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Drug Interactions between clopidogrel and voriconazole

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

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Interactions between your drugs

Moderate

clopidogrel voriconazole

Applies to: clopidogrel and voriconazole

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. (2002) "Product Information. Cordarone (amiodarone)." Wyeth-Ayerst Laboratories
  2. (2001) "Product Information. Plavix (clopidogrel)." Bristol-Myers Squibb
  3. Ohyama K, Nakajima M, Suzuki M, Shimada N, Yamazaki H, Yokoi T (2000) "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, p. 244-53
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. (2009) "Product Information. Kapidex (dexlansoprazole)." Takeda Pharmaceuticals America
  12. 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
  13. 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
  14. 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
  15. 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
  16. Lau WC, Gurbel PA (2009) "The drug-drug interaction between proton pump inhibitors and clopidogrel." CMAJ, 180, p. 699-700
  17. 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
  18. 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
  19. 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
View all 19 references

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Drug and food interactions

Moderate

voriconazole food

Applies to: voriconazole

ADJUST DOSING INTERVAL: Food reduces the oral absorption and bioavailability of voriconazole. According to the product labeling, administration of multiple doses of voriconazole with high-fat meals decreased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by 34% and 24%, respectively, when the drug is administered as a tablet, and by 58% and 37%, respectively, when administered as the oral suspension.

MANAGEMENT: To ensure maximal oral absorption, voriconazole tablets and oral suspension should be taken at least one hour before or after a meal.

References

  1. (2002) "Product Information. VFEND (voriconazole)." Pfizer U.S. Pharmaceuticals
  2. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT (2009) "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm, 66, p. 1438-67

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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.

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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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