Chemical: Drug
ticagrelor
Annotated Labels
- Annotation of FDA Label for ticagrelor and CYP2C19
- Annotation of EMA Label for ticagrelor and CYP2C19
1. Annotation of FDA Label for ticagrelor and CYP2C19
Summary
Ticagrelor is a platelet inhibitor used to reduce the risk of thrombotic cardiovascular events for patients with acute coronary syndrome. The FDA-approved drug label notes that thrombotic cardiovascular events did not depend on CYP2C19 loss of function status.
Annotation
Excerpts from the ticagrelor (BRILINTA) drug label:
Pharmacogenetics...In a genetic substudy cohort of PLATO, the rate of thrombotic CV events in the BRILINTA arm did not depend on CYP2C19 loss of function status.
For the complete drug label text with sections containing pharmacogenetic information highlighted, see the ticagrelor drug label.
*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.
Genes and/or phenotypes found in this label
-
Acute coronary syndrome
- Indications & usage section
- source: U.S. Food and Drug Administration
-
Dyspnea
- Warnings and precautions section
- source: U.S. Food and Drug Administration
-
Intracranial Hemorrhages
- Contraindications section
- source: U.S. Food and Drug Administration
-
Peptic Ulcer
- Contraindications section
- source: U.S. Food and Drug Administration
-
ABCB1
- other, Drug interactions section, Clinical pharmacology section, Pharmacokinetics section
- source: U.S. Food and Drug Administration
-
CYP1A2
- Clinical pharmacology section
- source: U.S. Food and Drug Administration
-
CYP2C19
- Clinical pharmacology section, Clinical studies section
- source: U.S. Food and Drug Administration
-
CYP2E1
- Clinical pharmacology section
- source: U.S. Food and Drug Administration
-
CYP3A4
- metabolism/PK, Drug interactions section, Clinical pharmacology section, Clinical studies section, Pharmacokinetics section, Warnings and precautions section
- source: U.S. Food and Drug Administration
-
CYP3A5
- metabolism/PK, Drug interactions section, Clinical pharmacology section, Pharmacokinetics section, Warnings and precautions section
- source: U.S. Food and Drug Administration
2. Annotation of EMA Label for ticagrelor and CYP2C19
Summary
The EMA European Public Assessment Report (EPAR) for ticagrelor (Brilique) contains information regarding a study in which CYP2C19 and ABCB1 genotyping was carried out (PLATO - platelet inhibition and patient outcomes). In patients with one or more CYP2C19 loss of function allele, non-coronary artery by-pass grafting (non-CABG) PLATO major bleeding was increased when treated with ticagrelor compared to clopidogrel, but was similar in patients with no loss of function alleles.
Annotation
Excerpt from the ticagrelor (Brilique) EPAR:
CYP2C19 and ABCB1 genotyping of 10,285 patients in PLATO provided associations of genotype groups with PLATO outcomes. The superiority of ticagrelor over clopidogrel in reducing major CV events was not significantly affected by patient CYP2C19 or ABCB1 genotype. Similar to the overall PLATO study, total PLATO Major bleeding did not differ between ticagrelor and clopidogrel, regardless of CYP2C19 or ABCB1 genotype. Non-CABG PLATO Major bleeding was increased with ticagrelor compared clopidogrel in patients with one or more CYP2C19 loss of function alleles, but similar to clopidogrel in patients with no loss of function allele.
This information is highlighted in the following sections: pharmacological properties.
The ticagrelor EPAR also includes information regarding its mechanism of action by interacting with P2RY12 to prevent ADP-mediated platelet activation and aggregation. It is metabolized predominantly by CYP3A4, and concomitant use of strong CYP3A4 inhibitors is contraindicated due to the possibility of increased exposure to ticagrelor. The EPAR does not mention pharmacogenetics or testing of genetic variants in the CYP3A4 or P2RY12 genes.
Excerpts from the ticagrelor (Brilique) EPAR:
Ticagrelor does not interact with the ADP binding site itself, but interacts with platelet P2Y12 ADP-receptor to prevent signal transduction.
Ticagrelor is primarily a CYP3A4 substrate and a mild inhibitor of CYP3A4. Ticagrelor is also a P-gp substrate and a weak P-gp inhibitor and may increase the exposure of P-gp substrates.
For the complete drug label text with sections containing pharmacogenetic information highlighted, see the ticagrelor (Brilique) EMA drug label.
*Disclaimer: The contents of this page have not been endorsed by the EMA and are the sole responsibility of PharmGKB.
Genes and/or phenotypes found in this 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.
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 ticagrelor
| Gene ? |
Variant?
(147) |
Alternate Names ? | Chemicals ? |
Alleles
?
