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Drug Interactions between cimetidine and Plavix

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

cimetidine clopidogrel

Applies to: cimetidine and Plavix (clopidogrel)

MONITOR: Coadministration with inhibitors of CYP450 2C19 may reduce the efficacy of clopidogrel, whose antiplatelet effect is dependent in part on bioactivation by the isoenzyme to a pharmacologically active metabolite. This is consistent with studies that reported decreased effectiveness of clopidogrel and poorer clinical outcome in patients who have common genetic polymorphisms of CYP450 2C19 resulting in reduced or absent enzyme activity. The interaction has been studied with omeprazole, a potent CYP450 2C19 inhibitor. In 72 healthy subjects administered clopidogrel (300 mg loading dose followed by 75 mg/day) alone and with omeprazole (80 mg) simultaneously for 5 days, systemic exposure to the active metabolite of clopidogrel decreased by 46% (Day 1) and 42% (Day 5) during coadministration with omeprazole, while mean inhibition of platelet aggregation (IPA) diminished by 47% (24 hours) and 30% (Day 5). Similar results were reported when the same doses of clopidogrel and omeprazole were administered 12 hours apart in another study. Data are not available for less potent inhibitors of CYP450 2C19. However, ineffective inhibition of platelet aggregation has been reported in association with a potential interaction with amiodarone, whose active metabolite, desethylamiodarone, has been shown to inhibit CYP450 2C19 in vitro.

MANAGEMENT: Based on existing data, it may be advisable to closely monitor the therapeutic efficacy of clopidogrel during concomitant treatment with CYP450 2C19 inhibitors.

References

  1. "Product Information. Cordarone (amiodarone)." Wyeth-Ayerst Laboratories PROD (2002):
  2. "Product Information. Plavix (clopidogrel)." Bristol-Myers Squibb PROD (2001):
  3. Ohyama K, Nakajima M, Suzuki M, Shimada N, Yamazaki H, Yokoi T "Inhibitory effects of amiodarone and its N-deethylated metabolite on human cytochrome P450 activities: Prediction of in vivo drug interactions." Br J Clin Pharmacol 49 (2000): 244-53
  4. Hulot JS, Bura A, Villard E, et al. "Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects." Blood (2006):
  5. Gilard M, Arnaud B, Le Gal G, Abgrall JF, Boschat J "Influence of omeprazol on the antiplatelet action of clopidogrel associated to aspirin." J Thromb Haemost 4 (2006): 2508-9
  6. Small DS, Farid NA, Payne CD, et al. "Effects of the proton pump inhibitor lansoprazole on the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel." J Clin Pharmacol 48 (2008): 475-84
  7. Frere C, Cuisset T, Morange PE, et al. "Effect of Cytochrome P450 Polymorphisms on Platelet Reactivity After Treatment With Clopidogrel in Acute Coronary Syndrome." Am J Cardiol 101 (2008): 1088-1093
  8. Gilard M, Arnaud B, Cornily JC, et al. "Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin: the randomized, double-blind OCLA (Omeprazole CLopidogrel Aspirin) study." J Am Coll Cardiol 51 (2008): 256-60
  9. Pezalla E, Day D, Pulliadath I "Initial assessment of clinical impact of a drug interaction between clopidogrel and proton pump inhibitors." J Am Coll Cardiol 52 (2008): 1038-9
  10. Siller-Matula JM, Spiel AO, Lang IM, Kreiner G, Christ G, Jilma B "Effects of pantoprazole and esomeprazole on platelet inhibition by clopidogrel." Am Heart J 157 (2009): 148.e1-5
  11. "Product Information. Kapidex (dexlansoprazole)." Takeda Pharmaceuticals America (2009):
  12. Juurlink DN, Gomes T, Ko DT, et al. "A population-based study of the drug interaction between proton pump inhibitors and clopidogrel." CMAJ 180 (2009): 713-8
  13. Li XQ, Andersson TB, Ahlstrom M, Weidolf L "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 (2004): 821-7
  14. Collet JP, Hulot JS, Pena A, et al. "Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study." Lancet 373 (2009): 309-17
  15. Mega JL, Close SL, Wiviott SD, et al. "Cytochrome p-450 polymorphisms and response to clopidogrel." N Engl J Med 360 (2009): 354-62
  16. Lau WC, Gurbel PA "The drug-drug interaction between proton pump inhibitors and clopidogrel." CMAJ 180 (2009): 699-700
  17. Moayyedi P, Sadowski DC "Proton pump inhibitors and clopidogrel -- hazardous drug interaction or hazardous interpretation of data?" Can J Gastroenterol 23 (2009): 251-2
  18. Simon T, Verstuyft C, Mary-Krause M, et al. "Genetic determinants of response to clopidogrel and cardiovascular events." N Engl J Med 360 (2009): 363-75
  19. Varenhorst C, Janes S, Erlinge D, et al. "Genetic variation of CYP2C19 affects both pharmacokinetic and pharmacodynamic responses to clopidogrel but not prasugrel in aspirin-treated patients with coronary artery disease." Eur Heart J 30 (2009): 1744-52
View all 19 references

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Drug and food interactions

Minor

cimetidine food

Applies to: cimetidine

Concurrent use of cimetidine and ethanol may result in increased ethanol concentrations. The mechanism appears to be due to inhibition of gastric alcohol dehydrogenase by cimetidine, leading to increased bioavailability of the alcohol and inhibition of hepatic metabolism of alcohol. The clinical significance of this interaction is limited. More importantly, patients requiring cimetidine for gastrointestinal disease should be counseled to avoid alcohol to prevent worsening of their disease. The other H-2 receptor antagonists appear to have minimal effects on the concentrations of alcohol.

References

  1. Feely J, Wood AJ "Effects of cimetidine on the elimination and actions of ethanol." JAMA 247 (1982): 2819-21
  2. Hansten PD "Effects of H2-receptor antagonists on blood alcohol levels." JAMA 267 (1992): 2469

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Minor

cimetidine food

Applies to: cimetidine

Caffeine effects may be increased in patients also taking cimetidine. The mechanism may be due to decreased caffeine metabolism induced by cimetidine. Although adequate clinical data are lacking, a reduction in dose or elimination of caffeine may be needed if excess CNS stimulation is observed.

References

  1. "Product Information. Tagamet (cimetidine)." SmithKline Beecham PROD (2001):
  2. Broughton LJ, Rodgers HJ "Decreased systenuc clearance of caffeine due to cimetidine." Br J Clin Pharmacol 12 (1981): 155-9

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Minor

cimetidine food

Applies to: cimetidine

H2 antagonists may reduce the clearance of nicotine. Cimetidine, 600 mg given twice a day for two days, reduced clearance of an intravenous nicotine dose by 30%. Ranitidine, 300 mg given twice a day for two days, reduced clearance by 10%. The clinical significance of this interaction is not known. Patients should be monitored for increased nicotine effects when using the patches or gum for smoking cessation and dosage adjustments should be made as appropriate.

References

  1. Bendayan R, Sullivan JT, Shaw C, Frecker RC, Sellers EM "Effect of cimetidine and ranitidine on the hepatic and renal elimination of nicotine in humans." Eur J Clin Pharmacol 38 (1990): 165-9

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

See also

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

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