Drug/Small Molecule:
clomipramine

Available Guidelines

  1. CPIC Dosing Guideline for clomipramine and CYP2C19,CYP2D6
  2. Dutch Pharmacogenetics Working Group Guideline for clomipramine and CYP2D6

last updated 01/16/2013

CPIC Dosing Guideline for clomipramine 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 clomipramine. In the guideline for amitriptyline, an alternative drug is recommended for CYP2D6 or CYP2C19 ultrarapid metabolizers and for CYP2D6 poor metabolizers. Consider a 50% dose reduction for CYP2C19 poor metabolizers and a 25% dose reduction for CYP2D6 intermediate metabolizers.

Annotation

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 S14), 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

Dutch Pharmacogenetics Working Group Guideline for clomipramine and CYP2D6

Summary

The Dutch Pharmacogenetics Working Group Guideline for clomipramine recommends to reduce the dose by 50% for CYP2D6 poor metabolizers, and select an alternative drug for ultrarapid metabolizers. Monitor (desmethyl)clomipramine plasma concentration.

Annotation

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for clomipramine based on CYP2D6 genotypes [Article:21412232]. They recommend lower dose for patients carrying the poor metabolizer (PM) 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 50% and monitor (desmethyl) clomipramine plasma concentration. 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 1.0-1.5x109/l; leucopenia 2.0-3.0x109/l; thrombocytopenia 50-75x109/l.
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) Insufficient data to allow calculation of dose adjustment. Monitor (desmethyl)clomipramine plasma concentration 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 1.0-1.5x109/l; leucopenia 2.0-3.0x109/l; thrombocytopenia 50-75x109/l.
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 (e.g., citalopram, sertralin) or monitor (desmethyl)clomipramine plasma concentration. Published case reports, well documented, and having relevant pharmacokinetic or clinical endpoints. Well documented case series. 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 1.0-1.5x109/l; leucopenia 2.0-3.0x109/l; thrombocytopenia 50-75x109/l.
  • *See Methods or PMID: 18253145 for definition of "good quality."
  • S: statistically significant difference.
  • Please see attached PDF for detailed information about the evaluated studies: Clomipramine 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 clomipramine and CYP2D6

Actionable PGx

Summary

The drug label for clomipramine (Anafranil) notes that CYP2D6 poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs), such as clomipramine, when given typical doses. Additionally, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. It is therefore desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be a CYP2D6 inhibitor.

Annotation

Clomipramine (Anafranil) is an antiobsessional drug belonging to the tricyclic antidepressants class. The FDA-approved drug label for clomipramine highlights information regarding CYP2D6 poor metabolizers, as well as information about usage of drugs that inhibit CYP2D6, one of the enzymes responsible for clomipramine metabolism.

Excerpt from the clomipramine (Anafranil) label:

The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6...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 P450 2D6 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). In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers...It is desirable to monitor TCA plasma levels whenever an agent of the tricyclic antidepressant class including Anafranil is going to be co-administered with another drug known to be an inhibitor of P450 2D6...

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the clomipramine 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
    • Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • Depression, Postpartum
    • Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • Inflammation
    • Adverse reactions section
    • source: PHONT
  • Neoplasms
    • Adverse reactions section, Precautions section
    • source: PHONT
  • Schizophrenia
    • Precautions section
    • source: PHONT
  • CYP1A2
    • Precautions section, metabolism/PK
    • source: FDA Label
  • CYP2D6
    • Precautions 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.

