Chemical: Drug
duloxetine

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Prescribing Info (1) Drug Labels (1) Clinical Annotations (4)

last updated 08/10/2011

1. Annotation of DPWG Guideline for duloxetine and CYP2D6

Summary

There are currently no dosing recommendations for duloxetine based on CYP2D6 genotype.

Annotation

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for duloxetine based on CYP2D6 genotypes [Article:21412232]. They conclude that there are no recommendations at this time.

Phenotype (Genotype)	Therapeutic Dose Recommendation	Level of Evidence	Clinical Relevance
PM (two inactive (3-8, 11-16, 19-21, 38, 40, *42) alleles)	No recommendation.	Data on file.	Clinical effect (not statistically significant difference).
IM (two decreased-activity (9, 10, 17, 29, 36, 41) alleles or carrying one active (1, 2, 33, 35) and one inactive (3-8, 11-16, 19-21, 38, 40, 42) allele, or carrying one decreased-activity (9, 10, 17, 29, 36, 41) allele and one inactive (3-8, 11-16, 19-21, 38, 40, 42) allele)	No recommendation.	No evidence.	--
UM (a gene duplication in absence of inactive (3-8, 11-16, 19-21, 38, 40, 42) or decreased-activity (9, 10, 17, 29, 36, *41) alleles)	No recommendation.	No evidence.	--

Please see attached PDF for detailed information about the evaluated studies: Duloxetine CYP2D6
See Methods or [Article:18253145] for more background information about the project.

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1. Annotation of FDA Label for duloxetine and CYP2D6

On FDA Biomarker List

Actionable PGx

Summary

Duloxetine (CYMBALTA) is metabolized by CYP2D6 and CYP1A2. The FDA-approved drug label notes that concomitant administration of duloxetine and fluvoxamine (a potent CYP1A2 inhibitor) to CYP2D6 poor metabolizers resulted in a 6-fold increase in duloxetine AUC and Cmax.

Annotation

Excerpts from duloxetine (CYMBALTA) drug label:

Both CYP1A2 and CYP2D6 are responsible for CYMBALTA metabolism.

Concomitant administration of duloxetine 40 mg twice daily with fluvoxamine 100 mg, a potent CYP1A2 inhibitor, to CYP2D6 poor metabolizer subjects (n=14) resulted in a 6-fold increase in duloxetine AUC and Cmax.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the duloxetine drug label.

*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.

Full label available at DailyMed

Genes and/or phenotypes found in this label

Anxiety Disorders
- Indications & usage section, Adverse reactions section
- source: PHONT
Depressive Disorder, Major
- Indications & usage section, Warnings section, Adverse reactions section
- source: PHONT
Fibromyalgia
- Indications & usage section, Warnings section, Adverse reactions section
- source: PHONT
neuropathic pain
- Indications & usage section, Warnings section, Adverse reactions section
- source: PHONT
CYP1A2
- metabolism/PK, Drug interactions section, Clinical pharmacology section, Warnings and precautions section
- source: U.S. Food and Drug Administration
CYP2D6
- metabolism/PK, Drug interactions section, Clinical pharmacology section, Warnings and precautions section
- source: U.S. Food and Drug Administration

PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

Clinical Annotation for rs963468 (DRD3), duloxetine and Anxiety Disorders (level 3 Efficacy)

Level of Evidence: Level 3
Type: Efficacy
Variant: rs963468
Genes: DRD3
Phenotypes: Anxiety Disorders
OMB Race: White

To see the rest of this clinical annotation please register or sign in.

Clinical Annotation for rs167770 (DRD3), duloxetine and Anxiety Disorders (level 3 Efficacy)

Level of Evidence: Level 3
Type: Efficacy
Variant: rs167770
Genes: DRD3
Phenotypes: Anxiety Disorders
OMB Race: White

To see the rest of this clinical annotation please register or sign in.

Clinical Annotation for rs324023 (DRD3), duloxetine and Anxiety Disorders (level 3 Efficacy)

Level of Evidence: Level 3
Type: Efficacy
Variant: rs324023
Genes: DRD3
Phenotypes: Anxiety Disorders
OMB Race: White

To see the rest of this clinical annotation please register or sign in.

