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Drug Interactions between Erythrocin Lactobionate and pseudoephedrine / terfenadine

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

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Interactions between your drugs

Major

erythromycin terfenadine

Applies to: Erythrocin Lactobionate (erythromycin) and pseudoephedrine / terfenadine

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

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Drug and food interactions

Major

terfenadine food

Applies to: pseudoephedrine / terfenadine

CONTRAINDICATED: The consumption of grapefruit juice has been associated with significantly increased plasma concentrations of terfenadine. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. Terfenadine in high serum levels has been associated with prolongation of the QT interval and development of torsade de pointes, a potentially fatal ventricular arrhythmia.

MANAGEMENT: Due to the risk of cardiotoxicity, patients receiving the drug should be advised to avoid consumption of grapefruit products. Loratadine, cetirizine, and fexofenadine may be safer alternatives in patients who may have trouble adhering to the dietary restriction.

References

  1. Honig PK, Woosley RL, Zamani K, Conner DP, Cantilena LR Jr (1992) "Changes in the pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine with concomitant administration of erythromycin." Clin Pharmacol Ther, 52, p. 231-8
  2. Zimmermann M, Duruz H, Guinand O, et al. (1992) "Torsades de Pointes after treatment with terfenadine and ketoconazole." Eur Heart J, 13, p. 1002-3
  3. Mathews DR, McNutt B, Okerholm R, et al. (1991) "Torsades de pointes occurring in association with terfenadine use." JAMA, 266, p. 2375-6
  4. Monahan BP, Ferguson CL, Killeavy ES, et al. (1990) "Torsades de pointes occurring in association with terfenadine use." JAMA, 264, p. 2788-90
  5. Honig PK, Wortham DC, Zamani K, et al. (1993) "Terfenadine-ketoconazole interaction: pharmacokinetic and electrocardiographic consequences." JAMA, 269, p. 1513-8
  6. Pohjola-Sintonen S, Viitasalo M, Toivonene L, Neuvonen P (1993) "Torsades de pointes after terfenadine-itraconazole interaction." BMJ, 306, p. 186
  7. Cortese LM, Bjornson DC (1992) "Potential interaction between terfenadine and macrolide antibiotics." Clin Pharm, 11, p. 675
  8. Paris DG, Parente TF, Bruschetta HR, Guzman E, Niarchos AP (1994) "Torsades-de-pointes induced by erythromycin and terfenadine." Am J Emerg Med, 12, p. 636-8
  9. Zechnich AD, Haxby DG (1996) "Drug interactions associated with terfenadine and related nonsedating antihistamines." West J Med, 164, p. 68-9
  10. Honig PK, Wortham DC, Lazarev A, Cantilena LR (1996) "Grapefruit juice alters the systemic bioavailability and cardiac repolarization of terfenadine in poor metabolizers of terfenadine." J Clin Pharmacol, 36, p. 345-51
  11. Woosley RL (1996) "Cardiac actions of antihistamines." Annu Rev Pharmacol Toxicol, 36, p. 233-52
  12. Benton RE, Honig PK, Zamani K, Cantilena LR, Woosley RL (1996) "Grapefruit juice alters terfenadine pharmacokinetics resulting in prolongation of repolarization on the electrocardiogram." Clin Pharmacol Ther, 59, p. 383-8
  13. Hsieh MH, Chen SA, Chiang CE, et al. (1996) "Drug-induced torsades de pointes in one patient with congenital long QT syndrome." Int J Cardiol, 54, p. 85-8
  14. Clifford CP, Adams DA, Murray S, Taylor GW, Wilkins MR, Boobis AR, Davies DS (1996) "Pharmacokinetic and cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice." Br J Clin Pharmacol, 42, p662
  15. Rau SE, Bend JR, Arnold JMO, Tran LT, Spence JD, Bailey DG (1997) "Grapefruit juice terfenadine single-dose interaction: Magnitude, mechanism, and relevance." Clin Pharmacol Ther, 61, p. 401-9
  16. Bailey DG, Malcolm J, Arnold O, Spence JD (1998) "Grapefruit juice-drug interactions." Br J Clin Pharmacol, 46, p. 101-10
  17. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
View all 17 references

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Moderate

erythromycin food

Applies to: Erythrocin Lactobionate (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 (1978) "Bioavailability of erythromycin stearate: influence of food and fluid volume." J Pharm Sci, 67, p. 764-6
  2. Welling PG, Elliott RL, Pitterle ME, et al. (1979) "Plasma levels following single and repeated doses of erythromycin estolate and erythromycin stearate." J Pharm Sci, 68, p. 150-5
  3. Welling PG (1977) "Influence of food and diet on gastrointestinal drug absorption: a review." J Pharmacokinet Biopharm, 5, p. 291-334
  4. Coyne TC, Shum S, Chun AH, Jeansonne L, Shirkey HC (1978) "Bioavailability of erythromycin ethylsuccinate in pediatric patients." J Clin Pharmacol, 18, p. 194-202
  5. Malmborg AS (1979) "Effect of food on absorption of erythromycin. A study of two derivatives, the stearate and the base." J Antimicrob Chemother, 5, p. 591-9
  6. Randinitis EJ, Sedman AJ, Welling PG, Kinkel AW (1989) "Effect of a high-fat meal on the bioavailability of a polymer-coated erythromycin particle tablet formulation." J Clin Pharmacol, 29, p. 79-84
  7. Kanazawa S, Ohkubo T, Sugawara K (2001) "The effects of grapefruit juice on the pharmacokinetics of erythromycin." Eur J Clin Pharmacol, 56, p. 799-803
View all 7 references

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Moderate

pseudoephedrine food

Applies to: pseudoephedrine / terfenadine

MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.

MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.

References

  1. Rosenblatt JE, Lake CR, van Kammen DP, Ziegler MG, Bunney WE Jr (1979) "Interactions of amphetamine, pimozide, and lithium on plasma norepineophrine and dopamine-beta-hydroxylase in schizophrenic patients." Psychiatry Res, 1, p. 45-52
  2. Cavanaugh JH, Griffith JD, Oates JA (1970) "Effect of amphetamine on the pressor response to tyramine: formation of p-hydroxynorephedrine from amphetamine in man." Clin Pharmacol Ther, 11, p. 656
  3. (2001) "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc
  4. (2001) "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals
  5. (2001) "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals
  6. (2001) "Product Information. Focalin (dexmethylphenidate)." Mikart Inc
  7. (2002) "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company
View all 7 references

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Minor

erythromycin food

Applies to: Erythrocin Lactobionate (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 (1990) "Influence of alcohol consumption on erythromycin ethylsuccinate kinetics." Int J Clin Pharmacol, 28, p. 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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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