Chemical: Drug
tropisetron
1. Annotation of CPIC Guideline for tropisetron and CYP2D6
Summary
The CPIC dosing guideline for tropisetron recommends selecting an alternate drug for CYP2D6 ultrarapid metabolizers. It is recommended that the alternate drug not be predominantly metabolized by CYP2D6 (eg. granisetron).
Annotation
This annotation is based on the CPIC® guideline for ondansetron and tropisetron and CYP2D6.
December 2016
- Guidelines regarding the use of pharmacogenomic tests in dosing for tropisetron were published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC).
- Excerpt from the 2016 tropisetron dosing guidelines:
- "Gene duplication has been shown to be associated with higher metabolism and clearance of ondansetron resulting in lower area under the plasma concentration-time curve. This translates clinically into a decreased response to ondansetron and tropisetron, specifically increased risk of vomiting in CYP2D6 ultrarapid metabolizers. If CYP2D6 genotype is known, alternative 5-HT3 receptor antagonist antiemetics not metabolized by CYP2D6 (e.g., granisetron) should be considered in CYP2D6 ultrarapid metabolizers. "
- Download and read:
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 Genotype and Use of Ondansetron and Tropisetron
- 2016 supplement
- Gene-specific Information Tables for CYP2D6
- Tropisetron Drug Resource Mappings
- Ondansetron Pre- and Post-Test Alerts and Flow Chart (note that while the title of the file does not state tropisetron, alerts for tropisetron are found in the file)
Table 1: Dosing recommendations for tropisetron based on CYP2D6 phenotype/genotype
Adapted from Tables 1 and 2 of the 2016 guideline manuscript.
| CYP2D6 Phenotype | Activity score | CYP2D6 Genotypesa | Examples of diplotypes | Implications | Therapeutic recommendations | Classification of Recommendationsb | Consideration for alternative 5-HT3 receptor antagonists antiemeticsc |
|---|---|---|---|---|---|---|---|
| Ultrarapid metabolizer | >2.0 | An individual carrying duplications of function alleles | *1/*1xN, *1/*2xN, *2/*2xNd | Increased metabolism to less active compounds when compared to normal metabolizers and is associated with decreased response to ondansetron and tropisetron (i.e. vomiting). | Select and alternative drug not predominantly metabolized by CYP2D6 (i.e. granisetron).e | Moderate | Dolasetron, palonosetron, and ramosetron are also metabolized by CYP2D6. Limited evidence is available regarding the utilization of CYP2D6 genetic variation to guide use of these drugs. |
| Normal metabolizer | 2.0-1.0f | An individual carrying two normal function alleles, or two decreased function alleles, or one normal function and one no function allele, or one normal function and one decreased function allele, or combinations of duplicated alleles that result in an activity score of 1.0-2.0 | *1/*1, *1/*2, *1/*4, *1/*5, *1/*9, *1/*41, *2/*2,*41/*41 | Normal metabolism | Initiate therapy with recommended starting dose. | Strong | |
| Intermediate metabolizer | 0.5 | An individual carrying one decreased function and one no function allele | *4/*10,*4/*41, *5/*9 | Very limited data available for CYP2D6 intermediate metabolizers | Insufficient evidence demonstrating clinical impact based on CYP2D6 genotype. Initiate therapy with recommended starting dose. | No recommendation | |
| Poor metabolizer | 0 | An individual carrying no functional alleles | *3/*4,*4/*4, *5/*5, *5/*6 | Very limited data available for CYP2D6 poor metabolizers | Insufficient evidence demonstrating clinical impact based on CYP2D6 genotype. Initiate therapy with recommended starting dose. | No recommendation |
a Assignment of allele function and citations for allele function can be found on PharmGKB: CYP2D6 Allele Definition Table and CYP2D6 Allele Functionality Table.
b Rating scheme is described in the 2016 Supplement
c CPIC strength of recommendation: No Recommendation. See rating scheme described in the Supplement.
d Where xN represents the number of CYP2D6 gene copies. For individuals with CYP2D6 duplications or multiplications, see supplemental data for additional information on how to translate diplotypes into phenotypes.
e Drug-drug interactions and other patient characteristics (e.g., age, renal function, and liver function) should be considered when selecting alternative therapy.
f Patients with an activity score of 1.0 may be classified as intermediate metabolizers by some reference laboratories.
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PharmGKB contains no Clinical Variants that meet the highest level of criteria.
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.
The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.
The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.
Links in the "Gene" column lead to PharmGKB Gene Pages.
List of all variant annotations for tropisetron
| Gene ? |
Variant?
