Drug/Small Molecule:
clozapine

last updated 08/10/2011

Dutch Pharmacogenetics Working Group Guideline for clozapine and CYP2D6

Summary

There are currently no dosing recommendations for Clozapine based on CYP2D6 genotypes.

Annotation

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

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

PharmGKB gathers information regarding PGx on FDA drug labels from the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels", and from FDA-approved FDA and EMA-approved (European Medicines Agency) EMA labels brought to our attention. Excerpts from the label and downloadable highlighted label PDFs are manually curated by PharmGKB.

Please note that some drugs may have been removed from or added to the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels" without our knowledge. We periodically check the table for additions to this table and update PharmGKB accordingly.

There is currently no such list for European drug labels - we are working with the EMA to establish a list of European Public Assessment Reports (EPAR)s that contain PGx information. We are constructing this list by initially searching for drugs for which we have PGx-containing FDA drug labels - of these 44 EMA EPARs were identified and are being curated for pgx information.

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


last updated 10/25/2013

FDA Label for clozapine and CYP2D6

This label is on the FDA Biomarker List
Actionable PGx

Summary

Clozapine is a substrate of CYP1A2, CYP3A4, and CYP2D6. The drug label notes to use caution when administering it concomitantly with drugs that are inducers or inhibitors of these enzymes. Additionally, it may be necessary to reduce the clozapine dose in patients with significant renal or hepatic impairment, or in CYP2D6 poor metabolizers.

Annotation

Clozapine is an atypical antipsychotic drug. It is approved for the treatment of severely ill patients with schizophrenia who fail to show an acceptable response to standard antipsychotic drug treatment. Clozapine is a substrate for many CYP450 isozymes, in particular 1A2, 2D6, and 3A4.

Excerpts from the Clozapine drug label:

Dose adjustments may be necessary in patients with concomitant use of: strong CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin, or enoxacin); moderate or weak CYP1A2 inhibitors (e.g., oral contraceptives, or caffeine); CYP2D6 or CYP3A4 inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, or sertraline); CYP3A4 inducers (e.g., phenytoin, carbamazepine, St. Johns wort, and rifampin); or CYP1A2 inducers (e.g., tobacco smoking).

It may be necessary to reduce the CLOZARIL dose in patients with significant renal or hepatic impairment, or in CYP2D6 poor metabolizers.

A subset (3%-10%) of the population has reduced activity of certain drug metabolizing enzymes such as the cytochrome P450 isozyme P450 2D6. Such individuals are referred to as "poor metabolizers" of drugs such as debrisoquin, dextromethorphan, the tricyclic antidepressants, and clozapine. These individuals may develop higher than expected plasma concentrations of clozapine when given usual doses. In addition, certain drugs that are metabolized by this isozyme, including many antidepressants (clozapine, selective serotonin reuptake inhibitors, and others), may inhibit the activity of this isozyme, and thus may make normal metabolizers resemble poor metabolizers with regard to concomitant therapy with other drugs metabolized by this enzyme system, leading to drug interaction.

Concomitant use of CLOZARIL with other drugs metabolized by CYP2D6 can increase levels of these CYPD26 substrates. Use caution when coadministering CLOZARIL with other drugs that are metabolized by CYP2D6. It may be necessary to use lower doses of such drugs than usually prescribed. Such drugs include specific antidepressants, phenothiazines, carbamazepine, and Type 1C antiarrhythmics (e.g., propafenone, flecainide, and encainide).

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

  • Agranulocytosis
    • Indications & usage section, Contraindications section, Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • Bradycardia
    • Dosage & administration section, Adverse reactions section, Warnings and precautions section
    • source: FDA Label
  • Hyperglycemia
    • Dosage & administration section, Adverse reactions section, Warnings and precautions section
    • source: FDA Label
  • Myocarditis
    • Dosage & administration section, Adverse reactions section, Warnings and precautions section
    • source: FDA Label
  • Psychotic Disorders
    • Indications & usage section, Warnings section, Adverse reactions section
    • source: PHONT
  • Schizophrenia
    • Indications & usage section, Warnings section, Adverse reactions section
    • source: PHONT
  • Seizures
    • Contraindications section, Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • tardive dyskinesia
    • Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • Weight gain
    • Adverse reactions section
    • source: PHONT
  • CYP1A2
    • Drug interactions section, Pharmacokinetics section, metabolism/PK
    • source: FDA Label
  • CYP2D6
    • Drug interactions section, Pharmacokinetics section, Use in specific populations section, metabolism/PK
    • source: FDA Label
  • CYP3A4
    • Drug interactions section, Pharmacokinetics section, metabolism/PK
    • source: FDA Label
  • DRD2
    • Clinical pharmacology section, other
    • source: FDA Label
  • HTR2A
    • Clinical pharmacology section, other
    • source: FDA Label

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

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

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?
Pgx Predict: CLOZAPINE HLA-DQB1 HLA-DQB1:G6672C
GenoChip CYP2D6 (PharmGenomics, GmbH) CYP2D6*5 , rs59421388 , rs28371725 , rs5030867 , rs5030656 , rs35742686 , rs3892097 , rs5030865 , rs5030655 , rs28371706 , rs5030863 , rs1065852 , CYP2D6 *xN (gene duplication)

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.

