Drug/Small Molecule:
nortriptyline

Available Guidelines

  1. CPIC Dosing Guideline for nortriptyline and CYP2D6
  2. Dutch Pharmacogenetics Working Group Guideline for nortriptyline and CYP2D6

last updated 01/16/2013

CPIC Dosing Guideline for nortriptyline and CYP2D6

Summary

The CPIC Dosing Guideline for nortriptyline recommends a 25% dose reduction for CYP2D6 intermediate metabolizers. For CYP2D6 ultrarapid or poor metabolizers, an alternative drug may be considered.

Annotation

May 2013

Advance online publication January 2013.

  • Guidelines regarding the use of pharmacogenomic tests in dosing of amitriptyline and nortriptyline have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC).
  • Excerpt from the 2013 dosing guidelines:
    • "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."
    • "At the time of the development of this recommendation, there is a lack of strong evidence available on the possible role of CYP2D6 in nortiptyline response in pediatric patient populations; however, there is no reason to suspect that CYP2D6 variant alleles would affect nortriptyline metabolism differently in children compared to adults."
  • The guideline includes dosing recommendation for nortriptyline based on:
  • Download and read:

Table 1: Dosing recommendations for nortriptyline based on CYP2D6 phenotype:a,b

Adapted from Tables 1 and 2 of the 2013 guideline manuscript.

The recommended starting dose of nortriptyline does not need adjustment based on genotype for CYP2D6 extensive metabolizers. A 25% reduction of the recommended dose may be considered for CYP2D6 intermediate metabolizers. Alternate agents are preferred for CYP2D6 ultrarapid metabolizers and CYP2D6 poor metabolizers.

Likely phenotype* Activity score Genotypes Examples of diplotypes Implications for TCA metabolism Therapeutic Recommendations Classification of recommendation for amitriptyline/nortriptyline therapy
Ultrarapid metabolizer (~1-2% of patients) >2.0 An individual carrying more than two copies of functional alleles *1/*1xN, *1/*2xN Increased metabolism of tricyclics to less active compounds when compared to extensive metabolizers. Lower plasma concentrations will increase probability of pharmacotherapy failure. Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6.
If a tricyclic is warranted, consider increasing the starting dose.a Utilize therapeutic drug monitoring to guide dose adjustments.
Strong
Extensive metabolizer (~77-92% of patients) 1.0-2.0** An individual carrying two alleles encoding full or reduced function or one full function allele together with either one nonfunctional or one reduced-function allele *1/*1, *1/*2, *2/*2, *1/*41, *1/*4, *2/*5, *10/*10 Normal metabolism of tricyclics. Initiate therapy with recommended starting dose. Strong
Intermediate metabolizer (~2-11% of patients) 0.5 An individual carrying one reduced and one nonfunctional allele *4/*10, *5/*41 Reduced metabolism of tricyclics to less active compounds when compared to extensive metabolizers. Higher plasma concentrations will increase the probability of side effects. Consider 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments. Moderate
Poor metabolizer (~5-10% of patients) 0 An individual carrying no functional alleles *4/*4, *4/*5, *5/*5, *4/*6 Greatly reduced metabolism of tricyclics to less active compounds when compared to extensive metabolizers. Higher plasma concentrations 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 tricyclic is warranted, consider 50% reduction of recommended starting dose.a Utilize therapeutic drug monitoring to guide dose adjustments.
Strong

*CYP2D6 metabolizer status frequencies are based on data from Caucasians and may differ from other ethnicities.
**Patients with an activity score of 1.0 may be classified as intermediate metabolizers by some reference laboratories. See Supplementary Table S4 for additional information about CYP2D6 activity score and its limitations.
a Patients may receive an initial low dose of tricyclics, 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. b Dosing recommendations only apply to higher initial doses of nortriptyline for treatment of conditions such as depression.


last updated 08/10/2011

Dutch Pharmacogenetics Working Group Guideline for nortriptyline and CYP2D6

Summary

The Dutch Pharmacogenetics Working Group Guideline for nortriptyline recommends to reduce the dose for CYP2D6 poor or intermediate metabolizer patients. For CYP2D6 ultrarapid metabolizers, select an alternative drug or increase the dose by 60%. Monitoring of nortriptyline and 10-hydroxynortriptyline plasma concentrations is recommended.

Annotation

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for nortriptyline based on CYP2D6 genotype [Article:21412232]. They recommend reducing the dose for poor and intermediate metabolizer patients and selecting an alternative drug or increasing the dose for ultra metabolizers.

Phenotype (Genotype) Therapeutic Dose Recommendation Level of Evidence Clinical Relevance
PM (2 inactive alleles) Reduce dose by 60% and monitor nortriptyline + 10-hydroxynortriptyline plasma concentrations. 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): long-standing discomfort (48-168 hr) without permanent injury e.g. failure of therapy with tricyclic antidepressants, atypical antipsychotic drugs; extrapyramidal side effects; parkinsonism; ADE resulting from increased bioavailability of tricyclic antidepressants, metoprolol, propafenone (central effects e.g. dizziness); INR 4.5-6.0; neutropenia 1.0-1.5x10^9/l; leucopenia 2.0-3.0x10^9/l; thrombocytopenia 50-75x10^9/l.
IM (2 decreased activity alleles, or 1 active and 1 inactive allele, or 1 decreased activity and 1 inactive allele) Reduce dose by 40% and monitor nortriptyline + 10-hydroxynortriptyline plasma concentrations. Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints. Clinical effect (S): long-standing discomfort (48-168 hr) without permanent injury e.g. failure of therapy with tricyclic antidepressants, atypical antipsychotic drugs; extrapyramidal side effects; parkinsonism; ADE resulting from increased bioavailability of tricyclic antidepressants, metoprolol, propafenone (central effects e.g. dizziness); INR 4.5-6.0; neutropenia 1.0-1.5x10^9/l; leucopenia 2.0-3.0x10^9/l; thrombocytopenia 50-75x10^9/l.
UM (gene duplication in absence of inactive or decreased activity alleles) Select alternative drug (e.g., citalopram, sertraline) or increase dose by 60% and monitor nortriptyline + 10-hydroxynortriptyline plasma concentrations. 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): long-standing discomfort (48-168 hr) without permanent injury e.g. failure of therapy with tricyclic antidepressants, atypical antipsychotic drugs; extrapyramidal side effects; parkinsonism; ADE resulting from increased bioavailability of tricyclic antidepressants, metoprolol, propafenone (central effects e.g. dizziness); INR 4.5-6.0; neutropenia 1.0-1.5x10^9/l; leucopenia 2.0-3.0x10^9/l; thrombocytopenia 50-75x10^9/l.
Allele Type Alleles
active *1, *2, *33, *35
decreased activity *9, *10, *17, *29, *36, *41
inactive *3-*8, *11-*16, *19-*21, *38, *40, *42
  • *See Methods or PMID: 18253145 for definition of "good" and "moderate" quality.
  • S: statistically significant difference.
  • Please see attached PDF for detailed information about the evaluated studies: Nortriptyline CYP2D6

PharmGKB annotates drug labels containing pharmacogenetic information approved by the US Food and Drug Administration (FDA), European Medicines Agency (EMA) and the Pharmaceuticals and Medical Devices Agency, Japan (PMDA). PharmGKB annotations provide a brief summary of the PGx in the label, an excerpt from the label and a downloadable highlighted label PDF file. A list of genes and phenotypes found within the label is mapped to label section headers and listed at the end of each annotation. PharmGKB also attempts to interpret the level of action implied in each label with the "PGx Level" tag.

