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Drug Interactions between Aerobid and MY-E

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

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Interactions between your drugs

Moderate

erythromycin flunisolide

Applies to: MY-E (erythromycin) and Aerobid (flunisolide)

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations and pharmacologic effects of corticosteroids, which are primarily metabolized by the isoenzyme. The interaction has been reported with potent inhibitors such as clarithromycin, erythromycin, itraconazole, nefazodone, cobicistat, and ritonavir during concomitant use of various corticosteroids, including inhaled, nasal, and ophthalmic formulations. Systemic corticosteroid adverse effects may occur following intensive or long-term continuous ophthalmic corticosteroid therapy. Cushing's syndrome and adrenal insufficiency have been attributed to the interaction.

MANAGEMENT: The possibility of increased corticosteroid effects should be considered during coadministration with potent and moderate CYP450 3A4 inhibitors. Some authorities advise against concomitant use unless the potential benefit outweighs the risk. If the combination is considered necessary, a lower dosage of the corticosteroid may be required. When indicated for intranasal or inhalational use, alternative corticosteroids such as beclomethasone, which is less dependent on CYP450 3A4 metabolism, should be considered, particularly if long term treatment is required. Patients should be monitored for signs and symptoms of hypercorticism such as acne, striae, thinning of the skin, easy bruising, moon facies, dorsocervical "buffalo" hump, truncal obesity, increased appetite, acute weight gain, edema, hypertension, hirsutism, hyperhidrosis, proximal muscle wasting and weakness, glucose intolerance, exacerbation of preexisting diabetes, depression, and menstrual disorders. Other systemic glucocorticoid effects may include adrenal suppression, immunosuppression, posterior subcapsular cataracts, glaucoma, bone loss, and growth retardation in children and adolescents. Following extensive use with a potent CYP450 3A4 inhibitor, a progressive dosage reduction may be required over a longer period if the corticosteroid is to be withdrawn from therapy, as there may be a significant risk of adrenal suppression. Signs and symptoms of adrenal insufficiency include anorexia, hypoglycemia, nausea, vomiting, weight loss, muscle wasting, fatigue, weakness, dizziness, postural hypotension, depression, and adrenal crisis manifested as inability to respond to stress (e.g., illness, infection, surgery, trauma).

