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Identification
NameVenlafaxine
Accession NumberDB00285  (APRD00125)
Typesmall molecule
Groupsapproved
Description

Venlafaxine (Effexor) is an antidepressant of the serotonin-norepinephrine reuptake inhibitor (SNRI) class first introduced by Wyeth in 1993. It is prescribed for the treatment of clinical depression and anxiety disorders. Due to the pronounced side effects and suspicions that venlafaxine may significantly increase the risk of suicide it is not recommended as a first line treatment of depression. However, it is often effective for depression not responding to SSRIs. Venlafaxine was the sixth most widely-used antidepressant based on the amount of retail prescriptions in the US (17.1 million) in 2006. [Wikipedia]

Structure
Thumb
SynonymsNot Available
Salts
Name/CAS Structure Properties
Venlafaxine Hydrochloride
Thumb
  • InChI Key: QYRYFNHXARDNFZ-UHFFFAOYNA-N
  • Monoisotopic Mass: 313.180856852
  • Average Mass: 313.863
DBSALT000186
Brand names
NameCompany
EffexorNot Available
Effexor XRNot Available
ElafaxNot Available
Brand mixturesNot Available
Categories
CAS number93413-69-5
WeightAverage: 277.4018
Monoisotopic: 277.204179113
Chemical FormulaC17H27NO2
InChI KeyPNVNVHUZROJLTJ-UHFFFAOYSA-N
InChI
InChI=1S/C17H27NO2/c1-18(2)13-16(17(19)11-5-4-6-12-17)14-7-9-15(20-3)10-8-14/h7-10,16,19H,4-6,11-13H2,1-3H3
IUPAC Name
1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl]cyclohexan-1-ol
SMILES
COC1=CC=C(C=C1)C(CN(C)C)C1(O)CCCCC1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassPhenols and Derivatives
Direct parentTyrosols and Derivatives
Alternative parentsPhenylpropylamines; Anisoles; Alkyl Aryl Ethers; Cyclohexanols; Tertiary Alcohols; Tertiary Amines; Cyclic Alcohols and Derivatives; Polyamines
Substituentsphenylpropylamine; phenol ether; anisole; cyclohexanol; alkyl aryl ether; tertiary alcohol; cyclic alcohol; tertiary amine; polyamine; ether; alcohol; organonitrogen compound; amine
Classification descriptionThis compound belongs to the tyrosols and derivatives. These are compounds containing an hydroxyethyl group atached to the C4 carbon of a phenol group.
Pharmacology
IndicationFor the management of major depressive disorder (MDD), generalized anxiety disorder (GAD), social anxiety disorder (social phobia), panic disorder with or without agoraphobia, vasomotor symptoms in women with breast cancer and in postmenopausal women, and neuropathic pain.
PharmacodynamicsVenlafaxine potentiates the neurotransmitter activity in the central nervous system. Furthermore, venlafaxine and its metabolite, O-desmethylvenlafaxine (ODV) potently inhibit the reuptake of serotonin and norepinephrine and weakly inhibit dopamine reuptake. Both molecules do not bind to muscarinic, histaminergic, or alpha-1 adrenergic receptors. Pharmacologic activity at these receptors is hypothesized to be associated with the various anticholinergic, sedative, and cardiovascular effects seen with other psychotropic drugs. Both also do not have any monoamine oxidase (MAO) inhibitory activity.
Mechanism of actionThe exact mechanism of action of venlafaxine is unknown, but appears to be associated with the its potentiation of neurotrasmitter activity in the CNS. Venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), inhibit the reuptake of both serotonin and norepinephrine with a potency greater for the 5-HT than for the NE reuptake process. Both venlafaxine and the ODV metabolite have weak inhibitory effects on the reuptake of dopamine but, unlike the tricyclics and similar to SSRIs, they are not active at histaminergic, muscarinic, or alpha(1)-adrenergic receptors.
AbsorptionVenlafaxine is well absorbed. Food does not effect the absorption of venlafaxine or its subsequent metabolism into ODV. Bioavailability is 45% following oral administration. Time to steady state = 3 days.
Volume of distribution
  • 7.5 ± 3.7 L/kg [venlafaxine]
  • 5.7 ± 1.8 L/kg [O-desmethylvenlafaxine(active metabolite)]
Protein bindingThe degree of binding of venlafaxine to human plasma is 27% ± 2% at concentrations ranging from 2.5 to 2215 ng/mL. The degree of ODV binding to human plasma is 30% ± 12% at concentrations ranging from 100 to 500 ng/mL. Protein-binding-induced drug interactions with venlafaxine are not expected.
Metabolism

