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Drug Interactions between Ilosone and Mycobutin

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

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Interactions between your drugs

Moderate

erythromycin rifabutin

Applies to: Ilosone (erythromycin) and Mycobutin (rifabutin)

GENERALLY AVOID: The coadministration of clarithromycin and rifabutin at normally recommended dosages has been reported to have resulted in significantly altered pharmacokinetics for both drugs. In a study of 34 clinically stable subjects with advanced HIV infection (CD4 less than 200 cells/mm3), the addition of rifabutin in patients stabilized on clarithromycin therapy slowly decreased the clarithromycin area under the plasma concentration-time curve (AUC) and C(max) up to an average of 44% and 41%, respectively, at the end of 4 weeks of combination therapy. In patients stabilized on rifabutin therapy, the addition of clarithromycin significantly increased rifabutin AUC and C(max) after the first dose. After 4 weeks, average increases of 99% and 69%, respectively, were reported. This bidirectional interaction is consistent with rifabutin's cumulative inducing effect over time on the CYP450 enzymatic pathway as well as clarithromycin's immediate inhibiting effect on the pathway. In the study, the combination was tolerated by more than 90% of the patients. However, 66% of them experienced gastrointestinal problems including nausea, vomiting and diarrhea. An increased incidence of uveitis has also been reported with this combination. In addition, the combination of clarithromycin and rifampin 600 mg/day (with multiple other drugs) decreased clarithromycin serum levels by approximately 90%. Other macrolide antibiotics may interact in a similar manner with rifamycins.

MANAGEMENT: Some experts recommend that this combination be avoided since it may result in decreased efficacy of the macrolide and increased rifamycin toxicity (e.g, neutropenia, uveitis).

References

  1. Wallace RJ, Brown BA, Griffith DE, Girard W, Tanaka K "Reduced serum levels of clarithromycin in patients treated with multidrug regimens including rifampin or rifabutin for Mycobacterium avium -M.intracellulare infection." J Infect Dis 171 (1995): 747-50
  2. Hafner R, Bethel J, Power M, et al. "Tolerance and pharmacokinetic interactions of rifabutin and clarithromycin in human immunodeficiency virus-infected volunteers." Antimicrob Agents Chemother 42 (1998): 631-9
  3. von Rosenstiel NA, Adam D "Macrolide antibacterials. Drug interactions of clinical significance." Drug Saf 13 (1995): 105-22
  4. Benson CA, Williams PL, Cohn DL, Becker S, Hojczyk P, Nevin T, Korvick JA, Heifets L, Child CC, Lederman MM, Reichman RC, "Clarithromycin or rifabutin alone or in combination for primary prophylaxis of Mycobacterium avium complex disease in patients with AIDS: A randomized, double-blind, placebo-controlled trial." J Infec Dis 181 (2000): 1289-97
  5. Benson CA, Williams PL, Currier JS, et al. "A Prospective, Randomized Trial Examining the Efficacy and Safety of Clarithromycin in Combination with Ethambutol, Rifabutin, or Both for the Treatment of Disseminated Mycobacterium avium Complex Disease in Persons with Acquired Immunodeficiency Syndrome" Clin Infect Dis 37 (2003): 1234-43
  6. Jordan MK, Polis MA, Kelly G, Narang PK, Masur H, Piscitelli SC "Effects of fluconazole and clarithromycin on rifabutin and 25-O-desacetylrifabutin pharmacokinetics." Antimicrob Agents Chemother 44 (2000): 2170-72
  7. Apseloff G, Foulds G, LaBoy-Goral L, Willavize S, Vincent J "Comparison of azithromycin and clarithromycin in their interactions with rifabutin in healthy volunteers." J Clin Pharmacol 38 (1998): 830-5
  8. Griffith DE, Brown BA, Girard WM, Wallace RJ Jr "Adverse events associated with high-dose rifabutin in macrolide-containing regimens for the treatment of Mycobacterium avium complex lung disease." Clin Infect Dis 21 (1995): 594-8
View all 8 references

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Drug and food interactions

Moderate

erythromycin food

Applies to: Ilosone (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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Minor

erythromycin food

Applies to: Ilosone (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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