Drug Interaction Report

MONITOR: The following interaction applies only to products containing sodium biphosphate that are used for bowel cleansing. It does not apply to products containing sodium biphosphate that are used for other, non-laxative related purposes.

The use of bowel cleansing preparations may increase the risk of ventricular arrhythmia, particularly torsade de pointes, in patients treated with drugs that prolong the QT interval. Severe and potentially fatal cases of electrolyte disorders and arrhythmias have been reported in elderly patients using bowel cleansing products. Electrolyte disturbances including hypokalemia and hypomagnesemia are known risk factors for torsade de pointes associated with QT interval prolongation.

MANAGEMENT: Caution is advised when bowel cleansing preparations are prescribed in patients treated with drugs that prolong the QT interval. Monitoring of baseline and posttreatment serum electrolyte levels is recommended, particularly in the elderly. Patients should be instructed to drink plenty of clear liquids before, during, and after the bowel preparation process. Consideration should be given to consumption of 36 to 48 fluid ounces of a carbohydrate-electrolyte solution in the six hours before the first dose. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

ADJUST DOSING INTERVAL: Bowel cleansing products can increase the gastrointestinal transit rate. Oral medications administered within one hour of the start of administration of the bowel cleansing solution may be flushed from the gastrointestinal tract and not properly absorbed.

MANAGEMENT: Patients should be advised that absorption of oral medications may be impaired during bowel cleansing treatment. Oral medications (e.g., anticonvulsants, oral contraceptives, antidiabetic agents, antibiotics) should not be administered during and within one hour of starting bowel cleansing treatment whenever possible. However, if concomitant use cannot be avoided, monitoring for reduced therapeutic effects may be advisable.

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.