? = Mouse-over for quick help

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 , Variant in CYP2C19 , 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 CYP2C19 , Variant in CYP2D6
VeraCode ADME Core Panel (Illumina, Inc) Variant in CYP2C19 , Variant in CYP2D6
TaqMan Drug Metabolism Genotyping Assay Sets (Applied Biosystems, Inc) Variant in CYP2C19 , Variant in CYP2D6
Laboratory Corporation of America Variant in CYP2C19 , Variant in CYP2D6
Quest Diagnostics, Inc Variant in CYP2D6
iPLEX ADME PGx (Sequenom, Inc) CYP2C19*1, CYP2C19*12, CYP2C19*17, CYP2C19*2, CYP2C19*3, CYP2C19*4, CYP2C19*5A, CYP2C19*5B, CYP2C19*6, CYP2C19*7, CYP2C19*8
AmpliChip CYP450 Test (Roche Molecular Systems, Inc) CYP2C19*2, CYP2C19*3
eSensor 2C19 Genotyping Test (GenMark Diagnostics, Inc) CYP2C19*10, CYP2C19*13, CYP2C19*17, CYP2C19*2, CYP2C19*3, CYP2C19*4, CYP2C19*5, CYP2C19*6, CYP2C19*7, CYP2C19*8, CYP2C19*9
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
Spartan RX CYP2C19 System CYP2C19*17, CYP2C19*2, CYP2C19*3 , rs12248560 , rs4986893 , rs4244285
INFINITI CYP2C19 (AutoGenomics, Inc) CYP2C19*17, CYP2C19*2, CYP2C19*3 , rs12248560 , rs4986893 , rs4244285
INFINITI CYP450 2C19+ (AutoGenomics, Inc) CYP2C19*10, CYP2C19*17, CYP2C19*2, CYP2C19*3, CYP2C19*4, CYP2C19*5, CYP2C19*6, CYP2C19*7, CYP2C19*8, CYP2C19*9 , rs12248560 , rs28399504 , rs41291556 , rs72552267 , rs17884712 , rs4986893 , rs6413438 , rs4244285 , rs72558186 , rs56337013
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 clomipramine variant annotations

Gene ? Variant?
(142)
Alternate Names ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available CA VA CYP2C19 *1 N/A N/A N/A
No VIP available CA VA CYP2C19 *2 N/A N/A N/A
VIP No VIP available No VIP available CYP2C19 *2A N/A N/A N/A
No VIP available CA VA CYP2C19 *3 N/A N/A N/A
VIP No VIP available No VIP available CYP2C19 *3A N/A N/A N/A
No VIP available CA VA CYP2C19 *17 N/A N/A N/A
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 VA CYP2D6 *6 N/A N/A N/A
VIP No VIP available No VIP available CYP2D6 *9 N/A N/A N/A
VIP No VIP available 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 CA VA SLC6A4 HTTLPR long form (L allele) N/A N/A N/A
No VIP available CA VA SLC6A4 HTTLPR short form (S allele) 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 No Clinical Annotations available VA
CYP2D6 poor metabolizers N/A N/A N/A
No VIP available No Clinical Annotations available Variant in CYP2D6
Variant in CYP2D6 N/A N/A N/A
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 CA VA
rs130058 -161A>T, 16293115T>A, 78173281T>A
T > A
5' Flanking
No VIP available CA VA
rs1360780 106-2636A>G, 35547571T>C, 35607571T>C, 93790A>G
T > C
Intronic
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
rs2032582 186947T>A, 186947T>G, 25193461A>C, 25193461A>T, 2677A, 2677G, 2677T, 2677T>A, 2677T>G, 3095G>T/A, 87160618A>C, 87160618A>T, 893 Ala, 893 Ser, 893 Thr, ABCB1*7, ABCB1: 2677G>T/A, ABCB1: 2677T/A>G, ABCB1: A893S, ABCB1: G2677T/A, ABCB1: c.2677G>T/A, ABCB1:2677G>A/T, ABCB1:2677G>T/A, ABCB1:A893T, Ala893Ser/Thr, MDR1, MDR1 G2677T/A, Ser893Ala, Ser893Thr, mRNA 3095G>T/A, p.Ala893Ser/Thr
A > T
A > C
Missense
Ser893Ala
Ser893Thr
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
rs4244285 24154G>A, 24154G>C, 47346080G>A, 47346080G>C, 681G>A, 681G>C, 96541616G>A, 96541616G>C, CYP2C19*2, CYP2C19:681G>A, CYP2C19:G681A, Pro227=
G > A
G > C
Synonymous
Pro227Pro
No VIP available No Clinical Annotations available VA
rs4680 1-5G>A, 19951271G>A, 27009G>A, 3103421G>A, 322G>A, 472G>A, COMP: Val158Met, COMT:Val108Met, Val108Met, Val158Met
G > A
5' Flanking
Val158Met
rs4986893 22948G>A, 47344874G>A, 636G>A, 96540410G>A, CYP2C19*3, CYP2C19:636G>A, CYP2C19:G636A, Trp212Ter
G > A
Stop Codon
Trp212null
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
rs5569 1287G>A, 47294G>A, 55731835G>A, 9346034G>A, 972G>A, Thr324=, Thr429=
G > A
Synonymous
Thr429Thr
rs59421388 1012G>A, 21914179C>T, 3271G>A, 42523610C>T, 8274G>A, 859G>A, CYP2D6: 3183G>A, Val287Met, Val338Met
G > T
G > C
Missense
Val287Met
No VIP available No Clinical Annotations available VA
rs6113 11119T>C, 150T>C, 76053849T>C, 95053849T>C, Phe50=
T > C
Synonymous
Phe50Phe
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 No Clinical Annotations available VA
rs6296 16292094C>G, 78172260C>G, 861G>C, Val287=
C > G
Synonymous
Val287Val
No VIP available No Clinical Annotations available VA
rs6305 264C>T, 28446622G>A, 47466622G>A, 516C>T, 9548C>T, Asp172=, Asp88=
G > A
Synonymous
Asp88Asp
No VIP available No Clinical Annotations available VA
rs6313 102C>T, 160+869C>T, 28449940G>A, 47469940G>A, 6230C>T, HTR2A:102C>T, HTR2A:T102C, Ser34=
G > A
Intronic
Ser34Ser
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 142
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • 3-Chloroimipramine
  • Chlorimipramine
  • Clomipramina [INN-Spanish]
  • Clomipramine HCL
  • Clomipraminum [INN-Latin]
  • Monochlorimipramine
Trade Names
  • Anafranil
  • Hydiphen
Brand Mixture Names