References

  1. Zurcher RM, Frey BM, Frey FJ "Impact of ketoconazole on the metabolism of prednisolone." Clin Pharmacol Ther 45 (1989): 366-72
  2. Yamashita SK, Ludwig EA, Middleton E Jr, Jusko WJ "Lack of pharmacokinetic and pharmacodynamic interactions between ketoconazole and prednisolone." Clin Pharmacol Ther 49 (1991): 558-70
  3. Ulrich B, Frey FJ, Speck RF, Frey BM "Pharmacokinetics/pharmacodynamics of ketoconazole-prednisolone interaction." J Pharmacol Exp Ther 260 (1992): 487-90
  4. Kandrotas RJ, Slaughter RL, Brass C, Jusko WJ "Ketoconazole effects on methylprednisolone disposition and their joint suppression of endogenous cortisol." Clin Pharmacol Ther 42 (1987): 465-70
  5. Glynn AM, Slaughter RL, Brass C, et al. "Effects of ketoconazole on methylprednisolone pharmacokinetics and cortisol secretion." Clin Pharmacol Ther 39 (1986): 654-9
  6. Itkin IH, Menzel ML "The use of macrolide antibiotic substances in the treatment of asthma." J Allergy Clin Immunol 45 (1970): 146-62
  7. LaForce CF, Szefler SJ, Miller MF, Ebling W, Brenner M "Inhibition of methylprednisolone elimination in the presence of erythromycin therapy." J Allergy Clin Immunol 72 (1983): 34-9
  8. Finkenbine RD, Frye MD "Case of psychosis due to prednisone-clarithromycin interaction." Gen Hosp Psychiat 20 (1998): 325-6
  9. Varis T, Kaukonen KM, Kivisto KT, Neuvonen PJ "Plasma concentrations and effects of oral methylprednisolone are considerably increased by itraconazole." Clin Pharmacol Ther 64 (1998): 363-8
  10. Hillebrand-Haverkort ME, Prummel MF, ten Veen JH "Ritonavir-induced Cushing's syndrome in a patient treated with nasal fluticasone." AIDS 13 (1999): 1803
  11. Varis T, Kivisto KT, Neuvonen PJ "The effect of itraconazole on the pharmacokinetics and pharmacodynamics of oral prednisolone." Eur J Clin Pharmacol 56 (2000): 57-60
  12. Varis T, Backman JT, Kivisto KT, Neuvonen PJ "Diltiazem and mibefradil increase the plasma concentrations and greatly enhance the adrenal-suppressant effect of oral methylprednisolone." Clin Pharmacol Ther 67 (2000): 215-21
  13. Garey KW, Rubinstein I, Gotfried MH, Khan IJ, Varma S, Danziger LH "Long-term clarithromycin decreases prednisone requirements in elderly patients with prednisone-dependent asthma." Chest 118 (2000): 1826-7
  14. Lebrun-Vignes B, Archer VC, Diquest B, et al. "Effect of itraconazole on the pharmacokinetics of prednisolone and methylprednisolone and cortisol secretion in healthy subjects." Br J Clin Pharmacol 51 (2001): 443-50
  15. Couturier J, Steele M, Hussey L, Pawliuk G "Steroid-induced mania in an adolescent: risk factors and management." Can J Clin Pharmacol 8 (2001): 109-12
  16. Gupta SK, Dube MP "Exogenous Cushing syndrome mimicking human immunodeficiency virus lipodystrophy." Clin Infect Dis 35 (2002): E69-71
  17. Raaska K, Niemi M, Neuvonen M, Neuvonen PJ, Kivisto KT "Plasma concentrations of inhaled budesonide and its effects on plasma cortisol are increased by the cytochrome P4503A4 inhibitor itraconazole." Clin Pharmacol Ther 72 (2002): 362-369
  18. Main KM, Skov M, Sillesen IB, et al. "Cushing's syndrome due to pharmacological interaction in a cystic fibrosis patient." Acta Paediatr 91 (2002): 1008-11
  19. Skov M, Main KM, Sillesen IB, Muller J, Koch C, Lanng S "Iatrogenic adrenal insufficiency as a side-effect of combined treatment of itraconazole and budesonide." Eur Respir J 20 (2002): 127-33
  20. Kotlyar M, Brewer ER, Golding M, Carson SW "Nefazodone inhibits methylprednisolone disposition and enhances its adrenal-suppressant effect." J Clin Psychopharmacol 23 (2003): 652-6
  21. Bolland MJ, Bagg W, Thomas MG, Lucas JA, Ticehurst R, Black PN "Cushing's syndrome due to interaction between inhaled corticosteroids and itraconazole." Ann Pharmacother 38 (2004): 46-9
  22. Edsbacker S, Andersson T "Pharmacokinetics of budesonide (Entocort EC) capsules for Crohn's disease." Clin Pharmacokinet 43 (2004): 803-21
  23. Samaras K, Pett S, Gowers A, McMurchie M, Cooper DA "Iatrogenic Cushing's syndrome with osteoporosis and secondary adrenal failure in HIV-infected patients receiving inhaled corticosteroids and ritonavir-boosted protease inhibitors: six cases." J Clin Endocrinol Metab 90 (2005): 4394-8
  24. Soldatos G, Sztal-Mazer S, Woolley I, Stockigt J "Exogenous glucocorticoid excess as a result of ritonavir-fluticasone interaction." Intern Med J 35 (2005): 67-8
  25. Penzak SR, Formentini E, Alfaro RM, Long M, Natarajan V, Kovacs J "Prednisolone pharmacokinetics in the presence and absence of ritonavir after oral prednisone administration to healthy volunteers." J Acquir Immune Defic Syndr 40 (2005): 573-80
  26. EMEA. European Medicines Agency "EPARs. European Union Public Assessment Reports. http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/medicines/medicines_landingpage.jsp&mid" (2007):
  27. Bhumbra NA, Sahloff EG, Oehrtman SJ, Horner JM "Exogenous Cushing syndrome with inhaled fluticasone in a child receiving lopinavir/ritonavir." Ann Pharmacother 41 (2007): 1306-9
  28. Busse KH, Formentini E, Alfaro RM, Kovacs JA, Penzak SR "Influence of antiretroviral drugs on the pharmacokinetics of prednisolone in HIV-infected individuals." J Acquir Immune Defic Syndr 48 (2008): 561-6
  29. Agencia Española de Medicamentos y Productos Sanitarios Healthcare "Centro de información online de medicamentos de la AEMPS - CIMA. https://cima.aemps.es/cima/publico/home.html" (2008):
View all 29 references

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Drug and food interactions

Moderate

erythromycin food

Applies to: MY-E (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: MY-E (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

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