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Drug Interactions between Ilosone and TheoCap

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

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Interactions between your drugs

Moderate

erythromycin theophylline

Applies to: Ilosone (erythromycin) and TheoCap (theophylline)

MONITOR: Coadministration with certain macrolide antibiotics may increase the serum concentrations of methylxanthines such as theophylline, which may result in toxicity. In one case report, a pediatric patient developed seizures in association with theophylline toxicity shortly after the addition of erythromycin. The proposed mechanism is macrolide inhibition of CYP450 3A4, the isoenzyme partially responsible for the metabolic clearance of theophylline. Data from pharmacokinetic studies suggest that the magnitude of the interaction is generally greatest with troleandomycin, followed by erythromycin. The interaction with clarithromycin appears to be mild and inconsistent. Azithromycin and dirithromycin are generally believed to have little, if any, effect on CYP450 3A4, and most studies have not found a significant effect on the pharmacokinetics of theophylline. However, a case report describes an unusual interaction with azithromycin in an elderly patient whereby reduced serum theophylline levels were repeatedly observed after the discontinuation of azithromycin. The changes were transient and did not require an adjustment in the theophylline dosage. Theophylline has been reported to decrease plasma concentrations of erythromycin by increasing its renal clearance.

MANAGEMENT: Pharmacologic response and serum theophylline levels should be monitored more closely whenever a macrolide antibiotic is added to or withdrawn from therapy, and the methylxanthine dosage adjusted as necessary. For patients with theophylline levels at the upper end of the therapeutic range (15 to 20 mcg/mL), some clinicians suggest an initial reduction of the methylxanthine dosage by 25% when given with erythromycin and 50% with troleandomycin. Patients should be advised to contact their physician if they experience signs and symptoms of theophylline toxicity such as nausea, vomiting, diarrhea, headache, restlessness, insomnia, or irregular heartbeat.

References

  1. Branigan TA, Robbins RA, Cady WJ, et al. "The effects of erythromycin on the absorption and disposition kinetics of theophylline." Eur J Clin Pharmacol 21 (1981): 115-20
  2. Zarowitz BJ, Szefler SJ, Lasezkay GM "Effect of erythromycin base on theophylline kinetics." Clin Pharmacol Ther 29 (1981): 601-5
  3. Prince RA, Wing DS, Weinberger MM, et al. "Effect of erythromycin on theophylline kinetics." J Allergy Clin Immunol 68 (1981): 427-31
  4. May DC, Jarboe CH, Ellenburg DT, et al. "The effects of erythromycin on theophylline elimination in normal males." J Clin Pharmacol 22 (1982): 125-30
  5. Iliopoulou A, Aldhous ME, Johnston A, Turner P "Pharmacokinetic interaction between theophylline and erythromycin." Br J Clin Pharmacol 14 (1982): 495-9
  6. Paulsen O, Hoglund P, Nilsson LG, Bengtsson HI "The interaction of erythromycin with theophylline." Eur J Clin Pharmacol 32 (1987): 493-8
  7. Hildebrandt R, Moller H, Gundert-Remy U "Influence of theophylline on the renal clearance of erythromycin." Int J Clin Pharmacol Ther Toxicol 25 (1987): 601-4
  8. Renton KW, Gray JD, Hung OR "Depression of theophylline elimination by erythromycin." Clin Pharmacol Ther 30 (1981): 422-6
  9. Richer C, Mathieu M, Bah H, Thuillez C, Duroux P, Giudicelli JF "Theophylline kinetics and ventilatory flow in bronchial asthma and chronic airflow obstruction: influence of erythromycin." Clin Pharmacol Ther 31 (1982): 579-86
  10. Upton RA "Pharmacokinetic interactions between theophylline and other medication (Part I)." Clin Pharmacokinet 20 (1991): 66-80
  11. Peters DH, Friedel HA, McTavish D "Azithromycin: a review of its antimicrobial activity, pharmacokinetic properties and clinical efficacy." Drugs 44 (1992): 750-99
  12. Maddux MS, Leeds NH, Organek HW, Hasegawa GR, Bauman JL "The effect of erythromycin on theophylline pharmacokinetics at steady state." Chest 81 (1982): 563-5
  13. Descotes J, Andre P, Evreux JC "Pharmacokinetic drug interactions with macrolide antibiotics." J Antimicrob Chemother 15 (1985): 659-64
  14. Ludden TM "Pharmacokinetic interactions of the macrolide antibiotics." Clin Pharmacokinet 10 (1985): 63-79
  15. Reisz G, Pingleton SK, Melethil S, Ryan PB "The effect of erythromycin on theophylline pharmacokinetics in chronic bronchitis." Am Rev Respir Dis 127 (1983): 581-4
  16. Jonkman JH, Upton RA "Pharmacokinetic drug interactions with theophylline." Clin Pharmacokinet 9 (1984): 309-34
  17. Pfeifer HJ, Greenblatt DJ, Friedman P "Effects of three antibiotics on theophylline kinetics." Clin Pharmacol Ther 26 (1979): 36-40
  18. Wiggins J, Arbab O, Ayres JG, Skinner C "Elevated serum theophylline concentration following cessation of erythromycin treatment." Eur J Respir Dis 68 (1986): 298-300
  19. Rockwood RP, Embardo LS "Theophylline, ciprofloxacin, erythromycin: a potentially harmful regimen." Ann Pharmacother 27 (1993): 651-2
  20. Kozak PP, Cummins LH, Gillman SH "Administration of erythromycin to patients on theophylline." J Allergy Clin Immunol 60 (1977): 149-51
  21. Parish RA, Haulman NJ, Burns RM "Interaction of theophylline with erythromycin base in a patient with seizure activity." Pediatrics 72 (1983): 828-30
  22. Tenenbein M "Theophylline toxicity due to drug interaction." J Emerg Med 7 (1989): 249-51
  23. Bachmann K, Nunlee M, Martin M, et al. "Changes in the steady-state pharmacokinetics of theophylline during treatment with dirithromycin." J Clin Pharmacol 30 (1990): 1001-5
  24. Bachmann K, Jauregui L, Sides G, Sullivan TJ "Steady-state pharmacokinetics of theophylline in COPD patients treated with dirithromycin." J Clin Pharmacol 33 (1993): 861-5
  25. Amsden GW "Macrolides versus azalides: a drug interaction update." Ann Pharmacother 29 (1995): 906-17
  26. Amsden GW "Erythromycin, clarithromycin, and azithromycin: are the differences real?" Clin Ther 18 (1996): 56-72
  27. Gillum JG, Israel DS, Scott RB, Climo MW, Polk RE "Effect of combination therapy with ciprofloxacin and clarithromycin on theophylline pharmacokinetics in healthy volunteers." Antimicrob Agents Chemother 40 (1996): 1715-6
  28. Pollak PT, Slayter KL "Reduced serum theophylline concentrations after discontinuation of azithromycin: evidence for an unusual interaction." Pharmacotherapy 17 (1997): 827-9
  29. Nahata M "Drug interactions with azithromycin and the macrolides: an overview." J Antimicrob Chemother 37 Suppl C (1996): 133-42
  30. von Rosenstiel NA, Adam D "Macrolide antibacterials. Drug interactions of clinical significance." Drug Saf 13 (1995): 105-22
  31. Principi N, Esposito S "Comparative tolerability of erythromycin and newer macrolide antibacterials in paediatric: Patients." Drug Safety 20 (1999): 25-41
  32. Kamada AK, Hill MR, Brenner AM, Szefler SJ "Effect of low-dose troleandomycin on theophylline clearance: implications for therapeutic drug monitoring." Pharmacotherapy 12 (1992): 98-102
View all 32 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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Moderate