PharmGKB Accession Id:
PA449048

Description

Clomipramine, the 3-chloro analog of imipramine, is a dibenzazepine-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, clomipramine does not affect mood or arousal, but may cause sedation. In depressed individuals, clomipramine exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Tertiary amine TCAs, such as clomipramine, 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. See toxicity section below for a complete listing of side effects. Clomipramine may be used to treat obsessive-compulsive disorder and disorders with an obsessive-compulsive component (e.g. depression, schizophrenia, Tourette's disorder). Unlabeled indications include panic disorder, chronic pain (e.g. central pain, idiopathic pain disorder, tension headache, diabetic peripheral neuropathy, neuropathic pain), cataplexy and associated narcolepsy, autistic disorder, trichotillomania, onchophagia, stuttering, premature ejaculation, and premenstrual syndrome. Clomipramine is rapidly absorbed from the gastrointestinal tract and demethylated in the liver to its primary active metabolite, desmethylclomipramine.

Source: Drug Bank

Indication

May be used to treat obsessive-compulsive disorder and disorders with an obsessive-compulsive component (e.g. depression, schizophrenia, Tourette's disorder).
Unlabeled indications include: depression, panic disorder, chronic pain (e.g. central pain, idiopathic pain disorder, tension headache, diabetic peripheral neuropathy, neuropathic pain), cataplexy and associated narcolepsy (limited evidence), autistic disorder (limited evidence), trichotillomania (limited evidence), onchophagia (limited evidence), stuttering (limited evidence), premature ejaculation, and premenstrual syndrome.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Clomipramine is a strong, but not completely selective serotonin reuptake inhibitor (SRI), as the active main metabolite desmethyclomipramine acts preferably as an inhibitor of noradrenaline reuptake. alpha 1-receptor blockage and beta-down-regulation have been noted and most likely play a role in the short term effects of clomipramine. A blockade of sodium-channels and NDMA-receptors might, as with other tricyclics, account for its effect in chronic pain, in particular the neuropathic type.

Source: Drug Bank

Pharmacology

Clomipramine, a tricyclic antidepressant, is the 3-chloro derivative of Imipramine. It was thought that tricyclic antidepressants work exclusively by inhibiting the re-uptake of the neurotransmitters norepinephrine and serotonin by nerve cells. However, this response occurs immediately, yet mood does not lift for around two weeks. It is now thought that changes occur in receptor sensitivity in the cerebral cortex and hippocampus. The hippocampus is part of the limbic system, a part of the brain involved in emotions. Presynaptic receptors are affected: alpha 1 and beta 1 receptors are sensitized, alpha 2 receptors are desensitized (leading to increased noradrenaline production). Tricyclics are also known as effective analgesics for different types of pain, especially neuropathic or neuralgic pain.

