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Drug Interactions between Ambien and Erythrocin Lactobionate

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

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Interactions between your drugs

Moderate

erythromycin zolpidem

Applies to: Erythrocin Lactobionate (erythromycin) and Ambien (zolpidem)

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of zolpidem, which is partially metabolized by the isoenzyme. When a single 5 mg dose of zolpidem was administered to 12 healthy study subjects following treatment with the potent CYP450 3A4 inhibitor ketoconazole (200 mg twice daily for 2 days), zolpidem peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 35% and 67%, respectively. Increased sedation and other pharmacodynamic effects were noted.

MANAGEMENT: Caution is advised when zolpidem is used with CYP450 3A4 inhibitors. Patients should be advised to avoid driving, operating machinery, or engaging in potentially hazardous activities requiring mental alertness and motor coordination until they know how the medications affect them, and to notify their physician if they experience excessive somnolence or dizziness.

References

  1. "Product Information. Ambien (zolpidem)." sanofi-aventis PROD (2001):
  2. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical PROD (2001):
  3. Luurila H, Kivisto KT, Neuvonen PJ "Effect of itraconazole on the pharmacokinetics and pharmacodynamics of zolpidem." Eur J Clin Pharmacol 54 (1998): 163-6
  4. Greenblatt DJ, vonMoltke LL, Harmatz JS, Mertzanis P, Graf JA, Durol ALB, Counihan M, RothSchechter B, Shader RI "Kinetic and dynamic interaction study of zolpidem with ketoconazole, itraconazole, and fluconazole." Clin Pharmacol Ther 64 (1998): 661-71
  5. Greenblatt DJ, von Moltke LL, Harmatz JS, et al. "Differential impairment of triazolam and zolpidem clearance by ritonavir." J Acquir Immune Defic Syndr 24 (2000): 129-36
  6. Saari TI, Laine K, Leino K, Valtonen M, Neuvonen PJ, Olkkola KT "Effect of voriconazole on the pharmacokinetics and pharmacodynamics of zolpidem in healthy subjects." Br J Clin Pharmacol 63 (2007): 116-20
  7. Farkas D, Volak L, Harmatz J, von Moltke L, Court M, Greenblatt D "Short-term clarithromycin administration impairs clearance and enhances pharmacodynamic effects of trazodone but not of zolpidem." Clin Pharmacol Ther 85 (2009): 644-50
View all 7 references

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Drug and food interactions

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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Moderate

zolpidem food

Applies to: Ambien (zolpidem)

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of zolpidem. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

ADJUST DOSING INTERVAL: Administration of zolpidem with food may delay the onset of hypnotic effects. In 30 healthy subjects, administration of zolpidem 20 minutes after a meal resulted in decreased mean peak plasma drug concentration (Cmax) and area under the concentration-time curve (AUC) by 25% and 15%, respectively, compared to fasting. The time to reach peak plasma drug concentration (Tmax) was prolonged by 60%, from 1.4 to 2.2 hours.

MANAGEMENT: Patients receiving zolpidem should be advised to avoid the consumption of alcohol. For faster sleep onset, zolpidem should not be administered with or immediately after a meal.

References

  1. "Product Information. Ambien (zolpidem)." sanofi-aventis PROD (2001):
  2. Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG "Drug-food interactions in clinical practice." J Fam Pract 40 (1995): 376-84

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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.

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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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