Sources:

  • FDA Information is gathered from the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels" and from FDA-approved labels brought to our attention. Please note that drugs may be removed from or added to the FDA's Table without our knowledge. We periodically check the Table for changes and update PharmGKB accordingly. Drugs listed on the Table to our knowledge are tagged with the Biomarker icon. A drug label that has been removed from the Table will not have the Biomarker icon but will continue to have an annotation on PharmGKB stating the label has been removed from the FDA's Table. We acquire label PDF files from DailyMed.
  • EMA European Public Assessment Reports (EPARs) that contain PGx information were identified from [Article:24433361] and also by searching for drugs for which we have PGx-containing FDA drug labels.

We welcome any information regarding drug labels containing PGx information approved by the FDA, EMA, PMDA or other Medicine Agencies around the world - please contact feedback.


last updated 10/25/2013

FDA Label for nortriptyline and CYP2D6

Actionable PGx

Summary

Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers; co-administration with these inhibitors' can make the patient abruptly toxic.

It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor.

Annotation

Nortriptyline is indicated for the relief of symptoms of depression. PGx information can be found in the Drug Interactions label section.

Excerpt from the nortriptyline label:

The biochemical activity of the drug metabolizing isozyme cytochrome P4502D6 (debrisoquin hydroxylase) is reduced in a subset of the Caucasian population (about 7% to 10% of Caucasians are so called 'poor metabolizers'); reliable estimates of the prevalence of reduced P4502D6 isozyme activity among Asian, African and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA).

An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide).

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

  • Depression
    • Indications & usage section, Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • Depressive Disorder
    • Indications & usage section, Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • Depressive Disorder, Major
    • Indications & usage section, Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • CYP2D6
    • Drug interactions section, metabolism/PK
    • source: FDA Label

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.

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.

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This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Gene?
Roche AmpliChip CYP450 Test CYP2D6*1, CYP2D6*10A, CYP2D6*10B, CYP2D6*11, CYP2D6*15, CYP2D6*17, CYP2D6*19, CYP2D6*20, CYP2D6*29, CYP2D6*2A, CYP2D6*2B, CYP2D6*2D, CYP2D6*3, CYP2D6*40, CYP2D6*41, CYP2D6*4A, CYP2D6*4B, CYP2D6*4D, CYP2D6*4J, CYP2D6*4K, CYP2D6*5, CYP2D6*6A, CYP2D6*6B, CYP2D6*6C, CYP2D6*7, CYP2D6*8, CYP2D6*9 , CYP2D6 CYP2D6*1XN , CYP2D6 CYP2D6*2XN , CYP2D6 CYP2D6*4XN , CYP2D6 CYP2D6*10XN , CYP2D6 CYP2D6*17XN , CYP2D6 CYP2D6*35XN , CYP2D6 CYP2D6*41XN , CYP2D6 *35 , CYP2D6 *36
DMET Plus (Affymetrix, Inc) Variant in CYP2D6
VeraCode ADME Core Panel (Illumina, Inc) Variant in CYP2D6
TaqMan Drug Metabolism Genotyping Assay Sets (Applied Biosystems, Inc) Variant in CYP2D6
Laboratory Corporation of America Variant in CYP2D6
Quest Diagnostics, Inc Variant in CYP2D6
iPLEX ADME PGx (Sequenom, Inc) CYP2D6*11, CYP2D6*12, CYP2D6*14A, CYP2D6*14B, CYP2D6*15, CYP2D6*17, CYP2D6*18, CYP2D6*19, CYP2D6*1A, CYP2D6*20, CYP2D6*21A, CYP2D6*21B, CYP2D6*3, CYP2D6*30, CYP2D6*38, CYP2D6*4, CYP2D6*40, CYP2D6*41, CYP2D6*42, CYP2D6*44, CYP2D6*4M, CYP2D6*56A, CYP2D6*56B, CYP2D6*58, CYP2D6*6, CYP2D6*64, CYP2D6*69, CYP2D6*7, CYP2D6*8, CYP2D6*9 , CYP2D6 Indistinguishable haplotypes with the current ADME core SNP: (CYP2D6*2A,CYP2D6*31,CYP2D6*51), (CYP2D6*2L,CYP2D6*35,CYP2D6*71), (CYP2D6*10,CYP2D6*36,CYP2D6*37,CYP2D6*47,CYP2D6*49,CYP2D6*52,CYP2D6*54,CYP2D6*57,CYP2D6*65,CYP2D6*72), CNV Assay: CYP2D6*5, CYP2D6*NxN (Haplotypes are identified manually)
Luminex xTAG CYP2D6 Assay CYP2D6*1, CYP2D6*10, CYP2D6*11, CYP2D6*15, CYP2D6*17, CYP2D6*2, CYP2D6*29, CYP2D6*3, CYP2D6*4, CYP2D6*41, CYP2D6*5, CYP2D6*6, CYP2D6*7, CYP2D6*8, CYP2D6*9 , CYP2D6 CYP2D6*XN , CYP2D6 *35
Cytochrome P450 2D6 (CYP2D6) CYP2D6*2, CYP2D6*5, CYP2D6*8 , rs28371725 , rs5030867 , rs5030656 , rs35742686 , rs3892097 , rs5030865 , rs5030655 , rs61736512 , rs28371706 , rs5030862 , rs1065852
GenoChip CYP2D6 (PharmGenomics, GmbH) CYP2D6*5 , rs59421388 , rs28371725 , rs5030867 , rs5030656 , rs35742686 , rs3892097 , rs5030865 , rs5030655 , rs28371706 , rs5030863 , rs1065852 , CYP2D6 *xN (gene duplication)
INFINITI CYP450 2D6I (AutoGenomics, Inc) CYP2D6*10, CYP2D6*12, CYP2D6*17, CYP2D6*2, CYP2D6*29, CYP2D6*3, CYP2D6*4, CYP2D6*41, CYP2D6*5, CYP2D6*6, CYP2D6*7, CYP2D6*8, CYP2D6*9 , rs28371725 , rs5030867 , rs5030656 , rs35742686 , rs3892097 , rs5030865 , rs5030655 , rs61736512 , rs28371706 , rs5030862 , rs1065852 , CYP2D6 CYP2D6*XN , CYP2D6 *14

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 nortriptyline variant annotations

