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Drug Interactions between astemizole and Ilosone

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

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Interactions between your drugs

Major

erythromycin astemizole

Applies to: Ilosone (erythromycin) and astemizole

CONTRAINDICATED: Coadministration with the ketolide, telithromycin, as well as certain macrolide antibiotics may significantly increase the plasma concentrations of astemizole and terfenadine. The mechanism is inhibition of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of astemizole and terfenadine. High plasma levels of these agents have been associated with prolongation of the QT interval on the ECG; ventricular arrhythmias including ventricular tachycardia, ventricular fibrillation, and torsade de pointes; cardiac arrest; and sudden death. Macrolides that may significantly inhibit CYP450 3A4 include clarithromycin, erythromycin, and troleandomycin. Azithromycin and dirithromycin are generally believed to have little, if any, effect on CYP450 3A4. In a study of 9 healthy volunteers, erythromycin (500 mg every 8 hours for 7 days) increased the mean steady-state peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of the pharmacologically active metabolite of terfenadine (60 mg twice a day) by 107% and 170%, respectively, compared to administration of terfenadine alone. Three of the subjects also had accumulation of unmetabolized terfenadine. Electrocardiographic data revealed changes in the QT interval in a subset of subjects who demonstrated drug accumulation.

MANAGEMENT: Given the potential for serious and life-threatening adverse cardiac events associated with increased plasma levels of astemizole and terfenadine, the use of these agents with clarithromycin, erythromycin, troleandomycin, or telithromycin is considered contraindicated. Loratadine, cetirizine, or fexofenadine may be safer alternatives during therapy with telithromycin or macrolides. Depending on organism susceptibility, azithromycin and dirithromycin may be appropriate alternatives during therapy with astemizole or terfenadine.

References

  1. Honig PK, Woosley RL, Zamani K, Conner DP, Cantilena LR Jr "Changes in the pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine with concomitant administration of erythromycin." Clin Pharmacol Ther 52 (1992): 231-8
  2. Cortese LM, Bjornson DC "Potential interaction between terfenadine and macrolide antibiotics." Clin Pharm 11 (1992): 675
  3. Kemp JP "Decreased antihistamine metabolism." Ann Allergy 69 (1992): 533
  4. "Product Information. Hismanal (astemizole)." Janssen Pharmaceuticals PROD (2002):
  5. Biglin KE, Faraon MS, Constance TD, Lieh-Lai M "Drug-induced torsades de pointes: a possible interaction of terfenadine and erythromycin." Ann Pharmacother 28 (1994): 282
  6. Paris DG, Parente TF, Bruschetta HR, Guzman E, Niarchos AP "Torsades-de-pointes induced by erythromycin and terfenadine." Am J Emerg Med 12 (1994): 636-8
  7. Amsden GW "Macrolides versus azalides: a drug interaction update." Ann Pharmacother 29 (1995): 906-17
  8. Brannan MD, Reidenberg P, Radwanski E, et al. "Loratadine administered concomitantly with erythromycin: pharmacokinetic and electrocardiographic evaluations." Clin Pharmacol Ther 58 (1995): 269-78
  9. Harris S, Hilligoss DM, Colangelo PM, Eller M, Okerholm R "Azithromycin and terfenadine: lack of drug interaction." Clin Pharmacol Ther 58 (1995): 310-5
  10. Hsieh MH, Chen SA, Chiang CE, et al. "Drug-induced torsades de pointes in one patient with congenital long QT syndrome." Int J Cardiol 54 (1996): 85-8
  11. Nahata M "Drug interactions with azithromycin and the macrolides: an overview." J Antimicrob Chemother 37 ( Suppl (1996): 133-42
  12. Ament PW, Paterson A "Drug interactions with the nonsedating antihistamines." Am Fam Physician 56 (1997): 223
  13. Jurima-Romet M, Crawford K, Cyr T, Inaba T "Terfenadine metabolism in human liver. In vitro inhibition by macrolide antibiotics and azole antifungals." Drug Metab Dispos 22 (1994): 849-57
  14. European Agency for the Evaluation of Medicinal Products. Committee for Proprietary Medicinal Products "European Public Assessment Report Ketek (telithromycin) (Rev. 2) http:www.emea.eu.int/humandocs/Humans/EPAR/Ketek/Ketek.htm" (2004):
View all 14 references

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Drug and food interactions

Major

astemizole food

Applies to: astemizole

GENERALLY AVOID: Some beverages such as tonic water contain varying amounts of quinine. Coadministration of a single 430 mg dose of quinine has been shown to increase plasma concentrations of astemizole and its metabolite, desmethylastemizole. Elevated levels of these agents may cause a prolongation of the electrocardiographic QT interval and potentially fatal ventricular arrhythmias. Although pharmacokinetic data have indicated that the amounts of quinine in beverages (up to 80 mg quinine in 32 oz of tonic water) are not sufficient to produce a significant effect, the potential for an interaction exists if large amounts of tonic water are ingested. Also, grapefruit juice has been shown to inhibit CYP450 enzymes, which may lead to increased serum astemizole concentrations. The risk of life-threatening ventricular arrhythmias may be increased.

MANAGEMENT: Patients should be counseled to limit consumption of quinine-containing beverages and avoid grapefruit juice while they are taking astemizole.

References

  1. "Product Information. Hismanal (astemizole)." Janssen Pharmaceuticals PROD (2002):

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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.

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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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