Clinical Annotation for rs324026 (DRD3), duloxetine and Anxiety Disorders (level 3 Efficacy)

Level of Evidence: Level 3
Type: Efficacy
Variant: rs324026
Genes: DRD3
Phenotypes: Anxiety Disorders
OMB Race: White

To see the rest of this clinical annotation please register or sign in.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

? = Mouse-over for quick help

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

List of all variant annotations for duloxetine

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	Gene ?	Variant? (147)	Alternate Names ?	Chemicals ?	Alleles ? (+ chr strand)	Function ?	Amino Acid? Translation
VA	CYP2C19	*1		citalopram clomipramine duloxetine escitalopram fluoxetine fluvoxamine mirtazapine paroxetine sertraline venlafaxine	N/A	N/A	N/A
VA	CYP2C19	*2		citalopram clomipramine duloxetine escitalopram fluoxetine fluvoxamine mirtazapine paroxetine sertraline venlafaxine	N/A	N/A	N/A
VA	CYP2C19	*3		citalopram clomipramine duloxetine escitalopram fluoxetine fluvoxamine mirtazapine paroxetine sertraline venlafaxine	N/A	N/A	N/A
VA	CYP2C19	*17		citalopram clomipramine duloxetine escitalopram fluoxetine fluvoxamine mirtazapine paroxetine sertraline venlafaxine	N/A	N/A	N/A
VA	CYP2D6	*1		citalopram clomipramine duloxetine escitalopram fluoxetine fluvoxamine mirtazapine paroxetine sertraline venlafaxine	N/A	N/A	N/A
VA	CYP2D6	*3		citalopram clomipramine duloxetine escitalopram fluoxetine fluvoxamine mirtazapine paroxetine sertraline venlafaxine	N/A	N/A	N/A
VA	CYP2D6	*4		citalopram clomipramine duloxetine escitalopram fluoxetine fluvoxamine mirtazapine paroxetine sertraline venlafaxine	N/A	N/A	N/A
VA	CYP2D6	*5		citalopram clomipramine duloxetine escitalopram fluoxetine fluvoxamine mirtazapine paroxetine sertraline venlafaxine	N/A	N/A	N/A
VA	CYP2D6	*10		citalopram clomipramine duloxetine escitalopram fluoxetine fluvoxamine mirtazapine paroxetine sertraline venlafaxine	N/A	N/A	N/A
VA	CYP2D6	*17		citalopram clomipramine duloxetine escitalopram fluoxetine fluvoxamine mirtazapine paroxetine sertraline venlafaxine	N/A	N/A	N/A
VA	CYP2D6	*41		citalopram clomipramine duloxetine escitalopram fluoxetine fluvoxamine mirtazapine paroxetine sertraline venlafaxine	N/A	N/A	N/A
VA	IL6	rs10242595	NC_000007.13:g.22774231G>A, NC_000007.14:g.22734612G>A, rs60125740	duloxetine	G > A	SNP
CA VA	DRD3	rs167770	NC_000003.11:g.113879562G>A, NC_000003.12:g.114160715G>A, NG_008842.2:g.43693C>T, NM_000796.5:c.271-848C>T, NM_001282563.2:c.271-848C>T, NM_001290809.1:c.271-848C>T, NM_033663.5:c.271-848C>T, XM_005247170.1:c.271-848C>T, XM_005247171.1:c.271-848C>T, XM_011512510.1:c.271-848C>T, XM_011512511.1:c.271-848C>T, XM_011512512.1:c.271-848C>T, rs1261958, rs56619079, rs61125319	duloxetine	G > A	SNP
VA	IL6	rs2066992	NC_000007.13:g.22768249G>T, NC_000007.14:g.22728630G>T, NG_011640.1:g.6484G>T, NM_000600.4:c.211-63G>T, NM_001318095.1:c.-18-63G>T, NR_131935.1:n.-1010C>A, XM_005249745.1:c.373-63G>T, XM_005249745.3:c.373-63G>T, XM_005249746.1:c.-18-63G>T, XM_011515390.1:c.211-63G>T, XM_011515391.1:c.-18-63G>T, rs17147236, rs58064907	duloxetine	G > T	SNP
CA VA	DRD3	rs324023	NC_000003.11:g.113885395T>C, NC_000003.12:g.114166548T>C, NG_008842.2:g.37860A>G, NM_000796.5:c.270+5175A>G, NM_001282563.2:c.270+5175A>G, NM_001290809.1:c.270+5175A>G, NM_033663.5:c.270+5175A>G, XM_005247170.1:c.270+5175A>G, XM_005247171.1:c.270+5175A>G, XM_011512510.1:c.270+5175A>G, XM_011512511.1:c.270+5175A>G, XM_011512512.1:c.270+5175A>G, rs17305602	duloxetine	T > C	SNP
CA VA	DRD3	rs324026	NC_000003.11:g.113891042C>T, NC_000003.12:g.114172195C>T, NG_008842.2:g.32213G>A, NM_000796.5:c.-35-168G>A, NM_001282563.2:c.-35-168G>A, NM_001290809.1:c.-35-168G>A, NM_033663.5:c.-35-168G>A, XM_005247170.1:c.-35-168G>A, XM_005247171.1:c.-35-168G>A, XM_011512510.1:c.-35-168G>A, XM_011512511.1:c.-35-168G>A, XM_011512512.1:c.-35-168G>A, rs60286476	duloxetine	C > T	SNP
VA	HTR2A	rs6313	NC_000013.10:g.47469940G>A, NC_000013.11:g.46895805G>A, NG_013011.1:g.6230C>T, NM_000621.4:c.102C>T, NM_001165947.2:c.160+869C>T, NP_000612.1:p.Ser34=, rs17367493, rs3742280, rs386602276, rs57425741	clomipramine venlafaxine Selective serotonin reuptake inhibitors desvenlafaxine duloxetine moclobemide	G > A	SNP	S34S
CA VA	DRD3	rs963468	NC_000003.11:g.113862887G>A, NC_000003.12:g.114144040G>A, NG_008842.2:g.60368C>T, NM_000796.5:c.526+3375C>T, NM_001282563.2:c.526+3375C>T, NM_001290809.1:c.526+3375C>T, NM_033663.5:c.526+3375C>T, XM_005247170.1:c.526+3375C>T, XM_005247171.1:c.526+3375C>T, XM_011512510.1:c.526+3375C>T, XM_011512511.1:c.526+3375C>T, XM_011512512.1:c.526+3375C>T, rs3773680, rs57220853	duloxetine	G > A	SNP

Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 147

[ see larger image ] [ see 3D structure ]

provided by PubChem

Overview

Generic Names

(+-)-duloxetine
Duloxetine HCl
Duloxetine Hydrochloride

Trade Names

Cymbalta
Yentreve

Brand Mixture Names

PharmGKB Accession Id

PA10066

Type(s):

Drug

Description

Duloxetine (brand names Cymbalta, Yentreve, and in parts of Europe, Xeristar or Ariclaim) is a drug which primarily targets major depressive disorder (MDD), generalized anxiety disorder (GAD), pain related to diabetic peripheral neuropathy and in some countries stress urinary incontinence (SUI). It is manufactured and marketed by Eli Lilly and Company. Duloxetine has not yet been FDA approved for stress urinary incontinence or for fibromyalgia. Duloxetine is a selective SNRI (selective serotonin-norepinephrine reuptake inhibitor). Duloxetine is a systemic drug therapy which affects the body as a whole. Known also under the code name LY248686, it is a potent dual reuptake inhibitor of serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE), possessing comparable affinities in binding to NE- and 5-HT transporter sites. It is a less potent inhibitor of dopamine reuptake.

Source: Drug Bank

Pharmacogenetics

Pharmacokinetics

The major biotransformation pathway of duloxetine is oxidation followed by glucuronidation. Studies in human liver microsomes identified that CYP2D6 and CYP1A2 enzymes are involved in the formation of 4-OH, 5-OH and 6-OH duloxetine [Articles:12920170, 18307373]. Duloxetine is a moderate inhibitor of CYP2D6 [Articles:19480470, 18691982, 12621382, 15057659]. But duloxetine is unlikely to have a clinically significant effect on the metabolism of drugs that are substrates of CYP1A2 [Article:18307373].

Clinically significant increases in duloxetine exposure were observed in the presence of [Chemical:fluvoxamine], a CYP1A2 inhibitor [Article:18307373].

Pharmacodynamics

The drug is approved for the treatment of Depressive Disorder, Major, Anxiety Disorders, Fibromyalgia, Urinary Incontinence, Stress, and the management of diabetic peripheral neuropathic pain [Articles:18408530, 19385712]. Duloxetine affects the reuptake of both serotonin and [Chemical:norepinephrine] via inhibition of SLC6A4 and SLC6A2, respectively [Articles:15892657, 11750180, 15184278]. Duloxetine has low affinity for dopamine transporter SLC6A3 [Article:11750180]. In one study, duloxetine had over 80 fold lower affinity for neuronal receptors than was expected, and therefore no significant interactions with adrenergic, muscarinic and histamine receptors [Article:11750180].