Undergoes extensive first pass metabolism in the liver to its major, active metabolite, ODV, and two minor, less active metabolites, N-desmethylvenlafaxine and N,O-didesmethylvenlafaxine. Formation of ODV is catalyzed by cytochrome P450 (CYP) 2D6, whereas N-demethylation is catalyzed by CYP3A4, 2C19 and 2C9. ODV possesses antidepressant activity that is comparable to that of venlfaxine.

SubstrateEnzymesProduct
Venlafaxine
O-DesmethylvenlafaxineDetails
Venlafaxine
N-DesmethylvenlafaxineDetails
O-Desmethylvenlafaxine
N,O-DidesmethylvenlafaxineDetails
N,O-Didesmethylvenlafaxine
Not Available
N,O-didesmethylvenlafaxine glucuronideDetails
N,O-Didesmethylvenlafaxine
Not Available
N,N,O-TridesmethylvenlafaxineDetails
O-Desmethylvenlafaxine
Not Available
O-Desmethylvenlafaxine glucuronideDetails
N-Desmethylvenlafaxine
N,O-DidesmethylvenlafaxineDetails
Route of eliminationRenal elimination of venlafaxine and its metabolites is the primary route of excretion. Approximately 87% of a venlafaxine dose is recovered in the urine within 48 hours as either unchanged venlafaxine (5%), unconjugated ODV (29%), conjugated ODV (26%), or other minor inactive metabolites (27%).
Half life5 hours
Clearance

Steady state plasma clearance, venlafaxine = 1.3 ± 0.6 L/h/kg;
Steady state plasma clearance, ODV = 0.4 ± 0.2 L/h/kg.

