Clopidogrel: Difference between revisions
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It is metabolized by [[cytochrome P-450]] [http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&TermToSearch=1557 2C19] [[allele]] and so may have drug interactions<ref>''''''[http://www.medicalletter.org/restricted/articles/w1303b.html PPI Interactions with Clopidogrel]. The Medical Letter.</ref> and inherited variations in metabolism.<ref name="pmid19106084">{{cite journal |author=Mega JL, Close SL, Wiviott SD, ''et al'' |title=Cytochrome P-450 Polymorphisms and Response to Clopidogrel |journal=N. Engl. J. Med. |volume= |issue= |pages= |year=2008 |month=December |pmid=19106084 |doi=10.1056/NEJMoa0809171 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=19106084&promo=ONFLNS19 |issn=}}</ref><ref name="pmid19108880">{{cite journal |author=Collet JP, Hulot JS, Pena A, ''et al'' |title=Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study |journal=Lancet |volume= |issue= |pages= |year=2008 |month=December |pmid=19108880 |doi=10.1016/S0140-6736(08)61845-0 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(08)61845-0 |issn=}}</ref><ref name="pmid19106083">{{cite journal |author=Simon T, Verstuyft C, Mary-Krause M, ''et al'' |title=Genetic Determinants of Response to Clopidogrel and Cardiovascular Events |journal=N. Engl. J. Med. |volume= |issue= |pages= |year=2008 |month=December |pmid=19106083 |doi=10.1056/NEJMoa0808227 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=19106083&promo=ONFLNS19 |issn=}}</ref> | It is metabolized by [[cytochrome P-450]] [http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&TermToSearch=1557 2C19] [[allele]] and so may have drug interactions<ref>''''''[http://www.medicalletter.org/restricted/articles/w1303b.html PPI Interactions with Clopidogrel]. The Medical Letter.</ref> and inherited variations in metabolism.<ref name="pmid19106084">{{cite journal |author=Mega JL, Close SL, Wiviott SD, ''et al'' |title=Cytochrome P-450 Polymorphisms and Response to Clopidogrel |journal=N. Engl. J. Med. |volume= |issue= |pages= |year=2008 |month=December |pmid=19106084 |doi=10.1056/NEJMoa0809171 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=19106084&promo=ONFLNS19 |issn=}}</ref><ref name="pmid19108880">{{cite journal |author=Collet JP, Hulot JS, Pena A, ''et al'' |title=Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study |journal=Lancet |volume= |issue= |pages= |year=2008 |month=December |pmid=19108880 |doi=10.1016/S0140-6736(08)61845-0 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(08)61845-0 |issn=}}</ref><ref name="pmid19106083">{{cite journal |author=Simon T, Verstuyft C, Mary-Krause M, ''et al'' |title=Genetic Determinants of Response to Clopidogrel and Cardiovascular Events |journal=N. Engl. J. Med. |volume= |issue= |pages= |year=2008 |month=December |pmid=19106083 |doi=10.1056/NEJMoa0808227 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=19106083&promo=ONFLNS19 |issn=}}</ref> | ||
30% of patients may have a reduced-function allele.<ref name="pmid19106084">{{cite journal |author=Mega JL, Close SL, Wiviott SD, ''et al'' |title=Cytochrome P-450 Polymorphisms and Response to Clopidogrel |journal=N. Engl. J. Med. |volume= |issue= |pages= |year=2008 |month=December |pmid=19106084 |doi=10.1056/NEJMoa0809171 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=19106084&promo=ONFLNS19 |issn=}}</ref> | 30% of patients may have a reduced-function allele.<ref name="pmid19106084">{{cite journal |author=Mega JL, Close SL, Wiviott SD, ''et al'' |title=Cytochrome P-450 Polymorphisms and Response to Clopidogrel |journal=N. Engl. J. Med. |volume= |issue= |pages= |year=2008 |month=December |pmid=19106084 |doi=10.1056/NEJMoa0809171 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=19106084&promo=ONFLNS19 |issn=}}</ref> and patients with a loss of function CYP2C19 allele have higher rates of cardiac events.<ref name="pmid19106084">{{cite journal| author=Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT et al.| title=Cytochrome p-450 polymorphisms and response to clopidogrel. | journal=N Engl J Med | year= 2009 | volume= 360 | issue= 4 | pages= 354-62 | pmid=19106084 | ||
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19106084 | doi=10.1056/NEJMoa0809171 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref><ref name="pmid19106083">{{cite journal |author=Simon T, Verstuyft C, Mary-Krause M, ''et al.'' |title=Genetic determinants of response to clopidogrel and cardiovascular events |journal=N. Engl. J. Med. |volume=360 |issue=4 |pages=363–75 |year=2009 |month=January |pmid=19106083 |doi=10.1056/NEJMoa0808227 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=19106083&promo=ONFLNS19 |issn=}}</ref> | |||
==Adverse effects== | ==Adverse effects== | ||