A study in duloxetine-treated patients with major depressive disorder found that polymorphisms in the catechol-O-methyltransferase (COMT) gene were associated with symptom changes [Article:19095219].

Studies in rats indicate that chronic duloxetine treatment influences brain-derived neurotrophic factor (BDNF) expression in the frontal cortex [Articles:17327885, 18172756, 19020498].

Nausea, dry mouth, headache, constipation, dizziness and fatigue were among the most common treatment-emergent adverse events [Articles:19480470, 15892657]. Duloxetine-treated patients demonstrated a modest, but statistically significant, mean pulse increase and a slight increase in mean systolic blood pressure [Article:15892657]. A review article about nonclinical and clinical trial data for hepatic effects of duloxetine found that duloxetine has an effect on the liver, manifested by transient, self-limiting transaminase elevations [Article:18690991]. Rare events characterized as hepatocellular injury, cholestatic injury, or mixed type of hepatic injury have been reported [Article:18690991].

Source: PharmGKB

Indication

For the acute and maintenance treatment of major depressive disorder (MDD), as well as acute management of generalized anxiety disorder. Also used for the management of neuropathic pain associated with diabetic peripheral neuropathy, and fibromyalgia. Has been used in the management of moderate to severe stress urinary incontinence (SUI) in women.

Source: Drug Bank

Other Vocabularies

MeSH: duloxetine (C058218)
ATC: Other antidepressants (N06AX)
UMLS: duloxetine (C0245561)
RxNorm: duloxetine (72625)
NDFRT: DULOXETINE (N0000148860)

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Duloxetine is a potent inhibitor of neuronal serotonin and norepinephrine reuptake and a less potent inhibitor of dopamine reuptake. Duloxetine has no significant affinity for dopaminergic, adrenergic, cholinergic, histaminergic, opioid, glutamate, and GABA receptors. The antidepressant and pain inhibitory actions of duloxetine are believed to be related to its potentiation of serotonergic and noradrenergic activity in the CNS. The mechanism of action of duloxetine in SUI has not been determined, but is thought to be associated with the potentiation of serotonin and norepinephrine activity in the spinal cord, which increases urethral closure forces and thereby reduces involuntary urine loss.

Source: Drug Bank

Pharmacology

Duloxetine is in a class of medications called selective serotonin and norepinephrine reuptake inhibitors (SSNRIs) and primarily targets major depressive disorders (MDD) and stress urinary incontinence (SUI). Duloxetine is also used to treat pain and tingling caused by diabetic neuropathy (damage to nerves that can develop in people who have diabetes). Known also as LY248686, it is a potent dual inhibitor of serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE) reuptake, possessing comparable affinities in binding to NE and 5-HT transport sites. Interestingly, its behavior contrasts to most other dual-reuptake inhibitors. Furthermore, duloxentine lacks affinity for monoamine receptors within the central nervous system.

Source: Drug Bank

Food Interaction

Food does not affect maximum levels reached, but delays it (from 6 to 10 hours) and total product exposure appears to be reduced by only 10%.|Take without regard to meals.|People taking this product who drink large amounts of alcohol are exposed to a higher risk of liver toxicity.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

The major biotransformation pathways for duloxetine involve oxidation of the naphthyl ring followed by conjugation and further oxidation. Both CYP2D6 and CYP1A2 catalyze the oxidation of the naphthyl ring in vitro. Metabolites found in plasma include 4-hydroxy duloxetine glucuronide and 5-hydroxy, 6-methoxy duloxetine sulfate. The major circulating metabolites have not been shown to contribute significantly to the pharmacologic activity of duloxetine.

Source: Drug Bank

Protein Binding

Protein binding is greater than 90%.

Source: Drug Bank

Absorption

Orally administered duloxetine hydrochloride is well absorbed.

Source: Drug Bank

Half-Life

12 hours (range 8-17 hours)

Source: Drug Bank

Toxicity

Oral, rat LD ~50~: 491 mg/kg for males and 279 mg/kg for females. Symptoms of overdose include tremors, convulsions, reduced activity, slow pupillary response, intermittent tremors, and rigidity.

