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Drug Interactions between amoxicillin / clarithromycin / omeprazole and eplerenone

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

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Interactions between your drugs

Major

clarithromycin eplerenone

Applies to: amoxicillin / clarithromycin / omeprazole and eplerenone

CONTRAINDICATED: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations and risk of adverse reactions of eplerenone, which is primarily metabolized by the isoenzyme. In a pharmacokinetic study, administration of a single 100 mg dose of eplerenone in combination with the potent CYP450 3A4 inhibitor ketoconazole (200 mg twice a day) resulted in 1.7- and 5.4-fold increases in eplerenone peak plasma concentration (Cmax) and systemic exposure (AUC), respectively.

MANAGEMENT: Concomitant use of eplerenone with potent CYP450 3A4 inhibitors is considered contraindicated. Some authorities consider concomitant administration of eplerenone and itraconazole to be contraindicated during and for 2 weeks after treatment with itraconazole.

References (3)
  1. (2002) "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals
  2. (2002) "Product Information. Inspra (eplerenone)." Searle
  3. Cerner Multum, Inc. "Australian Product Information."
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 (3)
  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
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 (3)
  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

Drug and food interactions

Major

eplerenone food

Applies to: eplerenone

GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of eplerenone. The primary mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Inhibition of hepatic CYP450 3A4 may also contribute. In drug interaction studies, administration of a single 100 mg dose of eplerenone in combination with grapefruit juice resulted in a 25% increase in eplerenone systemic exposure (AUC). High blood levels of eplerenone can increase the risk of side effects including hyperkalemia. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.

MANAGEMENT: It may be advisable for patients to avoid the consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with eplerenone.

References (3)
  1. (2002) "Product Information. Inspra (eplerenone)." Searle
  2. (2021) "Product Information. Eplerenone (eplerenone)." MSN Laboratories Europe Ltd
  3. (2023) "Product Information. Eplerenone (Apotex) (eplerenone)." Apotex Pty Ltd
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)
  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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