Chemical: Drug
doxepin

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Dosing Guidelines

Annotation of CPIC Guideline for doxepin and CYP2C19,CYP2D6
Annotation of DPWG Guideline for doxepin and CYP2D6

last updated 03/15/2017

1. Annotation of CPIC Guideline for doxepin and CYP2C19,CYP2D6

Summary

Tricyclic antidepressants have comparable pharmacokinetic properties, it may be reasonable to apply the CPIC Dosing Guideline for amitriptyline and CYP2C19, CYP2D6 to other tricyclics including doxepin. The CPIC Dosing Guideline update for amitriptyline recommends an alternative drug for CYP2D6 ultrarapid or poor metabolizers and CYP2C19 ultrarapid, rapid or poor metabolizers. If amitriptyline is warranted, consider a 50% dose reduction in CYP2D6 or CYP2C19 poor metabolizers. For CYP2D6 intermediate metabolizers, a 25% dose reduction should be considered.

Annotation

This annotation is based on the CPIC® guideline for tricyclic antidepressants and CYP2D6 and CYP2C19.

December 2016 Update

Advance online publication December 2016.

The 2016 update of CPIC guidelines regarding the use of pharmacogenomic tests in dosing of tricyclic antidepressants (TCAs) have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC). Literature up to July 2016 was reviewed, recommendations and supplemental information were updated.
Excerpt from the 2016 dosing guideline update:
- "Both amitriptyline and nortriptyline are used as representative TCAs for this guideline because the majority of pharmacogenomic studies have focused on these two drugs. However, the results of these studies may apply to other TCAs because these drugs have comparable pharmacokinetic properties."
- "There is substantial evidence linking CYP2D6 and CYP2C19 genotypes to phenotypic variability in tricyclic side-effect and pharmacokinetic profiles. Modifying pharmacotherapy for patients who have CYP2D6 or CYP2C19 genomic variants that affect drug efficacy and safety could potentially improve clinical outcomes and reduce the failure rate of initial treatment."
- " There are scarce studies focusing solely on CYP2D6 or CYP2C19 genotype and association with pharmacokinetic parameters or treatment outcomes of TCAs in pediatric patients. CYP2D6 activity is fully mature by early childhood, but CYP2C19 activity may be increased in children relative to adults. Although further genomic ontogeny studies are needed, there is a lack of evidence suggesting that this guideline cannot be extrapolated to pediatric patients."
The guideline includes dosing recommendation for TCAs based on:
- CYP2D6 phenotype (Table 1 below)
- CYP2C19 phenotype (Table 2 below)
Download and read:

Table 1: Dosing recommendations for TCAs based on CYP2D6 phenotype:

Adapted from Tables 1 and 2 of the 2016 guideline update.

Likely phenotype	Activity score	Genotypes	Examples of diplotypes	Implications	Therapeutic Recommendations^{a, b}	Classification of recommendation for other TCAs ^c
CYP2D6 Ultrarapid metabolizer (~1-20% of patients)^d	>2.0	An individual carrying more than two copies of functional alleles	1/1xN, 1/2xN	Increased metabolism of TCAs to less active compounds compared to normal metabolizers. Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure.	Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments.^e	Optional
CYP2D6 Normal metabolizer (~72-88% of patients)^d	1.0-2.0^f	An individual carrying two normal function alleles or two decreased function alleles or one normal and no function allele or one normal and decreased function allele or combinations of duplicated alleles that result in an activity score of 1.0-2.0	1/1, 1/2, 2/2, 1/9, 1/41, 41/41, 1/4, 1/5	Normal metabolism of TCAs.	Initiate therapy with recommended starting dose.^g	Strong
CYP2D6 Intermediate metabolizer (~1-13% of patients)^d	0.5	An individual carrying one decreased and one no function allele	4/41, 5/9, 4/10	Reduced metabolism of TCAs to less active compounds when compared to normal metabolizers. Higher plasma concentrations of active drug will increase the probability of side effects.	Consider 25% reduction of recommended starting dose.^g Utilize therapeutic drug monitoring to guide dose adjustments.^e	Optional
CYP2D6 Poor metabolizer (~1-10% of patients)^d	0	An individual carrying only no function alleles	4/4, 4/4xN, 3/4, 5/5, 5/6	Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers. Higher plasma concentrations of active drug will increase the probability of side effects.	Avoid tricyclic use due to potential for side effects. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider 50% reduction of recommended starting dose.^g Utilize therapeutic drug monitoring to guide dose adjustments.^e	Optional

^a For tertiary amines (e.g., amitriptyline), if CYP2C19 genotype results are also available, see Table 2 for CYP2C19-based dosing recommendations and Table 3 below for CYP2D6/CYP2C19-based dosing recommendations.

^b Dosing recommendations only apply to higher initial doses of TCAs for treatment of conditions such as depression. See other considerations in the guideline for dosing recommendations for conditions where lower initial doses are used, such as neuropathic pain.

^c The rating scheme for the recommendation of classification is described in the Supplement. It may be reasonable to apply amitriptyline recommendation to other TCAs also metabolized by CYP2D6 including clomipramine, desipramine, doxepin, imipramine, and trimipramine. There are fewer clinical and pharmacokinetic data supporting genotype-guided dose adjustments for these drugs when compared to amitriptyline or nortriptyline (Supplemental Tables S8-S16).

^d CYP2D6 and CYP2C19 metabolizer status frequencies are based on average multi-ethnic frequencies. See the CYP2C19 and CYP2D6 Frequency Tables for population-specific allele and phenotype frequencies.

^e Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.

^f Patients with an activity score of 1.0 may be classified as intermediate metabolizers by some reference laboratories.

^g Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose.

Table 2: Dosing recommendations for TCAs based on CYP2C19 phenotype:

Adapted from Tables 1 and 3 of the 2016 guideline update.

Likely phenotype	Genotypes	Examples of diplotypes	Implications	Therapeutic recommendations^a,b	Classification of recommendations for amitriptyline^c
CYP2C19 Ultrarapid metabolizer (~2-5% of patients)^d	An individual carrying two increased function alleles	17/17	Increased metabolism of tertiary amines compared to normal metabolizers. Greater conversion of tertiary amines to secondary amines may affect response or side effects.	Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.^e	Optional
CYP2C19 Rapid metabolizer (~2-30% of patients)^d	An individual carrying one normal and one increased function allele	1/17	Increased metabolism of tertiary amines compared to normal metabolizers. Greater conversion of tertiary amines to secondary amines may affect response or side effects.	Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.^e	Optional
CYP2C19 Normal metabolizer (~35-50% of patients)^d	An individual carrying two normal function alleles	1/1	Normal metabolism of tertiary amines.	Initiate therapy with recommended starting dose.^f	Strong
CYP2C19 Intermediate metabolizer (~18-45% of patients)^d	An individual carrying one normal and one no function allele or one no and one increased function allele	1/2, 1/3, 2/17^g	Reduced metabolism of tertiary amines compared to normal metabolizers.	Initiate therapy with recommended starting dose.^f	Optional
CYP2C19 Poor metabolizer (~2-15% of patients)^d	An individual carrying two no function alleles	2/2, 2/3, 3/3	Greatly reduced metabolism of tertiary amines compared to normal metabolizers. Decreased conversion of tertiary amines to secondary amines may affect response or side effects.	Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose.^f Utilize therapeutic drug monitoring to guide dose adjustments.^e	Optional

^a For tertiary amines (e.g., amitriptyline), if CYP2D6 genotype results are also available, see Table 1 for CYP2D6-based dosing recommendations above and Table 3 below for CYP2D6/CYP2C19-based dosing recommendations.

^c The rating scheme for the recommendation of classification is described in the Supplement. It may be reasonable to apply amitriptyline recommendation to other TCAs also metabolized by CYP2C19 including clomipramine, doxepin, imipramine, and trimipramine. There are fewer clinical and pharmacokinetic data supporting dose adjustments for these drugs when compared to amitriptyline or nortriptyline (Supplemental Tables S8-S16).

^e Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects.

^f Patients may receive an initial low dose of a tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose.

^g The predicted metabolizer phenotype for the*2/*17 genotype is a provisional classification. The currently available evidence indicates that the CYP2C19*17 increased function allele is unable to completely compensate for the CYP2C19*2 no function allele.

May 2013

Guidelines regarding the use of pharmacogenomic tests in dosing for tricyclic antidepressants have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC).

Download: article and supplement

Excerpt from the dosing guidelines:

Amitriptyline and nortriptyline are used as model drugs for this guideline because the majority of pharmacogenomic studies have focused on these two drugs. Because the tricyclics have comparable pharmacokinetic properties, it may be reasonable to apply this guideline to other tricyclics including clomipramine (Supplementary Table S16), with the acknowledgement that there are fewer data supporting dose adjustments for these drugs than for amitriptyline or nortriptyline.