Gene ? Variant?
(138)
Alternate Names / Tag SNPs ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No VIP available VA CYP1A2 *1A N/A N/A N/A
No VIP available No VIP available VA CYP1A2 *1F N/A N/A N/A
VIP No VIP available VA CYP2D6 *1 N/A N/A N/A
VIP No VIP available No VIP available CYP2D6 *2 N/A N/A N/A
VIP No VIP available VA CYP2D6 *3 N/A N/A N/A
VIP No VIP available VA CYP2D6 *4 N/A N/A N/A
No VIP available No VIP available VA CYP2D6 *5 N/A N/A N/A
VIP No VIP available 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 No VIP available 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 HLA-B *38:01:01 N/A N/A N/A
No VIP available No VIP available VA HLA-C *07:01:01 N/A N/A N/A
No VIP available No VIP available VA HLA-DPB1 *04:01:01:01 N/A N/A N/A
No VIP available No VIP available VA HLA-DQB1 *02:01:01 N/A N/A N/A
No VIP available No VIP available VA HLA-DQB1 *03:01:01:01 N/A N/A N/A
No VIP available No VIP available VA HLA-DQB1 *05:02:01 N/A N/A N/A
No VIP available No VIP available VA HLA-DRB1 *01:01:01 N/A N/A N/A
No VIP available No VIP available VA HLA-DRB1 *04:01:01 N/A N/A N/A
No VIP available No VIP available VA HLA-DRB3 *02:02:01:01 N/A N/A N/A
No VIP available No VIP available VA HLA-DRB5 *02:02 N/A N/A N/A
No VIP available No VIP available VA HTR2C 2--1--1 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 VIP available VA SLC6A4 L allele-rs25531C N/A N/A N/A
No VIP available No VIP available VA SLC6A4 L allele-rs25531T N/A N/A N/A
No VIP available No Clinical Annotations available VA
rs10193895 106269612A>G, 10943441A>G
A > G
Not Available
No VIP available CA VA
rs10248420 182579T>C, 2481+788T>C, 25197829A>G, 87164986A>G
A > G
Intronic
No VIP available No Clinical Annotations available 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
No VIP available No Clinical Annotations available VA
rs1049353 1260G>A, 1359G>A, 26973469C>T, 88853635C>T, Thr420=, Thr453=
C > T
Synonymous
Thr453Thr
No VIP available No Clinical Annotations available VA
rs1050450 *581C>T, 49334834G>A, 49394834G>A, 5958C>T, 599C>T
G > A
Missense
Pro200Leu
No VIP available CA VA
rs1062613 -24T>C, 113846006T>C, 17408422T>C, 210T>C, 5210T>C, HTR3A:C178T, Pro16Ser
T > C
Not Available
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
rs1079598 -31-870T>C, 113296274A>G, 16858690A>G, 54728T>C
A > G
Intronic
No VIP available No Clinical Annotations available VA
rs11146020 -855G>C, 140033084G>C, 4476G>C, 816087G>C
G > C
5' Flanking
No VIP available No Clinical Annotations available VA
rs1128397 100547T>A, 1070T>A, 1385T>A, 21550800A>T, 9408946A>T, 986T>A, Leu329Gln, Leu357Gln, Leu462Gln
A > T
Missense
Leu329Gln
No VIP available No Clinical Annotations available VA
rs1135840 1304G>G, 1457G>G, 21913182G>C, 42522613G>C, 9271G>G, CYP2D6: S486T, CYP2D6:4180G>C, Ser435=, Ser486=, part of CYP2D6*2A an extensive metabolizer haplotype.
G > C
Missense
Ser435Thr
No VIP available CA VA
rs1150226 -256A>G, -489A>G, 113845541A>G, 17407957A>G, 4745A>G
A > G
5' Flanking
No VIP available CA VA
rs11872992 -1005C>T, 4415C>T, 58040587G>A, 5831451G>A
G > A
5' Flanking
No VIP available No Clinical Annotations available VA
rs13064530 -1867G>A, -35-34775G>A, 11205914G>A, 11265914G>A
G > A
Intronic
No VIP available No Clinical Annotations available VA
rs13250096 21576409C>G, 396-12856G>C, 480-12856G>C, 74938G>C, 795-12856G>C, 9434555C>G
C > G
Intronic
No VIP available CA VA
rs13429709 13207378T>C, 162997960T>C
T > C
Not Available
No VIP available CA VA
rs1414334 114138144C>G, 324594C>G, 456-3008C>G, 551-3008C>G, 570476C>G
C > G
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 No Clinical Annotations available VA
rs17782313 5641961T>C, 57851097T>C
T > C
Not Available
No VIP available CA VA
rs1799732 -487_-486insC, 113346252_113346253insG, 16908668_16908669insG, 4749_4750insC, DRD2: -141C Ins/Del
- > G
5' Flanking
No VIP available CA VA
rs1800497 113270828G>A, 16833244G>A, 17316G>A, 2137G>A, 32806C>T, DRD2 Taq1A, DRD2:32806C>T, DRD2:Taq1A, DRD2:Taq1A A1, DRD2:TaqIA allele, Glu713Lys, Taq1A
G > A
Missense
Glu713Lys
No VIP available No Clinical Annotations available VA
rs2069514 (-2964)G>A, 28338G>A, 3860G>A, 45828777G>A, 75038220G>A, CYP1A2*1C
G > A
Not Available
No VIP available No Clinical Annotations available VA
rs2228622 414G>A, 4554432G>A, 4564432G>A, 79006G>A, Exon 4, SLC1A1:rs2228622G>A, SNP2, Thr138=, syn
G > A
Synonymous
Thr138Thr
No VIP available CA VA
rs2268639 1224+2107T>A, 38990622T>A, 39050622T>A
T > A
Intronic
No VIP available CA VA
rs2276302 113850140G>A, 17412556G>A, 219+141G>A, 282+141G>A, 515+141G>A, 9344G>A
G > A
Intronic
No VIP available No Clinical Annotations available VA
rs25531 -1936A>G, 28564346T>C, 3301340T>C, 3609A>G
T > C
5' Flanking
No VIP available No Clinical Annotations available VA
rs265976 174862420G>T, 19673693G>T
G > T
Not Available
No VIP available No Clinical Annotations available VA
rs265981 -684T>C, 174870902A>G, 19682175A>G, 5262T>C