Gene ? Variant?
(142)
Alternate Names ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
VIP CA VA CYP2D6 *1 N/A N/A N/A
No VIP available CA VA CYP2D6 *1XN N/A N/A N/A
VIP CA VA CYP2D6 *2 N/A N/A N/A
No VIP available CA VA CYP2D6 *2XN N/A N/A N/A
VIP CA VA CYP2D6 *3 N/A N/A N/A
VIP CA VA CYP2D6 *4 N/A N/A N/A
No VIP available CA VA CYP2D6 *5 N/A N/A N/A
VIP CA No VIP available CYP2D6 *6 N/A N/A N/A
VIP No VIP available No VIP available CYP2D6 *9 N/A N/A N/A
VIP CA VA CYP2D6 *10 N/A N/A N/A
VIP No VIP available VA CYP2D6 *17 N/A N/A N/A
VIP No VIP available No VIP available CYP2D6 *29 N/A N/A N/A
VIP No VIP available VA CYP2D6 *41 N/A N/A N/A
No VIP available No VIP available VA SLC6A4 HTTLPR long form (L allele) N/A N/A N/A
No VIP available No VIP available VA SLC6A4 HTTLPR short form (S allele) N/A N/A N/A
No VIP available No Clinical Annotations available VA
CYP2D6 poor metabolizers N/A N/A N/A
No VIP available No Clinical Annotations available VA
CYP2D6 poor metabolizer N/A N/A N/A
No VIP available CA VA
rs1045642 208920T>A, 208920T>C, 25171488A>G, 25171488A>T, 3435T>A, 3435T>C, 87138645A>G, 87138645A>T, ABCB1*6, ABCB1: 3435C>T, ABCB1: C3435T, ABCB1: c.3435C>T, ABCB1:3435C>T, Ile1145=, Ile1145Ile, MDR1 3435C>T, MDR1 C3435T, PGP C3435T, c.3435C>T, mRNA 3853C>T
A > T
A > G
Synonymous
Ile1145Ile
rs1065852 100C>T, 21917263G>A, 42526694G>A, 5190C>T, CYP2D6:100C>T, Pro34Ser, part of CYP2D6*4 and CYP2D6*10
G > A
Missense
Pro34Ser
No VIP available No Clinical Annotations available VA
rs11195419 *216C>A, 112839368C>A, 63643832C>A, 7579C>A
C > A
3' UTR
VIP No Clinical Annotations available No Variant Annotations available
rs16947 21914512A>G, 42523943A>G, 733C>C, 7941C>C, 886C>C, Arg245=, Arg296=, CYP2D6:2850C>T
A > G
Not Available
No VIP available CA VA
rs17060812 -16+3578C>T, -16+3907C>T, 10086974C>T, 22228828C>T
C > T
Intronic
No VIP available No Clinical Annotations available VA
rs2273623 *6045A>G, 41765245A>G, 57776A>G, 60765245A>G
A > G
3' UTR
No VIP available CA VA
rs2500535 149329267A>G, 53498724A>G, 682-11008A>G
A > G
Intronic
rs28371706 21916341G>A, 320C>T, 42525772G>A, 6112C>T, CYP2D6:1023 C>T, Thr107Ile
G > A
Missense
Thr107Ile
rs28371725 21914374C>T, 42523805C>T, 8079G>A, 832+39G>A, 985+39G>A, CYP2D6*41, CYP2D6:2988G>A, part of CYP2D6*41
C > T
Intronic
rs35742686 -1793delT, -1830delT, -1940delT, 23418678delT, 40+2664delT, 42128242delT, 50569delT, 50583delT, 598delA, 622delA, 6750delA, 775delA, Arg200Glyfs, Arg208Glyfs, Arg259Glyfs
T > -
Not Available
Arg208Gly
rs3892097 21915516C>T, 353-1G>A, 42524947C>T, 506-1G>A, 6937G>A, CYP2D6*4, CYP2D6:1846G>A, part of CYP2D6*4
C > T
Acceptor
rs5030655 -1098delA, -1563delA, -951delA, -988delA, 23419520delA, 277delT, 353-140delT, 40+3506delA, 42129084delA, 454delT, 51411delA, 51425delA, 5908delT, CYP2D6*6, CYP2D6:1707 del T, Trp152Glyfs, Trp93Glyfs, part of CYP2D6*6
A > -
Not Available
Trp152Gly
rs5030656 21914745_21914747delCTT, 42524176_42524178delCTT, 688_690delAAG, 7706_7708delAAG, 841_843delAAG, Lys230del, Lys281del
CTT > -
CTT > TTC
Non-synonymous
No VIP available No Clinical Annotations available VA
rs5443 10501C>T, 47295C>T, 6894875C>T, 6954875C>T, 825C>T, GNB3:825C>T, GNB3:Ser275Ser, Ser275=
C > T
Synonymous
Ser275Ser
rs59421388 1012G>A, 21914179C>T, 3271G>A, 42523610C>T, 8274G>A, 859G>A, CYP2D6: 3183G>A, Val287Met, Val338Met
G > T
G > C
Missense
Val287Met
rs61736512 1747G>A, 21915703C>T, 353-188G>A, 406G>A, 42525134C>T, 6750G>A, CYP2D6: 1659G>A, Val136Met
G > T
G > C
Intronic
Val136Met
No VIP available CA VA
rs962369 -22+6638A>C, -22+6638A>G, -22+6638A>T, -22+7473A>C, -22+7473A>G, -22+7473A>T, -22+7556A>C, -22+7556A>G, -22+7556A>T, -22+7771A>C, -22+7771A>G, -22+7771A>T, 14186A>C, 14186A>G, 14186A>T, 27674420T>A, 27674420T>C, 27674420T>G, 27734420T>A, 27734420T>C, 27734420T>G, 3+8539A>C, 3+8539A>G, 3+8539A>T
T > C
Intronic
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 142
2D structure from PubChem
provided by PubChem

Overview

Generic Names
Trade Names
  • AVENTYL HCL
  • Acetexa
  • Allegron
  • Altilev
  • Amitryptyline, Demethyl-
  • Ateben
  • Avantyl
  • Demethylamitriptylene
  • Demethylamitriptyline
  • Demethylamitryptyline
  • Desitriptilina
  • Desmethylamitriptyline
  • Lumbeck
  • Noramitriptyline
  • Noritren
  • Nortrilen
  • Nortriptyline Hcl
  • Nortryptiline
  • Norzepine
  • PAMELOR
  • Psychostyl
  • Sensaval
  • Sensival Ventyl
  • Sesaval
  • Vividyl
Brand Mixture Names

PharmGKB Accession Id:
PA450657

Description

Nortriptyline hydrochloride, the N-demethylated active metabolite of amitriptyline, is a dibenzocycloheptene-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, nortriptyline does not affect mood or arousal, but may cause sedation. In depressed individuals, nortriptyline exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Secondary amine TCAs, such as nortriptyline, are more potent inhibitors of norepinephrine reuptake than tertiary amine TCAs, such as amitriptyline. 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. See toxicity section below for a complete listing of side effects. Nortriptyline exerts less anticholinergic and sedative side effects compared to the tertiary amine TCAs, amitriptyline and clomipramine. Nortriptyline may be used to treat depression, chronic pain (unlabeled use), irritable bowel syndrome (unlabeled use), diabetic neuropathy (unlabeled use), post-traumatic stress disorder (unlabeled use), and for migraine prophylaxis (unlabeled use).