See amitriptyline for excerpts and tables that summarize CYP2D6-based and CYP2C19-based dosing recommendations for amitriptyline when higher initial starting doses are warranted (article).

last updated 08/10/2011

2. Annotation of DPWG Guideline for doxepin and CYP2D6

Summary

The Dutch Pharmacogenetics Working Group Guideline for doxepin recommends to reduce the dose by 60% for CYP2D6 poor metabolizers and by 20% for intermediate metabolizers. Select an alternative drug for CYP2D6 ultrarapid metabolizers.

Annotation

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for doxepin based on CYP2D6 genotypes [Article:21412232]. They recommend lower dose for patients carrying the poor metabolizer (PM) alleles and intermediate metabolizer alleles and alternative drug for patients carrying the ultrarapid metabolizer (UM) allleles.

Phenotype (Genotype)	Therapeutic Dose Recommendation	Level of Evidence	Clinical Relevance
PM (two inactive (3-8, 11-16, 19-21, 38, 40, *42) alleles)	Reduce dose by 60%. Adjust maintenance dose in response to (nor)doxepin plasma concentration	Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Clinical effect (S): death; arrhythmia; unanticipated myelosuppression.
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)	Reduce dose by 20%. Adjust maintenance dose in response to (nor)doxepin plasma concentration.	Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Minor clinical effect (S): QTc prolongation (<450 ms female, <470 ms male); INR increase < 4.5 Kinetic effect (S)
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)	Select alternative drug (citalopram, sertraline) or increase dose by 100%. Adjust maintenance dose in response to (nor)doxepin plasma concentration.	Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints.	Minor clinical effect (S): QTc prolongation (<450 ms female, <470 ms male); INR increase < 4.5 Kinetic effect (S).

*See Methods or [Article:18253145] for definition of "good" and "moderate" quality.
S: statistically significant difference.

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last updated 10/25/2013

1. Annotation of FDA Label for doxepin and CYP2C19,CYP2D6

On FDA Biomarker List

Actionable PGx

Summary

Doxepin is primarily metabolized by hepatic cytochrome P450 isozymes CYP2C19 and CYP2D6. The drug label notes that CYP2D6 and CYP2C19 poor metabolizers have higher than expected plasma concentrations of doxepin when given typical doses. Additionally, inhibitors of these CYP isozymes may increase the exposure of doxepin.

Annotation

Doxepin hydrochloride is a tricyclic psychotherapeutic agent (TCA). It is recommended for the treatment of psychoneurotic patients with depression and/or anxiety. Doxepin is primarily metabolized by CYP2D6.

Excerpts from the Doxepin drug label:

Silenor is primarily metabolized by hepatic cytochrome P450 isozymes CYP2C19 and CYP2D6, and to a lesser extent, by CYP1A2 and CYP2C9. Inhibitors of these isozymes may increase the exposure of doxepin.

Since doxepin is metabolized by CYP2C19 and CYP2D6, inhibitors of these CYP isozymes may increase the exposure of doxepin. ...A maximum dose of doxepin in adults and elderly should be 3 mg, when doxepin is co-administered with cimetidine.

Poor metabolizers of CYP2C19 and CYP2D6 may have higher doxepin plasma levels than normal subjects.

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

*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

Depression
- Indications & usage section, Warnings section, Adverse reactions section
- source: PHONT
Depression, Postpartum
- Warnings section, Adverse reactions section
- source: PHONT
CYP2C19
- metabolism/PK, Drug interactions section, Abuse section, Pharmacokinetics section
- source: U.S. Food and Drug Administration
CYP2D6
- metabolism/PK, Drug interactions section, Pharmacokinetics section
- source: U.S. Food and Drug Administration

Clinical Variants that meet the highest level of criteria, manually curated by PharmGKB, are shown below.

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

Clinical Annotation for rs3892097 (CYP2D6), amitriptyline, antidepressants, clomipramine, desipramine, doxepin, imipramine, nortriptyline, trimipramine and Depression (level 1A Dosage, Toxicity/ADR)

Level of Evidence: Level 1A
Type: Dosage, Toxicity/ADR
Variant: rs3892097
Genes: CYP2D6
Phenotypes: Depression
OMB Race: White

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Clinical Annotation for CYP2D61, CYP2D61xN, CYP2D62, CYP2D62xN, CYP2D63, CYP2D64, CYP2D6*5, doxepin (level 2A Efficacy)

Level of Evidence: Level 2A
Type: Efficacy
Variant: *1, *1xN, *2, *2xN, *3, *4, *5
Genes: CYP2D6
OMB Race: White

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Clinical Annotation for rs4244285 (CYP2C19), doxepin (level 3)

Level of Evidence: Level 3
Type: Other
Variant: rs4244285
Genes: CYP2C19
OMB Race: White

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Clinical Annotation for CYP2C91, CYP2C93, doxepin (level 3 Efficacy)

Level of Evidence: Level 3
Type: Efficacy
Variant: *1, *3
Genes: CYP2C9
OMB Race: White

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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 doxepin