(+ chr strand) |
Function ? |
Amino Acid?
Translation |
|
|---|---|---|---|---|---|---|---|
| rs113681054 | NC_000012.11:g.21402979T>C, NC_000012.12:g.21250045T>C |
T > C
|
SNP | ||||
| rs12041331 | NC_000001.10:g.156869714G>A, NC_000001.11:g.156899922G>A, NM_001080471.1:c.-9-3996G>A, XM_005245141.1:c.-168-2266G>A, XM_005245141.2:c.-168-2266G>A, XM_006711302.2:c.-168-2266G>A, XM_011509508.1:c.-164-2266G>A, XM_011509509.1:c.-107-2266G>A, XM_011509510.1:c.-107-2266G>A, XM_011509511.1:c.-168-2266G>A, XM_011509512.1:c.-494-3996G>A, rs56433638, rs60733787 |
G > A
|
SNP | ||||
| rs12566888 | NC_000001.10:g.156869047G>T, NC_000001.11:g.156899255G>T, NM_001080471.1:c.-9-4663G>T, XM_005245141.1:c.-168-2933G>T, XM_005245141.2:c.-168-2933G>T, XM_006711302.2:c.-168-2933G>T, XM_011509508.1:c.-164-2933G>T, XM_011509509.1:c.-107-2933G>T, XM_011509510.1:c.-107-2933G>T, XM_011509511.1:c.-168-2933G>T, XM_011509512.1:c.-494-4663G>T, rs60358480, rs74229806 |
G > T
|
SNP | ||||
| rs2242480 | NC_000007.13:g.99361466C>T, NC_000007.14:g.99763843C>T, NG_008421.1:g.25343G>A, NM_001202855.2:c.1023+12G>A, NM_017460.5:c.1026+12G>A, XM_011515841.1:c.1026+12G>A, XM_011515842.1:c.1023+12G>A, rs10364667, rs12721630, rs17161804, rs28969389, rs59491337, rs72494459, rs9655766 |
C > T
|
SNP | ||||
| rs3093135 |
A > T
|
SNP | |||||
| rs4149056 | NC_000012.11:g.21331549T>C, NC_000012.12:g.21178615T>C, NG_011745.1:g.52422T>C, NM_006446.4:c.521T>C, NP_006437.3:p.Val174Ala, rs52816141, rs60037639 |
T > C
|
SNP |
V174A
|
|||
| rs4244285 | NC_000010.10:g.96541616G>A, NC_000010.11:g.94781859G>A, NG_008384.2:g.24154G>A, NM_000769.1:c.681G>A, NM_000769.2:c.681G>A, NP_000760.1:p.Pro227=, rs116940633, rs17879456, rs60361278 |
G > A
|
SNP |
P227P
|
|||
| rs4661012 |
T > G
|
SNP | |||||
| rs56324128 | NC_000007.13:g.99375702C>T, NC_000007.14:g.99778079C>T, NG_008421.1:g.11107G>A, NM_001202855.2:c.167G>A, NM_017460.5:c.167G>A, NP_001189784.1:p.Gly56Asp, NP_059488.2:p.Gly56Asp, XM_011515841.1:c.167G>A, XM_011515842.1:c.167G>A, XP_011514143.1:p.Gly56Asp, XP_011514144.1:p.Gly56Asp, rs386626576, rs59765626 |
C > T
|
SNP |
G56D
|
|||
| rs61361928 | NC_000004.11:g.69962375T>C, NC_000004.12:g.69096657T>C, NM_001074.2:c.137T>C, NP_001065.2:p.Leu46Pro, XM_005265702.1:c.-26-1883T>C, XM_005265702.2:c.-26-1883T>C, XM_011532229.1:c.137T>C, XM_011532230.1:c.137T>C, XM_011532231.1:c.-26-1883T>C, XP_011530531.1:p.Leu46Pro, XP_011530532.1:p.Leu46Pro |
T > C
|
SNP |
L46P
|
|||
| rs62471956 | NC_000007.13:g.99421085G>A, NC_000007.14:g.99823462G>A, NG_007935.1:g.450G>A |
G > A
|
SNP | ||||