Source: Drug Bank

Indication

For the treatment of depression, chronic pain, irritable bowel syndrome, sleep disorders, diabetic neuropathy, agitation and insomnia, and migraine prophylaxis.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

It is believed that nortriptyline either inhibits the reuptake of the neurotransmitter serotonin at the neuronal membrane or acts at beta-adrenergic receptors. Tricyclic antidepressants do not inhibit monoamine oxidase nor do they affect dopamine reuptake.

Source: Drug Bank

Pharmacology

Similar to protriptyline, nortriptyline is a tricyclic antidepressant of the dibenzocycloheptene type and is the active metabolite of amitriptyline.

Source: Drug Bank

Food Interaction

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

Undergoes hepatic metabolism via the same pathway as other TCAs.

Source: Drug Bank

Protein Binding

Highly protein-bound in plasma and tissues.

Source: Drug Bank

Absorption

Well absorbed from the GI tract. Peak plasma concentrations occur 7-8.5 hours following oral administration.

Source: Drug Bank

Half-Life

16 to 90+ hours

Source: Drug Bank

Toxicity

Symptoms of overdose include cardiac dysrhythmias, severe hypotension, shock, congestive heart failure, pulmonary edema, 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

Route of Elimination

Approximately one-third of a single orally administered dose is excreted in urine within 24 hours. Small amounts are excreted in feces via biliary elimination.

Source: Drug Bank

Chemical Properties

Chemical Formula

C19H21N

Source: Drug Bank

Isomeric SMILES

CNCCC=C1c2ccccc2CCc3c1cccc3

Source: OpenEye

Canonical SMILES

CNCCC=C1C2=CC=CC=C2CCC2=CC=CC=C12

Source: Drug Bank

Average Molecular Weight

263.3767

Source: Drug Bank

Monoisotopic Molecular Weight

263.167399677

Source: Drug Bank

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 ?

Drug Targets

Gene Description
ADRA1A (source: Drug Bank)
ADRA1D (source: Drug Bank)
ALB (source: Drug Bank)
CHRM1 (source: Drug Bank)
CHRM2 (source: Drug Bank)
CHRM3 (source: Drug Bank)
CHRM4 (source: Drug Bank)
CHRM5 (source: Drug Bank)
HRH1 (source: Drug Bank)
HTR1A (source: Drug Bank)
HTR2A (source: Drug Bank)
SLC6A2 (source: Drug Bank)
SLC6A4 (source: Drug Bank)

