Proton pump inhibitor: Difference between revisions

From Citizendium
Jump to navigation Jump to search
imported>Robert Badgett
imported>Robert Badgett
Line 34: Line 34:
In the [[United States]], the [[Food and Drug Administration]] has issued warnings regarding combining PPIs with [[clopidogrel]].<ref>Anonymous. (2009) [http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm079520.htm Early Communication about an Ongoing Safety Review of clopidogrel bisulfate (marketed as Plavix)]</ref><ref>Anonymous (11/17/2009) [http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm190787.htm Information for Healthcare Professionals: Update to the labeling of Clopidogrel Bisulfate (marketed as Plavix) to alert healthcare professionals about a drug interaction with omeprazole (marketed as Prilosec and Prilosec OTC)]</ref>
In the [[United States]], the [[Food and Drug Administration]] has issued warnings regarding combining PPIs with [[clopidogrel]].<ref>Anonymous. (2009) [http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm079520.htm Early Communication about an Ongoing Safety Review of clopidogrel bisulfate (marketed as Plavix)]</ref><ref>Anonymous (11/17/2009) [http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm190787.htm Information for Healthcare Professionals: Update to the labeling of Clopidogrel Bisulfate (marketed as Plavix) to alert healthcare professionals about a drug interaction with omeprazole (marketed as Prilosec and Prilosec OTC)]</ref>
{| class="wikitable"
{| class="wikitable"
|+ Studies of [[drug interaction]]s between PPIs and [[clopidogrel]]<ref name="pmid20231564">{{cite journal| author=Ray WA, Murray KT, Griffin MR, Chung CP, Smalley WE, Hall K et al.| title=Outcomes with concurrent use of clopidogrel and proton-pump inhibitors: a cohort study. | journal=Ann Intern Med | year= 2010 | volume= 152 | issue= 6 | pages= 337-45 | pmid=20231564  
|+ Studies of [[drug interaction]]s between PPIs and [[clopidogrel]]<ref name="doi10.1001/archinternmed.2010.34">{{Cite journal | doi = 10.1001/archinternmed.2010.34 | volume = 170
| issue = 8 | pages = 704-710 | last = Stockl | first = Karen M. | coauthors = Lisa Le, Armen Zakharyan, Ann S. M. Harada, Brian K. Solow, Joseph E. Addiego, Scott Ramsey | title = Risk of Rehospitalization for Patients Using Clopidogrel With a Proton Pump Inhibitor | journal = Arch Intern Med | accessdate = 2010-04-27
| date = 2010-04-26 | url = http://archinte.ama-assn.org/cgi/content/abstract/170/8/704}}</ref><ref name="pmid20231564">{{cite journal| author=Ray WA, Murray KT, Griffin MR, Chung CP, Smalley WE, Hall K et al.| title=Outcomes with concurrent use of clopidogrel and proton-pump inhibitors: a cohort study. | journal=Ann Intern Med | year= 2010 | volume= 152 | issue= 6 | pages= 337-45 | pmid=20231564  
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=20231564 | doi=10.1059/0003-4819-152-6-201003160-00003 }} </ref><ref name="pmid19176635">{{cite journal| author=Juurlink DN, Gomes T, Ko DT, Szmitko PE, Austin PC, Tu JV et al.| title=A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. | journal=CMAJ | year= 2009 | volume= 180 | issue= 7 | pages= 713-8 | pmid=19176635  
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=20231564 | doi=10.1059/0003-4819-152-6-201003160-00003 }} </ref><ref name="pmid19176635">{{cite journal| author=Juurlink DN, Gomes T, Ko DT, Szmitko PE, Austin PC, Tu JV et al.| title=A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. | journal=CMAJ | year= 2009 | volume= 180 | issue= 7 | pages= 713-8 | pmid=19176635  
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19176635 | doi=10.1503/cmaj.082001 | pmc=PMC2659819 }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19687487 Review in: Ann Intern Med. 2009 Aug 18;151(4):JC2-13]  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19794029 Review in: Evid Based Med. 2009 Oct;14(5):154]</ref><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><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=19176635 | doi=10.1503/cmaj.082001 | pmc=PMC2659819 }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19687487 Review in: Ann Intern Med. 2009 Aug 18;151(4):JC2-13]  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19794029 Review in: Evid Based Med. 2009 Oct;14(5):154]</ref><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><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  
