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Drug Interactions between erythromycin and eszopiclone

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

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Interactions between your drugs

Moderate

erythromycin eszopiclone

Applies to: erythromycin and eszopiclone

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of both zopiclone and its pharmacologically active S(-) enantiomer, eszopiclone. Zopiclone has been shown in vitro to be metabolized by CYP450 3A4 and CYP450 2C8, while eszopiclone is primarily metabolized by CYP450 3A4 and 2E1 via demethylation and oxidation. In 18 healthy subjects, administration of a single 3 mg dose of eszopiclone with the potent CYP450 3A4 inhibitor ketoconazole (400 mg daily for 5 days) increased eszopiclone half-life, peak plasma concentration (Cmax) and systemic exposure (AUC) by 1.3-, 1.4- and 2.2-fold, respectively. In 10 healthy young subjects, itraconazole 200 mg daily given for 4 days increased the Cmax and AUC of a single 7.5 mg dose of zopiclone by 29% and 73%, respectively, and prolonged its half-life by 40%. A case report describes an 86-year-old woman who experienced morning drowsiness during coadministration of zopiclone and nefazodone, a known potent CYP450 3A4 inhibitor. Zopiclone plasma concentrations were measured both during and after withdrawal of nefazodone therapy. Following discontinuation of nefazodone due to lack of therapeutic effect, the plasma concentration of S(-) zopiclone decreased from 107 to 16.9 ng/mL, and that of R(+) zopiclone decreased from 20.6 to 1.45 ng/mL. Limited data are available regarding use with moderate CYP450 3A4 inhibitors. When 10 healthy young volunteers were given a single 7.5 mg dose of zopiclone on the 6th day of treatment with 500 mg erythromycin base three times daily, mean half-life, Cmax and AUC of zopiclone increased by approximately 42%, 38% and 77%, respectively, compared to administration with placebo. Plasma zopiclone concentration increased nearly 4-fold at 0.5 hour postdose and 2-fold at 1 hour postdose, and time to reach peak plasma concentration (Tmax) decreased from 2 hours to 1 hour, suggesting accelerated absorption due to increased gastric emptying induced by erythromycin.

MANAGEMENT: Caution is advised when zopiclone or eszopiclone is coadministered with moderate CYP450 3A4 inhibitors. A dosage reduction may be required if an interaction is suspected. Patients should be advised to avoid driving or operating hazardous machinery until they know how these medications affect them, preferably at least 12 hours after administration of the hypnotic.

References

  1. Dresser GK, Spence JD, Bailey DG "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet 38 (2000): 41-57
  2. Becquemont L, Mouajjah S, Escaffre O, Beaune P, Funck-Bretano C, Jaillon P "Cytochrome P-450 3A4 and 2C8 are involved in zopiclone metabolism." Drug Metab Dispos 27 (1999): 1068-73
  3. Alderman CP, Gebauer MG, Gilbert AL, Condon JT "Possible interaction of zopiclone and nefazodone." Ann Pharmacother 35 (2001): 1378-80
  4. "Product Information. Lunesta (eszopiclone)." Sepracor Inc (2004):
  5. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  6. Aranko K, Luurila H, Backman JT, Neuvonen PJ, Olkkola KT "The effect of erythromycin on the pharmacokinetics and pharmacodymanics of zopiclone." Br J Clin Pharmacol 38 (1994): 363-7
  7. "Product Information. Imovane (zopiclone)." Rhone-Poulenc Rorer Canada Inc (2014):
View all 7 references

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Drug and food interactions

Moderate

erythromycin food

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

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Moderate

eszopiclone food

Applies to: eszopiclone

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of zopiclone and eszopiclone. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

ADJUST DOSING INTERVAL: Administration of eszopiclone (the S-enantiomer of zopiclone) with or immediately after a high-fat/heavy meal may delay the onset of hypnotic effects. In healthy adults, administration of a 3 mg dose of eszopiclone after a high-fat meal decreased the mean peak plasma drug concentration (Cmax) by 21% and delayed the time to reach peak plasma drug concentration (Tmax) by approximately 1 hour. Theoretically, this interaction should also affect racemic zopiclone.

MANAGEMENT: Patients receiving zopiclone or eszopiclone should be advised to avoid consumption of alcohol. For faster sleep onset, eszopiclone and zopiclone should not be administered with or immediately after a high-fat/heavy meal.

References

  1. "Product Information. Lunesta (eszopiclone)." Sepracor Inc (2004):
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0

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Minor

erythromycin food

Applies to: 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 "Influence of alcohol consumption on erythromycin ethylsuccinate kinetics." Int J Clin Pharmacol 28 (1990): 426-9

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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

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

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