Drug Interactions

Drug Description
nortriptyline Increases the effect and toxicity of tricyclics (source: Drug Bank)
nortriptyline Atazanavir may increase the effect and toxicity of the tricyclic antidepressant, nortriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if atazanavir if initiated, discontinued or dose changed. (source: Drug Bank)
nortriptyline The tricyclic increases the effect of carbamazepine (source: Drug Bank)
nortriptyline Carbamazepine may decrease the serum concentration of the tricyclic antidepressant, nortriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if carbamazepine is initiated, discontinued or dose changed. (source: Drug Bank)
nortriptyline Increases the effect of tricyclic agent (source: Drug Bank)
nortriptyline Cimetidine may increase the effect of tricyclic antidepressant, nortriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if cimetidine is initiated, discontinued or dose changed. (source: Drug Bank)
nortriptyline Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
nortriptyline Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
nortriptyline The tricyclic decreases the effect of clonidine (source: Drug Bank)
nortriptyline The tricyclic antidepressant, nortriptyline, decreases the effect of clonidine. (source: Drug Bank)
nortriptyline Possible antagonism of action (source: Drug Bank)
nortriptyline Possible antagonism of action (source: Drug Bank)
nortriptyline Possible increase in the levels of this agent when used with duloxetine (source: Drug Bank)
nortriptyline Possible increase in the levels of this agent when used with duloxetine (source: Drug Bank)
nortriptyline The tricyclic increases the sympathomimetic effect (source: Drug Bank)
nortriptyline The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of epinephrine. (source: Drug Bank)
nortriptyline The tricyclic increases the sympathomimetic effect (source: Drug Bank)
nortriptyline The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of fenoterol. (source: Drug Bank)
nortriptyline The imidazole increases the effect and toxicity of the tricyclic (source: Drug Bank)
nortriptyline Fluconazole may increase the effect and toxicity of the tricyclic antidepressant, nortriptyline, by decreasing its metabolism. Additive QTc-prolonging effects may also occur. Monitor for changes in the therapeutic and adverse effects of nortriptyline if fluconazole is initiated, discontinued or dose changed. Monitor for the development of torsades de pointes during concomitant therapy. (source: Drug Bank)
nortriptyline Fluoxetine increases the effect and toxicity of tricyclics (source: Drug Bank)
nortriptyline The SSRI, fluoxetine, may increase the serum concentration of the tricyclic antidepressant, nortriptyline, 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 nortriptyline if fluoxetine is initiated, discontinued or dose changed. (source: Drug Bank)
nortriptyline Fluvoxamine increases the effect and toxicity of tricyclics (source: Drug Bank)
nortriptyline The SSRI, fluvoxamine, may increase the serum concentration of the tricyclic antidepressant, nortriptyline, 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 nortriptyline if fluvoxamine is initiated, discontinued or dose changed. (source: Drug Bank)
nortriptyline Possible antagonism of action (source: Drug Bank)
nortriptyline Possible antagonism of action (source: Drug Bank)
nortriptyline Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
nortriptyline Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
nortriptyline The tricyclic decreases the effect of guanethidine (source: Drug Bank)
nortriptyline The tricyclic antidepressant, nortriptyline, decreases the effect of guanethidine. (source: Drug Bank)
nortriptyline Possibility of severe adverse effects (source: Drug Bank)
nortriptyline Possibility of severe adverse effects (source: Drug Bank)
nortriptyline The imidazole increases the effect and toxicity of the tricyclic (source: Drug Bank)
nortriptyline Ketoconazole, a moderate CYP2D6 inhibitor, may increase the serum concentration of nortriptyline by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if ketoconazole is initiated, discontinued or dose changed. (source: Drug Bank)
nortriptyline Possible severe adverse reaction with this combination (source: Drug Bank)
nortriptyline Possible severe adverse reaction with this combination (source: Drug Bank)
altretamine Risk of hypotension (source: Drug Bank)
altretamine Risk of hypotension (source: Drug Bank)
atazanavir Atazanavir increases the effect and toxicity of tricyclics (source: Drug Bank)
atazanavir Atazanavir may increase the effect and toxicity of the tricyclic antidepressant, nortriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if atazanavir if initiated, discontinued or dose changed. (source: Drug Bank)
carbamazepine The tricyclic increases the effect of carbamazepine (source: Drug Bank)
carbamazepine Carbamazepine may decrease the serum concentration of the tricyclic antidepressant, nortriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if carbamazepine is initiated, discontinued or dose changed. (source: Drug Bank)
cimetidine Cimetidine increases the effect of tricyclic agent (source: Drug Bank)
cimetidine Cimetidine may increase the effect of the tricyclic antidepressant, nortriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if cimetidine is initiated, discontinued or dose changed. (source: Drug Bank)
cisapride Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
cisapride Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
clonidine The tricyclic decreases the effect of clonidine (source: Drug Bank)
clonidine The tricyclic antidepressant, nortriptyline, decreases the effect of clonidine. (source: Drug Bank)
dobutamine The tricyclic increases the sympathomimetic effect (source: Drug Bank)
dobutamine The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of dobutamine. (source: Drug Bank)
donepezil Possible antagonism of action (source: Drug Bank)
donepezil Possible antagonism of action (source: Drug Bank)
dopamine The tricyclic increases the sympathomimetic effect (source: Drug Bank)
dopamine The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of dopamine. (source: Drug Bank)
duloxetine Possible increase in the levels of this agent when used with duloxetine (source: Drug Bank)
duloxetine Possible increase in the levels of this agent when used with duloxetine (source: Drug Bank)
ephedra The tricyclic increases the sympathomimetic effect (source: Drug Bank)
ephedra The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of ephedra. (source: Drug Bank)
ephedrine The tricyclic increases the sympathomimetic effect (source: Drug Bank)
ephedrine The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of ephedrine. (source: Drug Bank)
epinephrine The tricyclic increases the sympathomimetic effect (source: Drug Bank)
epinephrine The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of epinephrine. (source: Drug Bank)
fenoterol The tricyclic increases the sympathomimetic effect (source: Drug Bank)
fenoterol The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of fenoterol. (source: Drug Bank)
fluconazole The imidazole increases the effect and toxicity of the tricyclic (source: Drug Bank)
fluconazole Fluconazole may increase the effect and toxicity of the tricyclic antidepressant, nortriptyline, by decreasing its metabolism. Additive QTc-prolonging effects may also occur. Monitor for changes in the therapeutic and adverse effects of nortriptyline if fluconazole is initiated, discontinued or dose changed. Monitor for the development of torsades de pointes during concomitant therapy. (source: Drug Bank)
fluoxetine Fluoxetine increases the effect and toxicity of tricyclics (source: Drug Bank)
fluoxetine The SSRI, fluoxetine, may increase the serum concentration of the tricyclic antidepressant, nortriptyline, 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 nortriptyline if fluoxetine is initiated, discontinued or dose changed. (source: Drug Bank)
fluvoxamine Fluvoxamine increases the effect and toxicity of tricyclics (source: Drug Bank)
fluvoxamine The SSRI, fluvoxamine, may increase the serum concentration of the tricyclic antidepressant, nortriptyline, 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 nortriptyline if fluvoxamine is initiated, discontinued or dose changed. (source: Drug Bank)
galantamine Possible antagonism of action (source: Drug Bank)
galantamine Possible antagonism of action (source: Drug Bank)
grepafloxacin Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
grepafloxacin Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
guanethidine The tricyclic decreases the effect of guanethidine (source: Drug Bank)
guanethidine The tricyclic antidepressant, nortriptyline, decreases the effect of guanethidine. (source: Drug Bank)
isocarboxazid Possibility of severe adverse effects (source: Drug Bank)
isocarboxazid Possibility of severe adverse effects (source: Drug Bank)
isoproterenol The tricyclic increases the sympathomimetic effect (source: Drug Bank)
isoproterenol The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of isoproterenol. (source: Drug Bank)
ketoconazole The imidazole increases the effect and toxicity of the tricyclic (source: Drug Bank)
ketoconazole Ketoconazole, a moderate CYP2D6 inhibitor, may increase the serum concentration of nortriptyline by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if ketoconazole is initiated, discontinued or dose changed. (source: Drug Bank)
mephentermine The tricyclic increases the sympathomimetic effect (source: Drug Bank)
mephentermine The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of mephentermine. (source: Drug Bank)