ToxicityMost patients overdosing with venlafaxine develop only mild symptoms. However, severe toxicity is reported with the most common symptoms being CNS depression, serotonin toxicity, seizure, or cardiac conduction abnormalities. Venlafaxine's toxicity appears to be higher than other SSRIs, with a fatal toxic dose closer to that of the tricyclic antidepressants than the SSRIs. Doses of 900 mg or more are likely to cause moderate toxicity. Deaths have been reported following large doses.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated Effects
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeEffectReference(s)
Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
Not AvailableCYP2D6*4A AllelePoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrhea16958828
Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
rs5030655 CYP2D6*6T deletionPoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrhea16958828
Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
rs5030655 CYP2D6*6T deletion, homozygotePoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrhea16958828
Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
Not AvailableCYP2D6*5DeletionPoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrhea16958828
Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
rs3892097 CYP2D6*4A AllelePoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrhea16958828
Multidrug resistance protein 1
Gene symbol: ABCB1
UniProt: P08183
rs2032583 Not AvailableC AlleleImproved response to antidepressant medication17913323
Multidrug resistance protein 1
Gene symbol: ABCB1
UniProt: P08183
rs2032583 Not AvailableA > GIncrease risk of adverse effects22641028
SNP Mediated Adverse Drug Reactions
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeAdverse ReactionReference(s)
Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
rs5030655 CYP2D6*4del T alleleNausea, vomiting diarrhea16958828
Cytochrome P450 2D6
Gene symbol: CYP2D6
UniProt: P10635
rs3892097 CYP2D6*6A alleleNausea, vomiting diarrhea16958828
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9782
Blood Brain Barrier + 0.9382
Caco-2 permeable + 0.852
P-glycoprotein substrate Substrate 0.6534
P-glycoprotein inhibitor I Inhibitor 0.7031
P-glycoprotein inhibitor II Inhibitor 0.8031
Renal organic cation transporter Non-inhibitor 0.5792
CYP450 2C9 substrate Non-substrate 0.7583
CYP450 2D6 substrate Substrate 0.8919
CYP450 3A4 substrate Substrate 0.7407
CYP450 1A2 substrate Non-inhibitor 0.7664
CYP450 2C9 substrate Non-inhibitor 0.6876
CYP450 2D6 substrate Inhibitor 0.7287
CYP450 2C19 substrate Non-inhibitor 0.7199
CYP450 3A4 substrate Non-inhibitor 0.8308
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8666
Ames test Non AMES toxic 0.8
Carcinogenicity Non-carcinogens 0.6762
Biodegradation Not ready biodegradable 0.9941
Rat acute toxicity 2.5404 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.5486
hERG inhibition (predictor II) Inhibitor 0.6627
Pharmacoeconomics
Manufacturers
  • Wyeth pharmaceuticals inc
  • Teva pharmaceuticals usa inc
  • Osmotica pharmaceutical corp
  • Actavis totowa llc
  • Amneal pharmaceuticals
  • Aurobindo pharma ltd
  • Caraco pharmaceutical laboratories ltd
  • Dr reddys laboratories ltd
  • Mylan pharmaceuticals inc
  • Pliva hrvatska doo
  • Sandoz inc
  • Vintage pharmaceuticals llc
  • Zydus pharmaceuticals usa inc
  • Wyeth
Packagers
Dosage forms
FormRouteStrength
Capsule, extended releaseOral150 mg
Capsule, extended releaseOral37.5 mg
Capsule, extended releaseOral75 mg
