arai Y, Sudoh K, Yatsu T, Sasamata M, Miyata K: Intravenous administration of conivaptan hydrochloride improves cardiac hemodynamics in rats with myocardial infarction-induced congestive heart failure. Eur J Pharmacol. 2005 Jan 10;507(1-3):145-51. Epub 2005 Jan 1. Pubmed
  3. Palm C, Pistrosch F, Herbrig K, Gross P: Vasopressin antagonists as aquaretic agents for the treatment of hyponatremia. Am J Med. 2006 Jul;119(7 Suppl 1):S87-92. Pubmed
  4. Ali F, Raufi MA, Washington B, Ghali JK: Conivaptan: a dual vasopressin receptor v1a/v2 antagonist [corrected]. Cardiovasc Drug Rev. 2007 Fall;25(3):261-79. Pubmed
  5. Wada K, Matsukawa U, Fujimori A, Arai Y, Sudoh K, Sasamata M, Miyata K: A novel vasopressin dual V1A/V2 receptor antagonist, conivaptan hydrochloride, improves hyponatremia in rats with syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Biol Pharm Bull. 2007 Jan;30(1):91-5. Pubmed
  6. Walter KA: Conivaptan: new treatment for hyponatremia. Am J Health Syst Pharm. 2007 Jul 1;64(13):1385-95. Pubmed
  7. Mao ZL, Stalker D, Keirns J: Pharmacokinetics of conivaptan hydrochloride, a vasopressin V(1A)/V(2)-receptor antagonist, in patients with euvolemic or hypervolemic hyponatremia and with or without congestive heart failure from a prospective, 4-day open-label study. Clin Ther. 2009 Jul;31(7):1542-50. Pubmed
  8. Ghali JK, Koren MJ, Taylor JR, Brooks-Asplund E, Fan K, Long WA, Smith N: Efficacy and safety of oral conivaptan: a V1A/V2 vasopressin receptor antagonist, assessed in a randomized, placebo-controlled trial in patients with euvolemic or hypervolemic hyponatremia. J Clin Endocrinol Metab. 2006 Jun;91(6):2145-52. Epub 2006 Mar 7. Pubmed
  9. Annane D, Decaux G, Smith N: Efficacy and safety of oral conivaptan, a vasopressin-receptor antagonist, evaluated in a randomized, controlled trial in patients with euvolemic or hypervolemic hyponatremia. Am J Med Sci. 2009 Jan;337(1):28-36. Pubmed
  10. Ghali JK, Farah JO, Daifallah S, Zabalawi HA, Zmily HD: Conivaptan and its role in the treatment of hyponatremia. Drug Des Devel Ther. 2009 Dec 29;3:253-68. Pubmed
  11. Ali F, Guglin M, Vaitkevicius P, Ghali JK: Therapeutic potential of vasopressin receptor antagonists. Drugs. 2007;67(6):847-58. Pubmed
  12. Hoque MZ, Arumugham P, Huda N, Verma N, Afiniwala M, Karia DH: Conivaptan: promise of treatment in heart failure. Expert Opin Pharmacother. 2009 Sep;10(13):2161-9. Pubmed

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Ali F, Raufi MA, Washington B, Ghali JK: Conivaptan: a dual vasopressin receptor v1a/v2 antagonist [corrected]. Cardiovasc Drug Rev. 2007 Fall;25(3):261-79. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12