metaraminol The tricyclic increases the sympathomimetic effect (source: Drug Bank)
metaraminol The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of metaraminol. (source: Drug Bank)
methoxamine The tricyclic increases the sympathomimetic effect (source: Drug Bank)
methoxamine The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of methoxamine. (source: Drug Bank)
moclobemide Possible severe adverse reaction with this combination (source: Drug Bank)
moclobemide Possible severe adverse reaction with this combination (source: Drug Bank)
norepinephrine The tricyclic increases the sympathomimetic effect (source: Drug Bank)
norepinephrine The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of norepinephrine. (source: Drug Bank)
orciprenaline The tricyclic increases the sympathomimetic effect (source: Drug Bank)
orciprenaline The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of orciprenaline. (source: Drug Bank)
phenelzine Possibility of severe adverse effects (source: Drug Bank)
phenelzine Possibility of severe adverse effects (source: Drug Bank)
phenylephrine The tricyclic increases the sympathomimetic effect (source: Drug Bank)
phenylephrine The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of phenylephrine. (source: Drug Bank)
phenylpropanolamine The tricyclic increases the sympathomimetic effect (source: Drug Bank)
phenylpropanolamine The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of phenylpropanolamine. (source: Drug Bank)
pirbuterol The tricyclic increases the sympathomimetic effect (source: Drug Bank)
pirbuterol The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of pirbuterol. (source: Drug Bank)
procaterol The tricyclic increases the sympathomimetic effect (source: Drug Bank)
procaterol The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of procaterol. (source: Drug Bank)
pseudoephedrine The tricyclic increases the sympathomimetic effect (source: Drug Bank)
pseudoephedrine The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of pseudoephedrine. (source: Drug Bank)
quinidine Quinidine increases the effect of tricyclic agent (source: Drug Bank)
quinidine Quinidine increases the effect of tricyclic agent (source: Drug Bank)
quinidine Quinidine barbiturate increases the effect of the tricyclic antidepressant, nortriptyline. (source: Drug Bank)
rasagiline Possibility of severe adverse effects (source: Drug Bank)
rasagiline Possibility of severe adverse effects (source: Drug Bank)
rifabutin The rifamycin decreases the effect of tricyclics (source: Drug Bank)
rifabutin The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, nortriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if rifabutin is initiated, discontinued or dose changed. (source: Drug Bank)
rifampin The rifamycin decreases the effect of tricyclics (source: Drug Bank)
rifampin The rifamycin, rifampin, may decrease the effect of the tricyclic antidepressant, nortriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if rifampin is initiated, discontinued or dose changed. (source: Drug Bank)
ritonavir Ritonavir increases the effect and toxicity of the tricyclics (source: Drug Bank)
ritonavir Ritonavir may increase the effect and toxicity of the tricyclic antidepressant, nortriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if ritonavir if initiated, discontinued or dose changed. (source: Drug Bank)
rivastigmine Possible antagonism of action (source: Drug Bank)
rivastigmine Possible antagonism of action (source: Drug Bank)
salbutamol The tricyclic increases the sympathomimetic effect (source: Drug Bank)
salbutamol The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of salbutamol. (source: Drug Bank)
sibutramine Increased risk of CNS adverse effects (source: Drug Bank)
sibutramine Increased risk of CNS adverse effects (source: Drug Bank)
sparfloxacin Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
sparfloxacin Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
terbinafine Terbinafine increases the effect and toxicity of the tricyclic (source: Drug Bank)
terbinafine Terbinafine increases the effect and toxicity of the tricyclic antidepressant, nortriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if terbinafine is initiated, discontinued or dose changed. (source: Drug Bank)
terbutaline The tricyclic increases the sympathomimetic effect (source: Drug Bank)
terbutaline The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of terbutaline. (source: Drug Bank)
terfenadine Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
terfenadine Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
tranylcypromine Possibility of severe adverse effects (source: Drug Bank)
tranylcypromine Possibility of severe adverse effects (source: Drug Bank)
nortriptyline The tricyclic increases the sympathomimetic effect (source: Drug Bank)
nortriptyline The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of orciprenaline. (source: Drug Bank)
nortriptyline Possibility of severe adverse effects (source: Drug Bank)
nortriptyline Possibility of severe adverse effects (source: Drug Bank)
nortriptyline The tricyclic increases the sympathomimetic effect (source: Drug Bank)
nortriptyline The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of phenylephrine. (source: Drug Bank)
nortriptyline The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of phenylpropanolamine. (source: Drug Bank)
nortriptyline The tricyclic increases the sympathomimetic effect (source: Drug Bank)
nortriptyline The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of pseudoephedrine. (source: Drug Bank)
nortriptyline Quinidine increases the effect of the tricyclic agent (source: Drug Bank)
nortriptyline Additive QTc-prolonging effects may occur. Quinidine may also increase the serum concentration of the tricyclic antidepressant, nortriptyline, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if quinidine is initiated, discontinued or dose changed. Monitor for the development of torsades de pointes during concomitant therapy. (source: Drug Bank)
nortriptyline Possibility of severe adverse effects (source: Drug Bank)
nortriptyline The rifamycin decreases the effect of tricyclics (source: Drug Bank)
nortriptyline The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, nortriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if rifabutin is initiated, discontinued or dose changed. (source: Drug Bank)
nortriptyline The rifamycin decreases the effect of tricyclics (source: Drug Bank)
nortriptyline The rifamycin, rifampin, may decrease the effect of the tricyclic antidepressant, nortriptyline, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of nortriptyline if rifampin is initiated, discontinued or dose changed. (source: Drug Bank)
nortriptyline The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Nortriptyline, 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)
nortriptyline The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Nortriptyline, 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)
nortriptyline Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution. (source: Drug Bank)
nortriptyline Terbinafine increases the effect and toxicity of the tricyclic (source: Drug Bank)
nortriptyline Terbinafine may reduce the metabolism and clearance of Nortriptyline. Consider alternate therapy or monitor for therapeutic/adverse effects of Nortriptyline if Terbinafine is initiated, discontinued or dose changed. (source: Drug Bank)
nortriptyline The tricyclic increases the sympathomimetic effect (source: Drug Bank)
nortriptyline The tricyclic antidepressant, nortriptyline, increases the sympathomimetic effect of terbutaline. (source: Drug Bank)
nortriptyline Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
nortriptyline Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
nortriptyline 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)
nortriptyline 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)
nortriptyline 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)
nortriptyline Tramadol increases the risk of serotonin syndrome and seizures. (source: Drug Bank)
nortriptyline 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)
nortriptyline Increased risk of serotonin syndrome. The 2D6 inhibitor, Trazodone, may also increase the efficacy of Nortriptyline by decreasing Nortriptyline metabolism and clearance. Monitor for symptoms of serotonin syndrome and changes in Nortriptyline efficacy if Trazodone is initiated, discontinued or dose changed. (source: Drug Bank)
nortriptyline Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank)
nortriptyline Trimethobenzamide and Nortriptyline, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects. (source: Drug Bank)
nortriptyline 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)
nortriptyline Triprolidine and Nortriptyline, 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)
nortriptyline Triprolidine and Nortriptyline, 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)
nortriptyline Trospium and Nortriptyline, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects. (source: Drug Bank)
nortriptyline Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank)
nortriptyline 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)
nortriptyline 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)
nortriptyline Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated. (source: Drug Bank)
nortriptyline Use of two serotonin modulators, such as zolmitriptan and nortriptyline, increases the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy. (source: Drug Bank)
nortriptyline 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 ?

