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Drug Interactions between ezogabine and MSIR

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

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Interactions between your drugs

Major

morphine ezogabine

Applies to: MSIR (morphine) and ezogabine

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 Close clinical and laboratory monitoring should be considered whenever a P-gp inhibitor is added to or withdrawn from therapy, and the morphine dosage adjusted as necessary.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. "Product Information. MS Contin (morphine)." Purdue Frederick Company PROD (2002):
  2. "Product Information. Kadian (morphine)." Astra-Zeneca Pharmaceuticals PROD (2001):
  3. Kharasch ED, Hoffer C, Whittington D, Sheffels P "Role of P-glycoprotein in the intestinal absorption and clinical effects of morphine." Clin Pharmacol Ther 74 (2003): 543-54
  4. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  5. Cerner Multum, Inc. "Australian Product Information." O 0
  6. Meissner K, Avram MJ, Yermolenka V, Francis AM, Blood J, Kharasch ED "Cyclosporine-inhibitable Blood-Brain Barrier Drug Transport Influences Clinical Morphine Pharmacodynamics." Anesthesiology (2013):
  7. Heiskanen T, Backman JT, Neuvonen M, Kontinen VK, Neuvonen PJ, Kalso E "Itraconazole, a potent inhibitor of P-glycoprotein, moderately increases plasma concentrations of oral morphine." Acta Anaesthesiol Scand 52 (2008): 1319-26
View all 7 references

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Drug and food interactions

Major

morphine food

Applies to: MSIR (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. "Product Information. Avinza (morphine)." Ligand Pharmaceuticals (2005):
  2. Ghalie R "Dear Health Care Professional. http://www.fda.gov/medwatch/safety/2005/AVINZA_DHCP_Letter_Oct2005.pdf" (2005):
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  4. Cerner Multum, Inc. "Canadian Product Information." O 0 (2015):
View all 4 references

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Moderate

ezogabine food

Applies to: ezogabine

GENERALLY AVOID: Alcohol may increase the plasma concentrations of ezogabine. In a study of healthy volunteers, the administration of ezogabine 200 mg in combination with ethanol 1g/kg (5 standard alcohol drinks) over 20 minutes resulted in an increase in the ezogabine peak plasma concentration (Cmax) and systemic exposure (AUC) by 23% and 37%, respectively.

Food does not significantly affect the bioavailability of ezogabine. According to the product labeling, high-fat food does not affect the extent to which ezogabine is absorbed, but increases peak plasma concentration (Cmax) by approximately 38% and delays the time to reach peak concentration (Tmax) by 0.75 hour.

MANAGEMENT: In general, alcohol consumption should be avoided or limited during treatment with CNS-depressant agents. Patients should be advised of the potential for increased dose-related adverse reactions of ezogabine (e.g., dizziness, somnolence, nausea, constipation, urinary retention, blurred vision, memory impairment, tremor) when taken with alcohol, and to avoid hazardous activities that require mental alertness and motor coordination until they know how the medication affects them. Ezogabine can be taken with or without food.

References

  1. "Product Information. Potiga (ezogabine)." GlaxoSmithKline (2011):

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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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