A > G
5' UTR
No VIP available No Clinical Annotations available VA
rs2740204 3002467G>T, 3062467G>T, 7904C>A
G > T
Not Available
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
No VIP available No Clinical Annotations available VA
rs2975226 -199T>A, 1435616A>T, 1445616A>T, 4928T>A
A > T
5' Flanking
No VIP available CA VA
rs324420 15823C>A, 16842679C>A, 385C>A, 46870761C>A, C385A, FAAH:385C>A, FAAH:Pro129Thr, Pro129Thr
C > A
Missense
Pro129Thr
No VIP available No Clinical Annotations available VA
rs35694136 -1635delT, 29731delT, 45830170delT, 75039613delT
T > -
5' Flanking
rs35742686 -1793delT, -1830delT, -1940delT, 23418678delT, 40+2664delT, 42128242delT, 50569delT, 50583delT, 598delA, 622delA, 6750delA, 775delA, Arg200Glyfs, Arg208Glyfs, Arg259Glyfs
T > -
Not Available
Arg208Gly
No VIP available No Clinical Annotations available VA
rs3780412 4562480T>C, 4572480T>C, 767+92T>C, 87054T>C, Intron 7, SLC1A1:rs3780412A>G, SNP4
T > C
Intronic
No VIP available No Clinical Annotations available VA
rs3780413 4557353C>G, 4567353C>G, 484-316C>G, 81927C>G, Intron 5, SLC1A1:rss3780413C>G, SNP3
C > G
Intronic
No VIP available No Clinical Annotations available VA
rs3813928 -1088G>A, -995, -997G>A, 113818282G>A, 250614G>A, 4732G>A, HTR2C c.-995G>A
G > A
5' Flanking
No VIP available No Clinical Annotations available VA
rs3813929 -759, -759C>T, -850C>T, 113818520C>T, 250852C>T, 4970C>T, HTR2C:, HTR2C: -759C/T
C > T
5' Flanking
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
No VIP available No Clinical Annotations available VA
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
rs4436578 -31-11361G>A, 113306765C>T, 16869181C>T, 44237G>A
C > T
Intronic
No VIP available No Clinical Annotations available VA
rs4532 -48G>A, 174870150C>T, 19681423C>T, 6014G>A
C > T
5' UTR
No VIP available No Clinical Annotations available VA
rs4567028 21580010G>A, 396-16457C>T, 480-16457C>T, 71337C>T, 795-16457C>T, 9438156G>A
G > A
Intronic
No VIP available No Clinical Annotations available VA
rs4880 160113872A>G, 47C-T, 47T>C, 5482T>C, 64283329A>G, Ala16Val, SOD1:Val16Ala, SOD2: Val16Ala, T47C, V16A
A > G
Missense
Val16Ala
No VIP available No Clinical Annotations available VA
rs4938013 10958A>C, 113264470A>C, 16826886A>C, 453A>C, Ile151=
A > C
Synonymous
Ile151Ile
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
rs518147 -697G>C, -788G>C, 113818582G>C, 250914G>C, 5032G>C, HTR2C: -697G/C
C > G
5' UTR
rs59421388 1012G>A, 21914179C>T, 3271G>A, 42523610C>T, 8274G>A, 859G>A, CYP2D6: 3183G>A, Val287Met, Val338Met
G > T
G > C
Missense
Val287Met
VIP No Clinical Annotations available No Variant Annotations available
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
rs6277 113283459G>A, 16845875G>A, 67543C>T, 870C>T, 957C>T, C957T, DRD2: C957T, DRD2:1035C>T, DRD2:1122C>T, DRD2:957C>T, Pro290=, Pro319=
G > A
Synonymous
Pro290Pro
No VIP available CA VA
rs6280 113890815C>T, 12085G>A, 20385961C>T, 25G>A, DRD3 Ser9Gly, DRD3 rs6280, DRD3: 9 Ser>Gly, DRD3: Gly9Ser, DRD3: Ser9Gly, DRD3:Ser9Gly, Gly9Ser, c.25T>C, p.S9G
C > T
Missense
Gly9Ser
No VIP available No Clinical Annotations available VA
rs6318 113965735G>C, 152185G>C, 398067G>C, 68G>C, Cys23Ser, HTR2C:23Ser, HTR2C:Cys23Ser
C > G
Missense
Cys23Ser
No VIP available No Clinical Annotations available VA
rs686 *62C>T, 174868700G>A, 19679973G>A, 7464C>T
G > A
3' UTR
No VIP available CA VA
rs72547516 1156A>G, 1156A>T, 34696A>G, 34696A>T, 45835135A>G, 45835135A>T, 75044578A>G, 75044578A>T, CYP1A2*4, CYP1A2:Ile386Phe, Ile386Phe, Ile386Val, rs72547516 A>T
A > T
A > G
Missense
Ile386Phe
Ile386Val
No VIP available CA VA
rs72547517 1367G>A, 37363G>A, 45837802G>A, 75047245G>A, Arg456His, CYP1A2*8, CYP1A2:Arg456His, rs72547517 G>A
G > A
Missense
Arg456His
No VIP available CA VA
rs742105 15513074C>T, 15573074C>T, 268+20216G>A, 406+20216G>A, 460+20216G>A, 511+20216G>A, 839+20216G>A, 95198G>A
C > T
Intronic
rs762551 -9-154C>A, 32035C>A, 45832474C>A, 75041917C>A, CYP1A2*1F, CYP1A2:734C>A
C > A
Intronic
No VIP available CA VA
rs7787082 190514C>T, 25189894G>A, 2685+3559C>T, 87157051G>A
G > A
Intronic
No VIP available No Clinical Annotations available VA
rs806378 -206-2026G>A, -63-4495G>A, 26979385C>T, 88859551C>T
C > T
Intronic
No VIP available No Clinical Annotations available VA
rs8087522 -896C>T, 4524C>T, 58040478G>A, 5831342G>A
G > A
5' Flanking
No VIP available No Clinical Annotations available VA
rs8175347 233760235_233760236TA[5][6][7][8], 5-TA insertion in promoter, 7-TA insertion in promoter, 8-TA insertion in promoter, UGT1A1*28, UGT1A1*36, UGT1A1*37, microsatellite, short tandem repeat
(TA)6 > (TA)8
(TA)6 > (TA)5
(TA)6 > (TA)7
Not Available
No VIP available No Clinical Annotations available VA
rs9852 *68C>T, 38139024C>T, 5298386C>T
C > T
3' UTR
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • Clozapin
Trade Names
  • Asaleptin
  • Clozaril
  • Fazaclo ODT
  • Iprox
  • Leponex
  • Lepotex
Brand Mixture Names