Line 42: Line 44:
! PPI!!Control
! PPI!!Control
|-
|-
|rowspan="2"|Tennessee Medicaid [[cohort study]]<ref name="pmid20231564"/>||rowspan="2"|20,596 patients hospitalized for [[myocardial infarction]], [[myocardial revascularization]], or unstable angina pectoris||rowspan="2"|7593 concurrent users of clopidogrel and PPIs<br/>&bull;&nbsp;62% used [[pantoprazole]]||rowspan="2"|13003 patients not taking PPIs||rowspan="2"|Serious cardiovascular disease||
|rowspan="2"|Stockl et al Retrospective [[cohort study]]<ref name="doi10.1001/archinternmed.2010.34"/><br/>2010 ||rowspan="2"|2,066  patients hospitalized for [[myocardial infarction]] or [[stent]]||rowspan="2"|1,033 concurrent users of clopidogrel and PPIs<br/>&bull;&nbsp;64% used [[pantoprazole]]||rowspan="2"|1,033 patients not taking PPIs||rowspan="2"|Serious cardiovascular disease||
|-
|-
| colspan="2"|"Serious cardiovascular disease was not increased; however, the 95% CI included a clinically important increased risk"
|colspan="2"|[[Odds ratio]] = 1.64 (95% [[Confidence interval|CI]] 1.16-2.32)<br/>"Patients who received clopidogrel plus a PPI had a significantly higher risk of rehospitalization for MI or coronary stent placement than did patients  receiving clopidogrel alone"
|-
|-
| Ontario nested [[case-control study]]<ref name="pmid19176635"/> || 13,636 subjects taking [[clopidogrel]] after [[myocardial infarction]]||782 subjects readmitted for [[myocardial infarction]]||2057 subjects not readmitted||Rate of PPI usage other than [[pantoprazole]]|| colspan="2"| [[Odds ratio]] = 1.40 (95% CI 1.10–1.77)
|rowspan="2"|Tennessee Medicaid [[cohort study]]<ref name="pmid20231564"/>||rowspan="2"|20,596  patients hospitalized for [[myocardial  infarction]], [[myocardial  revascularization]], or  unstable angina pectoris||rowspan="2"|7593 concurrent users of  clopidogrel and PPIs<br/>&bull;&nbsp;62%  used [[pantoprazole]]||rowspan="2"|13003  patients not taking PPIs||rowspan="2"|Serious cardiovascular disease||
|-
|  colspan="2"|"Serious cardiovascular disease was not increased; however, the 95% CI included a clinically important increased risk"
|-
| Ontario nested [[case-control study]]<ref name="pmid19176635"/> || 13,636 subjects taking [[clopidogrel]] after [[myocardial infarction]]||782 subjects readmitted for [[myocardial infarction]]||2057 subjects not readmitted||Rate of PPI usage other than [[pantoprazole]]|| colspan="2"| [[Odds ratio]] = 1.40 (95% [[Confidence interval|CI]] 1.10–1.77)
|-
|-
| rowspan="2"|[[Cohort study]] from the [[United States Veterans Health Administration|VA]] Cardiac Care Follow-up Clinical Study<ref name="pmid19258584"/> ||rowspan="2"| 8205 subjects with [[acute coronary syndrome]]||rowspan="2"| 64% were taking PPIs:<br/>&bull; 0.2% used [[pantoprazole]]<br/>&bull; 50% received [[stent]]s<br/>&bull; Probably < 50% used drug eluting [[stent]]s<ref name="pmid17967588">{{cite journal| author=Ho PM, Fihn SD, Wang L, Bryson CL, Lowy E, Maynard C et al.| title=Clopidogrel and long-term outcomes after stent implantation for acute coronary syndrome. | journal=Am Heart J | year= 2007 | volume= 154 | issue= 5 | pages= 846-51 | pmid=17967588  
| rowspan="2"|[[Cohort study]] from the [[United States Veterans Health Administration|VA]] Cardiac Care Follow-up Clinical Study<ref name="pmid19258584"/> ||rowspan="2"| 8205 subjects with [[acute coronary syndrome]]||rowspan="2"| 64% were taking PPIs:<br/>&bull; 0.2% used [[pantoprazole]]<br/>&bull; 50% received [[stent]]s<br/>&bull; Probably < 50% used drug eluting [[stent]]s<ref name="pmid17967588">{{cite journal| author=Ho PM, Fihn SD, Wang L, Bryson CL, Lowy E, Maynard C et al.| title=Clopidogrel and long-term outcomes after stent implantation for acute coronary syndrome. | journal=Am Heart J | year= 2007 | volume= 154 | issue= 5 | pages= 846-51 | pmid=17967588  
