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Drug Interactions between amoxicillin / clarithromycin / omeprazole and Eliquis

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

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Interactions between your drugs

Moderate

clarithromycin apixaban

Applies to: amoxicillin / clarithromycin / omeprazole and Eliquis (apixaban)

MONITOR: Coadministration with clarithromycin, a combined P-glycoprotein (P-gp) and strong CYP450 3A4 inhibitor, may increase the plasma concentrations of apixaban, which is a substrate of the efflux transporter as well as the isoenzyme. According to the manufacturer, clarithromycin (500 mg twice a day) led to 1.6- and 1.3-fold increases in apixaban AUC and Cmax, respectively. The clinical significance of these changes has not been established. In a retrospective cohort study that used data from the Taiwan National Health Insurance database and included 91,330 patients with nonvalvular atrial fibrillation who received at least 1 non-vitamin K oral anticoagulant (NOAC) prescription for apixaban, dabigatran, or rivaroxaban, the adjusted incidence rate for major bleeding was approximately 40% lower for concurrent use of clarithromycin or erythromycin compared to NOAC use alone.

MANAGEMENT: No dosage adjustment for apixaban is recommended during coadministration with clarithromycin. However, caution is advised and pharmacologic effects of apixaban should be monitored more closely whenever clarithromycin is added to or withdrawn from therapy. Patients should be routinely evaluated for signs and symptoms suggesting blood loss such as a decrease in hemoglobin and/or hematocrit, hypotension, or fetal distress (in pregnant women).

References

  1. (2001) "Product Information. Biaxin (clarithromycin)." Abbott Pharmaceutical
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  3. Cerner Multum, Inc. "Australian Product Information."
  4. (2012) "Product Information. Eliquis (apixaban)." Bristol-Myers Squibb Canada Inc
  5. Cerner Multum, Inc. (2015) "Canadian Product Information."
  6. Chang SH, Chou IJ, Yeh YH, et al. (2017) "Association between use of non–vitamin K oral anticoagulants with and without concurrent medications and risk of major bleeding in nonvalvular atrial fibrillation." JAMA, 318, p. 1250-9
View all 6 references

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Minor

amoxicillin clarithromycin

Applies to: amoxicillin / clarithromycin / omeprazole and amoxicillin / clarithromycin / omeprazole

Although some in vitro data indicate synergism between macrolide antibiotics and penicillins, other in vitro data indicate antagonism. When these drugs are given together, neither has predictable therapeutic efficacy. Data are available for erythromycin, although theoretically this interaction could occur with any macrolide. Except for monitoring of the effectiveness of antibiotic therapy, no special precautions appear to be necessary.

References

  1. Strom J (1961) "Penicillin and erythromycin singly and in combination in scarlatina therapy and the interference between them." Antibiot Chemother, 11, p. 694-7
  2. Cohn JR, Jungkind DL, Baker JS (1980) "In vitro antagonism by erythromycin of the bactericidal action of antimicrobial agents against common respiratory pathogens." Antimicrob Agents Chemother, 18, p. 872-6
  3. Penn RL, Ward TT, Steigbigel RT (1982) "Effects of erythromycin in combination with penicillin, ampicillin, or gentamicin on the growth of listeria monocytogenes." Antimicrob Agents Chemother, 22, p. 289-94

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Minor

clarithromycin omeprazole

Applies to: amoxicillin / clarithromycin / omeprazole and amoxicillin / clarithromycin / omeprazole

Clarithromycin may increase and prolong the omeprazole plasma concentration. The mechanism may be related to clarithromycin inhibition of hepatic cytochrome P450 enzymes responsible for omeprazole metabolism. Coadministration of omeprazole may result in an increase in clarithromycin and 14-(R)-hydroxyclarithromycin plasma concentrations. These increases may be due to the effect of omeprazole on gastric pH.

References

  1. Zhou Q, Yamamoto I, Fukuda T, Ohno M, Sumida A, Azuma J (1999) "CYP2C19 genotypes and omeprazole metabolism after single and repeated dosing when combined with clarithromycin." Eur J Clin Pharmacol, 55, p. 43-7
  2. Gustavson LE, Kaiser JF, Edmonds AL, Locke CS, DeBartolo ML, Schneck DW (1995) "Effect of omeprazole on concentrations of clarithromycin in plasma and gastric tissue at steady state." Antimicrob Agents Chemother, 39, p. 2078-83
  3. Furuta T, Ohashi K, Kobayashi K, Iida I, Yoshida H, Shirai N, Takashima M, Kosuge K, Hanai H, Chiba K, Ishizaki T, Kaneko E (1999) "Effects of clarithromycin on the metabolism of omeprazole in relation to CYP2C19 genotype status in humans." Clin Pharmacol Ther, 66, p. 265-74

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Drug and food interactions

Minor

clarithromycin food

Applies to: amoxicillin / clarithromycin / omeprazole

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

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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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