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	Gene ?	Variant? (147)	Alternate Names ?	Chemicals ?	Alleles ? (+ chr strand)	Function ?	Amino Acid? Translation
VA	CYP2C19	*1		doxepin	N/A	N/A	N/A
VA	CYP2C19	*2		doxepin	N/A	N/A	N/A
CA	CYP2C9	*1		doxepin	N/A	N/A	N/A
CA VA	CYP2C9	*3		doxepin	N/A	N/A	N/A
VIP CA VA	CYP2D6	*1		amitriptyline atomoxetine carvedilol chlorpheniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine fluvoxamine gefitinib haloperidol imipramine maprotiline metoprolol mexiletine mianserin morphine nortriptyline opipramol paroxetine perhexiline perphenazine propafenone risperidone sparteine tamoxifen thioridazine timolol tolterodine tramadol yohimbine zuclopenthixol	N/A	N/A	N/A
CA VA	CYP2D6	*1xN		doxepin	N/A	N/A	N/A
VIP CA VA	CYP2D6	*2		amitriptyline atomoxetine carvedilol chlorpheniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine fluvoxamine gefitinib haloperidol imipramine maprotiline metoprolol mexiletine mianserin morphine nortriptyline paroxetine perhexiline perphenazine propafenone risperidone sparteine tamoxifen thioridazine timolol tolterodine tramadol yohimbine zuclopenthixol	N/A	N/A	N/A
CA VA	CYP2D6	*2xN		doxepin	N/A	N/A	N/A
VIP CA VA	CYP2D6	*3		amitriptyline atomoxetine carvedilol chlorpheniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine fluvoxamine gefitinib haloperidol imipramine maprotiline metoprolol mexiletine mianserin morphine nortriptyline paroxetine perhexiline perphenazine propafenone risperidone sparteine tamoxifen thioridazine timolol tolterodine tramadol yohimbine zuclopenthixol	N/A	N/A	N/A
VIP CA VA	CYP2D6	*4		amitriptyline atomoxetine carvedilol chlorpheniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine fluvoxamine gefitinib haloperidol imipramine maprotiline metoprolol mexiletine mianserin morphine nortriptyline opipramol paroxetine perhexiline perphenazine propafenone risperidone sparteine tamoxifen thioridazine timolol tolterodine tramadol yohimbine zuclopenthixol	N/A	N/A	N/A
CA VA	CYP2D6	*5		doxepin	N/A	N/A	N/A
VIP	CYP2D6	*6		amitriptyline atomoxetine carvedilol chlorpheniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine fluvoxamine gefitinib haloperidol imipramine maprotiline metoprolol mexiletine mianserin morphine nortriptyline paroxetine perhexiline perphenazine propafenone risperidone sparteine tamoxifen thioridazine timolol tolterodine tramadol yohimbine zuclopenthixol	N/A	N/A	N/A
VIP VA	CYP2D6	*9		amitriptyline atomoxetine carvedilol chlorpheniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine fluvoxamine gefitinib haloperidol imipramine maprotiline metoprolol mexiletine mianserin morphine nortriptyline paroxetine perhexiline perphenazine propafenone risperidone sparteine tamoxifen thioridazine timolol tolterodine tramadol yohimbine zuclopenthixol	N/A	N/A	N/A
VIP VA	CYP2D6	*10		amitriptyline atomoxetine carvedilol chlorpheniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine fluvoxamine gefitinib haloperidol imipramine maprotiline metoprolol mexiletine mianserin morphine nortriptyline paroxetine perhexiline perphenazine propafenone risperidone sparteine tamoxifen thioridazine timolol tolterodine tramadol yohimbine zuclopenthixol	N/A	N/A	N/A
VIP	CYP2D6	*17		amitriptyline atomoxetine carvedilol chlorpheniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine fluvoxamine gefitinib haloperidol imipramine maprotiline metoprolol mexiletine mianserin morphine nortriptyline paroxetine perhexiline perphenazine propafenone risperidone sparteine tamoxifen thioridazine timolol tolterodine tramadol yohimbine zuclopenthixol	N/A	N/A	N/A
VIP	CYP2D6	*29		amitriptyline atomoxetine carvedilol chlorpheniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine fluvoxamine gefitinib haloperidol imipramine maprotiline metoprolol mexiletine mianserin morphine nortriptyline paroxetine perhexiline perphenazine propafenone risperidone sparteine tamoxifen thioridazine timolol tolterodine tramadol yohimbine zuclopenthixol	N/A	N/A	N/A
VA	CYP2D6	*35		doxepin	N/A	N/A	N/A
VA	CYP2D6	*35xN		doxepin	N/A	N/A	N/A
VIP VA	CYP2D6	*41		amitriptyline atomoxetine carvedilol chlorpheniramine chlorpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine fluvoxamine gefitinib haloperidol imipramine maprotiline metoprolol mexiletine mianserin morphine nortriptyline paroxetine perhexiline perphenazine propafenone risperidone sparteine tamoxifen thioridazine timolol tolterodine tramadol yohimbine zuclopenthixol	N/A	N/A	N/A
VIP	CYP2D6	rs1065852	NC_000022.10:g.42526694G=, NC_000022.10:g.42526694G>A, NC_000022.11:g.42130692G=, NC_000022.11:g.42130692G>A, NG_008376.3:g.4300C=, NG_008376.3:g.4300C>T, NM_000106.5:c.100C=, NM_000106.5:c.100C>T, NM_001025161.2:c.100C=, NM_001025161.2:c.100C>T, NP_000097.3:p.Pro34=, NP_000097.3:p.Pro34Ser, NP_001020332.2:p.Pro34=, NP_001020332.2:p.Pro34Ser, NT_187682.1:g.53033G=, NT_187682.1:g.53033G>A, NW_004504305.1:g.53019A=, NW_004504305.1:g.53019A>G, NW_009646208.1:g.16258A=, NW_009646208.1:g.16258A>G, XM_005278353.1:c.100T=, XM_005278353.1:c.100T>C, XM_005278354.1:c.-1454C>T, XM_005278354.1:c.-1454T>C, XM_005278354.3:c.-1454C>T, XM_005278354.3:c.-1454T>C, XM_011529966.1:c.100C=, XM_011529966.1:c.100C>T, XM_011529967.1:c.100C=, XM_011529967.1:c.100C>T, XM_011529968.1:c.100C=, XM_011529968.1:c.100C>T, XM_011529969.1:c.37+605C>T, XM_011529969.1:c.37+605T>C, XM_011529970.1:c.100C=, XM_011529970.1:c.100C>T, XM_011529971.1:c.37+605C>T, XM_011529971.1:c.37+605T>C, XM_011529972.1:c.100C=, XM_011529972.1:c.100C>T, XM_011547541.1:c.-1454C>T, XM_011547541.1:c.-1454T>C, XM_011547750.1:c.37+605C>T, XM_011547750.1:c.37+605T>C, XM_011547751.1:c.-1114C>T, XM_011547751.1:c.-1114T>C, XM_011547756.1:c.42+469A>G, XM_011547756.1:c.42+469G>A, XM_011548819.1:c.-1454C>T, XM_011548819.1:c.-1454T>C, XP_005278410.1:p.Ser34=, XP_005278410.1:p.Ser34Pro, XP_011528268.1:p.Pro34=, XP_011528268.1:p.Pro34Ser, XP_011528269.1:p.Pro34=, XP_011528269.1:p.Pro34Ser, XP_011528270.1:p.Pro34=, XP_011528270.1:p.Pro34Ser, XP_011528272.1:p.Pro34=, XP_011528272.1:p.Pro34Ser, XP_011528274.1:p.Pro34=, XP_011528274.1:p.Pro34Ser, XR_430455.2:n.328+4A>G, XR_430455.2:n.328+4G>A, XR_952536.1:n.-1751A>G, XR_952536.1:n.-1751G>A, XR_952537.1:n.-1751A>G, XR_952537.1:n.-1751G>A, XR_952538.1:n.-1751A>G, XR_952538.1:n.-1751G>A, XR_952539.1:n.-1462A>G, XR_952539.1:n.-1462G>A, XR_952745.1:n.1257C=, XR_952745.1:n.1257C>T, rs117813846, rs58862176		G > A	SNP	P34S
VIP	CYP2D6	rs16947	NC_000022.10:g.42523943A=, NC_000022.10:g.42523943A>G, NC_000022.11:g.42127941G=, NC_000022.11:g.42127941G>A, NG_008376.3:g.7051C=, NG_008376.3:g.7051C>T, NM_000106.5:c.886C=, NM_000106.5:c.886C>T, NM_001025161.2:c.733C=, NM_001025161.2:c.733C>T, NP_000097.3:p.Arg296=, NP_000097.3:p.Arg296Cys, NP_001020332.2:p.Arg245=, NP_001020332.2:p.Arg245Cys, NT_187682.1:g.50282A=, NT_187682.1:g.50282A>G, NW_004504305.1:g.50268G=, NW_004504305.1:g.50268G>A, NW_009646208.1:g.13507G=, NW_009646208.1:g.13507G>A, XM_005278353.1:c.742C=, XM_005278353.1:c.742C>T, XM_005278354.1:c.586C=, XM_005278354.1:c.586C>T, XM_005278354.3:c.586C=, XM_005278354.3:c.586C>T, XM_011529966.1:c.886C=, XM_011529966.1:c.886C>T, XM_011529967.1:c.886C=, XM_011529967.1:c.886C>T, XM_011529968.1:c.886C=, XM_011529968.1:c.886C>T, XM_011529969.1:c.742C=, XM_011529969.1:c.742C>T, XM_011529970.1:c.733C=, XM_011529970.1:c.733C>T, XM_011529971.1:c.742C=, XM_011529971.1:c.742C>T, XM_011529972.1:c.843+233C>T, XM_011529972.1:c.843+233T>C, XM_011547541.1:c.586C=, XM_011547541.1:c.586C>T, XM_011547750.1:c.742T=, XM_011547750.1:c.742T>C, XM_011547751.1:c.670T=, XM_011547751.1:c.670T>C, XM_011547756.1:c.-2094A>G, XM_011547756.1:c.-2094G>A, XM_011548819.1:c.586C=, XM_011548819.1:c.586C>T, XP_005278410.1:p.Arg248=, XP_005278410.1:p.Arg248Cys, XP_005278411.1:p.Arg196=, XP_005278411.1:p.Arg196Cys, XP_011528268.1:p.Arg296=, XP_011528268.1:p.Arg296Cys, XP_011528269.1:p.Arg296=, XP_011528269.1:p.Arg296Cys, XP_011528270.1:p.Arg296=, XP_011528270.1:p.Arg296Cys, XP_011528271.1:p.Arg248=, XP_011528271.1:p.Arg248Cys, XP_011528272.1:p.Arg245=, XP_011528272.1:p.Arg245Cys, XP_011528273.1:p.Arg248=, XP_011528273.1:p.Arg248Cys, XP_011545843.1:p.Arg196=, XP_011545843.1:p.Arg196Cys, XP_011546052.1:p.Cys248=, XP_011546052.1:p.Cys248Arg, XP_011546053.1:p.Cys224=, XP_011546053.1:p.Cys224Arg, XP_011547121.1:p.Arg196=, XP_011547121.1:p.Arg196Cys, XR_430455.2:n.-1930A>G, XR_430455.2:n.-1930G>A, XR_952745.1:n.2000+233C>T, XR_952745.1:n.2000+233T>C, rs117039205, rs57836231		A > G	SNP	R296C