Source: Drug Bank

Food Interaction

Avoid alcohol.|Take with food to reduce irritation.|Grapefruit and grapefruit juice should be avoided throughout treatment, grapefruit can modify serum levels of clomipramine and its metabolite desmethyl-clomipramine.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Extensively metabolized in the liver. The main active metabolite is desmethylclomipramine, which is formed by N-demethylation of clomipramine via CYP2C19, 3A4 and 1A2. Other metabolites and their glucuronide conjugates are also produced. Other metabolites of clomipramine include 8-hydroxyclomipramine formed via 8-hydroxylation, 2-hydroxyclomipramine formed via 2-hydroxylation, and clomipramine N-oxide formed by N-oxidation. Desmethylclomipramine is further metabolized to 8-hydroxydesmethylclomipramine and didesmethylclomipramine, which are formed by 8-hydroxylation and N-demethylation, respectively. 8-Hydroxyclomipramine and 8-hydroxydesmethylclomipramine are pharmacologically active; however, their clinical contribution remains unknown.

Source: Drug Bank

Protein Binding

Clomipramine is approximately 97-98% bound to plasma proteins, principally to albumin and possibly to alpha 1-acid glycoprotein. Desmethylclomipramine is 97-99% bound to plasma proteins.

Source: Drug Bank

Absorption

Well absorbed from the GI tract following oral administration. Bioavailability is approximately 50% orally due to extensive first-pass metabolism. Bioavailability is not affected by food. Peak plasma concentrations occur 2-6 hours following oral administration of a single 50 mg dose. Large interindividual variations in plasma concentrations occur, partly due to genetic differences in clomipramine metabolism. On average, steady state plasma concentrations are achieved in 1-2 weeks following multiple dose oral administration. Smoking appears to lower the steady-state plasma concentration of clomipramine, but not its active metabolite desmethylclomipramine.

Source: Drug Bank

Half-Life

Following oral administration of a single 150 mg dose of clomipramine, the average elimination half-life of clomipramine was 32 hours (range: 19-37 hours) and of desmethylclomipramine was 69 hours (range: 54-77 hours). Elimination half-life may vary substantially with different doses due to probably saturable kinetics (i.e. metabolism).

Source: Drug Bank

Toxicity

Signs and symptoms vary in severity depending upon factors such as the amount of drug absorbed, the age of the patient, and the time elapsed since drug ingestion. Critical manifestations of overdose include 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 toxicity. In U.S. clinical trials, 2 deaths occurred in 12 reported cases of acute overdosage with Anafranil either alone or in combination with other drugs. One death involved a patient suspected of ingesting a dose of 7000 mg. The second death involved a patient suspected of ingesting a dose of 5750 mg.
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

Urine (51-60%) and feces via biliary elimination (24-32%)

Source: Drug Bank

Volume of Distribution

Average ~ 17 L/kg (range: 9-25 L/kg)

Source: Drug Bank

Chemical Properties

Chemical Formula

C19H23ClN2

Source: Drug Bank

Isomeric SMILES

CN(C)CCCN1c2ccccc2CCc3c1cc(cc3)Cl

Source: OpenEye

Canonical SMILES

CN(C)CCCN1C2=CC=CC=C2CCC2=C1C=C(Cl)C=C2

Source: Drug Bank

Average Molecular Weight

314.852

Source: Drug Bank

Monoisotopic Molecular Weight

314.154976453

Source: Drug Bank

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Clomipramine Pathway, Pharmacokinetics
    Schematic representation of clomipramine metabolism in human liver.

External Pathways

Links to non-PharmGKB pathways.

PharmGKB contains no links to external pathways for this drug. To report a pathway, click here.

