Memotin Special Precautions

Seizures: Memantine has not been systematically evaluated in patient with a seizure disorder. In clinical studies, seizures occurred in 0.2% of patients receiving memantine and in 0.5% of patients receiving placebo.
Urinary Excretion: Conditions that increase urinary pH (e.g., dietary changes [e.g., from a high-protein to a vegetarian diet], concomitant use of drugs that alkalinize urine [e.g., carbonic anhydrase inhibitors, sodium bicarbonate], renal tubular acidosis, severe urinary tract infections) may decrease elimination of memantine, resulting in increased plasma memantine concentrations; use with caution under such conditions.
Hepatic impairment: Although pharmacokinetics have not been evaluated in patients with hepatic impairment, only a modest effect on clearance would be expected.
Renal impairment: Dosage adjustment is recommended in patients with severe renal impairment, but not in those with mild or moderate renal impairment.
Carcinogenicity: There was no evidence of carcinogenicity on 113-week oral study in mice at doses up to 40 mg per kg per day (10 times the maximum recommended human dose (MRHD) on a mg per m² basis). There was also no evidence of carcinogenicity in rats orally dosed at up to 40 mg per kg per day for 71 weeks followed by 20 mg per kg per day (20 times and 10 times the MRHD on a mg per m² basis, respectively) through 128 weeks.
Mutagenicity: Memantine produced no evidence of genotoxic potential when evaluated in the in vitro S. typhimurium and E. coli reverse mutation assays, the in vitro chromosomal aberration test in human lymphocytes, the in vivo cytogenesis assay for the chromosome damage in rats, and the in vivo mouse micronucleus assay. The results were equivocal in an in vitro gene mutation assay using Chinese hamster V79 cells.
Use in Children: Safety and efficacy not established in children.
Use in the Elderly: Clinical studies have been conducted principally in older patients since dementia of Alzheimer's type occurs mainly in an older patient population. Memantine pharmacokinetics were similar in elderly patients and younger adults.