Line 54: Line 60:
|-
|-
|rowspan="2"|[[Cohort study]] taken from TRITON-TIMI 38 [[randomized controlled trial]]s<ref name="pmid19726078"/><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  
|rowspan="2"|[[Cohort study]] taken from TRITON-TIMI 38 [[randomized controlled trial]]s<ref name="pmid19726078"/><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="pmid17982182">{{cite journal| author=Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S et al.| title=Prasugrel versus clopidogrel in patients with acute coronary syndromes. | journal=N Engl J Med | year= 2007 | volume= 357 | issue= 20 | pages= 2001-15 | pmid=17982182  
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19106084 | doi=10.1056/NEJMoa0809171 }}</ref><ref name="pmid17982182">{{cite journal| author=Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S et al.| title=Prasugrel versus clopidogrel in patients with acute coronary syndromes. | journal=N Engl J Med | year= 2007 | volume= 357 | issue= 20 | pages= 2001-15 | pmid=17982182  
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17982182 | doi=10.1056/NEJMoa0706482 }}</ref><br/>2 of 14 authors disclosed payments from AstraZenca, the maker of omeprazole and esomeprazole||rowspan="2"|6795 subjects with [[acute coronary syndrome]] who were randomized to the [[clopidogrel]] arm of the trial||rowspan="2"|33% (4529) were taking PPIs at randomization:<br/>&bull; 2814 took PPIs for duration of study<br/>&bull; 41% used [[pantoprazole]]<br/>&bull; 94% received [[stent]]s<br/>&bull; 47% received at least one drug eluting [[stent]]||rowspan="2"|Subjects not taking PPIs||rowspan="2"|Major vascular events || 11.8%||12.2%
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17982182 | doi=10.1056/NEJMoa0706482 }}</ref><br/>2 of 14 authors disclosed payments from AstraZenca, the maker of omeprazole and esomeprazole||rowspan="2"|6795 subjects with [[acute coronary syndrome]] who were randomized to the [[clopidogrel]] arm of the trial||rowspan="2"|33% (4529) were taking PPIs at randomization:<br/>&bull; 2814 took PPIs for duration of study<br/>&bull; 41% used [[pantoprazole]]<br/>&bull; 94% received [[stent]]s<br/>&bull; 47% received at least one drug eluting [[stent]]||rowspan="2"|Subjects not taking PPIs||rowspan="2"|Major vascular events || 11.8%||12.2%
|-
|-
| colspan="2"|&bull; Patients taking ''any'' PPI [[Hazards ratio|HR]] = 0.94, (95% CI 0.80–1.11)<br/>&bull; Patients taking ''any'' PPI for ''duration'' of study  [[Hazards ratio|HR]] = 1.05 (95% CI 0.85–1.30)<br/>&bull; Results similar for each individual PPI<br/>&bull; Results also insignificant when restricted to analysis of patients with a reduced function allele
| colspan="2"|&bull; Patients taking ''any'' PPI [[Hazards ratio|HR]] = 0.94, (95% [[Confidence interval|CI]] 0.80–1.11)<br/>&bull; Patients taking ''any'' PPI for ''duration'' of study  [[Hazards ratio|HR]] = 1.05 (95% [[Confidence interval|CI]] 0.85–1.30)<br/>&bull; Results similar for each individual PPI<br/>&bull; Results also insignificant when restricted to analysis of patients with a reduced function allele
|-
|-
|rowspan="2"|Medco [[cohort study]]<ref name="medco"/> ||rowspan="2"|16,718 subjects who took [[clopidogrel]] for 12 months after coronary [[stent]]||rowspan="2"|41% were taking PPIs:<br/>&bull; 24% used [[pantoprazole]]<br/>&bull; 100% received [[stent]]s<br/>&bull; Unknown use of drug eluting [[stent]]s||rowspan="2"|Subjects not taking PPIs||rowspan="2"|Major vascular events|| 24% to 29% ||17.9%
|rowspan="2"|Medco [[cohort study]]<ref name="medco"/> ||rowspan="2"|16,718 subjects who took [[clopidogrel]] for 12 months after coronary [[stent]]||rowspan="2"|41% were taking PPIs:<br/>&bull; 24% used [[pantoprazole]]<br/>&bull; 100% received [[stent]]s<br/>&bull; Unknown use of drug eluting [[stent]]s||rowspan="2"|Subjects not taking PPIs||rowspan="2"|Major vascular events|| 24% to 29% ||17.9%
Line 65: Line 71:


Proton pump inhibitors (especially inhibitors other than [[pantoprazole]]<ref name="pmid19176635">{{cite journal| author=Juurlink DN, Gomes T, Ko DT, Szmitko PE, Austin PC, Tu JV et al.| title=A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. | journal=CMAJ | year= 2009 | volume= 180 | issue= 7 | pages= 713-8 | pmid=19176635  
Proton pump inhibitors (especially inhibitors other than [[pantoprazole]]<ref name="pmid19176635">{{cite journal| author=Juurlink DN, Gomes T, Ko DT, Szmitko PE, Austin PC, Tu JV et al.| title=A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. | journal=CMAJ | year= 2009 | volume= 180 | issue= 7 | pages= 713-8 | pmid=19176635  
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19176635 | doi=10.1503/cmaj.082001 | pmc=PMC2659819 }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19687487 Review in: Ann Intern Med. 2009 Aug 18;151(4):JC2-13]  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19794029 Review in: Evid Based Med. 2009 Oct;14(5):154] <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></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=19176635 | doi=10.1503/cmaj.082001 | pmc=PMC2659819 }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19687487 Review in: Ann Intern Med. 2009 Aug 18;151(4):JC2-13]  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19794029 Review in: Evid Based Med. 2009 Oct;14(5):154]</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 when given to patients taking [[clopidogrel]] for [[coronary heart disease]].
| 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 }}</ref> increase adverse cardiac events when given to patients taking [[clopidogrel]] for [[coronary heart disease]].


