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Drug Interactions between Erythrocin Lactobionate and Omeclamox-Pak

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

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Interactions between your drugs

Major

erythromycin clarithromycin

Applies to: Erythrocin Lactobionate (erythromycin) and Omeclamox-Pak (amoxicillin / clarithromycin / omeprazole)

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may increase the plasma concentrations of erythromycin, which is primarily metabolized by the isoenzyme. The use of erythromycin has been associated with dose-related prolongation of the QT interval, thus elevated plasma levels of the drug may potentiate the risk of ventricular arrhythmias such as ventricular tachycardia and torsade de pointes. In a population-based retrospective study of 1476 cases of confirmed sudden death from cardiac causes, concurrent use of erythromycin and a CYP450 3A4 inhibitor (mostly verapamil or diltiazem) was associated with a marked increase in the risk of sudden death from cardiac causes as compared to nonuse of CYP450 3A4 inhibitors, erythromycin, or amoxicillin; concurrent use of amoxicillin and CYP450 3A4 inhibitors; use of CYP450 3A4 inhibitors without erythromycin or amoxicillin; and concurrent use of erythromycin and calcium channel blockers that do not significantly inhibit CYP450 3A4 (e.g., nifedipine). In fact, the risk was five times as high as that for nonuse of CYP450 3A4 inhibitors, erythromycin, or amoxicillin. In addition, erythromycin may increase the plasma concentrations of drugs that are substrates of CYP450 3A4.

MANAGEMENT: Concomitant use of erythromycin with potent CYP450 3A4 inhibitors should generally be avoided.

References

  1. Iannini PB (2002) "Cardiotoxicity of macrolides, ketolides and fluoroquinolones that prolong the QTc interval." Expert Opin Drug Saf, 1, p. 121-8
  2. Ray WA, Murray KT, Meredith S, Narasimhulu SS, Hall K, Stein CM (2004) "Oral erythromycin and the risk of sudden death from cardiac causes." N Engl J Med, 351, p. 1089-96

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Minor

erythromycin amoxicillin

Applies to: Erythrocin Lactobionate (erythromycin) and Omeclamox-Pak (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

amoxicillin clarithromycin

Applies to: Omeclamox-Pak (amoxicillin / clarithromycin / omeprazole) and Omeclamox-Pak (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: Omeclamox-Pak (amoxicillin / clarithromycin / omeprazole) and Omeclamox-Pak (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

Moderate

erythromycin food

Applies to: Erythrocin Lactobionate (erythromycin)

ADJUST DOSING INTERVAL: Food may variably affect the bioavailability of different oral formulations and salt forms of erythromycin. The individual product package labeling should be consulted regarding the appropriate time of administration in relation to food ingestion. Grapefruit juice may increase the plasma concentrations of orally administered erythromycin. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In an open-label, crossover study consisting of six healthy subjects, the coadministration with double-strength grapefruit juice increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of a single dose of erythromycin (400 mg) by 52% and 49%, respectively, compared to water. The half-life was not affected. The clinical significance of this potential interaction is unknown.

MANAGEMENT: In general, optimal serum levels are achieved when erythromycin is taken in the fasting state, one-half to two hours before meals. However, some erythromycin products may be taken without regard to meals.

References

  1. Welling PG, Huang H, Hewitt PF, Lyons LL (1978) "Bioavailability of erythromycin stearate: influence of food and fluid volume." J Pharm Sci, 67, p. 764-6
  2. Welling PG, Elliott RL, Pitterle ME, et al. (1979) "Plasma levels following single and repeated doses of erythromycin estolate and erythromycin stearate." J Pharm Sci, 68, p. 150-5
  3. Welling PG (1977) "Influence of food and diet on gastrointestinal drug absorption: a review." J Pharmacokinet Biopharm, 5, p. 291-334
  4. Coyne TC, Shum S, Chun AH, Jeansonne L, Shirkey HC (1978) "Bioavailability of erythromycin ethylsuccinate in pediatric patients." J Clin Pharmacol, 18, p. 194-202
  5. Malmborg AS (1979) "Effect of food on absorption of erythromycin. A study of two derivatives, the stearate and the base." J Antimicrob Chemother, 5, p. 591-9
  6. Randinitis EJ, Sedman AJ, Welling PG, Kinkel AW (1989) "Effect of a high-fat meal on the bioavailability of a polymer-coated erythromycin particle tablet formulation." J Clin Pharmacol, 29, p. 79-84
  7. Kanazawa S, Ohkubo T, Sugawara K (2001) "The effects of grapefruit juice on the pharmacokinetics of erythromycin." Eur J Clin Pharmacol, 56, p. 799-803
View all 7 references

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Minor

clarithromycin food

Applies to: Omeclamox-Pak (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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Minor

erythromycin food

Applies to: Erythrocin Lactobionate (erythromycin)

Ethanol, when combined with erythromycin, may delay absorption and therefore the clinical effects of the antibiotic. The mechanism appears to be due to slowed gastric emptying by ethanol. Data is available only for erythromycin ethylsuccinate. Patients should be advised to avoid ethanol while taking erythromycin salts.

References

  1. Morasso MI, Chavez J, Gai MN, Arancibia A (1990) "Influence of alcohol consumption on erythromycin ethylsuccinate kinetics." Int J Clin Pharmacol, 28, p. 426-9

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Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Macrolide-type antibiotics

Therapeutic duplication

The recommended maximum number of medicines in the 'macrolide-type antibiotics' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'macrolide-type antibiotics' category:

  • Erythrocin Lactobionate (erythromycin)
  • Omeclamox-Pak (amoxicillin/clarithromycin/omeprazole)

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

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

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

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