Drug Interaction Report

MONITOR: Omeprazole may increase the pharmacologic effects and serum levels of certain benzodiazepines via hepatic enzyme inhibition. Diazepam and triazolam are the only benzodiazepines that have been specifically studied in this regard.

MANAGEMENT: Patient should be observed for increased sedation. Reduced benzodiazepine dosage may be indicated, especially in the elderly. Benzodiazepines not metabolized via oxidation (i.e., lorazepam, oxazepam, temazepam) are not expected to interact and may be considered as alternatives.

MONITOR: Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients. Sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Cautious dosage titration may be required, particularly at treatment initiation. Ambulatory patients should be counseled to avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Coadministration of enteric-coated duloxetine with substances that raise gastrointestinal pH may result in earlier release of duloxetine from the formulation, potentially leading to gastric or duodenal irritation. The enteric coating is intended to resist drug dissolution until reaching a segment of the gastrointestinal tract where the pH exceeds 5.5. However, coadministration with aluminum- and magnesium-containing antacids (51 mEq) or famotidine has been shown to have no significant effect on the rate or extent of duloxetine absorption following administration of a 40 mg oral dose. It is unknown whether concomitant administration of proton pump inhibitors would affect duloxetine absorption.

Coadministration of enteric-coated duloxetine with substances that raise gastrointestinal pH may result in earlier release of duloxetine from the formulation, potentially leading to gastric or duodenal irritation. The enteric coating is intended to resist drug dissolution until reaching a segment of the gastrointestinal tract where the pH exceeds 5.5. However, coadministration with aluminum- and magnesium-containing antacids (51 mEq) or famotidine has been shown to have no significant effect on the rate or extent of duloxetine absorption following administration of a 40 mg oral dose. It is unknown whether concomitant administration of proton pump inhibitors would affect duloxetine absorption.

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

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

ADJUST DOSING INTERVAL: Food may interfere with the absorption of esomeprazole. The manufacturer reports that the area under the concentration-time curve for esomeprazole following a single 40 mg dose was 33% to 53% lower when administered after food intake as opposed to during fasting conditions.

MANAGEMENT: Esomeprazole should be taken at least one hour before meals. When administered to patients receiving continuous enteral nutrition, some experts recommend that the tube feeding should be interrupted for at least 1 hour before and 1 hour after the dose of esomeprazole is given.

GENERALLY AVOID: Use of duloxetine in conjunction with chronic alcohol consumption may potentiate the risk of liver injury. Duloxetine alone can increase serum transaminase levels. In clinical trials, 0.3% of patients discontinued duloxetine due to liver transaminase elevations. The median time to detection was about two months. Three duloxetine-treated patients had liver injury as manifested by transaminase and bilirubin elevations, with evidence of obstruction. Substantial intercurrent ethanol use was present in each of these cases, which may have contributed to the abnormalities observed. Duloxetine does not appear to enhance the central nervous system effects of alcohol. When duloxetine and ethanol were administered several hours apart so that peak concentrations of each would coincide, duloxetine did not increase the impairment of mental and motor skills caused by alcohol.

MANAGEMENT: Due to the risk of liver injury, patients prescribed duloxetine should be counseled to avoid excessive use of alcohol. Duloxetine should generally not be prescribed to patients with substantial alcohol use.

The recommended maximum number of medicines in the 'acid suppressant agents' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'acid suppressant agents' category:

• esomeprazole
• omeprazole

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.