Source: Drug Bank

Route of Elimination

Many additional metabolites have been identified in urine, some representing only minor pathways of elimination. Most (about 70%) of the duloxetine dose appears in the urine as metabolites of duloxetine; about 20% is excreted in the feces.

Source: Drug Bank

Volume of Distribution

* 1640 L

Source: Drug Bank

Chemical Properties

Chemical Formula

C18H19NOS

Source: Drug Bank

Average Molecular Weight

297.415

Source: Drug Bank

Monoisotopic Molecular Weight

297.118734925

Source: Drug Bank

SMILES

CNCC[C@@H](C1=CC=CS1)OC2=CC=CC3=CC=CC=C32

Source: PubChem

InChI String

InChI=1S/C18H19NOS/c1-19-12-11-17(18-10-5-13-21-18)20-16-9-4-7-14-6-2-3-8-15(14)16/h2-10,13,17,19H,11-12H2,1H3/t17-/m0/s1

Source: PubChem

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

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Evidence	Gene
DL	CYP1A2
VA	CYP2C19
DG DL VA	CYP2D6
CA VA	DRD3
VA	HTR2A
VA	IL6

Drug Targets

Gene	Description
SLC6A2	(source: Drug Bank )
SLC6A3	(source: Drug Bank )
SLC6A4	(source: Drug Bank )