VIP	CYP2D6	rs28371706	NC_000022.10:g.42525772G>A, NC_000022.11:g.42129770G>A, NG_008376.3:g.5222C>T, NM_000106.5:c.320C>T, NM_001025161.2:c.320C>T, NP_000097.3:p.Thr107Ile, NP_001020332.2:p.Thr107Ile, NT_187682.1:g.52111G>A, NW_004504305.1:g.52097G>A, NW_009646208.1:g.15336G>A, XM_005278353.1:c.320C>T, XM_005278354.1:c.-532C>T, XM_005278354.3:c.-532C>T, XM_011529966.1:c.320C>T, XM_011529967.1:c.320C>T, XM_011529968.1:c.320C>T, XM_011529969.1:c.177C>T, XM_011529970.1:c.320C>T, XM_011529971.1:c.177C>T, XM_011529972.1:c.320C>T, XM_011547541.1:c.-532C>T, XM_011547750.1:c.177C>T, XM_011547751.1:c.-192C>T, XM_011547756.1:c.-265G>A, XM_011548819.1:c.-532C>T, XP_005278410.1:p.Thr107Ile, XP_011528268.1:p.Thr107Ile, XP_011528269.1:p.Thr107Ile, XP_011528270.1:p.Thr107Ile, XP_011528271.1:p.His59=, XP_011528272.1:p.Thr107Ile, XP_011528273.1:p.His59=, XP_011528274.1:p.Thr107Ile, XP_011546052.1:p.His59=, XR_430455.2:n.-101G>A, XR_952745.1:n.1477C>T, rs587777915, rs59604033		G > A	SNP	T107I
VIP	CYP2D6	rs28371725	NC_000022.10:g.42523805C>T, NC_000022.11:g.42127803C>T, NG_008376.3:g.7189G>A, NM_000106.5:c.985+39G>A, NM_001025161.2:c.832+39G>A, NT_187682.1:g.50144C>T, NW_004504305.1:g.50130C>T, NW_009646208.1:g.13369C>T, XM_005278353.1:c.841+39G>A, XM_005278354.1:c.685+39G>A, XM_005278354.3:c.685+39G>A, XM_011529966.1:c.985+39G>A, XM_011529967.1:c.985+39G>A, XM_011529968.1:c.985+39G>A, XM_011529969.1:c.841+39G>A, XM_011529970.1:c.832+39G>A, XM_011529971.1:c.841+39G>A, XM_011529972.1:c.844-169G>A, XM_011547541.1:c.724G>A, XM_011547750.1:c.841+39G>A, XM_011547751.1:c.769+39G>A, XM_011548819.1:c.724G>A, XP_011545843.1:p.Glu242Lys, XP_011547121.1:p.Glu242Lys, XR_952745.1:n.2001-169G>A, rs57124011, rs587777916		C > T	SNP
VIP	CYP2D6	rs35742686	NC_000022.10:g.42524244delT, NC_000022.11:g.42128242delT, NG_008376.3:g.6750delA, NM_000106.5:c.775delA, NM_001025161.2:c.622delA, NP_000097.3:p.Arg259Glyfs, NP_001020332.2:p.Arg208Glyfs, NT_187682.1:g.50583delT, NW_004504305.1:g.50569delT, NW_009646208.1:g.13808delT, XM_005278353.1:c.631delA, XM_005278354.1:c.475delA, XM_005278354.3:c.475delA, XM_011529966.1:c.775delA, XM_011529967.1:c.775delA, XM_011529968.1:c.775delA, XM_011529969.1:c.631delA, XM_011529970.1:c.622delA, XM_011529971.1:c.631delA, XM_011529972.1:c.775delA, XM_011547541.1:c.475delA, XM_011547750.1:c.631delA, XM_011547751.1:c.559delA, XM_011547756.1:c.-1793delT, XM_011548819.1:c.475delA, XP_005278410.1:p.Arg211Glyfs, XP_005278411.1:p.Arg159Glyfs, XP_011528268.1:p.Arg259Glyfs, XP_011528269.1:p.Arg259Glyfs, XP_011528270.1:p.Arg259Glyfs, XP_011528271.1:p.Arg211Glyfs, XP_011528272.1:p.Arg208Glyfs, XP_011528273.1:p.Arg211Glyfs, XP_011528274.1:p.Arg259Glyfs, XP_011545843.1:p.Arg159Glyfs, XP_011546052.1:p.Arg211Glyfs, XP_011546053.1:p.Arg187Glyfs, XP_011547121.1:p.Arg159Glyfs, XR_430455.2:n.-1629delT, XR_952745.1:n.1932delA, rs45593132, rs60790764		T > - T > T	indel	R259G
VIP CA VA	CYP2D6	rs3892097	NC_000022.10:g.42524947C=, NC_000022.10:g.42524947C>T, NC_000022.11:g.42128945C=, NC_000022.11:g.42128945C>T, NG_008376.3:g.6047G=, NG_008376.3:g.6047G>A, NM_000106.5:c.506-1A>G, NM_000106.5:c.506-1G>A, NM_001025161.2:c.353-1A>G, NM_001025161.2:c.353-1G>A, NT_187682.1:g.51286C=, NT_187682.1:g.51286C>T, NW_004504305.1:g.51272T=, NW_004504305.1:g.51272T>C, NW_009646208.1:g.14511C=, NW_009646208.1:g.14511C>T, XM_005278353.1:c.363-2A>G, XM_005278353.1:c.363-2G>A, XM_005278354.1:c.207-2A>G, XM_005278354.1:c.207-2G>A, XM_005278354.3:c.207-2A>G, XM_005278354.3:c.207-2G>A, XM_011529966.1:c.506-1A>G, XM_011529966.1:c.506-1G>A, XM_011529967.1:c.506-1A>G, XM_011529967.1:c.506-1G>A, XM_011529968.1:c.506-1A>G, XM_011529968.1:c.506-1G>A, XM_011529969.1:c.363-2A>G, XM_011529969.1:c.363-2G>A, XM_011529970.1:c.353-1A>G, XM_011529970.1:c.353-1G>A, XM_011529971.1:c.363-2A>G, XM_011529971.1:c.363-2G>A, XM_011529972.1:c.506-1A>G, XM_011529972.1:c.506-1G>A, XM_011547541.1:c.207-2A>G, XM_011547541.1:c.207-2G>A, XM_011547750.1:c.363-2A>G, XM_011547750.1:c.363-2G>A, XM_011547751.1:c.290-1A>G, XM_011547751.1:c.290-1G>A, XM_011547756.1:c.-1090C>T, XM_011547756.1:c.-1090T>C, XM_011548819.1:c.207-2A>G, XM_011548819.1:c.207-2G>A, XR_430455.2:n.-926C>T, XR_430455.2:n.-926T>C, XR_952745.1:n.1663-1A>G, XR_952745.1:n.1663-1G>A, rs1800716, rs28371711, rs60082401, rs606231227	clomipramine nortriptyline opipramol maprotiline desipramine amitriptyline trimipramine imipramine antidepressants doxepin	C > T	SNP
CA VA	CYP2C19	rs4244285	NC_000010.10:g.96541616G>A, NC_000010.11:g.94781859G>A, NG_008384.2:g.24154G>A, NM_000769.1:c.681G>A, NM_000769.2:c.681G>A, NP_000760.1:p.Pro227=, rs116940633, rs17879456, rs60361278	doxepin	G > A	SNP	P227P
VIP	CYP2D6	rs5030655	NC_000022.10:g.42525086delA, NC_000022.11:g.42129084delA, NG_008376.3:g.5908delT, NM_000106.5:c.454delT, NM_001025161.2:c.353-140delT, NP_000097.3:p.Trp152Glyfs, NT_187682.1:g.51425delA, NW_004504305.1:g.51411delA, NW_009646208.1:g.14650delA, XM_005278353.1:c.363-141delT, XM_005278354.1:c.155delT, XM_005278354.3:c.155delT, XM_011529966.1:c.454delT, XM_011529967.1:c.454delT, XM_011529968.1:c.454delT, XM_011529969.1:c.311delT, XM_011529970.1:c.353-140delT, XM_011529971.1:c.311delT, XM_011529972.1:c.454delT, XM_011547541.1:c.155delT, XM_011547750.1:c.311delT, XM_011547751.1:c.238delT, XM_011547756.1:c.-951delA, XM_011548819.1:c.155delT, XP_005278411.1:p.Val52Glyfs, XP_011528268.1:p.Trp152Glyfs, XP_011528269.1:p.Trp152Glyfs, XP_011528270.1:p.Trp152Glyfs, XP_011528271.1:p.Val104Glyfs, XP_011528273.1:p.Val104Glyfs, XP_011528274.1:p.Trp152Glyfs, XP_011545843.1:p.Val52Glyfs, XP_011546052.1:p.Val104Glyfs, XP_011546053.1:p.Trp80Glyfs, XP_011547121.1:p.Val52Glyfs, XR_430455.2:n.-787delA, XR_952745.1:n.1611delT, rs11568727, rs28371709		A > - A > A	indel	W152G
VIP	CYP2D6	rs5030656	NC_000022.10:g.42524176_42524178delCTT, NC_000022.11:g.42128174_42128176delCTT, NG_008376.3:g.6816_6818delAAG, NM_000106.5:c.841_843delAAG, NM_001025161.2:c.688_690delAAG, NP_000097.3:p.Lys281del, NP_001020332.2:p.Lys230del, NT_187682.1:g.50515_50517delCTT, NW_004504305.1:g.50501_50503delCTT, NW_009646208.1:g.13740_13742delCTT, XM_005278353.1:c.697_699delAAG, XM_005278354.1:c.541_543delAAG, XM_005278354.3:c.541_543delAAG, XM_011529966.1:c.841_843delAAG, XM_011529967.1:c.841_843delAAG, XM_011529968.1:c.841_843delAAG, XM_011529969.1:c.697_699delAAG, XM_011529970.1:c.688_690delAAG, XM_011529971.1:c.697_699delAAG, XM_011529972.1:c.841_843delAAG, XM_011547541.1:c.541_543delAAG, XM_011547750.1:c.697_699delAAG, XM_011547751.1:c.625_627delAAG, XM_011547756.1:c.-1861_-1859del, XM_011548819.1:c.541_543delAAG, XP_005278410.1:p.Lys233del, XP_005278411.1:p.Lys181del, XP_011528268.1:p.Lys281del, XP_011528269.1:p.Lys281del, XP_011528270.1:p.Lys281del, XP_011528271.1:p.Lys233del, XP_011528272.1:p.Lys230del, XP_011528273.1:p.Lys233del, XP_011528274.1:p.Lys281del, XP_011545843.1:p.Lys181del, XP_011546052.1:p.Lys233del, XP_011546053.1:p.Lys209del, XP_011547121.1:p.Lys181del, XR_430455.2:n.-1697_-1695del, XR_952745.1:n.1998_2000delAAG, rs587777919		CTT > - CTT > CTT	indel
VIP	CYP2D6	rs59421388	NC_000022.10:g.42523610C>T, NC_000022.11:g.42127608C>T, NG_008376.3:g.7384G>A, NM_000106.5:c.1012G>A, NM_001025161.2:c.859G>A, NP_000097.3:p.Val338Met, NP_001020332.2:p.Val287Met, NT_187682.1:g.49949C>T, NW_004504305.1:g.49935C>T, NW_009646208.1:g.13174C>T, XM_005278353.1:c.868G>A, XM_005278354.1:c.712G>A, XM_005278354.3:c.712G>A, XM_011529966.1:c.1012G>A, XM_011529967.1:c.1012G>A, XM_011529968.1:c.1012G>A, XM_011529969.1:c.868G>A, XM_011529970.1:c.859G>A, XM_011529971.1:c.868G>A, XM_011529972.1:c.870G>A, XM_011547541.1:c.118G>A, XM_011547750.1:c.868G>A, XM_011547751.1:c.796G>A, XM_011548819.1:c.118G>A, XP_005278410.1:p.Val290Met, XP_005278411.1:p.Val238Met, XP_011528268.1:p.Val338Met, XP_011528269.1:p.Val338Met, XP_011528270.1:p.Val338Met, XP_011528271.1:p.Val290Met, XP_011528272.1:p.Val287Met, XP_011528273.1:p.Val290Met, XP_011528274.1:p.Thr290=, XP_011546052.1:p.Val290Met, XP_011546053.1:p.Val266Met, XR_952745.1:n.2027G>A		C > T	SNP	V338M
VIP	CYP2D6	rs61736512	NC_000022.10:g.42525134C>T, NC_000022.11:g.42129132C>T, NG_008376.3:g.5860G>A, NM_000106.5:c.406G>A, NM_001025161.2:c.353-188G>A, NP_000097.3:p.Val136Met, NT_187682.1:g.51473C>T, NW_004504305.1:g.51459C>T, NW_009646208.1:g.14698C>T, XM_005278353.1:c.363-189G>A, XM_005278354.1:c.107G>A, XM_005278354.3:c.107G>A, XM_011529966.1:c.406G>A, XM_011529967.1:c.406G>A, XM_011529968.1:c.406G>A, XM_011529969.1:c.263G>A, XM_011529970.1:c.353-188G>A, XM_011529971.1:c.263G>A, XM_011529972.1:c.406G>A, XM_011547541.1:c.107G>A, XM_011547750.1:c.263G>A, XM_011547751.1:c.190G>A, XM_011547756.1:c.-903C>T, XM_011548819.1:c.107G>A, XP_005278411.1:p.Arg36His, XP_011528268.1:p.Val136Met, XP_011528269.1:p.Val136Met, XP_011528270.1:p.Val136Met, XP_011528271.1:p.Arg88His, XP_011528273.1:p.Arg88His, XP_011528274.1:p.Val136Met, XP_011545843.1:p.Arg36His, XP_011546052.1:p.Arg88His, XP_011546053.1:p.Val64Ile, XP_011547121.1:p.Arg36His, XR_430455.2:n.-739C>T, XR_952745.1:n.1563G>A		C > T	SNP	V136M

