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Drug Interaction Report

2 potential interactions and/or warnings found for the following 2 drugs:

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Interactions between your drugs

Major

FLUoxetine clopidogrel

Applies to: Prozac (fluoxetine), Plavix (clopidogrel)

GENERALLY AVOID: Coadministration with potent 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.

MANAGEMENT: Based on existing data, patients treated with clopidogrel should preferably avoid the concomitant use of potent CYP450 2C19 inhibitors such as fluconazole, fluoxetine, fluvoxamine, and ticlopidine. Concomitant use of selective serotonin reuptake inhibitors or ticlopidine with clopidogrel may also potentiate the risk of bleeding complications due to additive or synergistic effects on the clotting cascade.

References

  1. Hulot JS, Bura A, Villard E, et al. (2006) "Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects." Blood
  2. Gilard M, Arnaud B, Le Gal G, Abgrall JF, Boschat J (2006) "Influence of omeprazol on the antiplatelet action of clopidogrel associated to aspirin." J Thromb Haemost, 4, p. 2508-9
  3. Small DS, Farid NA, Payne CD, et al. (2008) "Effects of the proton pump inhibitor lansoprazole on the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel." J Clin Pharmacol, 48, p. 475-84
  4. Frere C, Cuisset T, Morange PE, et al. (2008) "Effect of Cytochrome P450 Polymorphisms on Platelet Reactivity After Treatment With Clopidogrel in Acute Coronary Syndrome." Am J Cardiol, 101, p. 1088-1093
  5. Gilard M, Arnaud B, Cornily JC, et al. (2008) "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, p. 256-60
  6. Pezalla E, Day D, Pulliadath I (2008) "Initial assessment of clinical impact of a drug interaction between clopidogrel and proton pump inhibitors." J Am Coll Cardiol, 52, p. 1038-9
  7. Siller-Matula JM, Spiel AO, Lang IM, Kreiner G, Christ G, Jilma B (2009) "Effects of pantoprazole and esomeprazole on platelet inhibition by clopidogrel." Am Heart J, 157, 148.e1-5
  8. Juurlink DN, Gomes T, Ko DT, et al. (2009) "A population-based study of the drug interaction between proton pump inhibitors and clopidogrel." CMAJ, 180, p. 713-8
  9. Li XQ, Andersson TB, Ahlstrom 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, p. 821-7
  10. Collet JP, Hulot JS, Pena A, et al. (2009) "Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study." Lancet, 373, p. 309-17
  11. Mega JL, Close SL, Wiviott SD, et al. (2009) "Cytochrome p-450 polymorphisms and response to clopidogrel." N Engl J Med, 360, p. 354-62
  12. Lau WC, Gurbel PA (2009) "The drug-drug interaction between proton pump inhibitors and clopidogrel." CMAJ, 180, p. 699-700
  13. Moayyedi P, Sadowski DC (2009) "Proton pump inhibitors and clopidogrel -- hazardous drug interaction or hazardous interpretation of data?" Can J Gastroenterol, 23, p. 251-2
  14. Simon T, Verstuyft C, Mary-Krause M, et al. (2009) "Genetic determinants of response to clopidogrel and cardiovascular events." N Engl J Med, 360, p. 363-75
  15. Varenhorst C, Janes S, Erlinge D, et al. (2009) "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, p. 1744-52
  16. Hirsh-Rokach B, Spectre G, Shai E, et al. (2015) "Differential impact of selective serotonin reuptake inhibitors on platelet response to clopidogrel: a randomized, double-blind, crossover trial." Pharmacotherapy, 35, p. 140-147
View all 16 references

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Drug and food interactions

Moderate

FLUoxetine food

Applies to: Prozac (fluoxetine)

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References

  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
View all 4 references

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Therapeutic duplication warnings

No duplication 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.

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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.

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Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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