==References==
==References==
<references/>
<references/>

Revision as of 06:21, 27 April 2010

This article is a stub and thus not approved.
 Main Article
 Discussion
Related Articles  [?]
Bibliography  [?]
External Links  [?]
Citable Version  [?]
 
https://en.citizendium.org/wiki/index.php?title=Proton_pump_inhibitor&printable=yes
This editable Main Article is under development and subject to a disclaimer.

In medicine, proton pump inhibitors (PPI) are medications that "inhibit H(+)-K(+)-exchanging atpase. They are used as anti-ulcer agents and sometimes in place of histamine H2 antagonists for gastroesophageal reflux disease."[1] They are also used to eradicate Helicobacter pylori, in combination with antibiotics.

Metabolism

Proton pump inhibitors are metabolized by the CYP2C19 isoenzyme of cytochrome P-450. Lanzoprazole is the strongest inhibitor of CYP2C19,[2] This may be less true for pantoprazole and esomeprazole.[3] Pantoprazole is the strongest inhibitor of the CYP2C9 isoenzyme[2]

Effectiveness

Proton pump inhibitors may improve:

PPIs may reduce the risk of gastrointestinal hemorrhage among patients undering anticoagulation.[9]

Adverse effects

Proton pump inhibitors may be associated with spontaneous bacterial peritonitis.[10] Recent starting of these drugs may also be associated with pneumonia acquired in the community[11] or hospital[12]. These drugs may be associated with Clostridium difficile diarrhea, and fractures.

Starting proton pump inhibitors in healthy volunteers may induce acid-related symptoms when PPIs are stopped[13] This is problematic considering how often PPIs are incorrectly prescribed.[14]

Proton pump inhibitors may induce acid-related symptoms in healthy volunteers after withdrawal, presumably due to rebound acid hypersecretion.[13]

Drug interactions

In the United States, the Food and Drug Administration has issued warnings regarding combining PPIs with clopidogrel.[15][16]

Studies of drug interactions between PPIs and clopidogrel[17][18][19][20][21][22]
Trial Patients Intervention Comparison Outcome Results
PPI Control
Stockl et al Retrospective cohort study[17]
2010		 2,066 patients hospitalized for myocardial infarction or stent 1,033 concurrent users of clopidogrel and PPIs
• 64% used pantoprazole		 1,033 patients not taking PPIs Serious cardiovascular disease
Odds ratio = 1.64 (95% CI 1.16-2.32)
"Patients who received clopidogrel plus a PPI had a significantly higher risk of rehospitalization for MI or coronary stent placement than did patients receiving clopidogrel alone"
Tennessee Medicaid cohort study[18] 20,596 patients hospitalized for myocardial infarction, myocardial revascularization, or unstable angina pectoris 7593 concurrent users of clopidogrel and PPIs
• 62% used pantoprazole		 13003 patients not taking PPIs Serious cardiovascular disease
"Serious cardiovascular disease was not increased; however, the 95% CI included a clinically important increased risk"
Ontario nested case-control study[19] 13,636 subjects taking clopidogrel after myocardial infarction 782 subjects readmitted for myocardial infarction 2057 subjects not readmitted Rate of PPI usage other than pantoprazole Odds ratio = 1.40 (95% CI 1.10–1.77)
Cohort study from the VA Cardiac Care Follow-up Clinical Study[20] 8205 subjects with acute coronary syndrome 64% were taking PPIs:
• 0.2% used pantoprazole
• 50% received stents
• Probably < 50% used drug eluting stents[23]		 Subjects not taking PPIs Major vascular events 29.8% 20.8%
Odds ratio = 1.25 (95% CI: 1.11-1.41)
• "each 10% increase in the proportion of time taking clopidogrel plus PPI during follow-up was associated with a higher risk"
Cohort study taken from TRITON-TIMI 38 randomized controlled trials[21][24][25]
2 of 14 authors disclosed payments from AstraZenca, the maker of omeprazole and esomeprazole		 6795 subjects with acute coronary syndrome who were randomized to the clopidogrel arm of the trial 33% (4529) were taking PPIs at randomization:
• 2814 took PPIs for duration of study
• 41% used pantoprazole
• 94% received stents
• 47% received at least one drug eluting stent		 Subjects not taking PPIs Major vascular events 11.8% 12.2%
• Patients taking any PPI HR = 0.94, (95% CI 0.80–1.11)
• Patients taking any PPI for duration of study HR = 1.05 (95% CI 0.85–1.30)
• Results similar for each individual PPI
• Results also insignificant when restricted to analysis of patients with a reduced function allele
Medco cohort study[22] 16,718 subjects who took clopidogrel for 12 months after coronary stent 41% were taking PPIs:
• 24% used pantoprazole
• 100% received stents
• Unknown use of drug eluting stents		 Subjects not taking PPIs Major vascular events 24% to 29% 17.9%
• Pantoprazole HR=1.61 (pantoprazole had most GI bleeding)
• Esooprazole HR=1.57
• Lansoprazole HR=1.39
• Omeprazole HR=1.39
• Histamine H2 antagonists HR=1.14 (insignicant)

Proton pump inhibitors (especially inhibitors other than pantoprazole[19]), which are metabolized by the CYP2C19 isoenzyme of cytochrome P-450, may[20] or may not[21] increase adverse cardiac events when given to patients taking clopidogrel for coronary heart disease.