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

May Treat
Contraindicated With

Publications related to nortriptyline: 99

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Genetic differences in cytochrome P450 enzymes and antidepressant treatment response. Journal of psychopharmacology (Oxford, England). 2013. Hodgson Karen, et al. PubMed
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Challenges in pharmacogenetics. European journal of clinical pharmacology. 2013. Cascorbi Ingolf, et al. PubMed
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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. PubMed
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Cytochrome P450-mediated drug metabolism in the brain. Journal of psychiatry & neuroscience : JPN. 2012. Miksys Sharon, et al. PubMed
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Improvement of glycemic control using methylphenidate treatment of apathy: a preliminary report. Journal of the American Geriatrics Society. 2012. Padala Prasad R, et al. PubMed
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Risk assessment of accidental nortriptyline poisoning: The importance of cytochrome P450 for nortriptyline elimination investigated using a population-based pharmacokinetic simulator. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 2011. Jornil Jakob, et al. PubMed
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Sexual dysfunction during treatment with serotonergic and noradrenergic antidepressants: clinical description and the role of the 5-HTTLPR. The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry. 2011. Strohmaier Jana, et al. PubMed
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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. PubMed
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Variation in GNB3 predicts response and adverse reactions to antidepressants. Journal of psychopharmacology (Oxford, England). 2011. Keers Robert, et al. PubMed
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A polymorphism of the GTP-cyclohydrolase I feedback regulator gene alters transcriptional activity and may affect response to SSRI antidepressants. The pharmacogenomics journal. 2011. McHugh P C, et al. PubMed
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Nortriptyline reverses corticosteroid insensitivity by inhibition of phosphoinositide-3-kinase-delta. The Journal of pharmacology and experimental therapeutics. 2011. Mercado Nicolas, et al. PubMed
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Pharmacogenetics: From Bench to Byte- An Update of Guidelines. Clinical pharmacology and therapeutics. 2011. Swen J J, et al. PubMed
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Copy number variants in pharmacogenetic genes. Trends in molecular medicine. 2011. He Yijing, et al. PubMed
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Convergent animal and human evidence suggests a role of PPM1A gene in response to antidepressants. Biological psychiatry. 2011. Malki Karim, et al. PubMed
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From evidence based medicine to mechanism based medicine. Reviewing the role of pharmacogenetics. International journal of clinical pharmacy. 2011. Wilffert Bob, et al. PubMed
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Pharmacogenetics and gender association with psychotic episodes on nortriptyline lower doses: patient cases. ISRN pharmaceutics. 2011. Piatkov Irina, et al. PubMed
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Pharmacogenomic implications of variants of monoaminergic-related genes in geriatric psychiatry. Pharmacogenomics. 2010. Shiroma Paulo R, et al. PubMed
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Genome-wide association study of increasing suicidal ideation during antidepressant treatment in the GENDEP project. The pharmacogenomics journal. 2010. Perroud N, et al. PubMed
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Mu-opioid receptors are not necessary for nortriptyline treatment of neuropathic allodynia. European journal of pain (London, England). 2010. Bohren Yohann, et al. PubMed
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Antiplatelet effects of antidepressant treatment: a randomized comparison between escitalopram and nortriptyline. Thrombosis research. 2010. Flöck Anne, et al. PubMed
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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. PubMed
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Association between CYP2C19*17 and metabolism of amitriptyline, citalopram and clomipramine in Dutch hospitalized patients. The pharmacogenomics journal. 2010. de Vos A, et al. PubMed
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Genome-wide pharmacogenetics of antidepressant response in the GENDEP project. The American journal of psychiatry. 2010. Uher Rudolf, et al. PubMed
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Interaction between serotonin transporter gene variants and life events predicts response to antidepressants in the GENDEP project. The pharmacogenomics journal. 2010. Keers R, et al. PubMed
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Pharmacogenetic considerations in the treatment of psychiatric disorders. Expert opinion on pharmacotherapy. 2010. Lohoff Falk W, et al. PubMed
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Cytochrome P450 2D6. Pharmacogenetics and genomics. 2009. Owen Ryan P, et al. PubMed
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Pharmacokinetics and efficacy of fluvoxamine and amitriptyline in depression. Journal of pharmacological sciences. 2009. Vezmar Sandra, et al. PubMed
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Genetic predictors of increase in suicidal ideation during antidepressant treatment in the GENDEP project. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2009. Perroud Nader, et al. PubMed
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Moderation of antidepressant response by the serotonin transporter gene. The British journal of psychiatry : the journal of mental science. 2009. Huezo-Diaz Patricia, et al. PubMed
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Genetic predictors of response to antidepressants in the GENDEP project. The pharmacogenomics journal. 2009. Uher Rudolf, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
beta(2)-adrenoceptors are critical for antidepressant treatment of neuropathic pain. Annals of neurology. 2009. Yalcin Ipek, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics of selective serotonin reuptake inhibitors in pediatric depression and anxiety. Pharmacogenomics. 2008. Kronenberg Sefi, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
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. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
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. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Influence of the CYP2D6*4 polymorphism on dose, switching and discontinuation of antidepressants. British journal of clinical pharmacology. 2008. Bijl Monique J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Correlation of inter-individual variations of amitriptyline metabolism examined in hairs with CYP2C19 and CYP2D6 polymorphisms. International journal of legal medicine. 2008. Thieme Detlef, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
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. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
A fatal doxepin poisoning associated with a defective CYP2D6 genotype. The American journal of forensic medicine and pathology. 2007. Koski Anna, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Comparative metabolic capabilities and inhibitory profiles of CYP2D6.1, CYP2D6.10, and CYP2D6.17. Drug metabolism and disposition: the biological fate of chemicals. 2007. Shen Hongwu, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. British journal of pharmacology. 2007. Gillman P K. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
A poor metabolizer for cytochromes P450 2D6 and 2C19: a case report on antidepressant treatment. CNS spectrums. 2006. Johnson Maria, et al. PubMed
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Sequence-based CYP2D6 genotyping in the Korean population. Therapeutic drug monitoring. 2006. Lee Soo-Youn, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
ABCB1 (P-glycoprotein/MDR1) gene G2677T/a sequence variation (polymorphism): lack of association with side effects and therapeutic response in depressed inpatients treated with amitriptyline. Clinical chemistry. 2006. Laika Barbara, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
CYP2D6 and CYP2C19 genotypes and amitriptyline metabolite ratios in a series of medicolegal autopsies. Forensic science international. 2006. Koski Anna, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
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. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Rates of in vivo methylation of desipramine and nortriptyline. Pharmacotherapy. 2006. Kurpius Molly P, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The influence of P-glycoprotein on cerebral and hepatic concentrations of nortriptyline and its metabolites. Drug metabolism and drug interactions. 2006. Ejsing Thomas Broeng, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
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. PubMed
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Amitriptyline or not, that is the question: pharmacogenetic testing of CYP2D6 and CYP2C19 identifies patients with low or high risk for side effects in amitriptyline therapy. Clinical chemistry. 2005. Steimer Werner, et al. PubMed
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A case report of a poor metabolizer of CYP2D6 presented with unusual responses to nortriptyline medication. Journal of Korean medical science. 2004. Lee Soo-Youn, et al. PubMed
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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. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Clomipramine, fluoxetine and CYP2D6 metabolic capacity in depressed patients. Human psychopharmacology. 2004. Vandel P, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Impact of CYP2D6 intermediate metabolizer alleles on single-dose desipramine pharmacokinetics. Pharmacogenetics. 2004. Furman Katherine D, et al. PubMed
