Drug–Drug Interaction Between Clopidogrel and the Proton Pump Inhibitors

@article{Norgard2009DrugDrugIB,
  title={Drug–Drug Interaction Between Clopidogrel and the Proton Pump Inhibitors},
  author={Nicholas B. Norgard and Kathryn D. Mathews and Geoffrey C Wall},
  journal={Annals of Pharmacotherapy},
  year={2009},
  volume={43},
  pages={1266 - 1274}
}
Objective: To evaluate the interaction between clopidogrel and proton pump inhibitors (PPIs). Data Sources: Literature retrieval was accessed through PubMed (1980–January 2009), abstracts from 2008 American Heart Association and 2009 Society of Cardiovascular Angiography and Interventions Scientific Sessions, and media press releases using the terms clopidogrel, proton pump inhibitors, cytochrome 2C19, genetic cytochrome P450 polymorphisms, and drug interaction. In addition, reference citations… 

Figures from this paper

The potential interaction between clopidogrel and proton pump inhibitors: a systematic review

The observed association between clopidogrel and PPIs is found uniquely in studies judged to be of low quality and with an increased risk of bias, resulting in an inverse correlation between study quality and a reported statistically positive interaction.

Role of CYP450 in Antiplatelet Therapy: Considerations for Patients at Risk for Further Cardiovascular or Cerebrovascular Problems

This review spotlights the pharmacokinetic and pharmacodynamic influences that CYP450 isoenzymes exert on antiplatelet therapies and attempts to categorize the role of platelet reactivity testing in determining the clinical significance of drug interactions.

Antiplatelet agents and proton pump inhibitors – personalizing treatment

Patients on antiplatelet agents after a transient isChemic attack or ischemic stroke can safely use aspirin, and extended release dipyridamole/aspirin with proton pump inhibitors, and patients on clopidogrel may use other acid-reducing drugs besides proton pumping inhibitors.

Adverse drug reactions due to drug–drug interactions with proton pump inhibitors: assessment of systematic reviews with AMSTAR method

The safety of PPI use with respect to DDIs is critically evaluated with a meta-review of systematic reviews published between 1978 and 2015, assessing the evidence by their reliability, repeatability, transparency, and objectivity.

Proton pump inhibitors and clopidogrel: an association to avoid?

Dual antiplatelet therapy with aspirin and clopidogrel should be provisionally advocated only for patients at high risk of bleeding and avoiding PPIs with strong affinity for cytochrome CYP2C19, such as omeprazole and esomeprazole.

Comparison of prophylactic effect of UGIB and effects on platelet function between PPIs and H2RAs combined with DAPT: systematic review and meta-analysis

Limited evidence indicates that PPIs were better than H2RAs for prophylaxis of UGIB associated with DAPT and had no effect on platelet function.

Cytochrome P450-mediated cardiovascular drug interactions

  • A. Scheen
  • Biology, Medicine
    Expert opinion on drug metabolism & toxicology
  • 2011
Clinicians are encouraged to develop their knowledge of CYP-mediated DDIs so that they can choose safe drug combination regimens, adjust drug dosages appropriately and conduct therapeutic drug monitoring for drugs with narrow therapeutic indices.

A comprehensive comparative review of adenosine diphosphate receptor antagonists

Prasugrel and ticagrelor should be preferred over clopidogrel in patients who are at a high risk of thrombotic events with low risk of bleeding, and these two agents may offer advantage over clopsin in those patients who might have risk for drug resistance due to CYP2C19 polymorphism.

Impact of proton pump inhibitors or famotidine on the antiplatelet actions during dual-antiplatelet therapy in Japanese patients

The concomitant use of famotidine, rabeprazoles, lansoprazole, and omeprazole did not affect the antiplatelet action of clopidogrel in Japanese patients.

Pharmacokinetic drug interaction profile of omeprazole with adverse consequences and clinical risk management

Clinical professionals should enhance clinical risk management on adverse DDIs associated with omeprazole by rationally prescribing alternatives, checking the appropriateness of physician orders before dispensing, and performing therapeutic drug monitoring.
...

References

SHOWING 1-10 OF 99 REFERENCES

A population-based study of the drug interaction between proton pump inhibitors and clopidogrel

Among patients receiving clopidogrel following acute myocardial infarction, concomitant therapy with proton pump inhibitors other than pantoprazole was associated with a loss of the beneficial effects of clopIDogrel and an increased risk of reinfarction.

Pantoprazole: a new proton pump inhibitor.

Proton pump inhibitors and their drug interactions: an evidence-based approach.

The proton pump inhibitors are the most effective antisecretory agents used to treat acid-related disorders and are frequently prescribed for patients who are concurrently using other medications, but caution is indicated when certain drugs are co-prescribed with these agents.

Review article: relationship between the metabolism and efficacy of proton pump inhibitors – focus on rabeprazole

  • J. Horn
  • Medicine, Biology
    Alimentary pharmacology & therapeutics
  • 2004
The favourable pharmacokinetic/pharmacodynamic profile for rabeprazole has been shown to result in high eradication rates for H. pylori in both normal and poor metabolizers, and may be better suited than omeprazoles as on‐demand therapy for symptomatic gastro‐oesophageal reflux disease.

Pharmacokinetic Drug Interaction Profiles of Proton Pump Inhibitors

The potential for drug interactions should be taken into account when choosing a therapy for gastric acid-related disorders, especially for elderly patients in whom polypharmacy is common, or in those receiving a concomitant medication with a narrow therapeutic index.

Cytochrome p-450 polymorphisms and response to clopidogrel.

Carriers of a reduced-function CYP2C19 allele had significantly lower levels of the active metabolite of clopidogrel, diminished platelet inhibition, and a higher rate of major adverse cardiovascular events, including stent thrombosis, than did noncarriers.

Clopidogrel: review of bioanalytical methods, pharmacokinetics/pharmacodynamics, and update on recent trends in drug-drug interaction studies.

This review focuses distinctly on an in-depth coverage on the bioanalytical methods for the quantification of clopidogrel and its inactive carboxylic acid metabolite as well as the active metabolite in pre-clinical and clinical samples.

Effects of the Proton Pump Inhibitor Lansoprazole on the Pharmacokinetics and Pharmacodynamics of Prasugrel and Clopidogrel

The overall data suggest that a prasugrel dose adjustment is not likely warranted in an individual taking pr asugrel with a proton pump inhibitor such as lansoprazole.
...