(147) |
Alternate Names ? | Chemicals ? |
Alleles
?
(+ chr strand) |
Function ? |
Amino Acid?
Translation |
|
|---|---|---|---|---|---|---|---|
VA
|
CYP2D6 | *1 | N/A | N/A | N/A | ||
|
VA
|
CYP2D6 | *1xN | N/A | N/A | N/A | ||
|
VA
|
CYP2D6 | *3 | N/A | N/A | N/A | ||
| rs12208357 | NC_000006.11:g.160543148C>T, NC_000006.12:g.160122116C>T, NM_003057.2:c.181C>T, NM_153187.1:c.181C>T, NP_003048.1:p.Arg61Cys, NP_694857.1:p.Arg61Cys, XM_005267102.1:c.181C>T, XM_005267102.3:c.181C>T, XM_005267103.1:c.181C>T, XM_005267105.1:c.-485C>T, XM_005267105.3:c.-485C>T, XM_006715552.1:c.181C>T, XM_011536074.1:c.-895C>T, XP_005267159.1:p.Arg61Cys, XP_005267160.1:p.Arg61Cys, XP_006715615.1:p.Arg61Cys, rs56982873 |
C > T
|
SNP |
R61C
|
|||
| rs34059508 | NC_000006.11:g.160575837G>A, NC_000006.12:g.160154805G>A, NM_003057.2:c.1393G>A, NM_153187.1:c.1386-1170G>A, NP_003048.1:p.Gly465Arg, XM_005267102.1:c.1393G>A, XM_005267102.3:c.1393G>A, XM_005267103.1:c.1393G>A, XM_005267104.1:c.817G>A, XM_005267104.3:c.817G>A, XM_005267105.1:c.817G>A, XM_005267105.3:c.817G>A, XM_006715552.1:c.1386-3711G>A, XM_011536074.1:c.817G>A, XP_005267159.1:p.Gly465Arg, XP_005267160.1:p.Gly465Arg, XP_005267161.1:p.Gly273Arg, XP_005267162.1:p.Gly273Arg, XP_011534376.1:p.Gly273Arg, rs45476695, rs57829971 |
G > A
|
SNP |
G465R
|
|||
| rs34130495 | NC_000006.11:g.160560824G>A, NC_000006.12:g.160139792G>A, NM_003057.2:c.1201G>A, NM_153187.1:c.1201G>A, NP_003048.1:p.Gly401Ser, NP_694857.1:p.Gly401Ser, XM_005267102.1:c.1201G>A, XM_005267102.3:c.1201G>A, XM_005267103.1:c.1201G>A, XM_005267104.1:c.625G>A, XM_005267104.3:c.625G>A, XM_005267105.1:c.625G>A, XM_005267105.3:c.625G>A, XM_006715552.1:c.1201G>A, XM_011536074.1:c.625G>A, XP_005267159.1:p.Gly401Ser, XP_005267160.1:p.Gly401Ser, XP_005267161.1:p.Gly209Ser, XP_005267162.1:p.Gly209Ser, XP_006715615.1:p.Gly401Ser, XP_011534376.1:p.Gly209Ser, rs45512393 |
G > A
|
SNP |
G401S
|
|||
| rs72552763 | NC_000006.11:g.160560883_160560885delGAT, NC_000006.12:g.160139851_160139853delGAT, NM_003057.2:c.1260_1262delGAT, NM_153187.1:c.1260_1262delGAT, NP_003048.1:p.Met420del, NP_694857.1:p.Met420del, XM_005267102.1:c.1260_1262delGAT, XM_005267102.3:c.1260_1262delGAT, XM_005267103.1:c.1260_1262delGAT, XM_005267104.1:c.684_686delGAT, XM_005267104.3:c.684_686delGAT, XM_005267105.1:c.684_686delGAT, XM_005267105.3:c.684_686delGAT, XM_006715552.1:c.1260_1262delGAT, XM_011536074.1:c.684_686delGAT, XP_005267159.1:p.Met420del, XP_005267160.1:p.Met420del, XP_005267161.1:p.Met228del, XP_005267162.1:p.Met228del, XP_006715615.1:p.Met420del, XP_011534376.1:p.Met228del |
GAT > -
|
indel |
Overview
PharmGKB Accession Id
PA161925594
Type(s):
Drug
Other Vocabularies
- UMLS: tropisetron (C0063322)
- RxNorm: tropisetron (27392)
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 ?
Curated Information ?
Publications related to tropisetron: 7
Clinical Trials
These are trials that mention tropisetron and are related to either pharmacogenetics or pharmacogenomics.
NURSA Datasets
No NURSA datasets available.