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Drug Interactions between Arymo ER and erythromycin

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

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Interactions between your drugs

Major

erythromycin morphine

Applies to: erythromycin and Arymo ER (morphine)

MONITOR CLOSELY: Coadministration with P-glycoprotein (P-gp) inhibitors may increase the plasma concentrations of morphine and its risk of adverse effects, including hypotension, respiratory and CNS depression, profound sedation, coma, and death. The proposed mechanism may involve inhibition of the intestinal P-gp efflux transporter, resulting in enhanced oral bioavailability of morphine, a P-gp substrate. The interaction may be more significant for orally administered morphine. According to some authorities, the concomitant use of a P-gp inhibitor with oral morphine may increase the systemic exposure of morphine by approximately 2-fold. However, in a pharmacokinetic study involving 12 healthy subjects, itraconazole (200 mg daily for 4 days), a strong P-gp inhibitor, increased the morphine (0.3 mg/kg as a single oral dose) peak plasma concentration (Cmax) and systemic exposure (AUC) by 28% and 22%, respectively. Plasma concentrations of intravenously administered morphine appear less affected. In a crossover study involving 14 healthy volunteers, intravenous administration of P-gp inhibitor cyclosporine followed by an intravenous infusion of morphine 0.1 mg/kg led to a minimal increase of morphine AUC to 100 ng/mL*h compared to 85 ng/mL*h when administered after control (no infusion). In the same study, cyclosporine appeared to prolong morphine-induced miosis.

MANAGEMENT: Caution is recommended whenever morphine, particularly orally administered morphine, is used concomitantly with a P-gp inhibitor. Close clinical and laboratory monitoring should be considered whenever a P-gp inhibitor is added to or withdrawn from therapy, and the morphine dosage adjusted as necessary. Patients should be monitored closely for signs and symptoms of respiratory depression and sedation that may be greater than otherwise expected. In addition, patients should be advised to avoid driving or operating hazardous machinery until they know how these medications affect them.

References

  1. (2002) "Product Information. MS Contin (morphine)." Purdue Frederick Company
  2. (2001) "Product Information. Kadian (morphine)." Astra-Zeneca Pharmaceuticals
  3. Kharasch ED, Hoffer C, Whittington D, Sheffels P (2003) "Role of P-glycoprotein in the intestinal absorption and clinical effects of morphine." Clin Pharmacol Ther, 74, p. 543-54
  4. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  5. Cerner Multum, Inc. "Australian Product Information."
  6. Meissner K, Avram MJ, Yermolenka V, Francis AM, Blood J, Kharasch ED (2013) "Cyclosporine-inhibitable Blood-Brain Barrier Drug Transport Influences Clinical Morphine Pharmacodynamics." Anesthesiology
  7. Heiskanen T, Backman JT, Neuvonen M, Kontinen VK, Neuvonen PJ, Kalso E (2008) "Itraconazole, a potent inhibitor of P-glycoprotein, moderately increases plasma concentrations of oral morphine." Acta Anaesthesiol Scand, 52, p. 1319-26
View all 7 references

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Drug and food interactions

Major

morphine food

Applies to: Arymo ER (morphine)

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including morphine and diamorphine. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

GENERALLY AVOID: Consumption of alcohol while taking some sustained-release formulations of morphine may cause rapid release of the drug, resulting in high systemic levels of morphine that may be potentially lethal. Alcohol apparently can disrupt the release mechanism of some sustained-release formulations. The interaction was observed in in vitro studies using a 24-hour morphine formulation (Avinza 30 mg capsule, available in the U.S. from Ligand Pharmaceuticals). When the capsule was mixed with 900 mL of buffer solutions containing ethanol 20% and 40%, the dose of morphine that was released was alcohol concentration-dependent, leading to a more rapid release of morphine. Although the clinical relevance of this finding is unknown, 'dose-dumping' into the bloodstream is conceivable.

MANAGEMENT: Until more information is available, patients taking sustained-release formulations of morphine should not consume alcohol or use medications that contain alcohol. In general, potent narcotics such as morphine or diamorphine should not be combined with alcohol.

References

  1. (2005) "Product Information. Avinza (morphine)." Ligand Pharmaceuticals
  2. Ghalie R (2005) Dear Health Care Professional. http://www.fda.gov/medwatch/safety/2005/AVINZA_DHCP_Letter_Oct2005.pdf
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  4. Cerner Multum, Inc. (2015) "Canadian Product Information."
View all 4 references

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Moderate

erythromycin food

Applies to: 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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Minor

erythromycin food

Applies to: 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.

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

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

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