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Increased incidence of CYP2D6 gene duplication in patients with persistent mood disorders: ultrarapid metabolism of antidepressants as a cause of nonresponse. A pilot study. European journal of clinical pharmacology. 2004. Kawanishi Chiaki, et al. PubMed
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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. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Trimipramine pharmacokinetics after intravenous and oral administration in carriers of CYP2D6 genotypes predicting poor, extensive and ultrahigh activity. Pharmacogenetics. 2003. Kirchheiner Julia, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Effects of polymorphisms in CYP2D6, CYP2C9, and CYP2C19 on trimipramine pharmacokinetics. Journal of clinical psychopharmacology. 2003. Kirchheiner Julia, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Disposition of debrisoquine and nortriptyline in Korean subjects in relation to CYP2D6 genotypes, and comparison with Caucasians. British journal of clinical pharmacology. 2003. Dalén P, et al. PubMed
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Inhibitory effects of tricyclic antidepressants (TCAs) on human cytochrome P450 enzymes in vitro: mechanism of drug interaction between TCAs and phenytoin. Drug metabolism and disposition: the biological fate of chemicals. 2002. Shin Jae-Gook, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Contributions of CYP2D6, CYP2C9 and CYP2C19 to the biotransformation of E- and Z-doxepin in healthy volunteers. Pharmacogenetics. 2002. Kirchheiner Julia, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The role of CYP2C19 in amitriptyline N-demethylation in Chinese subjects. European journal of clinical pharmacology. 2002. Jiang Zhi-Ping, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The role of noradrenaline and selective noradrenaline reuptake inhibition in depression. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. 2002. Brunello N, et al. PubMed
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A common P-glycoprotein polymorphism is associated with nortriptyline-induced postural hypotension in patients treated for major depression. The pharmacogenomics journal. 2002. Roberts R L, et al. PubMed
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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. PubMed
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Inhibition of cytochrome P4502D6 activity with paroxetine normalizes the ultrarapid metabolizer phenotype as measured by nortriptyline pharmacokinetics and the debrisoquin test. Clinical pharmacology and therapeutics. 2001. Laine K, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Quantitative pharmacogenetics of nortriptyline: a novel approach. Clinical pharmacokinetics. 2001. Kvist E E, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Allelic variation in the serotonin transporter promoter affects onset of paroxetine treatment response in late-life depression. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2000. Pollock B G, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The treatment of neuropathic pain: antidepressants and opioids. The Clinical journal of pain. 2000. Watson C P. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Science, medicine, and the future: Pharmacogenetics. BMJ (Clinical research ed.). 2000. Wolf C R, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Steady-state plasma levels of nortriptyline and its hydroxylated metabolites in Japanese patients: impact of CYP2D6 genotype on the hydroxylation of nortriptyline. Journal of clinical psychopharmacology. 2000. Morita S, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Clomipramine dose-effect study in patients with depression: clinical end points and pharmacokinetics. Danish University Antidepressant Group (DUAG). Clinical pharmacology and therapeutics. 1999. PubMed
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Nortriptyline E-10-hydroxylation in vitro is mediated by human CYP2D6 (high affinity) and CYP3A4 (low affinity): implications for interactions with enzyme-inducing drugs. Journal of clinical pharmacology. 1999. Venkatakrishnan K, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
CYP2D6 phenotype-genotype relationships in African-Americans and Caucasians in Los Angeles. Pharmacogenetics. 1998. Leathart J B, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Pharmacokinetics of nortriptyline and its 10-hydroxy metabolite in Chinese subjects of different CYP2D6 genotypes. Clinical pharmacology and therapeutics. 1998. Yue Q Y, et al. PubMed
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. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Inhibition of human hepatic cytochrome P4502E1 by azole antifungals, CNS-active drugs and non-steroidal anti-inflammatory agents. Xenobiotica; the fate of foreign compounds in biological systems. 1998. Tassaneeyakul W, et al. PubMed
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Steady-state plasma levels of nortriptyline and its 10-hydroxy metabolite: relationship to the CYP2D6 genotype. Psychopharmacology. 1996. Dahl M L, et al. PubMed
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Steady-state kinetics of fluoxetine and amitriptyline in patients treated with a combination of these drugs as compared with those treated with amitriptyline alone. Journal of clinical pharmacology. 1995. el-Yazigi A, et al. PubMed
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Single-dose kinetics of clomipramine: relationship to the sparteine and S-mephenytoin oxidation polymorphisms. Clinical pharmacology and therapeutics. 1994. Nielsen K K, et al. PubMed
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Molecular basis for rational megaprescribing in ultrarapid hydroxylators of debrisoquine. Lancet. 1993. Bertilsson L, et al. PubMed
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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. PubMed
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Comparative cardiotoxicity of nortriptyline and its isomeric 10-hydroxymetabolites. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 1992. Pollock B G, et al. PubMed
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Electrocardiographic changes with nortriptyline and 10-hydroxynortriptyline in elderly depressed outpatients. Journal of clinical psychopharmacology. 1988. Schneider L S, et al. PubMed
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High blood concentrations of imipramine or clomipramine and therapeutic failure: a case report study using drug monitoring data. Therapeutic drug monitoring. 1989. Balant-Gorgia A E, et al. PubMed
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Plasma 10-hydroxynortriptyline and renal function in elderly depressives. Biological psychiatry. 1987. Young R C, et al. PubMed
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Effects of nortriptyline and its 10-hydroxy metabolite on plasma noradrenaline (NA) concentrations, heart rate and blood pressure during intravenous NA infusion. Methods and findings in experimental and clinical pharmacology. 1987. Nordin C, et al. PubMed
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Clinical and biochemical effects during treatment of depression with nortriptyline: the role of 10-hydroxynortriptyline. Clinical pharmacology and therapeutics. 1987. Nordin C, et al. PubMed
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Disposition of single oral doses of E-10-hydroxynortriptyline in healthy subjects, with some observations on pharmacodynamic effects. Clinical pharmacology and therapeutics. 1986. Bertilsson L, et al. PubMed
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Amitriptyline metabolism: association with debrisoquin hydroxylation in nonsmokers. Clinical pharmacology and therapeutics. 1986. Mellström B, et al. PubMed
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CSF and plasma levels of nortriptyline and its 10-hydroxy metabolite. British journal of clinical pharmacology. 1985. Nordin C, et al. PubMed
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Plasma concentrations of nortriptyline and its 10-hydroxy metabolite in depressed patients--relationship to the debrisoquine hydroxylation metabolic ratio. British journal of clinical pharmacology. 1985. Nordin C, et al. PubMed
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Extremely rapid hydroxylation of debrisoquine: a case report with implication for treatment with nortriptyline and other tricyclic antidepressants. Therapeutic drug monitoring. 1985. Bertilsson L, et al. PubMed
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Nortriptyline and debrisoquine hydroxylations in Ghanaian and Swedish subjects. Clinical pharmacology and therapeutics. 1984. Woolhouse N M, et al. PubMed
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The nonlinear kinetics of desipramine and 2-hydroxydesipramine in plasma. Clinical pharmacology and therapeutics. 1984. Cooke R G, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
E- and Z-10-hydroxylation of nortriptyline: relationship to polymorphic debrisoquine hydroxylation. Clinical pharmacology and therapeutics. 1981. Mellström B, et al. PubMed
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Slow hydroxylation of nortriptyline and concomitant poor debrisoquine hydroxylation: clinical implications. Lancet. 1981. Bertilsson L, et al. PubMed
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Nortriptyline and antipyrine clearance in relation to debrisoquine hydroxylation in man. Life sciences. 1980. Bertilsson L, et al. PubMed
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The clinical application of tricyclic antidepressant pharmacokinetics and plasma levels. The American journal of psychiatry. 1980. Amsterdam J, et al. PubMed
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Relationship between plasma level and therapeutic effect of nortriptyline. British medical journal. 1971. Asberg M, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
54868-2835-2
DrugBank:
DB00540
ChEBI:
7640
KEGG Compound:
C07274
PubChem Compound:
4543
PubChem Substance:
149239
46507783
IUPHAR Ligand:
2404
Drugs Product Database (DPD):
2240789
ChemSpider:
4384
Therapeutic Targets Database:
DAP001152
FDA Drug Label at DailyMed:
7b4a3438-57b4-4d88-9843-cc9da529f6f2

Clinical Trials

These are trials that mention nortriptyline and are related to either pharmacogenetics or pharmacogenomics.

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