Drug Interactions

Interaction	Description
amitriptyline - duloxetine	Possible increase in the levels of this agent when used with duloxetine (source: Drug Bank )
amitriptyline - duloxetine	Possible increase in the levels of this agent when used with duloxetine (source: Drug Bank )
ciprofloxacin - duloxetine	Increases the effect/toxicity of duloxetine (source: Drug Bank )
ciprofloxacin - duloxetine	Increases the effect/toxicity of duloxetine (source: Drug Bank )
desipramine - duloxetine	Possible increase in the levels of this agent when used with duloxetine (source: Drug Bank )
desipramine - duloxetine	Possible increase in the levels of this agent when used with duloxetine (source: Drug Bank )
duloxetine - amitriptyline	Possible increase in the levels of this agent when used with duloxetine (source: Drug Bank )
duloxetine - amitriptyline	Possible increase in the levels of this agent when used with duloxetine (source: Drug Bank )
duloxetine - ciprofloxacin	Ciprofloxacin increases the effect/toxicity of duloxetine (source: Drug Bank )
duloxetine - ciprofloxacin	Ciprofloxacin increases the effect/toxicity of duloxetine (source: Drug Bank )
duloxetine - desipramine	Possible increase in the levels of this agent when used with duloxetine (source: Drug Bank )
duloxetine - desipramine	Possible increase in the levels of this agent when used with duloxetine (source: Drug Bank )
duloxetine - flecainide	Possible increase in the levels of this agent when used with duloxetine (source: Drug Bank )
duloxetine - flecainide	Possible increase in the levels of this agent when used with duloxetine (source: Drug Bank )
duloxetine - fluvoxamine	Fluvoxamine increases the effect and toxicity of duloxetine (source: Drug Bank )
duloxetine - fluvoxamine	Fluvoxamine increases the effect and toxicity of duloxetine (source: Drug Bank )
duloxetine - imipramine	Possible increase in the levels of this agent when used with duloxetine (source: Drug Bank )
duloxetine - imipramine	Possible increase in the levels of this agent when used with duloxetine (source: Drug Bank )
duloxetine - isocarboxazid	Possible severe adverse reaction with this combination (source: Drug Bank )
duloxetine - isocarboxazid	Possible severe adverse reaction with this combination (source: Drug Bank )
duloxetine - nortriptyline	Possible increase in the levels of this agent when used with duloxetine (source: Drug Bank )
duloxetine - nortriptyline	Possible increase in the levels of this agent when used with duloxetine (source: Drug Bank )
duloxetine - phenelzine	Possible severe adverse reaction with this combination (source: Drug Bank )
duloxetine - phenelzine	Possible severe adverse reaction with this combination (source: Drug Bank )
duloxetine - propafenone	Possible increase in the levels of this agent when used with duloxetine (source: Drug Bank )
duloxetine - propafenone	Possible increase in the levels of this agent when used with duloxetine (source: Drug Bank )
duloxetine - rasagiline	Possible severe adverse reaction with this combination (source: Drug Bank )
duloxetine - rasagiline	Possible severe adverse reaction with this combination (source: Drug Bank )
duloxetine - thioridazine	Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank )
duloxetine - thioridazine	Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank )
duloxetine - tranylcypromine	Possible severe adverse reaction with this combination (source: Drug Bank )
duloxetine - tranylcypromine	Possible severe adverse reaction with this combination (source: Drug Bank )
flecainide - duloxetine	Possible increase in the levels of this agent when used with duloxetine (source: Drug Bank )
flecainide - duloxetine	Possible increase in the levels of this agent when used with duloxetine (source: Drug Bank )
isocarboxazid - duloxetine	Possible severe adverse reaction with this combination (source: Drug Bank )
isocarboxazid - duloxetine	Possible severe adverse reaction with this combination (source: Drug Bank )
nortriptyline - duloxetine	Possible increase in the levels of this agent when used with duloxetine (source: Drug Bank )
nortriptyline - duloxetine	Possible increase in the levels of this agent when used with duloxetine (source: Drug Bank )
phenelzine - duloxetine	Possible severe adverse reaction with this combination (source: Drug Bank )
phenelzine - duloxetine	Possible severe adverse reaction with this combination (source: Drug Bank )
propafenone - duloxetine	Possible increase in the levels of this agent when used with duloxetine (source: Drug Bank )
propafenone - duloxetine	Possible increase in the levels of this agent when used with duloxetine (source: Drug Bank )
rasagiline - duloxetine	Possible severe adverse reaction with this combination (source: Drug Bank )
tamoxifen - duloxetine	Duloxetine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy. (source: Drug Bank )
tamoxifen - duloxetine	Duloxetine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy. (source: Drug Bank )
tamsulosin - duloxetine	Duloxetine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Duloxetine is initiated, discontinued, or dose changed. (source: Drug Bank )
tamsulosin - duloxetine	Duloxetine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Duloxetine is initiated, discontinued, or dose changed. (source: Drug Bank )
thiabendazole - duloxetine	The strong CYP1A2 inhibitor, Thiabendazole, may increase the effects and toxicity of Duloxetine by decreasing Duloxetine metabolism and clearance. Monitor for changes in the therapeutic and adverse effects of Duloxetine if Thiabendazole is initiated, discontinued or dose changed. (source: Drug Bank )
thioridazine - duloxetine	Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank )
thioridazine - duloxetine	Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank )
tramadol - duloxetine	Duloxetine may decrease the effect of Tramadol by decreasing active metabolite production. Increased risk of serotonin syndrome. Monitor for Tramadol efficacy and symptoms of serotonin syndrome. (source: Drug Bank )
tranylcypromine - duloxetine	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. (source: Drug Bank )
trazodone - duloxetine	Increased risk of serotonin syndrome. The 2D6 inhibitor, Trazodone, may also increase the efficacy of Duloxetine by decreasing Duloxetine metabolism and clearance. Monitor for symptoms of serotonin syndrome and changes in Duloxetine efficacy if Trazodone is initiated, discontinued or dose changed. (source: Drug Bank )
trazodone - duloxetine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
trimipramine - duloxetine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
triprolidine - duloxetine	The CNS depressants, Triprolidine and Duloxetine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy. (source: Drug Bank )
triprolidine - duloxetine	The CNS depressants, Triprolidine and Duloxetine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy. (source: Drug Bank )
venlafaxine - duloxetine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
zolmitriptan - duloxetine	Use of two serotonin modulators, such as zolmitriptan and duloxetine, increases the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy. (source: Drug Bank )

Curated Information ?

view legend

Evidence	Disease
DL CA VA	Anxiety Disorders
DL VA	Depressive Disorder, Major
DL	Fibromyalgia
DL	neuropathic pain
VA	Obsessive-Compulsive Disorder
VA	Overdose
VA	Serotonin Syndrome

