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Drug Interactions between ezogabine and Mellaril

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

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Interactions between your drugs

Major

thioridazine ezogabine

Applies to: Mellaril (thioridazine) and ezogabine

CONTRAINDICATED: Thioridazine can cause dose-related prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. Thioridazine treatment alone has been associated with several reported cases of torsade de pointes and sudden death. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). The extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s). In addition, certain agents with anticholinergic properties (e.g., sedating antihistamines; antispasmodics; neuroleptics; phenothiazines; skeletal muscle relaxants; tricyclic antidepressants; disopyramide) may have additive parasympatholytic and central nervous system-depressant effects when used in combination with thioridazine. Excessive parasympatholytic effects may include paralytic ileus, hyperthermia, mydriasis, blurred vision, tachycardia, urinary retention, psychosis, and seizures.

MANAGEMENT: Coadministration of thioridazine with other drugs that can prolong the QT interval is considered contraindicated.

References

  1. Fletcher GF, Kazamias TM (1969) "Cardiotoxic effects of Mellaril: conduction disturbances and supraventricular arrhythmias." Am Heart J, 78, p. 135-8
  2. Liberatore MA, Robinson DS (1984) "Torsade de pointes: a mechanism for sudden death associated with neuroleptic drug therapy?" J Clin Psychopharmacol, 4, p. 143-6
  3. (2001) "Product Information. Mellaril (thioridazine)." Sandoz Pharmaceuticals Corporation
  4. Hartigan-Go K, Bateman DN, Nyberg G, Martensson E, Thomas SHL (1996) "Concentration-related pharmacodynamic effects of thioridazine and its metabolites in humans." Clin Pharmacol Ther, 60, p. 543-53
  5. Glassman AH, Bigger JT Jr (2001) "Antipsychotic drugs: prolonged QTc interval, torsade de pointes, and sudden death." Am J Psychiatry, 158, p. 1774-82
  6. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  7. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  8. Cerner Multum, Inc. "Australian Product Information."
  9. EMA. European Medicines Agency. European Union (2013) EMA - List of medicines under additional monitoring. http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000366.jsp&mid=WC0b01ac058067c852
View all 9 references

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Drug and food interactions

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

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Moderate

thioridazine food

Applies to: Mellaril (thioridazine)

GENERALLY AVOID: Concurrent use of ethanol and phenothiazines may result in additive CNS depression and psychomotor impairment. Also, ethanol may precipitate dystonic reactions in patients who are taking phenothiazines. The two drugs probably act on different sites in the brain, although the exact mechanism of the interaction is not known.

MANAGEMENT: Patients should be advised to avoid alcohol during phenothiazine therapy.

References

  1. Lutz EG (1976) "Neuroleptic-induced akathisia and dystonia triggered by alcohol." JAMA, 236, p. 2422-3
  2. Freed E (1981) "Alcohol-triggered-neuroleptic-induced tremor, rigidity and dystonia." Med J Aust, 2, p. 44-5

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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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