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Drug Interactions between Erythrocin Lactobionate and Orap

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

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Interactions between your drugs

Major

erythromycin pimozide

Applies to: Erythrocin Lactobionate (erythromycin) and Orap (pimozide)

CONTRAINDICATED: Coadministration with the ketolide, telithromycin, as well as certain macrolide antibiotics may increase the plasma concentrations of pimozide. The mechanism is inhibition of pimozide metabolism via CYP450 3A4. High plasma levels of pimozide 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. In a study involving 12 healthy subjects, clarithromycin (500 mg orally every 12 hours for 5 days) increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of pimozide (6 mg single oral dose) by 39% and 113%, respectively, compared to placebo. These alterations corresponded with significant prolongations of the maximum QTc interval that exceeded those produced by pimozide alone. Isolated cases of sudden death have been reported following addition of clarithromycin to ongoing pimozide therapy.

MANAGEMENT: The use of pimozide with telithromycin or macrolide antibiotics is considered contraindicated by the manufacturers, although azithromycin and dirithromycin are generally believed to have little, if any, effect on CYP450 3A4.

References

  1. Amsden GW "Macrolides versus azalides: a drug interaction update." Ann Pharmacother 29 (1995): 906-17
  2. "Product Information. Orap (pimozide)." Gate Pharmaceuticals PROD
  3. Desta Z, Kerbusch T, Flockhart DA "Effect of clarithromycin on the pharmacokinetics and pharmacodynamics of pimozide in healthy poor and extensive metabolizers of cytochrome P450 2D6 (CYP2D6)." Clin Pharmacol Ther 65 (1999): 10-20
  4. Desta Z, Soukhova N, Flockhart DA "In Vitro Inhibition of Pimozide N-Dealkylation by Selective Serotonin Reuptake Inhibitors and Azithromycin." J Clin Psychopharmacol 22 (2002): 162-168
  5. Krahenbuhl S, Sauter B, Kupferschmidt H, Krause M, Wyss PA, Meier PJ "Case report: reversible QT prolongation with torsades de pointes in a patient with pimozide intoxication." Am J Med Sci 309 (1995): 315-6
  6. Flockhart DA, Drici MD, Kerbusch T, et al. "Studies on the mechanism of a fatal clarithromycin-pimozide interaction in a patient with tourette syndrome." J Clin Psychopharmacol 20 (2000): 317-24
  7. "Product Information. Ketek (telithromycin)." Aventis Pharmaceuticals (2004):
  8. 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 8 references

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Drug and food interactions

Major

pimozide food

Applies to: Orap (pimozide)

GENERALLY AVOID: Theoretically, the coadministration with grapefruit juice may increase the plasma concentrations of pimozide. The mechanism is decreased clearance of pimozide due to inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The use of pimozide alone has been associated with dose-dependent prolongation of the QT interval. Although clinical data are lacking, this interaction may result in potentiation of the proarrhythmic effect of pimozide and consequently an increased risk of ventricular arrhythmias such as ventricular tachycardia and torsade de pointes. In addition, alcohol may potentiate some of the pharmacologic effects of pimozide. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: The manufacturer recommends avoiding grapefruit juice (and probably grapefruits) during therapy with pimozide. Patients should also be advised to avoid or limit consumption of alcohol.

References

  1. "Product Information. Orap (pimozide)." Gate Pharmaceuticals PROD
  2. Dresser GK, Spence JD, Bailey DG "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet 38 (2000): 41-57

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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 "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: 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 "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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