TabletOral100 mg
TabletOral25 mg
TabletOral37.5 mg
TabletOral50 mg
TabletOral75 mg
Prices
Unit descriptionCostUnit
Venlafaxine HCl 30 225 mg 24 Hour tablet Bottle276.98USDbottle
Effexor XR 30 37.5 mg 24 Hour Capsule Bottle144.33USDbottle
Venlafaxine HCl 30 37.5 mg 24 Hour tablet Bottle114.46USDbottle
Effexor 30 75 mg tablet Bottle87.83USDbottle
Effexor 30 25 mg tablet Bottle74.82USDbottle
Effexor XR 150 mg 24 Hour Capsule5.87USDcapsule
Effexor xr 150 mg capsule5.65USDcapsule
Effexor XR 75 mg 24 Hour Capsule5.39USDcapsule
Effexor xr 75 mg capsule4.76USDcapsule
Venlafaxine HCl 150 mg 24 Hour tablet4.72USDtablet
Effexor xr 37.5 mg capsule4.63USDcapsule
Venlafaxine HCl 75 mg 24 Hour tablet4.42USDtablet
Effexor 100 mg tablet2.92USDtablet
Effexor 75 mg tablet2.7USDtablet
Effexor 50 mg tablet2.6USDtablet
Effexor 37.5 mg tablet2.5USDtablet
Effexor 25 mg tablet2.4USDtablet
Venlafaxine hcl 100 mg tablet2.36USDtablet
Venlafaxine hcl 75 mg tablet2.23USDtablet
Effexor Xr 150 mg Extended-Release Capsule2.16USDcapsule
Venlafaxine hcl 50 mg tablet2.1USDtablet
Effexor Xr 75 mg Extended-Release Capsule2.05USDcapsule
Venlafaxine hcl 37.5 mg tablet2.04USDtablet
Venlafaxine hcl 25 mg tablet1.98USDtablet
Apo-Venlafaxine Xr 150 mg Extended-Release Capsule1.2USDcapsule
Co Venlafaxine Xr 150 mg Extended-Release Capsule1.2USDcapsule
Mylan-Venlafaxine Xr 150 mg Extended-Release Capsule1.2USDcapsule
Novo-Venlafaxine Xr 150 mg Extended-Release Capsule1.2USDcapsule
Pms-Venlafaxine Xr 150 mg Extended-Release Capsule1.2USDcapsule
Ratio-Venlafaxine Xr 150 mg Extended-Release Capsule1.2USDcapsule
Sandoz Venlafaxine Xr 150 mg Extended-Release Capsule1.2USDcapsule
Apo-Venlafaxine Xr 75 mg Extended-Release Capsule1.14USDcapsule
Co Venlafaxine Xr 75 mg Extended-Release Capsule1.14USDcapsule
Mylan-Venlafaxine Xr 75 mg Extended-Release Capsule1.14USDcapsule
Novo-Venlafaxine Xr 75 mg Extended-Release Capsule1.14USDcapsule
Pms-Venlafaxine Xr 75 mg Extended-Release Capsule1.14USDcapsule
Ratio-Venlafaxine Xr 75 mg Extended-Release Capsule1.14USDcapsule
Sandoz Venlafaxine Xr 75 mg Extended-Release Capsule1.14USDcapsule
Effexor Xr 37.5 mg Extended-Release Capsule1.02USDcapsule
Apo-Venlafaxine Xr 37.5 mg Extended-Release Capsule0.57USDcapsule
Co Venlafaxine Xr 37.5 mg Extended-Release Capsule0.57USDcapsule
Mylan-Venlafaxine Xr 37.5 mg Extended-Release Capsule0.57USDcapsule
Novo-Venlafaxine Xr 37.5 mg Extended-Release Capsule0.57USDcapsule
Pms-Venlafaxine Xr 37.5 mg Extended-Release Capsule0.57USDcapsule
Ratio-Venlafaxine Xr 37.5 mg Extended-Release Capsule0.57USDcapsule
Sandoz Venlafaxine Xr 37.5 mg Extended-Release Capsule0.57USDcapsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States62741711997-09-202017-09-20
United States59169231993-06-282013-06-28
Canada21263052006-10-172014-06-20
Canada21997782005-12-202017-03-12
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point215-217 °C (Hydrochloride salt)Not Available
water solubility572 mg/ml (Hydrochloride salt)Not Available
Predicted Properties
PropertyValueSource
water solubility2.30e-01 g/lALOGPS
logP2.69ALOGPS
logP2.74ChemAxon
logS-3.1ALOGPS
pKa (strongest acidic)14.42ChemAxon
pKa (strongest basic)8.91ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count3ChemAxon
hydrogen donor count1ChemAxon
polar surface area32.7ChemAxon
rotatable bond count5ChemAxon
refractivity83.02ChemAxon
polarizability32.33ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleNoChemAxon
Spectra
Spectra1D NMR2D NMR
References
Synthesis Reference