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

[ see larger image ] [ see 3D structure ]

provided by PubChem

Overview

Generic Names

Doxepin Hcl
Doxepin, Hydrochloride
Doxepina [INN-Spanish]
Doxepine
Doxepinum [INN-Latin]

Trade Names

Adapin
Aponal
Curatin
Quitaxon
Sinequan
Triadapin
Zonalon

Brand Mixture Names

PharmGKB Accession Id

PA449409

Type(s):

Drug

Description

Doxepin hydrochloride is a dibenzoxepin-derivative tricyclic antidepressant (TCA). TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, doxepin does not affect mood or arousal, but may cause sedation. In depressed individuals, doxepin exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Tertiary amine TCAs, such as doxepin and amitriptyline, are more potent inhibitors of serotonin reuptake than secondary amine TCAs, such as nortriptyline and desipramine. TCAs also down-regulate cerebral cortical beta-adrenergic receptors and sensitize post-synaptic serotonergic receptors with chronic use. The antidepressant effects of TCAs are thought to be due to an overall increase in serotonergic neurotransmission. TCAs also block histamine H ~1~ receptors, alpha ~1~-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e.g. blurred vision, dry mouth, constipation, urinary retention), respectively. Doxepin has less sedative and anticholinergic effects than amitriptyline. See toxicity section below for a complete listing of side effects. Doxepin may be used to treat depression and insomnia. Unlabeled indications include chronic and neuropathic pain, and anxiety. Doxepin may also be used as a second line agent to treat idiopathic urticaria.

Source: Drug Bank

Indication

Labeled indications: depression and insomnia. Unlabeled indications: chronic and neuropathic pain, anxiety, idiopathic urticaria.

Source: Drug Bank

Other Vocabularies

ATC: Non-selective monoamine reuptake inhibitors (N06AA)
UMLS: Doxepin (C0013085)
RxNorm: Doxepin (3638)
NDFRT: DOXEPIN (N0000147828)

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

The mechanism of action of doxepin is not completely understood. It is thought that Like amitriptyline, doxepin enhances the actions of norepinephrine and serotonin by blocking their reuptake at the neuronal membrane. Doxepin may also act on histamine H ~1~-receptors, resulting in sedative effects, and beta-adrenergic receptors.

Source: Drug Bank

Pharmacology

Doxepin, a tricyclic antidepressant of the dibenzoxepin type, is used to treat depression and anxiety and, topically, pruritus associated with eczema. Doxepin has substantial anticholinergic and sedative effects.

Source: Drug Bank

Food Interaction

Avoid St.John's Wort.|Avoid alcohol.|Avoid excessive quantities of coffee or tea (caffeine).|Take with food to reduce irritation.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Extensively metabolized in the liver via the same pathways as other TCAs. _N_-demethylation produces an active metabolite, _N_-desmethyldoxepin.

Source: Drug Bank

Protein Binding

Highly bound to plasma proteins.

Source: Drug Bank

Absorption

Well-absorbed from the GI tract. Peak plasma concentrations occur within 2 hours of oral administration.

Source: Drug Bank

Half-Life

6 - 24.5 hours

Source: Drug Bank

Toxicity

LD ~50~=26 (mg/kg) (in mice, iv); LD ~50~=16 (mg/kg) (in rats, iv); Cardiac dysrhythmias, severe hypotension, convulsions, and CNS depression, including coma. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic antidepressant toxicity. Side effects include: sedation, hypotension, blurred vision, dry mouth, constipation, urinary retention, postural hypotension, tachycardia, hypertension, ECG changes, heart failure, impaired memory and delirium, and precipitation of hypomanic or manic episodes in bipolar depression. Withdrawal symptoms include gastrointestinal disturbances, anxiety, and insomnia.

Source: Drug Bank

Chemical Properties

Chemical Formula

C19H21NO

Source: Drug Bank

Average Molecular Weight

279.3761

Source: Drug Bank

Monoisotopic Molecular Weight

279.162314299

Source: Drug Bank

SMILES

CN(C)CC/C=C/1\C2=CC=CC=C2COC3=CC=CC=C31

Source: PubChem

InChI String

InChI=1S/C19H21NO/c1-20(2)13-7-11-17-16-9-4-3-8-15(16)14-21-19-12-6-5-10-18(17)19/h3-6,8-12H,7,13-14H2,1-2H3/b17-11+

Source: PubChem

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

Doxepin Pathway, Pharmacokinetics
Stylized liver cell showing candidate genes involved in the metabolism of the tricyclic doxepin.