PharmGKB Accession Id:
PA449061

Description

A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent.

Source: Drug Bank

Indication

For use in patients with treatment-resistant schizophrenia.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Clozapine's antipsychotic action is likely mediated through a combination of antogistic effects at D2 receptors in the mesolimbic pathway and 5-HT2A receptors in the frontal cortex. D2 antagonism relieves positive symptoms while 5-HT2A antagonism alleviates negative symptoms.

Source: Drug Bank

Pharmacology

Clozapine is a psychotropic agent belonging to the chemical class of benzisoxazole derivatives and is indicated for the treatment of schizophrenia. Clozapine is a selective monoaminergic antagonist with high affinity for the serotonin Type 2 (5HT 2), dopamine Type 2 (D2), 1 and 2 adrenergic, and H1 histaminergic receptors. Clozapine acts as an antagonist at other receptors, but with lower potency. Antagonism at receptors other than dopamine and 5HT 2 with similar receptor affinities may explain some of the other therapeutic and side effects of Clozapine. Clozapine's antagonism of muscarinic M1-5 receptors may explain its anticholinergic effects. Clozapine's antagonism of histamine H1 receptors may explain the somnolence observed with this drug. Clozapine's antagonism of adrenergic a1 receptors may explain the orthostatic hypotension observed with this drug.

Source: Drug Bank

Food Interaction

Avoid alcohol.|Limit caffeine intake (may reduce clozapine matabolism).|Take without regard to meals.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic

Source: Drug Bank

Protein Binding

97% (bound to serum proteins)

Source: Drug Bank

Absorption

Rapid and almost complete

Source: Drug Bank

Half-Life

8 hours (range 4-12 hours)

Source: Drug Bank

Toxicity

Clozapine carries a black-box warning for agranulocytosis.

Source: Drug Bank

Route of Elimination

Approximately 50% of the administered dose is excreted in the urine and 30% in the feces.

