warnings and cautions
5 WARNINGS AND PRECAUTIONS • Memantine and donepezil hydrochlorides extended-release capsules are likely to exaggerate succinylcholine-type muscle relaxation during anesthesia. ( 5.1 ) • Memantine and donepezil hydrochlorides extended-release capsules may have vagotonic effects on the sinoatrial and atrioventricular nodes manifesting as bradycardia or heart block. ( 5.2 ) • Monitor patients for symptoms of active or occult gastrointestinal bleeding, especially those at increased risk for developing ulcers. ( 5.3 ) • Memantine and donepezil hydrochlorides extended-release capsules can cause diarrhea, nausea, and vomiting. ( 5.4 ) • Memantine and donepezil hydrochlorides extended-release capsules may cause bladder outflow obstructions. ( 5.5 ) • Conditions that raise urine pH may decrease the urinary elimination of memantine, resulting in increased plasma levels of memantine. ( 5.5 , 7.1 ) 5.1 Anesthesia Donepezil hydrochloride, an active ingredient in memantine and donepezil hydrochlorides extended-release capsules, as a cholinesterase inhibitor, is likely to exaggerate succinylcholine-type muscle relaxation during anesthesia. 5.2 Cardiovascular Conditions Because of their pharmacological action, cholinesterase inhibitors may have vagotonic effects on the sinoatrial and atrioventricular nodes. This effect may manifest as bradycardia or heart block in patients both with and without known underlying cardiac conduction abnormalities. Syncopal episodes have been reported in association with the use of donepezil hydrochloride, an active ingredient in memantine and donepezil hydrochlorides extended-release capsules. 5.3 Peptic Ulcer Disease and Gastrointestinal Bleeding Through their primary action, cholinesterase inhibitors may be expected to increase gastric acid secretion due to increased cholinergic activity. Clinical studies of donepezil hydrochloride in a dose of 5 mg/day to 10 mg/day have shown no increase, relative to placebo, in the incidence of either peptic ulcer disease or gastrointestinal bleeding. Patients treated with memantine and donepezil hydrochlorides extended-release capsules should be monitored closely for symptoms of active or occult gastrointestinal bleeding, especially those at increased risk for developing ulcers, e.g., those with a history of ulcer disease or those receiving concurrent nonsteroidal anti-inflammatory drugs (NSAIDs). 5.4 Nausea and Vomiting Donepezil hydrochloride, an active ingredient in memantine and donepezil hydrochlorides extended-release capsules, when initiated, as a predictable consequence of its pharmacological properties, has been shown to produce diarrhea, nausea, and vomiting. Although in most cases, these effects have been mild and transient, sometimes lasting one to three weeks, and have resolved during continued use of donepezil hydrochloride, patients should be observed closely at the initiation of treatment. 5.5 Genitourinary Conditions Although not observed in clinical trials of donepezil hydrochloride, an active ingredient in memantine and donepezil hydrochlorides extended-release capsules, cholinomimetics may cause bladder outflow obstruction. Conditions that raise urine pH may decrease the urinary elimination of memantine, an active ingredient in memantine and donepezil hydrochlorides extended-release capsules, resulting in increased plasma levels of memantine [see Drug Interactions ( 7.1 )]. 5.6 Seizures Cholinomimetics, including donepezil hydrochloride, an active ingredient in memantine and donepezil hydrochlorides extended-release capsules, are believed to have some potential to cause generalized convulsions. However, seizure activity also may be a manifestation of Alzheimer's disease. 5.7 Pulmonary Conditions Because of their cholinomimetic actions, cholinesterase inhibitors should be prescribed with care to patients with a history of asthma or obstructive pulmonary disease.