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 ?

view legend

Evidence	Gene
PW	CYP1A2
DG DL CA VA PW	CYP2C19
CA VA PW	CYP2C9
DG DL CA VA VIP PW	CYP2D6
PW	CYP3A4
VIP	KCNH2

Drug Targets

Gene	Description
ADRA1A	(source: Drug Bank )
ADRA1B	(source: Drug Bank )
ADRA1D	(source: Drug Bank )
ADRA2A	(source: Drug Bank )
ADRA2B	(source: Drug Bank )
ADRA2C	(source: Drug Bank )
CHRM1	(source: Drug Bank )
CHRM2	(source: Drug Bank )
CHRM3	(source: Drug Bank )
CHRM4	(source: Drug Bank )
CHRM5	(source: Drug Bank )
DRD2	(source: Drug Bank )
HRH1	(source: Drug Bank )
HRH2	(source: Drug Bank )
HTR1A	(source: Drug Bank )
HTR2A	(source: Drug Bank )
HTR2B	(source: Drug Bank )
HTR2C	(source: Drug Bank )
SLC6A2	(source: Drug Bank )
SLC6A4	(source: Drug Bank )

Drug Interactions

Interaction	Description
atazanavir - doxepin	Increases the effect and toxicity of tricyclics (source: Drug Bank )
atazanavir - doxepin	Atazanavir may increase the effect and toxicity of the tricyclic antidepressant, doxepin, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of doxepin if atazanavir if initiated, discontinued or dose changed. (source: Drug Bank )
carbamazepine - doxepin	The tricyclic increases the effect of carbamazepine (source: Drug Bank )
carbamazepine - doxepin	Carbamazepine may decrease the serum concentration of the tricyclic antidepressant, doxepin, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of doxepin if carbamazepine is initiated, discontinued or dose changed. (source: Drug Bank )
cimetidine - doxepin	Increases the effect of tricyclic agent (source: Drug Bank )
cimetidine - doxepin	Cimetidine may increase the effect of tricyclic antidepressant, doxepin, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of doxepin if cimetidine is initiated, discontinued or dose changed. (source: Drug Bank )
cisapride - doxepin	Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank )
cisapride - doxepin	Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank )
clonidine - doxepin	The tricyclic decreases the effect of clonidine (source: Drug Bank )
clonidine - doxepin	The tricyclic antidepressant, doxepin, decreases the effect of clonidine. (source: Drug Bank )
donepezil - doxepin	Possible antagonism of action (source: Drug Bank )
donepezil - doxepin	Possible antagonism of action (source: Drug Bank )
doxepin - altretamine	Risk of severe hypotension (source: Drug Bank )
doxepin - altretamine	Risk of severe hypotension (source: Drug Bank )
doxepin - atazanavir	Atazanavir increases the effect and toxicity of tricyclics (source: Drug Bank )
doxepin - atazanavir	Atazanavir may increase the effect and toxicity of the tricyclic antidepressant, doxepin, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of doxepin if atazanavir if initiated, discontinued or dose changed. (source: Drug Bank )
doxepin - carbamazepine	The tricyclic increases the effect of carbamazepine (source: Drug Bank )
doxepin - carbamazepine	Carbamazepine may decrease the serum concentration of the tricyclic antidepressant, doxepin, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of doxepin if carbamazepine is initiated, discontinued or dose changed. (source: Drug Bank )
doxepin - cimetidine	Cimetidine increases the effect of tricyclic agent (source: Drug Bank )
doxepin - cimetidine	Cimetidine may increase the effect of the tricyclic antidepressant, doxepin, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of doxepin if cimetidine is initiated, discontinued or dose changed. (source: Drug Bank )
doxepin - cisapride	Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank )
doxepin - cisapride	Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank )
doxepin - clonidine	The tricyclic decreases the effect of clonidine (source: Drug Bank )
doxepin - clonidine	The tricyclic antidepressant, doxepin, decreases the effect of clonidine. (source: Drug Bank )
doxepin - dobutamine	The tricyclic increases the sympathomimetic effect (source: Drug Bank )
doxepin - dobutamine	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of dobutamine. (source: Drug Bank )
doxepin - donepezil	Possible antagonism of action (source: Drug Bank )
doxepin - donepezil	Possible antagonism of action (source: Drug Bank )
doxepin - dopamine	The tricyclic increases the sympathomimetic effect (source: Drug Bank )
doxepin - dopamine	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of dopamine. (source: Drug Bank )
doxepin - ephedra	The tricyclic increases the sympathomimetic effect (source: Drug Bank )
doxepin - ephedra	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of ephedra. (source: Drug Bank )
doxepin - ephedrine	The tricyclic increases the sympathomimetic effect (source: Drug Bank )
doxepin - ephedrine	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of ephedrine. (source: Drug Bank )
doxepin - fenoterol	The tricyclic increases the sympathomimetic effect (source: Drug Bank )
doxepin - fenoterol	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of fenoterol. (source: Drug Bank )
doxepin - fluoxetine	Fluoxetine increases the effect and toxicity of tricyclics (source: Drug Bank )
doxepin - fluoxetine	The SSRI, fluoxetine, may increase the serum concentration of the tricyclic antidepressant, doxepin, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of doxepin if fluoxetine is initiated, discontinued or dose changed. (source: Drug Bank )
doxepin - fluvoxamine	Fluvoxamine increases the effect and toxicity of tricyclics (source: Drug Bank )
doxepin - fluvoxamine	The SSRI, fluvoxamine, may increase the serum concentration of the tricyclic antidepressant, doxepin, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of doxepin if fluvoxamine is initiated, discontinued or dose changed. (source: Drug Bank )
doxepin - galantamine	Possible antagonism of action (source: Drug Bank )
doxepin - galantamine	Possible antagonism of action (source: Drug Bank )
doxepin - grepafloxacin	Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank )
doxepin - grepafloxacin	Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank )
doxepin - guanethidine	The tricyclics decreases the effect of guanethidine (source: Drug Bank )
doxepin - guanethidine	The tricyclic antidepressant, doxepin, decreases the effect of guanethidine. (source: Drug Bank )
doxepin - isocarboxazid	Possibility of severe adverse effects (source: Drug Bank )
doxepin - isocarboxazid	Possibility of severe adverse effects (source: Drug Bank )
doxepin - isoproterenol	The tricyclic increases the sympathomimetic effect (source: Drug Bank )
doxepin - isoproterenol	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of isoproterenol. (source: Drug Bank )
doxepin - mephentermine	The tricyclic increases the sympathomimetic effect (source: Drug Bank )
doxepin - mephentermine	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of mephentermine. (source: Drug Bank )
doxepin - mesoridazine	Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank )
doxepin - mesoridazine	Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank )
doxepin - metaraminol	The tricyclic increases the sympathomimetic effect (source: Drug Bank )
doxepin - metaraminol	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of metaraminol. (source: Drug Bank )
doxepin - methoxamine	The tricyclic increases the sympathomimetic effect (source: Drug Bank )
doxepin - methoxamine	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of methoxamine. (source: Drug Bank )
doxepin - moclobemide	Possible severe adverse reaction with this combination (source: Drug Bank )
doxepin - moclobemide	Possible severe adverse reaction with this combination (source: Drug Bank )
doxepin - norepinephrine	The tricyclic increases the sympathomimetic effect (source: Drug Bank )
doxepin - norepinephrine	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of norepinephrine. (source: Drug Bank )
doxepin - orciprenaline	The tricyclic increases the sympathomimetic effect (source: Drug Bank )
doxepin - orciprenaline	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of orciprenaline. (source: Drug Bank )
doxepin - phenelzine	Possibility of severe adverse effects (source: Drug Bank )
doxepin - phenelzine	Possibility of severe adverse effects (source: Drug Bank )
doxepin - phenylephrine	The tricyclic increases the sympathomimetic effect (source: Drug Bank )
doxepin - phenylephrine	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of phenylephrine. (source: Drug Bank )
doxepin - phenylpropanolamine	The tricyclic increases the sympathomimetic effect (source: Drug Bank )
doxepin - phenylpropanolamine	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of phenylpropanolamine. (source: Drug Bank )
doxepin - pirbuterol	The tricyclic increases the sympathomimetic effect (source: Drug Bank )
doxepin - pirbuterol	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of pirbuterol. (source: Drug Bank )
doxepin - procaterol	The tricyclic increases the sympathomimetic effect (source: Drug Bank )
doxepin - procaterol	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of procaterol. (source: Drug Bank )
doxepin - pseudoephedrine	The tricyclic increases the sympathomimetic effect (source: Drug Bank )
doxepin - pseudoephedrine	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of pseudoephedrine. (source: Drug Bank )
doxepin - quinidine	Quinidine increases the effect of tricyclic agent (source: Drug Bank )
doxepin - quinidine	Quinidine increases the effect of tricyclic agent (source: Drug Bank )
doxepin - quinidine	Quinidine barbiturate increases the effect of tricyclic antidepressant, doxepin. (source: Drug Bank )
doxepin - rasagiline	Possibility of severe adverse effects (source: Drug Bank )
doxepin - rasagiline	Possibility of severe adverse effects (source: Drug Bank )
doxepin - rifabutin	The rifamycin decreases the effect of tricyclics (source: Drug Bank )
doxepin - rifabutin	The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, doxepin, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of doxepin if rifabutin is initiated, discontinued or dose changed. (source: Drug Bank )
doxepin - rifampin	The rifamycin decreases the effect of tricyclics (source: Drug Bank )