Source: Drug Bank

Chemical Properties

Chemical Formula

C18H19ClN4

Source: Drug Bank

Isomeric SMILES

CN1CCN(CC1)C2=Nc3cc(ccc3Nc4c2cccc4)Cl

Source: OpenEye

Canonical SMILES

CN1CCN(CC1)C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12

Source: Drug Bank

Average Molecular Weight

326.823

Source: Drug Bank

Monoisotopic Molecular Weight

326.129824335

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)
ADRA1B (source: Drug Bank)
ADRA2A (source: Drug Bank)
ADRA2B (source: Drug Bank)
ADRA2C (source: Drug Bank)
CALY (source: Drug Bank)
CHRM1 (source: Drug Bank)
CHRM2 (source: Drug Bank)
CHRM3 (source: Drug Bank)
CHRM4 (source: Drug Bank)
CHRM5 (source: Drug Bank)
DRD1 (source: Drug Bank)
DRD2 (source: Drug Bank)
DRD3 (source: Drug Bank)
DRD4 (source: Drug Bank)
HRH1 (source: Drug Bank)
HRH4 (source: Drug Bank)
HTR1A (source: Drug Bank)
HTR1B (source: Drug Bank)
HTR1D (source: Drug Bank)
HTR1E (source: Drug Bank)
HTR2A (source: Drug Bank)
HTR2C (source: Drug Bank)
HTR3A (source: Drug Bank)
HTR6 (source: Drug Bank)
HTR7 (source: Drug Bank)