| rs6785930 | NC_000003.11:g.151056616G>A, NC_000003.12:g.151338828G>A, NG_016019.1:g.50929C>T, NG_021244.1:g.256941G>A, NM_022788.4:c.18C>T, NM_053002.5:c.2146-11231G>A, NM_176876.2:c.18C>T, NP_073625.1:p.Asn6=, NP_795345.1:p.Asn6=, XM_005247096.1:c.2251-11231G>A, XM_006713487.2:c.2251-11231G>A, XM_011512386.1:c.2251-11231G>A, XM_011512387.1:c.2251-11231G>A, XM_011512388.1:c.2251-11231G>A, XM_011512389.1:c.2146-11231G>A, XM_011512390.1:c.2146-11231G>A, XM_011512391.1:c.1981-11231G>A, XM_011512392.1:c.1795-11231G>A, XM_011512393.1:c.2251-11231G>A, XM_011512394.1:c.2251-11231G>A, XM_011512395.1:c.2251-11231G>A, XM_011512396.1:c.676-11231G>A, XM_011512398.1:c.46-11231G>A, XM_011512399.1:c.2251-11231G>A, rs11538892, rs117076892, rs386491364 |
G > A
|
SNP |
N6N
|
|||
| rs6787801 | NC_000003.11:g.151099741A>G, NC_000003.12:g.151381953A>G, NG_016019.1:g.7804T>C, NG_021244.1:g.300066A>G, NM_022788.4:c.-180+2739T>C, NM_053002.5:c.4486-703A>G, XM_005247096.1:c.4591-703A>G, XM_006713487.2:c.4591-703A>G, XM_011512386.1:c.4591-703A>G, XM_011512387.1:c.4588-703A>G, XM_011512388.1:c.4591-703A>G, XM_011512389.1:c.4486-703A>G, XM_011512390.1:c.4486-703A>G, XM_011512391.1:c.4321-703A>G, XM_011512392.1:c.4135-703A>G, XM_011512393.1:c.4591-703A>G, XM_011512394.1:c.4591-703A>G, XM_011512395.1:c.4591-703A>G, XM_011512396.1:c.3016-703A>G, XM_011512397.1:c.2458-703A>G, XM_011512398.1:c.2386-703A>G, XM_011512400.1:c.1408-703A>G, rs17204473, rs56558253, rs58287028 |
A > G
|
SNP | ||||
| rs776746 | NC_000007.13:g.99270539C>T, NC_000007.14:g.99672916T>C, NG_007938.1:g.12083G=, NG_007938.1:g.12083G>A, NM_000777.4:c.219-237A>G, NM_000777.4:c.219-237G>A, NM_001190484.2:c.219-237A>G, NM_001190484.2:c.219-237G>A, NM_001291829.1:c.-253-1A>G, NM_001291829.1:c.-253-1G>A, NM_001291830.1:c.189-237A>G, NM_001291830.1:c.189-237G>A, NR_033807.2:n.717-1A>G, NR_033807.2:n.717-1G>A, NR_033808.1:n.689-1G>A, NR_033809.1:n.581-237G>A, NR_033810.1:n.689-1G>A, NR_033811.1:n.321-1G>A, NR_033812.1:n.321-1G>A, XM_005250169.1:c.189-237G>A, XM_005250170.1:c.-357-1G>A, XM_005250171.1:c.-253-1G>A, XM_005250172.1:c.-254G>A, XM_005250173.1:c.-331-237G>A, XM_005250198.1:c.806-4288C>T, XM_006715859.2:c.219-237A>G, XM_011515843.1:c.-254A>G, XM_011515844.1:c.-229-237A>G, XM_011515845.1:c.-463-1A>G, XM_011515846.1:c.-331-237A>G, XM_011515847.1:c.-571-1A>G, XR_927383.1:n.344-237A>G, XR_927402.1:n.1466+48736T>C, rs10361242, rs11266830, rs386613022, rs58244770 |
C > T
|
SNP |
Overview
PharmGKB Accession Id
PA165374673
Type(s):
Drug
Metabolite(s):
Other Vocabularies
- UMLS: Ticagrelor (C1999375)
- RxNorm: Ticagrelor (1116632)
- NDFRT: TICAGRELOR (N0000182973)
Information pulled from DrugBank has not been reviewed by PharmGKB.
Chemical Properties
SMILES
CCCSC1=NC2=C(C(=N1)N[C@@H]3C[C@H]3C4=CC(=C(C=C4)F)F)N=NN2[C@@H]5C[C@@H]([C@H]([C@H]5O)O)OCCO
Source: PubChem
InChI String
InChI=1S/C23H28F2N6O4S/c1-2-7-36-23-27-21(26-15-9-12(15)11-3-4-13(24)14(25)8-11)18-22(28-23)31(30-29-18)16-10-17(35-6-5-32)20(34)19(16)33/h3-4,8,12,15-17,19-20,32-34H,2,5-7,9-10H2,1H3,(H,26,27,28)/t12-,15+,16+,17-,19-,20+/m0/s1
Source: PubChem
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 ?
| Evidence | Disease |
|---|---|
| Acute coronary syndrome | |
| Dyspnea | |
| Intracranial Hemorrhages | |
| Peptic Ulcer |
