FAQ

More QuickView FAQs

QuickView

0
Meta-
Analysis

Bookmark Forward

QuickView for Venlafaxine (compound)

Summary
General Info

PubChem

PubChem Compound 11846745

Name:	venlafaxine
PubChem Compound ID:	11846745
Molecular formula:	C₁₇H₂₈ClNO₂
Molecular weight:	313.862 g/mol

DrugBank

Identification

Name:	venlafaxine
Name (isomeric):	DB00285
Drug Type:	small molecule
Synonyms:	Venlafaxina [INN-Spanish]; Venlafaxine [INN:Ban]; Venlafaxinum [INN-Latin]
Brand:	Effexor, Effexor XR, Elafax
Category:	Antidepressants, Analgesics, Antidepressive Agents, Second-Generation, Serotonin Uptake Inhibitors
CAS number:	93413-69-5

Pharmacology

Indication:	For the management of major depressive disorder (MDD), generalized anxiety disorder (GAD), social anxiety disorder (social phobia), panic disorder with or without agoraphobia, and vasomotor symptoms in women with breast cancer and in postmenopausal women.
Pharmacology:	Venlafaxine, an antidepressant agent structurally and pharmacologically unrelated to other antidepressants and agents used to treat generalized anxiety disorder, is used to treat melancholia, generalized anxiety disorder (GAD), panic disorder, post-traumatic stress disorder, and hot flashes in breast cancer survivors.
Mechanism of Action:	The 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. B... show more » The 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. show less «
Absorption:	Bioavailability is 45% following oral administration.
Protein binding:	venlafaxine, 27%; ODV, 30%
Biotransformation:	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.
Route of elimination:	Renal elimination of venlafaxine and its metabolites is the primary route of excretion.
Half Life:	5 hours
Clearance:	1.3 +/- 0.6 L/h/kg
Toxicity:	Most 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

Interactions

Food interaction:

Avoid St.John's Wort.

Avoid alcohol.

Take with food.

Drug interaction:

Fosamprenavir	Fosamprenavir, 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.
Chlorpromazine	Chlorpromazine, 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.
Ketoconazole	Ketoconazole, 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.
Tramadol	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Meperidine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Fosamprenavir	Fosamprenavir, 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.
Chlorpromazine	Chlorpromazine, 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.
Ketoconazole	Ketoconazole, 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.
Tramadol	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Meperidine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Sertraline	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Trimipramine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Lithium	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Phenelzine	Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
Maprotiline	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Nortriptyline	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Fluvoxamine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Miconazole	Miconazole, 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.
Dihydroergotamine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Tranylcypromine	Increased 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.
Phentermine	Risk of serotoninergic syndrome
Ergonovine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Dipivefrin	Venlafaxine 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.
Terbinafine	Terbinafine, 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.
Fenfluramine	Risk of serotoninergic syndrome
Nicardipine	Nicardipine, 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.
Conivaptan	Conivaptan, 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.
Darunavir	Darunavir, 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.
Saquinavir	Saquinavir, 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.
Clomipramine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
St. John's Wort	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Trazodone	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Propafenone	Propafenone increases the effect and toxicity of venlafaxine
Dextromethorphan	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Indinavir	Indinavir, 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.
Zolmitriptan	Use 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.
Triprolidine	The CNS depressants, Triprolidine and Venlafaxine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Ritonavir	Ritonavir, 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.
Frovatriptan	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Posaconazole	Posaconazole, 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.
Quinupristin	This combination presents an increased risk of toxicity
Amprenavir	Amprenavir, 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.
Ergoloid mesylate	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Epinephrine	Venlafaxine 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.
Cinacalcet	Cinacalcet, 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.
Doxepin	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Furazolidone	Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
Rizatriptan	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Atazanavir	Atazanavir, 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.
Imatinib	Imatinib, 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.
Citalopram	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Dexfenfluramine	Risk of serotoninergic syndrome
Norepinephrine	Venlafaxine 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.
Buspirone	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Mazindol	Risk of serotoninergic syndrome
Promethazine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Ergotamine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Lopinavir	Lopinavir, 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.
Nefazodone	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Almotriptan	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Ephedrine	Venlafaxine 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.
Mirtazapine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Isocarboxazid	Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
Duloxetine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Diethylpropion	Risk of serotoninergic syndrome
Eletriptan	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Pseudoephedrine	Venlafaxine 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.
Sumatriptan	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Phenylpropanolamine	Risk of serotoninergic syndrome
Fluoxetine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Delavirdine	Delaviridine, 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.
Desipramine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Bromocriptine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Escitalopram	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Desvenlafaxine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Voriconazole	Voriconazole, 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.
Clarithromycin	Clarithromycin, 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.
Protriptyline	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Milnacipran	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Imipramine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Linezolid	Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
Nelfinavir	Nelfinavir, 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.
Quinidine	Quinidine, 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.
Selegiline	Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
Sibutramine	Increased risk of serotonin syndrome. Concurrent therapy should be avoided.
Paroxetine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Metoclopramide	Possible serotoninergic syndrome with this combination
Methylergonovine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Naratriptan	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Amoxapine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Isoniazid	Isoniazid, 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.
Pergolide	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Moclobemide	Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
Amitriptyline	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Itraconazole	Itraconaole, 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.
Telithromycin	Telithromycin, 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.
Cabergoline	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Rasagiline	Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
Procarbazine	Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
S-Adenosylmethionine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Cocaine	Cocaine, 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.

show less «

Targets

Sodium-dependent serotonin transporter

Terminates the action of serotonine by its high affinity sodium-dependent reuptake into presynaptic terminals

UniProt ID:

P31645

Gene:

SLC6A4

Actions:

inhibitor

References:

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.
View Article

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.
View Article

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.
View Article

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.
View Article

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.
View Article

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.
View Article

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.
View Article

Westenberg HG: Recent advances in understanding and treating social anxiety disorder. CNS Spectr. 2009 Feb;14(2 Suppl 3):24-33.
View Article

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.
View Article

Sodium-dependent noradrenaline transporter

Sodium-dependent dopamine transporter

Enzymes

Transporters

Multidrug resistance protein 1