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
GSTP1 (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

Drug Description
clomipramine Increases the effect and toxicity of tricyclics (source: Drug Bank)
clomipramine Atazanavir may increase the effect and toxicity of the tricyclic antidepressant, clomipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine if atazanavir if initiated, discontinued or dose changed. (source: Drug Bank)
clomipramine Increases the effect of tricyclic agent (source: Drug Bank)
clomipramine Cimetidine may increase the effect of the tricyclic antidepressant, clomipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine if cimetidine is initiated, discontinued or dose changed. (source: Drug Bank)
clomipramine Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
clomipramine Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
altretamine Risk of severe hypotension (source: Drug Bank)
altretamine Risk of severe 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, clomipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine if atazanavir if 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, clomipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine 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 tricycli decreases the effect of clonidine (source: Drug Bank)
clonidine The tricycli decreases the effect of clonidine (source: Drug Bank)
dobutamine The tricyclic increases the sympathomimetic effect (source: Drug Bank)
dobutamine The tricyclic antidepressant, clomipramine, 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, clomipramine, increases the sympathomimetic effect of dopamine. (source: Drug Bank)
ephedra The tricyclic increases the sympathomimetic effect (source: Drug Bank)
ephedra The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of ephedra. (source: Drug Bank)
ephedrine The tricyclic increases the sympathomimetic effect (source: Drug Bank)
ephedrine The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of ephedrine. (source: Drug Bank)
epinephrine The tricyclic increases the sympathomimetic effect (source: Drug Bank)
epinephrine The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of epinephrine. (source: Drug Bank)
fenoterol The tricyclic increases the sympathomimetic effect (source: Drug Bank)
fenoterol The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of fenoterol. (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, clomipramine, 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 clomipramine 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, clomipramine, 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 clomipramine 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, clomipramine, 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, clomipramine, increases the sympathomimetic effect of isoproterenol. (source: Drug Bank)
mephentermine The tricyclic increases the sympathomimetic effect (source: Drug Bank)
mephentermine The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of mephentermine. (source: Drug Bank)
metaraminol The tricyclic increases the sympathomimetic effect (source: Drug Bank)
metaraminol The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of metaraminol. (source: Drug Bank)
methoxamine The tricyclic increases the sympathomimetic effect (source: Drug Bank)
methoxamine The tricyclic antidepressant, clomipramine, 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, clomipramine, increases the sympathomimetic effect of norepinephrine. (source: Drug Bank)
orciprenaline The tricyclic increases the sympathomimetic effect (source: Drug Bank)
orciprenaline The tricyclic antidepressant, clomipramine, 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, clomipramine, increases the sympathomimetic effect of phenylephrine. (source: Drug Bank)
phenylpropanolamine The tricyclic increases the sympathomimetic effect (source: Drug Bank)
phenylpropanolamine The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of phenylpropanolamine. (source: Drug Bank)
pirbuterol The tricyclic increases the sympathomimetic effect (source: Drug Bank)
pirbuterol The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of pirbuterol. (source: Drug Bank)
procaterol The tricyclic increases the sympathomimetic effect (source: Drug Bank)
procaterol The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of procaterol. (source: Drug Bank)
pseudoephedrine The tricyclic increases the sympathomimetic effect (source: Drug Bank)
pseudoephedrine The tricyclic antidepressant, clomipramine, 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 tricyclic antidepressant, clomipramine. (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, clomipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine 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, clomipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine if rifampin is initiated, discontinued or dose changed. (source: Drug Bank)
ritonavir Ritonavir increases the effect and toxicity of tricyclics (source: Drug Bank)
ritonavir Ritonavir may increase the effect and toxicity of the tricyclic antidepressant, clomipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine 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, clomipramine, 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)
terbutaline The tricyclic increases the sympathomimetic effect (source: Drug Bank)
terbutaline The tricyclic antidepressant, clomipramine, 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)
clomipramine The tricyclic decreases the effect of clonidine (source: Drug Bank)
clomipramine The tricyclic antidepressant, clomipramine, decreases the effect of clonidine. (source: Drug Bank)
clomipramine Possible antagonism of action (source: Drug Bank)
clomipramine Possible antagonism of action (source: Drug Bank)
clomipramine The tricyclic increases the sympathomimetic effect (source: Drug Bank)
clomipramine The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of epinephrine. (source: Drug Bank)
clomipramine The tricyclic increases the sympathomimetic effect (source: Drug Bank)
clomipramine The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of fenoterol. (source: Drug Bank)
clomipramine Fluoxetine increases the effect and toxicity of tricyclics (source: Drug Bank)
clomipramine The SSRI, fluoxetine, may increase the serum concentration of the tricyclic antidepressant, clomipramine, 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 clomipramine if fluoxetine is initiated, discontinued or dose changed. (source: Drug Bank)
clomipramine Fluvoxamine increases the effect and toxicity of tricyclics (source: Drug Bank)