References

  1. ↑ Anonymous (2024), Proton pump inhibitor (English). Medical Subject Headings. U.S. National Library of Medicine.
  2. ↑ 2.0 2.1 Li XQ, Andersson TB, Ahlström M, Weidolf L (2004). "Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities.". Drug Metab Dispos 32 (8): 821-7. PMID 15258107.
  3. ↑ Siller-Matula JM, Spiel AO, Lang IM, Kreiner G, Christ G, Jilma B (January 2009). "Effects of pantoprazole and esomeprazole on platelet inhibition by clopidogrel". Am. Heart J. 157 (1): 148.e1–5. DOI:10.1016/j.ahj.2008.09.017. PMID 19081411. Research Blogging.
  4. ↑ Moayyedi P, Soo S, Deeks J, Delaney B, Innes M, Forman D (2006). "Pharmacological interventions for non-ulcer dyspepsia.". Cochrane Database Syst Rev (4): CD001960. DOI:10.1002/14651858.CD001960.pub3. PMID 17054151. Research Blogging. Review in: Evid Based Med. 2007 Jun;12(3):79
  5. ↑ van Pinxteren B, Numans ME, Bonis PA, Lau J (2006). "Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease.". Cochrane Database Syst Rev 3: CD002095. DOI:10.1002/14651858.CD002095.pub3. PMID 16855986. Research Blogging.
  6. ↑ Pace F, Tonini M, Pallotta S, Molteni P, Porro GB (2007). "Systematic review: maintenance treatment of gastro-oesophageal reflux disease with proton pump inhibitors taken 'on-demand'.". Aliment Pharmacol Ther 26 (2): 195-204. DOI:10.1111/j.1365-2036.2007.03381.x. PMID 17593065. Research Blogging. Review in: Evid Based Med. 2007 Dec;12(6):177 Review in: ACP J Club. 2007 Nov-Dec;147(3):69
  7. ↑ Bardhan KD, Müller-Lissner S, Bigard MA, Bianchi Porro G, Ponce J, Hosie J et al. (1999). "Symptomatic gastro-oesophageal reflux disease: double blind controlled study of intermittent treatment with omeprazole or ranitidine. The European Study Group.". BMJ 318 (7182): 502-7. PMID 10024259. PMC PMC27748.
  8. ↑ Khan M, Santana J, Donnellan C, Preston C, Moayyedi P (2007). "Medical treatments in the short term management of reflux oesophagitis.". Cochrane Database Syst Rev (2): CD003244. DOI:10.1002/14651858.CD003244.pub2. PMID 17443524. Research Blogging.
  9. ↑ Massó González EL, García Rodríguez LA (2008). "Proton pump inhibitors reduce the long-term risk of recurrent upper gastrointestinal bleeding: an observational study.". Aliment Pharmacol Ther 28 (5): 629-37. DOI:10.1111/j.1365-2036.2008.03780.x. PMID 18616644. Research Blogging.
  10. ↑ Bajaj JS, Zadvornova Y, Heuman DM, et al. (May 2009). "Association of proton pump inhibitor therapy with spontaneous bacterial peritonitis in cirrhotic patients with ascites". Am. J. Gastroenterol. 104 (5): 1130–4. DOI:10.1038/ajg.2009.80. PMID 19337238. Research Blogging.
  11. ↑ Sarkar M, Hennessy S, Yang YX. Proton-pump inhibitor use and the risk for community-acquired pneumonia. Ann Intern Med. 2008 Sep 16;149(6):391-8. PMID 18794558
  12. ↑ Herzig SJ, Howell MD, Ngo LH, Marcantonio ER. Acid-suppressive medication use and the risk for hospital-acquired pneumonia. JAMA. 2009 May 27;301(20):2120-8. PMID 19470989
