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Drug Interactions between Entocort EC and Ilosone

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

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Interactions between your drugs

Moderate

erythromycin budesonide

Applies to: Ilosone (erythromycin) and Entocort EC (budesonide)

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the systemic bioavailability of budesonide, which undergoes extensive first-pass and systemic metabolism via intestinal and hepatic CYP450 3A4. In pharmacokinetic studies, 6- to 8-fold increases in budesonide systemic exposure (AUC) have been observed during coadministration of the potent CYP450 3A4 inhibitor ketoconazole with different oral formulations of budesonide. When ketoconazole was administered 12 hours after budesonide in one study, the AUC increase was approximately half that reported during simultaneous administration. In a prospective study of a cystic fibrosis center patient population, 11 of 25 patients receiving high-dose itraconazole (400 to 600 mg/day) and budesonide oral inhalation therapy (800 to 1600 mcg/day) were found to have adrenal insufficiency, including one who developed Cushing's syndrome, compared to none in a group of 12 patients treated with itraconazole alone. There was also no adrenal insufficiency in a group of 30 cystic fibrosis patients retrospectively included as controls, 24 of whom had been treated with high-dose inhaled budesonide for several years. Adrenal function improved, but did not normalize, in 10 of the 11 patients during a follow-up of two to ten months after discontinuation of itraconazole and institution of hydrocortisone replacement therapy. Limited pharmacokinetic data indicate that itraconazole (200 mg once daily) may increase the plasma levels of budesonide by about 4-fold following inhalation of a single 1000 mcg dose, which may be mainly due to increased bioavailability of the swallowed portion of the dose.

MANAGEMENT: The possibility of increased systemic adverse effects of budesonide should be considered during coadministration with CYP450 3A4 inhibitors. If concomitant use cannot be avoided, the dosing times between budesonide and the CYP450 3A4 inhibitor should be separated by as much as possible. In addition, the lowest effective dosage of budesonide should be prescribed, and further adjustments made as necessary according to therapeutic response and tolerance. 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.

References

  1. Jonsson G, Astrom A, Andersson P "Budesonide is metabolized by cytochrome P450 3A (CYP3A) enzymes in human liver." Drug Metab Dispos 23 (1995): 137-42
  2. "Product Information. Entocort (budesonide)." AstraZeneca Pharma Inc (2001):
  3. 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
  4. 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
  5. 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
  6. De Wachter E, Vanbesien J, De Schutter I, Malfroot A, De Schepper J "Rapidly developing Cushing syndrome in a 4-year-old patient during combined treatment with itraconazole and inhaled budesonide." Eur J Pediatr (2003):
  7. 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
  8. Edsbacker S, Andersson T "Pharmacokinetics of budesonide (Entocort EC) capsules for Crohn's disease." Clin Pharmacokinet 43 (2004): 803-21
  9. De Wachter E, Malfroot A, De Schutter I, Vanbesien J, De Schepper J "Inhaled budesonide induced Cushing's syndrome in cystic fibrosis patients, due to drug inhibition of cytochrome P450." J Calif Dent Assoc 2 (2003): 72-5
  10. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  11. Cerner Multum, Inc. "Australian Product Information." O 0
  12. Molimard M, Girodet PO, Pollet C, et al. "Inhaled corticosteroids and adrenal insufficiency: prevalence and clinical presentation." Drug Saf 31 (2008): 769-74
  13. Daveluy A, Raignoux C, Miremont-Salame G, et al. "Drug interactions between inhaled corticosteroids and enzymatic inhibitors." Eur J Clin Pharmacol (2009):
  14. Kedem E, Shahar E, Hassoun G, Pollack S "Iatrogenic Cushing's syndrome due to coadministration of ritonavir and inhaled budesonide in an asthmatic human immunodeficiency virus infected patient." J Asthma 47 (2010): 830-1
  15. "Product Information. Victrelis (boceprevir)." Schering-Plough Corporation (2011):
  16. "Product Information. Incivek (telaprevir)." Vertex Pharmaceuticals (2011):
View all 16 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

budesonide food

Applies to: Entocort EC (budesonide)

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations and systemic effects of orally administered budesonide. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. According to the manufacturer, the systemic exposure of oral budesonide approximately doubles after extensive intake of grapefruit juice.

MANAGEMENT: Patients receiving budesonide should avoid the regular consumption of grapefruits and grapefruit juice to prevent undue increases in plasma budesonide levels and systemic effects.

References

  1. "Product Information. Entocort (budesonide)." AstraZeneca Pharma Inc (2001):

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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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