Thomas P. Jerussi, Chrisantha H. Senanayake, “Derivatives of (+)-venlafaxine and methods of preparing and using the same.” U.S. Patent US6197828, issued June, 1994.

US6197828
General Reference
  1. Golden RN, Nicholas L: Antidepressant efficacy of venlafaxine. Depress Anxiety. 2000;12 Suppl 1:45-9. Pubmed
  2. Thase ME, Clayton AH, Haight BR, Thompson AH, Modell JG, Johnston JA: A double-blind comparison between bupropion XL and venlafaxine XR: sexual functioning, antidepressant efficacy, and tolerability. J Clin Psychopharmacol. 2006 Oct;26(5):482-8. Pubmed
  3. Bielski RJ, Ventura D, Chang CC: A double-blind comparison of escitalopram and venlafaxine extended release in the treatment of major depressive disorder. J Clin Psychiatry. 2004 Sep;65(9):1190-6. Pubmed
  4. Rowbotham MC, Goli V, Kunz NR, Lei D: Venlafaxine extended release in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study. Pain. 2004 Aug;110(3):697-706. Pubmed
  5. Ozyalcin SN, Talu GK, Kiziltan E, Yucel B, Ertas M, Disci R: The efficacy and safety of venlafaxine in the prophylaxis of migraine. Headache. 2005 Feb;45(2):144-52. Pubmed
  6. Whirl-Carrillo M, McDonagh EM, Hebert JM, Gong L, Sangkuhl K, Thorn CF, Altman RB, Klein TE: Pharmacogenomics knowledge for personalized medicine. Clin Pharmacol Ther. 2012 Oct;92(4):414-7. doi: 10.1038/clpt.2012.96. Pubmed
  7. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
External Links
ResourceLink
KEGG DrugD08670
KEGG CompoundC07187
PubChem Compound5656
PubChem Substance46504593
ChemSpider5454
ChEBI9943
ChEMBLCHEMBL637
Therapeutic Targets DatabaseDAP000054
PharmGKBPA451866
Drug Product Database2237279
RxListhttp://www.rxlist.com/cgi/generic/venlafax.htm
Drugs.comhttp://www.drugs.com/venlafaxine.html
PDRhealthhttp://www.pdrhealth.com/drugs/rx/rx-mono.aspx?contentFileName=eff1794.html&contentName=Effexor%20XR&contentId=277
WikipediaVenlafaxine
ATC CodesN06AX16N06AX23
AHFS Codes
  • 28:16.04.92
PDB EntriesNot Available
FDA labelshow(3.38 MB)
MSDSshow(36.5 KB)
Interactions
Drug Interactions
Drug
AlmotriptanIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
AmitriptylineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
AmoxapineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
AmprenavirAmprenavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Amprenavir is initiated, discontinued, or dose changed.
AtazanavirAtazanavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Atazanavir is initiated, discontinued, or dose changed.
BromocriptineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
BuspironeIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
CabergolineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
ChlorpromazineChlorpromazine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Chlorpromazine is initiated, discontinued, or dose changed.
CinacalcetCinacalcet, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Cinacalcet is initiated, discontinued, or dose changed.
CitalopramIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
ClarithromycinClarithromycin, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Clarithromycin is initiated, discontinued, or dose changed.
ClomipramineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
CocaineCocaine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Cocaine is initiated, discontinued, or dose changed.
ConivaptanConivaptan, 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.
DarunavirDarunavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Darunavir is initiated, discontinued, or dose changed.
DelavirdineDelaviridine, a CYP2D6 and CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP2D6 and CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Delavirdine is initiated, discontinued, or dose changed.
DesipramineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
DesvenlafaxineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
DexfenfluramineRisk of serotoninergic syndrome
DextromethorphanIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
DiethylpropionRisk of serotoninergic syndrome
DihydroergotamineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
DipivefrinVenlafaxine may increase the tachycardic and vasopressor effects of dipivefrin. Consider alternate therapy or monitor for increased sympathomimetic effects, such as increased blood pressure, chest pain and headache.
DoxepinIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
DuloxetineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
EletriptanIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
EphedrineVenlafaxine may increase the tachycardic and vasopressor effects of ephedrine. Consider alternate therapy or monitor for increased sympathomimetic effects, such as increased blood pressure, chest pain and headache.
EpinephrineVenlafaxine may increase the tachycardic and vasopressor effects of epinephrine. Consider alternate therapy or monitor for increased sympathomimetic effects, such as increased blood pressure, chest pain and headache.
Ergoloid mesylateIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
ErgonovineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
ErgotamineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
EscitalopramIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
FenfluramineRisk of serotoninergic syndrome
FluoxetineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
FluvoxamineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
FosamprenavirFosamprenavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Fosamprenavir is initiated, discontinued, or dose changed.
FrovatriptanIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
FurazolidoneIncreased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
ImatinibImatinib, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Imatinib is initiated, discontinued, or dose changed.
ImipramineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
IndinavirIndinavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Indinavir is initiated, discontinued, or dose changed.
IsocarboxazidIncreased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
IsoniazidIsoniazid, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Isoniazid is initiated, discontinued, or dose changed.
ItraconazoleItraconaole, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Itraconazole is initiated, discontinued, or dose changed.
KetoconazoleKetoconazole, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Ketoconazole is initiated, discontinued, or dose changed.
LinezolidIncreased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
LithiumIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
LopinavirLopinavir, a CYP2D6 and CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP2D6 and CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Lopinavir is initiated, discontinued, or dose changed.
MaprotilineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
MazindolRisk of serotoninergic syndrome
MethylergometrineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
MetoclopramidePossible serotoninergic syndrome with this combination
MiconazoleMiconazole, a CYP2D6 and CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP2D6 and CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Miconazole is initiated, discontinued, or dose changed.
MilnacipranIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
MirtazapineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
MoclobemideIncreased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
NaratriptanIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
NefazodoneIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
NelfinavirNelfinavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Nelfinavir is initiated, discontinued, or dose changed.
NicardipineNicardipine, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Nicardipine is initiated, discontinued, or dose changed.
NorepinephrineVenlafaxine may increase the tachycardic and vasopressor effects of Norepinephrine. Consider alternate therapy or monitor for increased sympathomimetic effects, such as increased blood pressure, chest pain and headache.
NortriptylineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
ParoxetineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
PergolideIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
PethidineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
PhenelzineIncreased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
PhentermineRisk of serotoninergic syndrome
PhenylpropanolamineRisk of serotoninergic syndrome
PosaconazolePosaconazole, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Posaconazole is initiated, discontinued, or dose changed.
ProcarbazineIncreased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
PromethazineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
PropafenonePropafenone increases the effect and toxicity of venlafaxine
ProtriptylineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
PseudoephedrineVenlafaxine may increase the tachycardic and vasopressor effects of Pseudoephedrine. Consider alternate therapy or monitor for increased sympathomimetic effects, such as increased blood pressure, chest pain and headache.
QuinidineQuinidine, a CYP2D6 and CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP2D6 and CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Quinidine is initiated, discontinued, or dose changed.
QuinupristinThis combination presents an increased risk of toxicity
RasagilineIncreased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
RitonavirRitonavir, a CYP2D6 and CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP2D6 and CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Ritonavir is initiated, discontinued, or dose changed.
RizatriptanIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
S-AdenosylmethionineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
SaquinavirSaquinavir, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Saquinavir is initiated, discontinued, or dose changed.
SelegilineIncreased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
SertralineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
SibutramineIncreased risk of serotonin syndrome. Concurrent therapy should be avoided.
St. John's WortIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
SumatriptanIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
TelithromycinTelithromycin, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Telithromycin is initiated, discontinued, or dose changed.
TerbinafineTerbinafine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Terbinafine is initiated, discontinued, or dose changed.
TramadolIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
TranylcypromineIncreased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.
TrazodoneIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
TrimipramineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
TriprolidineThe CNS depressants, Triprolidine and Venlafaxine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
VoriconazoleVoriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of venlafaxine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of venlafaxine if voriconazole is initiated, discontinued or dose changed.
ZolmitriptanUse of two serotonin modulators, such as zolmitriptan and venlafaxine, may increase the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
Food Interactions
  • Avoid alcohol.
  • Avoid St.John's Wort.
  • Take with food.