  13. ↑ 13.0 13.1 Reimer C, Søndergaard B, Hilsted L, Bytzer P (2009). "Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy.". Gastroenterology 137 (1): 80-7, 87.e1. DOI:10.1053/j.gastro.2009.03.058. PMID 19362552. Research Blogging. Cite error: Invalid <ref> tag; name "pmid19362552" defined multiple times with different content
  14. ↑ Wohlt PD, Hansen LA, Fish JT (2007). "Inappropriate continuation of stress ulcer prophylactic therapy after discharge.". Ann Pharmacother 41 (10): 1611-6. DOI:10.1345/aph.1K227. PMID 17848420. Research Blogging.
  15. ↑ Anonymous. (2009) Early Communication about an Ongoing Safety Review of clopidogrel bisulfate (marketed as Plavix)
  16. ↑ Anonymous (11/17/2009) Information for Healthcare Professionals: Update to the labeling of Clopidogrel Bisulfate (marketed as Plavix) to alert healthcare professionals about a drug interaction with omeprazole (marketed as Prilosec and Prilosec OTC)
  17. ↑ 17.0 17.1 Stockl, Karen M.; Lisa Le, Armen Zakharyan, Ann S. M. Harada, Brian K. Solow, Joseph E. Addiego, Scott Ramsey (2010-04-26). "Risk of Rehospitalization for Patients Using Clopidogrel With a Proton Pump Inhibitor". Arch Intern Med 170 (8): 704-710. DOI:10.1001/archinternmed.2010.34. Retrieved on 2010-04-27. Research Blogging.
  18. ↑ 18.0 18.1 Ray WA, Murray KT, Griffin MR, Chung CP, Smalley WE, Hall K et al. (2010). "Outcomes with concurrent use of clopidogrel and proton-pump inhibitors: a cohort study.". Ann Intern Med 152 (6): 337-45. DOI:10.1059/0003-4819-152-6-201003160-00003. PMID 20231564. Research Blogging.
  19. ↑ 19.0 19.1 19.2 Juurlink DN, Gomes T, Ko DT, Szmitko PE, Austin PC, Tu JV et al. (2009). "A population-based study of the drug interaction between proton pump inhibitors and clopidogrel.". CMAJ 180 (7): 713-8. DOI:10.1503/cmaj.082001. PMID 19176635. PMC PMC2659819. Research Blogging. Review in: Ann Intern Med. 2009 Aug 18;151(4):JC2-13 Review in: Evid Based Med. 2009 Oct;14(5):154
  20. ↑ 20.0 20.1 20.2 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.
  21. ↑ 21.0 21.1 21.2 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.
  22. ↑ 22.0 22.1 Stanek EJ et al. (2009) A National Study of the Effect of Individual Proton Pump Inhibitors on Cardiovascular Outcomes in Patients Treated with Clopidogrel Following Coronary Stenting: The Clopidogrel Medco Outcomes Study Society for Cardiovascular Angiography and Interventions 2009 Annual Meeting
  23. ↑ Ho PM, Fihn SD, Wang L, Bryson CL, Lowy E, Maynard C et al. (2007). "Clopidogrel and long-term outcomes after stent implantation for acute coronary syndrome.". Am Heart J 154 (5): 846-51. DOI:10.1016/j.ahj.2007.08.028. PMID 17967588. Research Blogging.
  24. ↑ Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT et al. (2009). "Cytochrome p-450 polymorphisms and response to clopidogrel.". N Engl J Med 360 (4): 354-62. DOI:10.1056/NEJMoa0809171. PMID 19106084. Research Blogging.
  25. ↑ Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S et al. (2007). "Prasugrel versus clopidogrel in patients with acute coronary syndromes.". N Engl J Med 357 (20): 2001-15. DOI:10.1056/NEJMoa0706482. PMID 17982182. Research Blogging.
Retrieved from "https://citizendium.org/wiki/index.php?title=Proton_pump_inhibitor&oldid=618643"