Drug Interactions

Drug Description
clozapine Increased risk of toxicity (source: Drug Bank)
clozapine Increased risk of toxicity (source: Drug Bank)
clozapine Bromazepam may increase the adverse effects of clozapine. Consider alternate therapy or a reduction in the bromazepam dose. Monitor for respiratory depression and hypotension if concomitant therapy is initiated. (source: Drug Bank)
clozapine Decreases the effect of clozapine/hematologic toxicity (source: Drug Bank)
clozapine Decreases the effect of clozapine/hematologic toxicity (source: Drug Bank)
clozapine Increased risk of toxicity (source: Drug Bank)
clozapine Increased risk of toxicity (source: Drug Bank)
clozapine Increases the effect of clozapine (source: Drug Bank)
clozapine Increases the effect of clozapine (source: Drug Bank)
clozapine Ciprofloxacin may increase clozapine serum levels (source: Drug Bank)
clozapine Ciprofloxacin may increase clozapine serum levels (source: Drug Bank)
clozapine The antidepressant increases the effect of clozapine (source: Drug Bank)
clozapine The antidepressant increases the effect of clozapine (source: Drug Bank)
clozapine Increased risk of toxicity (source: Drug Bank)
clozapine Increased risk of toxicity (source: Drug Bank)
clozapine Increased risk of toxicity (source: Drug Bank)
clozapine Increased risk of toxicity (source: Drug Bank)
clozapine Increased risk of toxicity (source: Drug Bank)
alprazolam Increased risk of toxicity (source: Drug Bank)
alprazolam Increased risk of toxicity (source: Drug Bank)
bromazepam Increased risk of toxicity (source: Drug Bank)
bromazepam Increased risk of toxicity (source: Drug Bank)
caffeine Caffeine increases the effect and toxicity of clozapine (source: Drug Bank)
caffeine Caffeine increases the effect and toxicity of clozapine (source: Drug Bank)
carbamazepine Carbamazepine decreases the effect of clozapine, hematologic toxicity (source: Drug Bank)
carbamazepine Carbamazepine decreases the effect of clozapine, hematologic toxicity (source: Drug Bank)
chlordiazepoxide Increased risk of toxicity (source: Drug Bank)
chlordiazepoxide Increased risk of toxicity (source: Drug Bank)
cimetidine Cimetidine increases the effect of clozapine (source: Drug Bank)
cimetidine Cimetidine increases the effect of clozapine (source: Drug Bank)
cinolazepam Increased risk of toxicity (source: Drug Bank)
cinolazepam Increased risk of toxicity (source: Drug Bank)
ciprofloxacin Ciprofloxacin may increase clozapine serum levels (source: Drug Bank)
ciprofloxacin Ciprofloxacin may increase clozapine serum levels (source: Drug Bank)
citalopram The antidepressant increases the effect of clozapine (source: Drug Bank)
citalopram The antidepressant increases the effect of clozapine (source: Drug Bank)
clobazam Increased risk of toxicity (source: Drug Bank)
clobazam Increased risk of toxicity (source: Drug Bank)
clonazepam Increased risk of toxicity (source: Drug Bank)
clonazepam Increased risk of toxicity (source: Drug Bank)
clorazepate Increased risk of toxicity (source: Drug Bank)
clorazepate Increased risk of toxicity (source: Drug Bank)
diazepam Increased risk of toxicity (source: Drug Bank)
diazepam Increased risk of toxicity (source: Drug Bank)
donepezil Possible antagonism of action (source: Drug Bank)
donepezil Possible antagonism of action (source: Drug Bank)
erythromycin Erythromycin increases the effect of clozapine (source: Drug Bank)
erythromycin Erythromycin increases the effect of clozapine (source: Drug Bank)
estazolam Increased risk of toxicity (source: Drug Bank)
estazolam Increased risk of toxicity (source: Drug Bank)
ethotoin Hydantoin decreases the effect of clozapine (source: Drug Bank)
ethotoin Hydantoin decreases the effect of clozapine (source: Drug Bank)
flunitrazepam Increased risk of toxicity (source: Drug Bank)
flunitrazepam Increased risk of toxicity (source: Drug Bank)
fluoxetine The antidepressant increases the effect of clozapine (source: Drug Bank)
fluoxetine The antidepressant increases the effect of clozapine (source: Drug Bank)
flurazepam Increased risk of toxicity (source: Drug Bank)
flurazepam Increased risk of toxicity (source: Drug Bank)
fluvoxamine The antidepressant increases the effect of clozapine (source: Drug Bank)
fluvoxamine The antidepressant increases the effect of clozapine (source: Drug Bank)
fosphenytoin Hydantoin decreases the effect of clozapine (source: Drug Bank)
fosphenytoin Hydantoin decreases the effect of clozapine (source: Drug Bank)
galantamine Possible antagonism of action (source: Drug Bank)
galantamine Possible antagonism of action (source: Drug Bank)
halazepam Increased risk of toxicity (source: Drug Bank)
halazepam Increased risk of toxicity (source: Drug Bank)
haloperidol Increases the effect and toxicity of haloperidol (source: Drug Bank)
haloperidol Increases the effect and toxicity of haloperidol (source: Drug Bank)
josamycin Erythromycin increases the effect of clozapine (source: Drug Bank)
josamycin Erythromycin increases the effect of clozapine (source: Drug Bank)
ketazolam Increased risk of toxicity (source: Drug Bank)
ketazolam Increased risk of toxicity (source: Drug Bank)
lamotrigine Lamotrigine increases the effect and toxicity of clozapine (source: Drug Bank)
lamotrigine Lamotrigine increases the effect and toxicity of clozapine (source: Drug Bank)
lisinopril Lisinopril increases the effect and toxicity of clozapine (source: Drug Bank)
lisinopril Lisinopril increases the effect and toxicity of clozapine (source: Drug Bank)
lorazepam Increased risk of toxicity (source: Drug Bank)
lorazepam Increased risk of toxicity (source: Drug Bank)
mephenytoin Hydantoin decreases the effect of clozapine (source: Drug Bank)
mephenytoin Hydantoin decreases the effect of clozapine (source: Drug Bank)
midazolam Increased risk of toxicity (source: Drug Bank)
midazolam Increased risk of toxicity (source: Drug Bank)
modafinil Modafinil increases the effect and toxicity of clozapine (source: Drug Bank)
modafinil Modafinil increases the effect and toxicity of clozapine (source: Drug Bank)
nitrazepam Increased risk of toxicity (source: Drug Bank)
nitrazepam Increased risk of toxicity (source: Drug Bank)
norfloxacin Ciprofloxacin may increase clozapine serum levels (source: Drug Bank)
norfloxacin Ciprofloxacin may increase clozapine serum levels (source: Drug Bank)
oxazepam Increased risk of toxicity (source: Drug Bank)
oxazepam Increased risk of toxicity (source: Drug Bank)
phenytoin Hydantoin decreases the effect of clozapine (source: Drug Bank)
phenytoin Hydantoin decreases the effect of clozapine (source: Drug Bank)
prazepam Increased risk of toxicity (source: Drug Bank)
prazepam Increased risk of toxicity (source: Drug Bank)
quazepam Increased risk of toxicity (source: Drug Bank)
quazepam Increased risk of toxicity (source: Drug Bank)
rifabutin Rifabutin decreases the effect of clozapine (source: Drug Bank)
rifabutin Rifabutin decreases the effect of clozapine (source: Drug Bank)
rifampin Rifampin decreases the effect of clozapine (source: Drug Bank)
rifampin Rifampin decreases the effect of clozapine (source: Drug Bank)
ritonavir Ritonavir increases the effect and toxicity of clozapine (source: Drug Bank)
ritonavir Ritonavir increases the effect and toxicity of clozapine (source: Drug Bank)
rivastigmine Possible antagonism of action (source: Drug Bank)
rivastigmine Possible antagonism of action (source: Drug Bank)
sertraline The antidepressant increases the effect of clozapine (source: Drug Bank)
sertraline The antidepressant increases the effect of clozapine (source: Drug Bank)
temazepam The benzodiazepine, Temazepam, may increase the adverse effects of Clozapine. Monitor for respiratory depression and hypotension if concomitant therapy is initiated. (source: Drug Bank)
temazepam The benzodiazepine, Temazepam, may increase the adverse effects of Clozapine. Monitor for respiratory depression and hypotension if concomitant therapy is initiated. (source: Drug Bank)
triazolam Increased risk of toxicity (source: Drug Bank)
triazolam Increased risk of toxicity (source: Drug Bank)
clozapine Increased risk of toxicity (source: Drug Bank)
clozapine Increased risk of toxicity (source: Drug Bank)
clozapine Possible antagonism of action (source: Drug Bank)
clozapine Possible antagonism of action (source: Drug Bank)
clozapine Erythromycin increases the effect of clozapine (source: Drug Bank)
clozapine Erythromycin increases the effect of clozapine (source: Drug Bank)
clozapine Increased risk of toxicity (source: Drug Bank)
clozapine Increased risk of toxicity (source: Drug Bank)
clozapine The antidepressant increases the effect of clozapine (source: Drug Bank)
clozapine The antidepressant increases the effect of clozapine (source: Drug Bank)
clozapine Increased risk of toxicity (source: Drug Bank)
clozapine Increased risk of toxicity (source: Drug Bank)
clozapine The antidepressant increases the effect of clozapine (source: Drug Bank)
clozapine The antidepressant increases the effect of clozapine (source: Drug Bank)
clozapine Hydantoin decreases the effect of clozapine (source: Drug Bank)
clozapine Possible antagonism of action (source: Drug Bank)
clozapine Possible antagonism of action (source: Drug Bank)
clozapine Clozapine increases the effect and toxicity of haloperidol (source: Drug Bank)
clozapine Clozapine increases the effect and toxicity of haloperidol (source: Drug Bank)
clozapine Lamotrigine increases the effect and toxicity of clozapine (source: Drug Bank)
clozapine Lamotrigine increases the effect and toxicity of clozapine (source: Drug Bank)
clozapine Increases the effect and toxicity of clozapine (source: Drug Bank)
clozapine Increases the effect and toxicity of clozapine (source: Drug Bank)
clozapine Increased risk of toxicity (source: Drug Bank)
clozapine Increased risk of toxicity (source: Drug Bank)
clozapine Increased risk of toxicity (source: Drug Bank)
clozapine Increased risk of toxicity (source: Drug Bank)
clozapine Modafinil increases the effect and toxicity of clozapine (source: Drug Bank)
clozapine Modafinil increases the effect and toxicity of clozapine (source: Drug Bank)
clozapine Ciprofloxacin may increase clozapine serum levels (source: Drug Bank)
clozapine Ciprofloxacin may increase clozapine serum levels (source: Drug Bank)
clozapine Increased risk of toxicity (source: Drug Bank)
clozapine Increased risk of toxicity (source: Drug Bank)
clozapine The hydantoin decreases the effect of clozapine (source: Drug Bank)
clozapine The hydantoin decreases the effect of clozapine (source: Drug Bank)
clozapine Rifabutin decreases the effect of clozapine (source: Drug Bank)
clozapine Rifabutin decreases the effect of clozapine (source: Drug Bank)
clozapine Rifampin decreases the effect of clozapine (source: Drug Bank)
clozapine Rifampin decreases the effect of clozapine (source: Drug Bank)
clozapine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Clozapine, 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)
clozapine The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Clozapine, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents. (source: Drug Bank)
clozapine Clozapine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy. (source: Drug Bank)
clozapine Clozapine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy. (source: Drug Bank)
clozapine Clozapine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Clozapine is initiated, discontinued, or dose changed. (source: Drug Bank)
clozapine Clozapine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Clozapine is initiated, discontinued, or dose changed. (source: Drug Bank)
clozapine Increased risk of toxicity (source: Drug Bank)
clozapine The benzodiazepine, Temazepam, may increase the adverse effects of Clozapine. Monitor for respiratory depression and hypotension if concomitant therapy is initiated. (source: Drug Bank)
clozapine May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects. (source: Drug Bank)
clozapine The strong CYP1A2 inhibitor, Thiabendazole, may increase the effects and toxicity of Clozapine by decreasing Clozapine metabolism and clearance. Monitor for changes in the therapeutic and adverse effects of Clozapine if Thiabendazole is initiated, discontinued or dose changed. (source: Drug Bank)
clozapine Clozapine may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank)
clozapine Increased risk of toxicity (source: Drug Bank)
clozapine Increased risk of toxicity (source: Drug Bank)
clozapine Trimethobenzamide and Clozapine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects. (source: Drug Bank)
clozapine Triprolidine and Clozapine, 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)
clozapine Triprolidine and Clozapine, 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)
clozapine Trospium and Clozapine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects. (source: Drug Bank)

Curated Information ?