Targets

1. Sodium-dependent serotonin transporter

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Sodium-dependent serotonin transporter P31645 Details

References:

  1. Chen F, Larsen MB, Sanchez C, Wiborg O: The S-enantiomer of R,S-citalopram, increases inhibitor binding to the human serotonin transporter by an allosteric mechanism. Comparison with other serotonin transporter inhibitors. Eur Neuropsychopharmacol. 2005 Mar;15(2):193-8. Pubmed
  2. Gould GG, Altamirano AV, Javors MA, Frazer A: A comparison of the chronic treatment effects of venlafaxine and other antidepressants on serotonin and norepinephrine transporters. Biol Psychiatry. 2006 Mar 1;59(5):408-14. Epub 2005 Sep 2. Pubmed
  3. Shang Y, Gibbs MA, Marek GJ, Stiger T, Burstein AH, Marek K, Seibyl JP, Rogers JF: Displacement of serotonin and dopamine transporters by venlafaxine extended release capsule at steady state: a [123I]2beta-carbomethoxy-3beta-(4-iodophenyl)-tropane single photon emission computed tomography imaging study. J Clin Psychopharmacol. 2007 Feb;27(1):71-5. Pubmed
  4. Malizia AL, Melichar JM, Brown DJ, Gunn RN, Reynolds A, Jones T, Nutt DJ: Demonstration of clomipramine and venlafaxine occupation at serotonin reuptake sites in man in vivo. J Psychopharmacol. 1997;11(3):279-81. Pubmed
  5. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. Pubmed
  6. Van Ameringen M, Mancini C, Patterson B, Simpson W: Pharmacotherapy for social anxiety disorder: an update. Isr J Psychiatry Relat Sci. 2009;46(1):53-61. Pubmed
  7. Beique J, de Montigny C, Blier P, Debonnel G: Effects of sustained administration of the serotonin and norepinephrine reuptake inhibitor venlafaxine: I. in vivo electrophysiological studies in the rat. Neuropharmacology. 2000 Jul 24;39(10):1800-12. Pubmed
  8. Westenberg HG: Recent advances in understanding and treating social anxiety disorder. CNS Spectr. 2009 Feb;14(2 Suppl 3):24-33. Pubmed
  9. Sindrup SH, Otto M, Finnerup NB, Jensen TS: Antidepressants in the treatment of neuropathic pain. Basic Clin Pharmacol Toxicol. 2005 Jun;96(6):399-409. Pubmed

2. Sodium-dependent noradrenaline transporter

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Sodium-dependent noradrenaline transporter P23975 Details

References:

  1. Vaishnavi SN, Nemeroff CB, Plott SJ, Rao SG, Kranzler J, Owens MJ: Milnacipran: a comparative analysis of human monoamine uptake and transporter binding affinity. Biol Psychiatry. 2004 Feb 1;55(3):320-2. Pubmed
  2. Mitchell HA, Ahern TH, Liles LC, Javors MA, Weinshenker D: The effects of norepinephrine transporter inactivation on locomotor activity in mice. Biol Psychiatry. 2006 Nov 15;60(10):1046-52. Epub 2006 Aug 7. Pubmed
  3. Beique JC, Lavoie N, de Montigny C, Debonnel G: Affinities of venlafaxine and various reuptake inhibitors for the serotonin and norepinephrine transporters. Eur J Pharmacol. 1998 May 15;349(1):129-32. Pubmed
  4. Van Ameringen M, Mancini C, Patterson B, Simpson W: Pharmacotherapy for social anxiety disorder: an update. Isr J Psychiatry Relat Sci. 2009;46(1):53-61. Pubmed
  5. Beique J, de Montigny C, Blier P, Debonnel G: Effects of sustained administration of the serotonin and norepinephrine reuptake inhibitor venlafaxine: I. in vivo electrophysiological studies in the rat. Neuropharmacology. 2000 Jul 24;39(10):1800-12. Pubmed
  6. Westenberg HG: Recent advances in understanding and treating social anxiety disorder. CNS Spectr. 2009 Feb;14(2 Suppl 3):24-33. Pubmed
  7. Sindrup SH, Otto M, Finnerup NB, Jensen TS: Antidepressants in the treatment of neuropathic pain. Basic Clin Pharmacol Toxicol. 2005 Jun;96(6):399-409. Pubmed

3. Sodium-dependent dopamine transporter

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Sodium-dependent dopamine transporter Q01959 Details

References:

  1. Dawson LA, Nguyen HQ, Geiger A: Effects of venlafaxine on extracellular concentrations of 5-HT and noradrenaline in the rat frontal cortex: augmentation via 5-HT1A receptor antagonism. Neuropharmacology. 1999 Aug;38(8):1153-63. Pubmed
  2. Bourin M: [Psychopharmacological profile of venlafaxine] Encephale. 1999 Jun;25 Spec No 2:21-2; discussion 23-5. Pubmed
  3. Barkin RL, Fawcett J: The management challenges of chronic pain: the role of antidepressants. Am J Ther. 2000 Jan;7(1):31-47. Pubmed
  4. Lemke MR: [Antidepressant effects of dopamine agonists. Experimental and clinical findings] Nervenarzt. 2007 Jan;78(1):31-8. Pubmed

Enzymes

1. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  4. Fogelman SM, Schmider J, Venkatakrishnan K, von Moltke LL, Harmatz JS, Shader RI, Greenblatt DJ: O- and N-demethylation of venlafaxine in vitro by human liver microsomes and by microsomes from cDNA-transfected cells: effect of metabolic inhibitors and SSRI antidepressants. Neuropsychopharmacology. 1999 May;20(5):480-90. Pubmed
  5. Lexicomp

2. 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. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  3. Lexicomp

3. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 2C19

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 2B6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2B6 P20813 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  2. Lexicomp

Transporters

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. Weiss J, Dormann SM, Martin-Facklam M, Kerpen CJ, Ketabi-Kiyanvash N, Haefeli WE: Inhibition of P-glycoprotein by newer antidepressants. J Pharmacol Exp Ther. 2003 Apr;305(1):197-204. Pubmed
  2. Uhr M, Grauer MT, Holsboer F: Differential enhancement of antidepressant penetration into the brain in mice with abcb1ab (mdr1ab) P-glycoprotein gene disruption. Biol Psychiatry. 2003 Oct 15;54(8):840-6. Pubmed
  3. Karlsson L, Schmitt U, Josefsson M, Carlsson B, Ahlner J, Bengtsson F, Kugelberg FC, Hiemke C: Blood-brain barrier penetration of the enantiomers of venlafaxine and its metabolites in mice lacking P-glycoprotein. Eur Neuropsychopharmacol. 2010 Sep;20(9):632-40. doi: 10.1016/j.euroneuro.2010.04.004. Epub 2010 May 13. Pubmed

2. ATP-binding cassette sub-family G member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
ATP-binding cassette sub-family G member 2 Q9UNQ0 Details

References:

  1. Bachmeier CJ, Beaulieu-Abdelahad D, Ganey NJ, Mullan MJ, Levin GM: Induction of drug efflux protein expression by venlafaxine but not desvenlafaxine. Biopharm Drug Dispos. 2011 May;32(4):233-44. doi: 10.1002/bdd.753. Epub 2011 Mar 28. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:09