Inadequate effect in patients with [[coronary heart disease]] can be due to CYP2C19 loss-of-function alleles which are associated with more cardiovascular events.<ref name="pmid19106083">{{cite journal |author=Simon T, Verstuyft C, Mary-Krause M, ''et al.'' |title=Genetic determinants of response to clopidogrel and cardiovascular events |journal=N. Engl. J. Med. |volume=360 |issue=4 |pages=363–75 |year=2009 |month=January |pmid=19106083 |doi=10.1056/NEJMoa0808227 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=19106083&promo=ONFLNS19 |issn=}}</ref> Proton pump inhibitors, which are metabolized by the CYP2C19 isoenzyme of [[cytochrome P-450]], may<ref name="pmid19258584">{{cite journal |author=Ho PM, Maddox TM, Wang L, ''et al.'' |title=Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome |journal=JAMA |volume=301 |issue=9 |pages=937–44 |year=2009 |month=March |pmid=19258584 |doi=10.1001/jama.2009.261 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=19258584 |issn=}}</ref> | Inadequate effect in patients with [[coronary heart disease]] can be due to CYP2C19 loss-of-function alleles which are associated with more cardiovascular events.<ref name="pmid19106084">{{cite journal| author=Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT et al.| title=Cytochrome p-450 polymorphisms and response to clopidogrel. | journal=N Engl J Med | year= 2009 | volume= 360 | issue= 4 | pages= 354-62 | pmid=19106084 | ||
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19106084 | doi=10.1056/NEJMoa0809171 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref><ref name="pmid19106083">{{cite journal |author=Simon T, Verstuyft C, Mary-Krause M, ''et al.'' |title=Genetic determinants of response to clopidogrel and cardiovascular events |journal=N. Engl. J. Med. |volume=360 |issue=4 |pages=363–75 |year=2009 |month=January |pmid=19106083 |doi=10.1056/NEJMoa0808227 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=19106083&promo=ONFLNS19 |issn=}}</ref> Proton pump inhibitors (especially inhibitors other than pantoprazole<ref name="pmid19176635">Juurlink DN, Gomes T, Ko DT, Szmitko PE, Austin PC, Tu JV, Henry DA, Kopp A, Mamdani MM. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ. 2009 Mar 31;180(7):713-8. Epub 2009 Jan 28. PMID 19176635</ref>), which are metabolized by the CYP2C19 isoenzyme of [[cytochrome P-450]], may<ref name="pmid19258584">{{cite journal |author=Ho PM, Maddox TM, Wang L, ''et al.'' |title=Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome |journal=JAMA |volume=301 |issue=9 |pages=937–44 |year=2009 |month=March |pmid=19258584 |doi=10.1001/jama.2009.261 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=19258584 |issn=}}</ref> or may not<ref name="pmid19726078">{{cite journal| author=O'Donoghue ML, Braunwald E, Antman EM, Murphy SA, Bates ER, Rozenman Y et al.| title=Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials. | journal=Lancet | year= 2009 | volume= 374 | issue= 9694 | pages= 989-97 | pmid=19726078 | |||
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19726078 | doi=10.1016/S0140-6736(09)61525-7 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref> increase adverse cardiac events. | |||
==External links== | ==External links== | ||
Revision as of 19:06, 8 October 2009
In medicine, clopidogrel is a thienopyridine class platelet aggregation inhibitor. It is used in the secondary prevention of stroke and coronary heart disease.
Metabolism
It is metabolized by cytochrome P-450 2C19 allele and so may have drug interactions[1] and inherited variations in metabolism.[2][3][4]
30% of patients may have a reduced-function allele.[2] and patients with a loss of function CYP2C19 allele have higher rates of cardiac events.[2][4]
Adverse effects
Inadequate effect in patients with coronary heart disease can be due to CYP2C19 loss-of-function alleles which are associated with more cardiovascular events.[2][4] Proton pump inhibitors (especially inhibitors other than pantoprazole[5]), which are metabolized by the CYP2C19 isoenzyme of cytochrome P-450, may[6] or may not[7] increase adverse cardiac events.
External links
The most up-to-date information about Clopidogrel and other drugs can be found at the following sites.
- Clopidogrel - FDA approved drug information (drug label) from DailyMed (U.S. National Library of Medicine).
- Clopidogrel - Drug information for consumers from MedlinePlus (U.S. National Library of Medicine).
- Clopidogrel - Detailed information from DrugBank.
References
- ↑ 'PPI Interactions with Clopidogrel. The Medical Letter.
- ↑ 2.0 2.1 2.2 2.3 Mega JL, Close SL, Wiviott SD, et al (December 2008). "Cytochrome P-450 Polymorphisms and Response to Clopidogrel". N. Engl. J. Med.. DOI:10.1056/NEJMoa0809171. PMID 19106084. Research Blogging.
Cite error: Invalid
<ref>tag; name "pmid19106084" defined multiple times with different content Cite error: Invalid<ref>tag; name "pmid19106084" defined multiple times with different content - ↑ Collet JP, Hulot JS, Pena A, et al (December 2008). "Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study". Lancet. DOI:10.1016/S0140-6736(08)61845-0. PMID 19108880. Research Blogging.
- ↑ 4.0 4.1 4.2 Simon T, Verstuyft C, Mary-Krause M, et al (December 2008). "Genetic Determinants of Response to Clopidogrel and Cardiovascular Events". N. Engl. J. Med.. DOI:10.1056/NEJMoa0808227. PMID 19106083. Research Blogging.
Cite error: Invalid
<ref>tag; name "pmid19106083" defined multiple times with different content Cite error: Invalid<ref>tag; name "pmid19106083" defined multiple times with different content - ↑ Juurlink DN, Gomes T, Ko DT, Szmitko PE, Austin PC, Tu JV, Henry DA, Kopp A, Mamdani MM. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ. 2009 Mar 31;180(7):713-8. Epub 2009 Jan 28. PMID 19176635
- ↑ Ho PM, Maddox TM, Wang L, et al. (March 2009). "Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome". JAMA 301 (9): 937–44. DOI:10.1001/jama.2009.261. PMID 19258584. Research Blogging.
- ↑ O'Donoghue ML, Braunwald E, Antman EM, Murphy SA, Bates ER, Rozenman Y et al. (2009). "Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials.". Lancet 374 (9694): 989-97. DOI:10.1016/S0140-6736(09)61525-7. PMID 19726078. Research Blogging.