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Drug Interactions between E.E.S. Granules and Rapamune

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

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Interactions between your drugs

Major

erythromycin sirolimus

Applies to: E.E.S. Granules (erythromycin) and Rapamune (sirolimus)

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 and/or P-glycoprotein (P-gp) may significantly increase the plasma concentrations of sirolimus following oral administration. Sirolimus is a substrate of both CYP450 3A4 isoenzyme and P-gp efflux transporter, thus their inhibition in the intestine can enhance the absorption of sirolimus. In 23 healthy volunteers, administration of a single 5 mg dose of sirolimus with the potent dual CYP450 3A4/P-gp inhibitor ketoconazole (200 mg/day orally for 10 days) increased mean sirolimus peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 4- and 11-fold, respectively. Likewise, posaconazole (400 mg oral suspension twice a day for 16 days) increased mean Cmax and AUC of a single 2 mg dose of sirolimus by nearly 7- and 9-fold, respectively, while voriconazole (400 mg orally every 12 hours for 1 day, then 200 mg every 12 hours for 8 days) increased the same values by 7- and 11-fold, respectively. Another dual inhibitor, boceprevir (800 mg three times a day for 11 days), increased the Cmax and AUC of a single 2 mg dose of sirolimus by 10- and 17-fold, respectively. When sirolimus 2 mg once a day was coadministered with the moderate dual inhibitor erythromycin (ethylsuccinate salt 800 mg every 8 hours) in 24 study subjects, sirolimus Cmax and AUC increased by more than 4-fold each, while erythromycin Cmax and AUC also increased by more than 1.5-fold each.

MANAGEMENT: Concomitant use of sirolimus with potent CYP450 3A4 and/or P-gp inhibitors should generally be avoided. The manufacturers of posaconazole and voriconazole consider coadministration with sirolimus to be contraindicated. Some authorities recommend avoiding concomitant use of sirolimus during and for 2 weeks after treatment with itraconazole.

References

  1. (2002) "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals
  2. (2001) "Product Information. Rapamune (sirolimus)." Wyeth-Ayerst Laboratories
  3. Claesson K, Brattstrom C, Burke JT (2001) "Sirolimus and erythromycin interaction: two cases." Transplant Proc, 33, p. 2136
  4. Floren LC, Christians U, Zimmerman JJ, et al. (1999) "Sirolimus oral bioavailability increases ten-fold with concomitant ketoconazole." Clin Pharmacol Ther, 65, p. 159
  5. (2002) "Product Information. VFEND (voriconazole)." Pfizer U.S. Pharmaceuticals
  6. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  7. (2006) "Product Information. Noxafil (posaconazole)." Schering-Plough Corporation
  8. Cerner Multum, Inc. "Australian Product Information."
  9. Dodds-Ashley E (2010) "Management of drug and food interactions with azole antifungal agents in transplant recipients." Pharmacotherapy, 30, p. 842-54
  10. (2011) "Product Information. Victrelis (boceprevir)." Schering-Plough Corporation
View all 10 references

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Drug and food interactions

Moderate

erythromycin food

Applies to: E.E.S. Granules (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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Moderate

sirolimus food

Applies to: Rapamune (sirolimus)

ADJUST DOSING INTERVAL: Consumption of food can decrease the rate and extent of gastrointestinal absorption of sirolimus. Also, the consumption of grapefruit juice may result in increased sirolimus trough concentrations.

MANAGEMENT: Experts recommend that this drug be taken either at least one hour prior to eating or consistently with or without food to avoid variations in sirolimus blood levels. The manufacturer recommends against using grapefruit juice for dilution of sirolimus doses. Patients should be monitored for clinical and laboratory evidence of altered immunosuppressant effects.

References

  1. (2001) "Product Information. Rapamune (sirolimus)." Wyeth-Ayerst Laboratories

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Minor

erythromycin food

Applies to: E.E.S. Granules (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

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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