Drug Interactions between donepezil and famotidine / ibuprofen

MONITOR: The concomitant use of acetylcholinesterase inhibitors (ACHEIs) (e.g., donepezil, galantamine, benzgalantamine physostigmine, rivastigmine, tacrine) with nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of gastrointestinal (GI) bleeding. ACHEIs can increase gastric acid secretion due to their cholinergic effects and NSAIDS may increase the risk of GI bleeding and ulceration. In a Swedish retrospective case study of 70,060 patients aged 65 years and older with new prescriptions for both ACHEIs and NSAIDs, 1500 persons were diagnosed with incident peptic ulcer. The results suggested that the risk of peptic ulcer was significantly increased for the combination of ACHEIs and NSAIDs compared to NSAIDs alone. No increased risks were found for the use of ACHEIs alone.


MANAGEMENT: Caution and clinical monitoring are recommended if concomitant use of ACHEIs and NSAIDs is required, especially in patients with a prior history of peptic ulcer disease, the elderly, or debilitated patients. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence gastrointestinal bleeding such as black or tarry stools, bright red blood in vomit, coffee ground like vomit, abdominal pain or cramping, diarrhea, dizziness or lightheadedness, weakness or fatigue and pale skin.

MONITOR: Acetylcholinesterase inhibitors may have vagotonic effects on the sinoatrial and atrioventricular nodes, which occasionally manifest as bradycardia or heart block (<2%). Because bradycardia is a risk factor for torsade de pointes, a theoretical risk exists when combined with agents that prolong the QT interval. 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 including, but not limited to congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation may vary depending on the dosage(s) and specific drug(s) involved.

MANAGEMENT: Caution is advised when acetylcholinesterase inhibitors are used with drugs that can prolong the QT interval. Patients should be monitored for bradycardia, atrioventricular block and syncope, and advised to seek medical attention if they experience dizziness, lightheadedness, fainting, shortness of breath, or slow or irregular heartbeat.

H2 antagonists may alter the pharmacokinetic disposition of some nonsteroidal anti-inflammatory drugs (NSAIDs), resulting in increased or decreased plasma concentrations. Data have been varied, even for the same NSAID. The mechanism may involve inhibition of metabolism, changes in gastric pH resulting in altered absorption, and/or reduced urinary elimination of the affected NSAIDs. Statistically significant changes have been small and of limited clinical significance when interactions have been observed.