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

May Treat
Contraindicated With

Publications related to clozapine: 105

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Genetic variation in the GCG and in the GLP1R genes and antipsychotic-induced weight gain. Pharmacogenomics. 2014. Brandl Eva J, et al. PubMed
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The CYP1A2 -163C>A polymorphism is associated with clozapine-induced generalized tonic-clonic seizures in Brazilian schizophrenia patients. Psychiatry research. 2013. Kohlrausch Fabiana Barzotti, et al. PubMed
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Role of ethnicity in antipsychotic-induced weight gain and tardive dyskinesia: genes or environment?. Pharmacogenomics. 2013. Chan Lai Fong, 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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Exploratory study on association of genetic variation in TBC1D1 with antipsychotic-induced weight gain. Human psychopharmacology. 2013. Brandl Eva J, 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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Outcome definitions and clinical predictors influence pharmacogenetic associations between HTR3A gene polymorphisms and response to clozapine in patients with schizophrenia. Psychopharmacology. 2012. Rajkumar A P, et al. PubMed
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Strengths and weaknesses of pharmacogenetic studies of antipsychotic drugs: the potential value of the PEPs study. Pharmacogenomics. 2012. Mas Sergi, et al. PubMed
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Association study of 27 annotated genes for clozapine pharmacogenetics: validation of preexisting studies and identification of a new candidate gene, ABCB1, for treatment response. Journal of clinical psychopharmacology. 2012. Lee Seung-Tae, et al. PubMed
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Glucuronidation of the second-generation antipsychotic clozapine and its active metabolite N-desmethylclozapine. Potential importance of the UGT1A1 A(TA)₇TAA and UGT1A4 L48V polymorphisms. Pharmacogenetics and genomics. 2012. Erickson-Ridout Kathryn K, et al. PubMed
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Pharmacogenomics of the heptahelical receptor regulators G-protein-coupled receptor kinases and arrestins: the known and the unknown. Pharmacogenomics. 2012. Lymperopoulos Anastasios, et al. PubMed
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Genetic association study between antipsychotic-induced weight gain and the melanocortin-4 receptor gene. The pharmacogenomics journal. 2012. Chowdhury N I, et al. PubMed
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Pharmacogenetic testing to predict antipsychotic-induced weight gain: a systematic review. Pharmacogenomics. 2011. Risselada Arne J, et al. PubMed
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Sexual dysfunction in male schizophrenia: influence of antipsychotic drugs, prolactin and polymorphisms of the dopamine D2 receptor genes. Pharmacogenomics. 2011. Zhang Xiang Rong, et al. PubMed
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Association of Disrupted in Schizophrenia 1 (DISC1) missense variants with ultra-resistant schizophrenia. The pharmacogenomics journal. 2011. Mouaffak F, et al. PubMed
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Polymorphisms of the LEP, LEPR and HTR2C gene: obesity and BMI change in patients using antipsychotic medication in a naturalistic setting. Pharmacogenomics. 2011. Gregoor Jochem G, et al. PubMed
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Association of an UCP4 (SLC25A27) haplotype with ultra-resistant schizophrenia. Pharmacogenomics. 2011. Mouaffak Fayçal, et al. PubMed
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Gene-gene interaction analyses between NMDA receptor subunit and dopamine receptor gene variants and clozapine response. Pharmacogenomics. 2011. Hwang Rudi, et al. PubMed
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Influence of serotonin transporter gene polymorphisms on clozapine response in Brazilian schizophrenics. Journal of psychiatric research. 2010. Kohlrausch Fabiana B, et al. PubMed
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Polymorphisms of the HTR2C gene and antipsychotic-induced weight gain: an update and meta-analysis. Pharmacogenomics. 2010. Sicard Michelle N, et al. PubMed
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Systematic review of pharmacoeconomic studies of pharmacogenomic tests. Pharmacogenomics. 2010. Beaulieu Mathieu, et al. PubMed
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Weight gain related to treatment with atypical antipsychotics is due to activation of PKC-beta. The pharmacogenomics journal. 2010. Pavan C, et al. PubMed
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Gene-gene interactions of the INSIG1 and INSIG2 in metabolic syndrome in schizophrenic patients treated with atypical antipsychotics. The pharmacogenomics journal. 2010. Liou Y-J, et al. PubMed
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Endocannabinoid Pro129Thr FAAH functional polymorphism but not 1359G/A CNR1 polymorphism is associated with antipsychotic-induced weight gain. Journal of clinical psychopharmacology. 2010. Monteleone Palmiero, et al. PubMed
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Genetic association of the GDNF alpha-receptor genes with schizophrenia and clozapine response. Journal of psychiatric research. 2010. Souza Renan P, et al. PubMed
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PharmGKB summary: dopamine receptor D2. Pharmacogenetics and genomics. 2010. Mi Huaiyu, et al. PubMed
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Pharacogenetic effects of dopamine transporter gene polymorphisms on response to chlorpromazine and clozapine and on extrapyramidal syndrome in schizophrenia. Progress in neuro-psychopharmacology & biological psychiatry. 2010. Xu Mingqing, et al. PubMed
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Association between HTR2C gene polymorphisms and the metabolic syndrome in patients using antipsychotics: a replication study. The pharmacogenomics journal. 2010. Risselada A J, et al. PubMed
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Systematic analysis of dopamine receptor genes (DRD1-DRD5) in antipsychotic-induced weight gain. The pharmacogenomics journal. 2010. Müller D J, et al. PubMed
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D2 receptor genetic variation and clinical response to antipsychotic drug treatment: a meta-analysis. The American journal of psychiatry. 2010. Zhang Jian-Ping, et al. PubMed
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Schizophrenia severity and clozapine treatment outcome association with oxytocinergic genes. The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP). 2010. Souza Renan P, 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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Dopamine receptor D2 gene is associated with weight gain in schizophrenic patients under long-term atypical antipsychotic treatment. Pharmacogenetics and genomics. 2010. Hong Chen-Jee, et al. PubMed
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Effect of dopamine D3 receptor gene polymorphisms and clozapine treatment response: exploratory analysis of nine polymorphisms and meta-analysis of the Ser9Gly variant. The pharmacogenomics journal. 2010. Hwang R, et al. PubMed
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A common polymorphism in the cannabinoid receptor 1 (CNR1) gene is associated with antipsychotic-induced weight gain in Schizophrenia. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2010. Tiwari Arun K, et al. PubMed
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Influence of serotonin 3A and 3B receptor genes on clozapine treatment response in schizophrenia. Pharmacogenetics and genomics. 2010. Souza Renan P, et al. PubMed
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Human lymphoblastoid cell line panels: novel tools for assessing shared drug pathways. Pharmacogenomics. 2010. Morag Ayelet, et al. PubMed
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Functional characterization of eight human cytochrome P450 1A2 gene variants by recombinant protein expression. The pharmacogenomics journal. 2010. Palma B Brito, et al. PubMed
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Metabolic side effects of antipsychotic drug treatment--pharmacological mechanisms. Pharmacology & therapeutics. 2010. Reynolds Gavin P, et al. PubMed
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Lack of association of GPX1 and MnSOD genes with symptom severity and response to clozapine treatment in schizophrenia subjects. Human psychopharmacology. 2009. Souza Renan P, et al. PubMed
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Association of the glutamate transporter gene SLC1A1 with atypical antipsychotics-induced obsessive-compulsive symptoms. Archives of general psychiatry. 2009. Kwon Jun Soo, et al. PubMed
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Clozapine, GABA(B), and the treatment of resistant schizophrenia. Clinical pharmacology and therapeutics. 2009. Daskalakis Z J, et al. PubMed
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ABCB1 and cytochrome P450 polymorphisms: clinical pharmacogenetics of clozapine. Journal of clinical psychopharmacology. 2009. Jaquenoud Sirot Eveline, et al. PubMed
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ABCB1 polymorphisms are associated with clozapine plasma levels in psychotic patients. Pharmacogenomics. 2009. Consoli Giorgio, et al. PubMed
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Clinically available pharmacogenomics tests. Clinical pharmacology and therapeutics. 2009. Flockhart D A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Cytochrome P450 2D6. Pharmacogenetics and genomics. 2009. Owen Ryan 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
Association of the alpha 2A adrenergic receptor -1291C/G polymorphism and antipsychotic-induced weight gain in European-Americans. Pharmacogenomics. 2009. Sickert Laertes, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
The efficacies of clozapine and haloperidol in refractory schizophrenia are related to DTNBP1 variation. Pharmacogenetics and genomics. 2009. Zuo Lingjun, et al. PubMed
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ADME pharmacogenetics: current practices and future outlook. Expert opinion on drug metabolism & toxicology. 2009. Grossman Iris. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Variants of the dopamine D2 receptor gene and risperidone-induced hyperprolactinemia in children and adolescents. Pharmacogenetics and genomics. 2009. Calarge Chadi A, 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
Further evidence for association of the RGS2 gene with antipsychotic-induced parkinsonism: protective role of a functional polymorphism in the 3'-untranslated region. The pharmacogenomics journal. 2009. Greenbaum L, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Effects of DRD2/ANKK1 gene variations and clinical factors on aripiprazole efficacy in schizophrenic patients. Journal of psychiatric research. 2009. Shen Yu-Chih, et al. PubMed
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HTR2C gene polymorphisms and the metabolic syndrome in patients with schizophrenia: a replication study. Journal of clinical psychopharmacology. 2009. Mulder Hans, 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
DRD4 48 bp VNTR but not 5-HT 2C Cys23Ser receptor polymorphism is related to antipsychotic-induced weight gain. The pharmacogenomics journal. 2009. Popp J, et al. PubMed
