Drug Interaction Report

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.

Coadministration with rizatriptan may alter the plasma concentrations of drugs that are primarily metabolized by CYP450 2D6. Rizatriptan has been shown to be a competitive inhibitor of CYP450 2D6 in vitro, but only at high, clinically irrelevant concentrations and a clinically significant inhibitory effect on CYP450 2D6 has not been demonstrated in clinical drug interaction studies. Based on these observations, rizatriptan may be administered with CYP450 2D6 substrates without the need for increased clinical monitoring