doxepin - rifampin	The rifamycin, rifampin, may decrease the effect of the tricyclic antidepressant, doxepin, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of doxepin if rifampin is initiated, discontinued or dose changed. (source: Drug Bank )
doxepin - ritonavir	Ritonavir increases the effect and toxicity of tricyclics (source: Drug Bank )
doxepin - ritonavir	Ritonavir may increase the effect and toxicity of the tricyclic antidepressant, doxepin, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of doxepin if ritonavir if initiated, discontinued or dose changed. (source: Drug Bank )
doxepin - rivastigmine	Possible antagonism of action (source: Drug Bank )
doxepin - rivastigmine	Possible antagonism of action (source: Drug Bank )
doxepin - salbutamol	The tricyclic increases the sympathomimetic effect (source: Drug Bank )
doxepin - salbutamol	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of salbutamol. (source: Drug Bank )
doxepin - sibutramine	Increased risk of CNS adverse effects (source: Drug Bank )
doxepin - sibutramine	Increased risk of CNS adverse effects (source: Drug Bank )
doxepin - sparfloxacin	Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank )
doxepin - sparfloxacin	Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank )
doxepin - terbutaline	The tricyclic increases the sympathomimetic effect (source: Drug Bank )
doxepin - terbutaline	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of terbutaline. (source: Drug Bank )
doxepin - terfenadine	Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank )
doxepin - terfenadine	Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank )
doxepin - thioridazine	Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank )
doxepin - thioridazine	Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank )
doxepin - tranylcypromine	Possibility of severe adverse effects (source: Drug Bank )
doxepin - tranylcypromine	Possibility of severe adverse effects (source: Drug Bank )
epinephrine - doxepin	The tricyclic increases the sympathomimetic effect (source: Drug Bank )
epinephrine - doxepin	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of epinephrine. (source: Drug Bank )
fenoterol - doxepin	The tricyclic increases the sympathomimetic effect (source: Drug Bank )
fenoterol - doxepin	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of fenoterol. (source: Drug Bank )
fluoxetine - doxepin	Fluoxetine increases the effect and toxicity of tricyclics (source: Drug Bank )
fluoxetine - doxepin	The SSRI, fluoxetine, may increase the serum concentration of the tricyclic antidepressant, doxepin, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of doxepin if fluoxetine is initiated, discontinued or dose changed. (source: Drug Bank )
galantamine - doxepin	Possible antagonism of action (source: Drug Bank )
galantamine - doxepin	Possible antagonism of action (source: Drug Bank )
grepafloxacin - doxepin	Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank )
grepafloxacin - doxepin	Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank )
guanethidine - doxepin	The tricyclic decreases the effect of guanethidine (source: Drug Bank )
guanethidine - doxepin	The tricyclic antidepressant, doxepin, decreases the effect of guanethidine. (source: Drug Bank )
isocarboxazid - doxepin	Possibility of severe adverse effects (source: Drug Bank )
isocarboxazid - doxepin	Possibility of severe adverse effects (source: Drug Bank )
mesoridazine - doxepin	Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank )
mesoridazine - doxepin	Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank )
moclobemide - doxepin	Possible severe adverse reaction with this combination (source: Drug Bank )
moclobemide - doxepin	Possible severe adverse reaction with this combination (source: Drug Bank )
orciprenaline - doxepin	The tricyclic increases the sympathomimetic effect (source: Drug Bank )
orciprenaline - doxepin	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of orciprenaline. (source: Drug Bank )
phenelzine - doxepin	Possibility of severe adverse effects (source: Drug Bank )
phenelzine - doxepin	Possibility of severe adverse effects (source: Drug Bank )
phenylephrine - doxepin	The tricyclic increases the sympathomimetic effect (source: Drug Bank )
phenylephrine - doxepin	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of phenylephrine. (source: Drug Bank )
phenylpropanolamine - doxepin	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of phenylpropanolamine. (source: Drug Bank )
pseudoephedrine - doxepin	The tricyclic increases the sympathomimetic effect (source: Drug Bank )
pseudoephedrine - doxepin	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of pseudoephedrine. (source: Drug Bank )
quinidine - doxepin	Quinidine increases the effect of the tricyclic agent (source: Drug Bank )
quinidine - doxepin	Additive QTc-prolonging effects may occur. Quinidine may also increase the serum concentration of the tricyclic antidepressant, doxepin, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amitriptyline if doxepin is initiated, discontinued or dose changed. Monitor for the development of torsades de pointes during concomitant therapy. (source: Drug Bank )
rasagiline - doxepin	Possibility of severe adverse effects (source: Drug Bank )
rifabutin - doxepin	The rifamycin decreases the effect of tricyclics (source: Drug Bank )
rifabutin - doxepin	The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, doxepin, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of doxepin if rifabutin is initiated, discontinued or dose changed. (source: Drug Bank )
rifampin - doxepin	The rifamycin decreases the effect of tricyclics (source: Drug Bank )
rifampin - doxepin	The rifamycin, rifampin, may decrease the effect of the tricyclic antidepressant, doxepin, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of doxepin if rifampin is initiated, discontinued or dose changed. (source: Drug Bank )
tacrine - doxepin	The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Doxepin, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents. (source: Drug Bank )
tacrine - doxepin	The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Doxepin, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents. (source: Drug Bank )
telithromycin - doxepin	Telithromycin may reduce clearance of Doxepin. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Doxepin if Telithromycin is initiated, discontinued or dose changed. (source: Drug Bank )
terbutaline - doxepin	The tricyclic increases the sympathomimetic effect (source: Drug Bank )
terbutaline - doxepin	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of terbutaline. (source: Drug Bank )
terfenadine - doxepin	Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank )
terfenadine - doxepin	Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank )
thiabendazole - doxepin	The strong CYP1A2 inhibitor, Thiabendazole, may increase the effects and toxicity of Doxepin by decreasing Doxepin metabolism and clearance. Monitor for changes in the therapeutic and adverse effects of Doxepin if Thiabendazole is initiated, discontinued or dose changed. (source: Drug Bank )
thioridazine - doxepin	Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank )
thioridazine - doxepin	Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank )
thiothixene - doxepin	May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration. (source: Drug Bank )
thiothixene - doxepin	May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration. (source: Drug Bank )
toremifene - doxepin	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration. (source: Drug Bank )
tramadol - doxepin	Tramadol increases the risk of serotonin syndrome and seizures. (source: Drug Bank )
tranylcypromine - doxepin	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 - doxepin	Increased risk of serotonin syndrome. The 2D6 inhibitor, Trazodone, may also increase the efficacy of Doxepin by decreasing Doxepin metabolism and clearance. Monitor for symptoms of serotonin syndrome and changes in Doxepin efficacy if Trazodone is initiated, discontinued or dose changed. (source: Drug Bank )
trazodone - doxepin	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
trimethobenzamide - doxepin	Trimethobenzamide and Doxepin, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects. (source: Drug Bank )
trimipramine - doxepin	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Additive QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution. (source: Drug Bank )
triprolidine - doxepin	Triprolidine and Doxepin, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects. (source: Drug Bank )
triprolidine - doxepin	Triprolidine and Doxepin, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects. (source: Drug Bank )
trospium - doxepin	Trospium and Doxepin, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects. (source: Drug Bank )
venlafaxine - doxepin	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank )
voriconazole - doxepin	Additive QTc prolongation may occur. Voriconazole, a strong CYP3A4 inhibitor, may also increase the serum concentration of doxepin by decreasing its metabolism. Consider alternate therapy or monitor for QTc prolongation and changes in the therapeutic and adverse effects of doxepin if voriconazole is initiated, discontinued or dose changed. (source: Drug Bank )
vorinostat - doxepin	Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP). (source: Drug Bank )
ziprasidone - doxepin	Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated. (source: Drug Bank )
zolmitriptan - doxepin	Use of two serotonin modulators, such as zolmitriptan and doxepin, increases the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy. (source: Drug Bank )
zuclopenthixol - doxepin	Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP). (source: Drug Bank )

Curated Information ?

view legend

Evidence	Disease
DL CA VA	Depression
DL	Depression, Postpartum
VA	Mental Disorders
VA	Poisoning

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Treat

Contraindicated With

doxepin contraindicated with Drug Hypersensitivity
doxepin contraindicated with Glaucoma, Angle-Closure
doxepin contraindicated with Myocardial Infarction
doxepin contraindicated with Urinary Retention