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Network and pathway analysis of compound-protein interactions. Methods in molecular biology (Clifton, N.J.). 2009. Brennan Richard 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
G-protein gene 825C>T polymorphism is associated with response to clozapine in Brazilian schizophrenics. Pharmacogenomics. 2008. Kohlrausch Fabiana B, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Gene polymorphism influencing treatment response in psychotic patients in a naturalistic setting. Journal of psychiatric research. 2008. Alenius Malin, 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
Clozapine-induced agranulocytosis and its genetic determinants. Pharmacogenomics. 2008. Opgen-Rhein Carolin, 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
Allelic variation in ApoC3, ApoA5 and LPL genes and first and second generation antipsychotic effects on serum lipids in patients with schizophrenia. The pharmacogenomics journal. 2008. Smith R C, 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
Caffeine as a marker substrate for testing cytochrome P450 activity in human and rat. Pharmacological reports : PR. 2008. Kot Marta, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
HTR2C haplotypes and antipsychotics-induced weight gain: X-linked multimarker analysis. Human psychopharmacology. 2007. De Luca Vincenzo, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
The relationship between the therapeutic response to risperidone and the dopamine D2 receptor polymorphism in Chinese schizophrenia patients. The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP). 2007. Xing Qinghe, et al. PubMed
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Clozapine-induced agranulocytosis in schizophrenic Caucasians: confirming clues for associations with human leukocyte class I and II antigens. The pharmacogenomics journal. 2007. Dettling M, et al. PubMed
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Genetic susceptibility to Tardive Dyskinesia in chronic schizophrenia subjects: V. Association of CYP1A2 1545 C>T polymorphism. The pharmacogenomics journal. 2007. Tiwari A K, et al. PubMed
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Association study of four dopamine D1 receptor gene polymorphisms and clozapine treatment response. Journal of psychopharmacology (Oxford, England). 2007. Hwang Rudi, et al. PubMed
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Human leukocyte antigens and drug hypersensitivity. Current opinion in allergy and clinical immunology. 2007. Chung Wen-Hung, et al. PubMed
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The association between HTR2C gene polymorphisms and the metabolic syndrome in patients with schizophrenia. Journal of clinical psychopharmacology. 2007. Mulder Hans, et al. PubMed
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No evidence for binding of clozapine, olanzapine and/or haloperidol to selected receptors involved in body weight regulation. The pharmacogenomics journal. 2007. Theisen F M, et al. PubMed
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Impact of CYP1A2 and CYP2D6 polymorphisms on drug metabolism and on insulin and lipid elevations and insulin resistance in clozapine-treated patients. The Journal of clinical psychiatry. 2007. Melkersson Kristina I, et al. PubMed
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Risk of extrapyramidal syndrome in schizophrenic patients treated with antipsychotics: a population-based study. Clinical pharmacology and therapeutics. 2007. Yang S-Y, et al. PubMed
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RGS4 genotype is not associated with antipsychotic medication response in schizophrenia. Journal of neural transmission (Vienna, Austria : 1996). 2006. Kampman O, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
DRD2 promoter region variation as a predictor of sustained response to antipsychotic medication in first-episode schizophrenia patients. The American journal of psychiatry. 2006. Lencz Todd, et al. PubMed
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Apolipoprotein D is associated with long-term outcome in patients with schizophrenia. The pharmacogenomics journal. 2006. Hansen T, et al. PubMed
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cDNA array reveals increased expression of glucose-dependent insulinotropic polypeptide following chronic clozapine treatment: role in atypical antipsychotic drug-induced adverse metabolic effects. The pharmacogenomics journal. 2006. Sondhi S, et al. PubMed
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Association study of 12 polymorphisms spanning the dopamine D(2) receptor gene and clozapine treatment response in two treatment refractory/intolerant populations. Psychopharmacology. 2005. Hwang Rudi, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Response to chlorpromazine treatment may be associated with polymorphisms of the DRD2 gene in Chinese schizophrenic patients. Neuroscience letters. 2005. Wu Shengnan, et al. PubMed
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Clozapine-induced weight gain associated with the 5HT2C receptor -759C/T polymorphism. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics. 2005. Miller Del D, et al. PubMed
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Antipsychotic drugs activate SREBP-regulated expression of lipid biosynthetic genes in cultured human glioma cells: a novel mechanism of action?. The pharmacogenomics journal. 2005. Fernø J, et al. PubMed
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Time response of cytochrome P450 1A2 activity on cessation of heavy smoking. Clinical pharmacology and therapeutics. 2004. Faber Mirko S, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Prolactin levels in antipsychotic treatment of patients with schizophrenia carrying the DRD2*A1 allele. The British journal of psychiatry : the journal of mental science. 2004. Young Ross McD, et al. PubMed
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Pharmacogenetics of psychotropic drug response. The American journal of psychiatry. 2004. Malhotra Anil K, et al. PubMed
Nonresponse to clozapine and ultrarapid CYP1A2 activity: clinical data and analysis of CYP1A2 gene. Journal of clinical psychopharmacology. 2004. Eap Chin B, et al. PubMed
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Identification of a novel splice-site mutation in the CYP1A2 gene. British journal of clinical pharmacology. 2003. Allorge Delphine, et al. PubMed
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Preliminary electrochemical characterisation of cytochrome P4501A2-clozapine interaction. IEE proceedings. Nanobiotechnology. 2003. Antonini M, et al. PubMed
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The effect of smoking and cytochrome P450 CYP1A2 genetic polymorphism on clozapine clearance and dose requirement. Pharmacogenetics. 2003. van der Weide Jan, et al. PubMed
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Pharmacogenomics in schizophrenia: the quest for individualized therapy. Human molecular genetics. 2002. Basile Vincenzo S, et al. PubMed
Treatment-resistance to clozapine in association with ultrarapid CYP1A2 activity and the C-->A polymorphism in intron 1 of the CYP1A2 gene: effect of grapefruit juice and low-dose fluvoxamine. Journal of clinical psychopharmacology. 2001. Ozdemir V, et al. PubMed
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Med-psych drug-drug interactions update. Psychosomatics. 2002. Armstrong Scott C, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
The -141C Ins/Del polymorphism in the dopamine D2 receptor gene promoter region is associated with anxiolytic and antidepressive effects during treatment with dopamine antagonists in schizophrenic patients. Pharmacogenetics. 2001. Suzuki A, et al. PubMed
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Further evidence of human leukocyte antigen-encoded susceptibility to clozapine-induced agranulocytosis independent of ancestry. Pharmacogenetics. 2001. Dettling M, et al. PubMed
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Genetic determinants of clozapine-induced agranulocytosis: recent results of HLA subtyping in a non-jewish caucasian sample. Archives of general psychiatry. 2001. Dettling M, et al. PubMed
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Long-term therapeutic drug monitoring of clozapine and metabolites in psychiatric in- and outpatients. Psychopharmacology. 2000. Dettling M, et al. PubMed
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Science, medicine, and the future: Pharmacogenetics. BMJ (Clinical research ed.). 2000. Wolf C R, et al. PubMed
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Dopamine D3 receptor gene polymorphism and response to clozapine in schizophrenic Pakastani patients. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. 1999. Scharfetter J, et al. PubMed
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Could discontinuing smoking be hazardous for patients administered clozapine medication? A case report. Therapeutic drug monitoring. 1999. Skogh E, 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
Serotonin-6 receptor variant (C267T) and clinical response to clozapine. Neuroreport. 1999. Yu Y W, 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
T102C polymorphism in the 5HT2A gene and schizophrenia: relation to phenotype and drug response variability. Journal of psychiatry & neuroscience : JPN. 1999. Joober R, et al. PubMed
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Lack of association between a polymorphism in the promoter region of the dopamine-2 receptor gene and clozapine response. Pharmacogenetics. 1998. Arranz M J, et al. PubMed
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Functional polymorphism of -141C Ins/Del in the dopamine D2 receptor gene promoter and schizophrenia. Psychiatry research. 1998. Ohara K, et al. PubMed
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HLA-B38 and clozapine-induced agranulocytosis in Israeli Jewish schizophrenic patients. European journal of immunogenetics : official journal of the British Society for Histocompatibility and Immunogenetics. 1998. Valevski A, et al. PubMed
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Association between clozapine response and allelic variation in the 5-HT2C receptor gene. Neuroreport. 1995. Sodhi M S, et al. PubMed
Cytochrome P4502D6 genotype does not determine response to clozapine. British journal of clinical pharmacology. 1995. Arranz M J, et al. PubMed
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Metabolism and bioactivation of clozapine by human liver in vitro. The Journal of pharmacology and experimental therapeutics. 1995. Pirmohamed M, et al. PubMed
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Disposition of clozapine in man: lack of association with debrisoquine and S-mephenytoin hydroxylation polymorphisms. British journal of clinical pharmacology. 1994. Dahl M L, et al. PubMed
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HLA-B38, DR4, DQw3 and clozapine-induced agranulocytosis in Jewish patients with schizophrenia. Archives of general psychiatry. 1990. Lieberman J A, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
57664-345-88
DrugBank:
DB00363
ChEBI:
3766
KEGG Compound:
C06924
KEGG Drug:
D00283
PubChem Compound:
2818
PubChem Substance:
46506474
7847349
IUPHAR Ligand:
38
Drugs Product Database (DPD):
2240669
BindingDB:
22869
ChemSpider:
2716
Therapeutic Targets Database:
DAP000029
FDA Drug Label at DailyMed:
53bdb79c-c4cf-4818-b1f0-225e67a14536

Clinical Trials

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

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