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Drug Interactions between clarithromycin and clopidogrel

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

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Interactions between your drugs

Moderate

clarithromycin clopidogrel

Applies to: clarithromycin and clopidogrel

MONITOR: The concomitant administration of some macrolide antibiotics may reduce the metabolic activation of the prodrug clopidogrel and its antiplatelet effects. The proposed mechanism is inhibition of CYP450 3A4 enzymatic activity, which is responsible for the conversion of clopidogrel to its active metabolite. After coadministration of erythromycin stearate 250 mg four times a day and clopidogrel 75 mg/day to healthy subjects (n=9), the percent platelet aggregation was 42% with clopidogrel alone, 55% with clopidogrel plus erythromycin, and 93% at baseline. After coadministration of single doses of troleandomycin 500 mg and clopidogrel 450 mg, the percent platelet aggregation was 45% with clopidogrel alone, 78% with clopidogrel plus troleandomycin, and 93% at baseline. Clarithromycin also inhibits CYP450 3A4 activity and is also expected to affect clopidogrel metabolism.

MANAGEMENT: Until more information is available, monitoring for altered efficacy of clopidogrel may be advisable if a macrolide is coadministered with clopidogrel. Azithromycin and dirithromycin do not inhibit CYP450 3A4 and are theoretically not expected to interact with clopidogrel.

References (2)
  1. Lau WC, Waskell LA, Watkins PB, et al. (2003) "Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation: a new drug-drug interaction." Circulation, 107, p. 32-7
  2. Clarke TA, Waskell LA (2003) "The metabolism of clopidogrel is catalyzed by human cytochrome P450 3A and is inhibited by atorvastatin." Drug Metab Dispos, 31, p. 53-9

Drug and food interactions

Minor

clarithromycin food

Applies to: clarithromycin

Grapefruit juice may delay the gastrointestinal absorption of clarithromycin but does not appear to affect the overall extent of absorption or inhibit the metabolism of clarithromycin. The mechanism of interaction is unknown but may be related to competition for intestinal CYP450 3A4 and/or absorptive sites. In an open-label, randomized, crossover study consisting of 12 healthy subjects, coadministration with grapefruit juice increased the time to reach peak plasma concentration (Tmax) of both clarithromycin and 14-hydroxyclarithromycin (the active metabolite) by 80% and 104%, respectively, compared to water. Other pharmacokinetic parameters were not significantly altered. This interaction is unlikely to be of clinical significance.

References (1)
  1. Cheng KL, Nafziger AN, Peloquin CA, Amsden GW (1998) "Effect of grapefruit juice on clarithromycin pharmacokinetics." Antimicrob Agents Chemother, 42, p. 927-9

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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