Publications related to doxepin: 46

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	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.
	Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC®) for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants: 2016 Update. Clinical pharmacology and therapeutics. 2016. Kevin Hicks J, et al.
	Pharmacogenomically actionable medications in a safety net health care system. SAGE open medicine. 2016. Carpenter Janet S, et al.
	Integrated Patient and Tumor Genetic Testing for Individualized Cancer Therapy. Clinical pharmacology and therapeutics. 2015. Hertz Daniel L, et al.
	The genetics of pro-arrhythmic adverse drug reactions. British journal of clinical pharmacology. 2014. Petropoulou Evmorfia, et al.
	Challenges in pharmacogenetics. European journal of clinical pharmacology. 2013. Cascorbi Ingolf, et al.
VA	Fatal doxepin intoxication--suicide or slow gradual intoxication?. Forensic science international. 2013. Neukamm M A, et al.
	Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants. Clinical pharmacology and therapeutics. 2013. Hicks J K, et al.
CA	Prolonged toxicity after amitriptyline overdose in a patient deficient in CYP2D6 activity. Journal of medical toxicology : official journal of the American College of Medical Toxicology. 2011. Smith Jennifer Cohen, et al.
	Pharmacogenetics: From Bench to Byte- An Update of Guidelines. Clinical pharmacology and therapeutics. 2011. Swen J J, et al.
CA	Pharmacogenetics and gender association with psychotic episodes on nortriptyline lower doses: patient cases. ISRN pharmaceutics. 2011. Piatkov Irina, et al.
VIP	KCNH2 pharmacogenomics summary. Pharmacogenetics and genomics. 2010. Oshiro Connie, 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.
CA	Association between CYP2C1917 and metabolism of amitriptyline, citalopram and clomipramine in Dutch hospitalized patients. The pharmacogenomics journal.* 2010. de Vos A, et al.
VIP	Cytochrome P450 2D6. Pharmacogenetics and genomics. 2009. Owen Ryan P, et al.
CA	Life-threatening dextromethorphan intoxication associated with interaction with amitriptyline in a poor CYP2D6 metabolizer: a single case re-exposure study. Journal of pain and symptom management. 2008. Forget Patrice, et al.
CA	Association of graded allele-specific changes in CYP2D6 function with imipramine dose requirement in a large group of depressed patients. Molecular psychiatry. 2008. Schenk P W, et al.
CA VA	Influence of the CYP2D64 polymorphism on dose, switching and discontinuation of antidepressants. British journal of clinical pharmacology.* 2008. Bijl Monique J, et al.
CA	The CYP2D6 polymorphism in relation to the metabolism of amitriptyline and nortriptyline in the Faroese population. British journal of clinical pharmacology. 2008. Halling Jónrit, et al.
CA VA	A fatal doxepin poisoning associated with a defective CYP2D6 genotype. The American journal of forensic medicine and pathology. 2007. Koski Anna, et al.
VIP	Inhibition of the HERG potassium channel by the tricyclic antidepressant doxepin. Biochemical pharmacology. 2007. Duncan R S, et al.
CA	A poor metabolizer for cytochromes P450 2D6 and 2C19: a case report on antidepressant treatment. CNS spectrums. 2006. Johnson Maria, et al.
CA	CYP2D6 and CYP2C19 genotypes and amitriptyline metabolite ratios in a series of medicolegal autopsies. Forensic science international. 2006. Koski Anna, et al.
	Serotonin transporter polymorphisms and side effects in antidepressant therapy--a pilot study. Pharmacogenomics. 2006. Popp Johannes, et al.
CA	Adverse drug reactions following nonresponse in a depressed patient with CYP2D6 deficiency and low CYP 3A4/5 activity. Pharmacopsychiatry. 2006. Stephan P L, et al.
	The complexity of active metabolites in therapeutic drug monitoring of psychotropic drugs. Pharmacopsychiatry. 2006. Hendset M, et al.
CA	Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2005. Goetz Matthew P, et al.
CA VA	Impact of the CYP2D6 ultra-rapid metabolizer genotype on doxepin pharmacokinetics and serotonin in platelets. Pharmacogenetics and genomics. 2005. Kirchheiner Julia, et al.
CA	Allele-specific change of concentration and functional gene dose for the prediction of steady-state serum concentrations of amitriptyline and nortriptyline in CYP2C19 and CYP2D6 extensive and intermediate metabolizers. Clinical chemistry. 2004. Steimer Werner, et al.
CA	Clomipramine, fluoxetine and CYP2D6 metabolic capacity in depressed patients. Human psychopharmacology. 2004. Vandel P, et al.
CA	Impact of CYP2D6 intermediate metabolizer alleles on single-dose desipramine pharmacokinetics. Pharmacogenetics. 2004. Furman Katherine D, et al.
CA	No evidence of increased adverse drug reactions in cytochrome P450 CYP2D6 poor metabolizers treated with fluoxetine or nortriptyline. Human psychopharmacology. 2004. Roberts Rebecca L, et al.
CA	Trimipramine pharmacokinetics after intravenous and oral administration in carriers of CYP2D6 genotypes predicting poor, extensive and ultrahigh activity. Pharmacogenetics. 2003. Kirchheiner Julia, et al.
CA	Effects of polymorphisms in CYP2D6, CYP2C9, and CYP2C19 on trimipramine pharmacokinetics. Journal of clinical psychopharmacology. 2003. Kirchheiner Julia, et al.
CA VA VIP	Contributions of CYP2D6, CYP2C9 and CYP2C19 to the biotransformation of E- and Z-doxepin in healthy volunteers. Pharmacogenetics. 2002. Kirchheiner Julia, et al.
	The N-demethylation of the doxepin isomers is mainly catalyzed by the polymorphic CYP2C19. Pharmaceutical research. 2002. Härtter Sebastian, et al.
CA	CYP2D6 genotyping with oligonucleotide microarrays and nortriptyline concentrations in geriatric depression. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2001. Murphy G M, et al.
VA	Role of cytochrome P450 2D6 (CYP2D6) in the stereospecific metabolism of E- and Z-doxepin. Pharmacogenetics. 2000. Haritos V S, et al.
CA	Clomipramine dose-effect study in patients with depression: clinical end points and pharmacokinetics. Danish University Antidepressant Group (DUAG). Clinical pharmacology and therapeutics. 1999.
CA	CYP2D6 phenotype-genotype relationships in African-Americans and Caucasians in Los Angeles. Pharmacogenetics. 1998. Leathart J B, et al.
CA	10-Hydroxylation of nortriptyline in white persons with 0, 1, 2, 3, and 13 functional CYP2D6 genes. Clinical pharmacology and therapeutics. 1998. Dalén P, et al.
CA	Steady-state plasma levels of nortriptyline and its 10-hydroxy metabolite: relationship to the CYP2D6 genotype. Psychopharmacology. 1996. Dahl M L, et al.
CA	Single-dose kinetics of clomipramine: relationship to the sparteine and S-mephenytoin oxidation polymorphisms. Clinical pharmacology and therapeutics. 1994. Nielsen K K, et al.
CA VA	Debrisoquine hydroxylation phenotypes of patients with high versus low to normal serum antidepressant concentrations. Journal of clinical psychopharmacology. 1992. Tacke U, et al.
CA	Analysis of the CYP2D6 gene in relation to debrisoquin and desipramine hydroxylation in a Swedish population. Clinical pharmacology and therapeutics. 1992. Dahl M L, et al.
	The clinical application of tricyclic antidepressant pharmacokinetics and plasma levels. The American journal of psychiatry. 1980. Amsterdam J, et al.

LinkOuts

Web Resource:: Wikipedia
National Drug Code Directory:: 0378-1049-01
DrugBank:: DB01142

ChEBI:: 4710
KEGG Compound:: C06971
PubChem Compound:: 667477

PubChem Substance:: 158785
IUPHAR Ligand:: 1225
Drugs Product Database (DPD):: 1913425
Therapeutic Targets Database:: DAP000177
FDA Drug Label at DailyMed:: 1533343b-f1ed-4c3a-bb36-23a748452b05

Clinical Trials

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Sources for PharmGKB drug information: DrugBank, PubChem.

Chemical: Drug doxepin

Available Prescribing Info

Summary

Annotation

December 2016 Update

Table 1: Dosing recommendations for TCAs based on CYP2D6 phenotype:

Table 2: Dosing recommendations for TCAs based on CYP2C19 phenotype:

May 2013

Excerpt from the dosing guidelines:

Summary

Annotation

Summary

Annotation

Genes and/or phenotypes found in this label

Overview

PharmGKB Accession Id

Type(s):

Description

Indication

Other Vocabularies

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Pharmacology

Food Interaction

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Protein Binding

Absorption

Half-Life

Toxicity

Chemical Properties

Chemical Formula

Average Molecular Weight

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SMILES

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PharmGKB Curated Pathways

Curated Information ?

Drug Targets

Drug Interactions

Curated Information ?

May Treat

Contraindicated With

Publications related to doxepin: 46

LinkOuts

Chemical: Drug
doxepin