clomipramine The SSRI, fluvoxamine, may increase the serum concentration of the tricyclic antidepressant, clomipramine, 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 clomipramine if fluvoxamine is initiated, discontinued or dose changed. (source: Drug Bank)
clomipramine Possible antagonism of action (source: Drug Bank)
clomipramine Possible antagonism of action (source: Drug Bank)
clomipramine Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
clomipramine Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
clomipramine The tricyclic decreases the effect of guanethidine (source: Drug Bank)
clomipramine The tricyclic antidepressant, clomipramine, decreases the effect of guanethidine. (source: Drug Bank)
clomipramine Possibility of severe adverse effects (source: Drug Bank)
clomipramine Possibility of severe adverse effects (source: Drug Bank)
clomipramine Possible severe adverse reaction with this combination (source: Drug Bank)
clomipramine Possible severe adverse reaction with this combination (source: Drug Bank)
clomipramine The tricyclic increases the sympathomimetic effect (source: Drug Bank)
clomipramine The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of orciprenaline. (source: Drug Bank)
clomipramine Possibility of severe adverse effects (source: Drug Bank)
clomipramine Possibility of severe adverse effects (source: Drug Bank)
clomipramine The tricyclic increases the sympathomimetic effect (source: Drug Bank)
clomipramine The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of phenylephrine. (source: Drug Bank)
clomipramine The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of phenylpropanolamine. (source: Drug Bank)
clomipramine The tricyclic increases the sympathomimetic effect (source: Drug Bank)
clomipramine The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of pseudoephedrine. (source: Drug Bank)
clomipramine Quinidine increases the effect of the tricyclic agent (source: Drug Bank)
clomipramine Additive QTc-prolonging effects may occur. Quinidine may also increase the serum concentration of the tricyclic antidepressant, clomipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine if quinidine is initiated, discontinued or dose changed. Monitor for the development of torsades de pointes during concomitant therapy. (source: Drug Bank)
clomipramine Possibility of severe adverse effects (source: Drug Bank)
clomipramine The rifamycin decreases the effect of tricyclics (source: Drug Bank)
clomipramine The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, clomipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine if rifabutin is initiated, discontinued or dose changed. (source: Drug Bank)
clomipramine The rifamycin decreases the effect of tricyclics (source: Drug Bank)
clomipramine The rifamycin, rifampin, may decrease the effect of the tricyclic antidepressant, clomipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine if rifampin is initiated, discontinued or dose changed. (source: Drug Bank)
clomipramine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Clomipramine, 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)
clomipramine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Clomipramine, 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)
clomipramine Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution. (source: Drug Bank)
clomipramine Clomipramine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy. (source: Drug Bank)
clomipramine Clomipramine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy. (source: Drug Bank)
clomipramine Clomipramine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Clomipramine is initiated, discontinued, or dose changed. (source: Drug Bank)
clomipramine Clomipramine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Clomipramine is initiated, discontinued, or dose changed. (source: Drug Bank)
clomipramine Terbinafine may reduce the metabolism and clearance of Clomipramine. Consider alternate therapy or monitor for therapeutic/adverse effects of Clomipramine if Terbinafine is initiated, discontinued or dose changed. (source: Drug Bank)
clomipramine The tricyclic increases the sympathomimetic effect (source: Drug Bank)
clomipramine The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of terbutaline. (source: Drug Bank)
clomipramine Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
clomipramine Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
clomipramine The strong CYP1A2 inhibitor, Thiabendazole, may increase the effects and toxicity of Clomipramine by decreasing Clomipramine metabolism and clearance. Monitor for changes in the therapeutic and adverse effects of Clomipramine if Thiabendazole is initiated, discontinued or dose changed. (source: Drug Bank)
clomipramine 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)
clomipramine 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)
clomipramine Ticlopidine may decrease the metabolism and clearance of Clomipramine. Consider alternate therapy or monitor for adverse/toxic effects of Clomipramine if Ticlopidine is initiated, discontinued or dose changed. (source: Drug Bank)
clomipramine 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)
clomipramine Tramadol increases the risk of serotonin syndrome and seizures. Clomipramine may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank)
clomipramine 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)
clomipramine Increased risk of serotonin syndrome. The 2D6 inhibitor, Trazodone, may also increase the efficacy of Clomipramine by decreasing Clomipramine metabolism and clearance. Monitor for symptoms of serotonin syndrome and changes in Clomipramine efficacy if Trazodone is initiated, discontinued or dose changed. (source: Drug Bank)
clomipramine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank)
clomipramine Trimethobenzamide and Clomipramine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects. (source: Drug Bank)
clomipramine 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)
clomipramine Triprolidine and Clomipramine, 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)
clomipramine Triprolidine and Clomipramine, 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)
clomipramine Trospium and Clomipramine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects. (source: Drug Bank)
clomipramine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. (source: Drug Bank)
clomipramine 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)
clomipramine 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)
clomipramine Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated. (source: Drug Bank)
clomipramine Use of two serotonin modulators, such as zolmitriptan and clomipramine, increases the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy. (source: Drug Bank)
clomipramine 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 clomipramine: 66