Publications related to duloxetine: 25

view legend

	Clinical Impact of Pharmacogenetic-Guided Treatment for Patients Exhibiting Neuropsychiatric Disorders: A Randomized Controlled Trial. The primary care companion for CNS disorders. 2017. Olson Marilyn C, et al.
	Genetic Variation among 82 Pharmacogenes: the PGRN-Seq data from the eMERGE Network. Clinical pharmacology and therapeutics. 2016. Bush William S, et al.
VA	Genetic variation in IL-1beta, IL-2, IL-6, TSPO and BDNF and response to duloxetine or placebo treatment in major depressive disorder. Pharmacogenomics. 2015. Maciukiewicz Malgorzata, et al.
VA	Serotonin toxicity from antidepressant overdose and its association with the T102C polymorphism of the 5-HT2A receptor. The pharmacogenomics journal. 2014. Cooper J M, et al.
VA	Influence of CYP2D6 and CYP2C19 gene variants on antidepressant response in obsessive-compulsive disorder. The pharmacogenomics journal. 2013. Brandl E J, et al.
	Literature based drug interaction prediction with clinical assessment using electronic medical records: novel myopathy associated drug interactions. PLoS computational biology. 2012. Duke Jon D, et al.
CA VA	Pharmacogenetic investigation of response to duloxetine treatment in generalized anxiety disorder. The pharmacogenomics journal. 2012. Perlis R H, et al.
	Augmentative effects of fluvoxamine on duloxetine plasma levels in depressed patients. Pharmacopsychiatry. 2011. Paulzen M, et al.
	Coprescription of tamoxifen and medications that inhibit CYP2D6. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2010. Sideras Kostandinos, et al.
	Acute and Chronic Pain Management in Fibromyalgia: Updates on Pharmacotherapy. American journal of therapeutics. 2010. Hsu Eric S.
	Drug discovery. Repurposing with a difference. Science (New York, N.Y.). 2009. Boguski Mark S, et al.
	Variation in catechol-O-methyltransferase is associated with duloxetine response in a clinical trial for major depressive disorder. Biological psychiatry. 2009. Perlis Roy H, et al.
	Assessment of the impact of renal impairment on systemic exposure of new molecular entities: evaluation of recent new drug applications. Clinical pharmacology and therapeutics. 2009. Zhang Y, et al.
	Duloxetine: a review of its use in the treatment of generalized anxiety disorder. CNS drugs. 2009. Carter Natalie J, et al.
	Population pharmacokinetics of orally administered duloxetine in patients: implications for dosing recommendation. Clinical pharmacokinetics. 2009. Lobo Evelyn D, et al.
	Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation. Analytical and bioanalytical chemistry. 2008. Zanger Ulrich M, et al.
	The influence of smoking on the serum level of duloxetine. Pharmacopsychiatry. 2008. Fric M, et al.
	In vitro and in vivo evaluations of cytochrome P450 1A2 interactions with duloxetine. Clinical pharmacokinetics. 2008. Lobo Evelyn D, et al.
VA	Duloxetine pharmacokinetics are similar in Japanese and Caucasian subjects. British journal of clinical pharmacology. 2007. Chan Clark, et al.
	Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. British journal of pharmacology. 2007. Gillman P K.
	Comparison of duloxetine, escitalopram, and sertraline effects on cytochrome P450 2D6 function in healthy volunteers. Journal of clinical psychopharmacology. 2007. Preskorn Sheldon H, et al.
VA	Pharmacokinetics and tolerability of duloxetine following oral administration to healthy Chinese subjects. Clinical pharmacokinetics. 2007. Tianmei Si, et al.
	The dual transporter inhibitor duloxetine: a review of its preclinical pharmacology, pharmacokinetic profile, and clinical results in depression. Current pharmaceutical design. 2005. Bymaster Frank P, et al.
	Duloxetine is both an inhibitor and a substrate of cytochrome P4502D6 in healthy volunteers. Clinical pharmacology and therapeutics. 2003. Skinner Michael H, et al.
	Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2001. Bymaster F P, et al.

LinkOuts

Web Resource:: Wikipedia
National Drug Code Directory:: 54868-5215-2
DrugBank:: DB00476
ChEBI:: 36795

KEGG Drug:: D01179
PubChem Compound:: 60835
PubChem Substance:: 46507937; 704934
IUPHAR Ligand:: 202

ChemSpider:: 54822
Therapeutic Targets Database:: DAP000494
FDA Drug Label at DailyMed:: 81a06b90-50d3-40c1-98ca-0e344c76b2c4

Clinical Trials

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Sources for PharmGKB drug information: DrugBank, PubChem.

Chemical: Drug duloxetine

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Pharmacogenetics

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Pharmacology

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Curated Information ?

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Curated Information ?

Publications related to duloxetine: 25

LinkOuts

Chemical: Drug
duloxetine