theophylline food

Applies to: TheoCap (theophylline)

GENERALLY AVOID: Coadministration with caffeine may increase the serum concentrations of theophylline. The proposed mechanism involves competitive inhibition of theophylline metabolism via CYP450 1A2, as well as metabolic conversion of caffeine to theophylline in vivo and saturation of theophylline metabolism at higher serum concentrations. In six healthy male volunteers (all smokers), serum concentrations of theophylline (administered as aminophylline 400 mg single oral dose) were significantly higher following consumption of caffeine (2 to 7 cups of instant coffee over 24 hours, equivalent to approximately 120 to 630 mg of caffeine) than after caffeine deprivation for 48 hours. Caffeine consumption also increased the apparent elimination half-life of theophylline by an average of 32% and reduced its total body clearance by 23%. In another study, steady-state concentration and area under the concentration-time curve of theophylline (1200 mg intravenously over 24 hours) increased by 23% and 40%, respectively, in eight healthy volunteers following administration of caffeine (300 mg orally three times a day).

MANAGEMENT: Given the narrow therapeutic index of theophylline, patients should limit or avoid significant fluctuations in their intake of pharmacologic as well as dietary caffeine.

ADJUST DOSING INTERVAL: Administration of theophylline with continuous enteral nutrition may reduce the serum levels or the rate of absorption of theophylline. The mechanism has not been reported. In one case, theophylline levels decreased by 53% in a patient receiving continuous nasogastric tube feedings and occurred with both theophylline tablet and liquid formulations, but not with intravenous aminophylline.

MANAGEMENT: When administered to patients receiving continuous enteral nutrition , some experts recommend that the tube feeding should be interrupted for at least 1 hour before and 1 hour after the dose of theophylline is given; rapid-release formulations are preferable, and theophylline levels should be monitored.

References

  1. Jonkman JH, Sollie FA, Sauter R, Steinijans VW "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther 49 (1991): 248-55
  2. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol 44 (1993): 295-8
  3. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm 66 (2009): 1438-67

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Moderate

theophylline food

Applies to: TheoCap (theophylline)

GENERALLY AVOID: Coadministration with caffeine may increase the serum concentrations of theophylline. The proposed mechanism involves competitive inhibition of theophylline metabolism via CYP450 1A2, as well as metabolic conversion of caffeine to theophylline in vivo and saturation of theophylline metabolism at higher serum concentrations. In six healthy male volunteers (all smokers), serum concentrations of theophylline (administered as aminophylline 400 mg single oral dose) were significantly higher following consumption of caffeine (2 to 7 cups of instant coffee over 24 hours, equivalent to approximately 120 to 630 mg of caffeine) than after caffeine deprivation for 48 hours. Caffeine consumption also increased the apparent elimination half-life of theophylline by an average of 32% and reduced its total body clearance by 23%. In another study, steady-state concentration and area under the concentration-time curve of theophylline (1200 mg intravenously over 24 hours) increased by 23% and 40%, respectively, in eight healthy volunteers following administration of caffeine (300 mg orally three times a day).

MANAGEMENT: Given the narrow therapeutic index of theophylline, patients should limit or avoid significant fluctuations in their intake of pharmacologic as well as dietary caffeine.

References

  1. Jonkman JH, Sollie FA, Sauter R, Steinijans VW "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther 49 (1991): 248-55
  2. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol 44 (1993): 295-8

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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.

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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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