No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Serotonin toxicity from antidepressant overdose and its association with the T102C polymorphism of the 5-HT2A receptor. The pharmacogenomics journal. 2014. Cooper J M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Challenges in pharmacogenetics. European journal of clinical pharmacology. 2013. Cascorbi Ingolf, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Pharmacogenetics in major depression: a comprehensive meta-analysis. Progress in neuro-psychopharmacology & biological psychiatry. 2013. Niitsu Tomihisa, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Influence of CYP2D6 and CYP2C19 gene variants on antidepressant response in obsessive-compulsive disorder. The pharmacogenomics journal. 2013. Brandl E 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
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
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Cytochrome P450-mediated drug metabolism in the brain. Journal of psychiatry & neuroscience : JPN. 2012. Miksys Sharon, 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 AmpliChip® CYP450 test and response to treatment in schizophrenia and obsessive compulsive disorder: a pilot study and focus on cases with abnormal CYP2D6 drug metabolism. Genetic testing and molecular biomarkers. 2012. Müller Daniel J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
PharmGKB summary: very important pharmacogene information for cytochrome P450, family 2, subfamily C, polypeptide 19. Pharmacogenetics and genomics. 2011. Scott Stuart A, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
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
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics: From Bench to Byte- An Update of Guidelines. Clinical pharmacology and therapeutics. 2011. Swen J J, et al. PubMed
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Clinical and genetic correlates of suicidal ideation during antidepressant treatment in a depressed outpatient sample. Pharmacogenomics. 2011. Perroud Nader, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Association study between genetic monoaminergic polymorphisms and OCD response to clomipramine treatment. Arquivos de neuro-psiquiatria. 2011. Miguita Karen, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
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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Meta-analysis of FKBP5 gene polymorphisms association with treatment response in patients with mood disorders. Neuroscience letters. 2010. Zou Yan-Feng, 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
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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Role of human UGT2B10 in N-glucuronidation of tricyclic antidepressants, amitriptyline, imipramine, clomipramine, and trimipramine. Drug metabolism and disposition: the biological fate of chemicals. 2010. Zhou Diansong, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
FKBP5 polymorphisms and antidepressant response in geriatric depression. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics. 2010. Sarginson Jane E, et al. PubMed
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Cytochrome P450 2D6. Pharmacogenetics and genomics. 2009. Owen Ryan P, 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 No Variant Annotation available No VIP available No VIP available
Genetic variants in FKBP5 affecting response to antidepressant drug treatment. Pharmacogenomics. 2008. Kirchheiner Julia, et al. PubMed
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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
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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
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Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic and clinical aspects. Pharmacology & therapeutics. 2007. Ingelman-Sundberg Magnus, et al. PubMed
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A fatal doxepin poisoning associated with a defective CYP2D6 genotype. The American journal of forensic medicine and pathology. 2007. Koski Anna, et al. PubMed
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Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. British journal of pharmacology. 2007. Gillman P K. PubMed
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Genetic variability at HPA axis in major depression and clinical response to antidepressant treatment. Journal of affective disorders. 2007. Papiol Sergi, et al. PubMed
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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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CYP2D6 and CYP2C19 genotypes and amitriptyline metabolite ratios in a series of medicolegal autopsies. Forensic science international. 2006. Koski Anna, et al. PubMed
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Serotonin transporter polymorphisms and side effects in antidepressant therapy--a pilot study. Pharmacogenomics. 2006. Popp Johannes, et al. PubMed
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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
