Caution is recommended in patients with epilepsy, past history of convulsions or patients with predisposing factors for epilepsy.
Treatment with memantine hydrochloride should be initiated and supervised by a physician experienced in the diagnosis and treatment of dementia; diagnosis should be based on current guidelines. Therapy should be initiated only when a caregiver is available who will monitor patient compliance. Treatment with memantine hydrochloride should be continued only where there is a therapeutic benefit to the patient; therapeutic benefit should be reassessed on a regular basis.
The clearance of memantine hydrochloride was reduced by about 80% under alkaline urine conditions (pH 8). Thus, alterations of urine pH towards the alkaline condition may lead to an accumulation of the drug with a possible increase in adverse effects. Some factors that may raise urine pH may require careful patient monitoring. These factors include drastic changes in diet (e.g., from a carnivore to a vegetarian diet, or a massive ingestion of alkalizing gastric buffers), drugs (e.g., carbonic anhydrase inhibitors, sodium bicarbonate) and the clinical state of the patient (e.g., renal tubular acidosis or severe infections of the urinary tract with Proteus bacteria).
Moderate to severe Alzheimer's disease usually causes impairment of driving performance and compromises the ability to use machinery. Furthermore, memantine hydrochloride may change reactivity and therefore patients should be warned to take special care when driving a vehicle or operating heavy machinery.
Patients with recent myocardial infarction, uncompensated congestive heart failure (NYHA III-IV) or uncontrolled hypertension were excluded in most clinical trials. As a result, only limited data are available and patients with these conditions should be closely supervised.
Ocular toxicity: Animal studies have shown adverse effects of memantine hydrochloride on the visual system. Dietary administration of memantine hydrochloride to rats for one year was associated with abnormal lysosomal storage in ganglion cells and retinal pigment cells at systemic exposures (plasma AUC) of 10-fold the anticipated clinical exposure at the recommended dose, while administration for eight weeks was associated with lens opacity, increased corneal and lens capsular densities, and histological changes in corneal and lens at exposures (plasma AUC) of 20-fold the clinical exposure. Oral administration of memantine hydrochloride to dogs with systemic exposures (plasma AUC) of 3- to 8-fold the clinical exposure was associated with corneal clouding/opacity and baboons showed swollen lenticular fibers in the eyes after oral memantine hydrochloride for three months at less than clinical exposure.
In a 6-month double-blind, placebo-controlled clinical study, specific ophthalmological examinations including slit lamp tests did not show any ocular changes. In the following 6-month open-label extension period, 368 patients underwent eye examinations. At the end of open label treatment, the incidence of cataract (lens previously clear but unclear at end of open label treatment) was reported in 11 of 197 patients (6%) treated with memantine hydrochloride for 12 months compared with 5 of 171 patients (3%) who received placebo in the double-blind period and then memantine hydrochloride for 6 months (p=0.3059).
Use in Children: There are no adequate and well-controlled studies on the efficacy and safety of memantine hydrochloride in any illness occurring in children.