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The complexity of active metabolites in therapeutic drug monitoring of psychotropic drugs. Pharmacopsychiatry. 2006. Hendset M, 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
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Hippocampal upregulation of the cyclooxygenase-2 gene following neonatal clomipramine treatment (a model of depression). The pharmacogenomics journal. 2006. Cassano P, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
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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Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment. Nature genetics. 2004. Binder Elisabeth B, 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
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Clomipramine, fluoxetine and CYP2D6 metabolic capacity in depressed patients. Human psychopharmacology. 2004. Vandel P, et al. PubMed
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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
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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
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Effects of polymorphisms in CYP2D6, CYP2C9, and CYP2C19 on trimipramine pharmacokinetics. Journal of clinical psychopharmacology. 2003. Kirchheiner Julia, et al. PubMed
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Contributions of CYP2D6, CYP2C9 and CYP2C19 to the biotransformation of E- and Z-doxepin in healthy volunteers. Pharmacogenetics. 2002. Kirchheiner Julia, et al. PubMed
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The effect of CYP2C19 and CYP2D6 genotypes on the metabolism of clomipramine in Japanese psychiatric patients. Journal of clinical psychopharmacology. 2001. Yokono A, 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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CYP2D6 and CYP2C19 genotype-based dose recommendations for antidepressants: a first step towards subpopulation-specific dosages. Acta psychiatrica Scandinavica. 2001. Kirchheiner J, et al. PubMed
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Serotonin transporter (5-HTT) promoter genotype may influence the prolactin response to clomipramine. Psychopharmacology. 2000. Whale R, et al. PubMed
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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 No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pronounced differences in the dispositon of clomipramine between Japanese and Swedish patients. Journal of clinical psychopharmacology. 1999. Shimoda K, et al. PubMed
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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CYP2D6 phenotype-genotype relationships in African-Americans and Caucasians in Los Angeles. Pharmacogenetics. 1998. Leathart J B, et al. PubMed
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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
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Ultrarapid metabolism of clomipramine in a therapy-resistant depressive patient, as confirmed by CYP2 D6 genotyping. Pharmacopsychiatry. 1998. Baumann P, et al. PubMed
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Pharmacogenetics of antidepressants: clinical aspects. Acta psychiatrica Scandinavica. Supplementum. 1997. Bertilsson L, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
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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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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Debrisoquine hydroxylation phenotypes of patients with high versus low to normal serum antidepressant concentrations. Journal of clinical psychopharmacology. 1992. Tacke U, 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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Steady-state plasma levels of clomipramine and its metabolites: impact of the sparteine/debrisoquine oxidation polymorphism. Danish University Antidepressant Group. European journal of clinical pharmacology. 1992. Nielsen K K, 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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High plasma concentrations of desmethylclomipramine after chronic administration of clomipramine to a poor metabolizer. European journal of clinical pharmacology. 1987. Balant-Gorgia A E, 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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Plasma levels of chlorimipramine and its demethyl metabolite during treatment of depression. Clinical pharmacology and therapeutics. 1979. Träskman L, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0781-2027-31
DrugBank:
DB01242
PDB:
CXX
ChEBI:
47780
KEGG Compound:
C06918
PubChem Compound:
2801
PubChem Substance:
152550
46505157
IUPHAR Ligand:
2398
Drugs Product Database (DPD):
2244818
BindingDB:
50021927
ChemSpider:
2699
HET:
CXX
Therapeutic Targets Database:
DAP000742
FDA Drug Label at DailyMed:
3823106e-6be3-4154-a607-caa3a69dc75c

Clinical Trials

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

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Sources for PharmGKB drug information: DrugBank, Open Eye Scientific Software.