Namenda Warnings, Precautions, Pregnancy, Nursing, Abuse - Memantine

Namenda Warnings, Precautions, Pregnancy, Nursing, Abuse - Memantine

WARNINGS

No specific information available.

Information for Patients and Caregivers: Caregivers should be instructed in the recommended administration (twice per day for doses above 5 mg) and dose escalation (minimum interval of one week between dose increases).

Seizures: NAMENDA has not been systematically evaluated in patients with a seizure disorder. In clinical trials of NAMENDA, seizures occurred in 0.2% of patients treated with NAMENDA and 0.5% of patients treated with placebo.

Conditions that raise urine pH may decrease the urinary elimination of memantine resulting in increased plasma levels of memantine.

NAMENDA undergoes partial hepatic metabolism, but the major fraction of a dose (57-82%) is excreted unchanged in urine. The pharmacokinetics of memantine in patients with hepatic impairment have not been investigated, but would be expected to be only modestly affected.

There are inadequate data available in patients with mild, moderate, and severe renal impairment but it is likely that patients with moderate renal impairment will have higher exposure than normal subjects. Dose reduction in these patients should be considered. The use of NAMENDA in patients with severe renal impairment is not recommended.

There was no evidence of carcinogenicity in a 113-week oral study in mice at doses up to 40 mg/kg/day (10 times the maximum recommended human dose [MRHD] on a mg/m² basis). There was also no evidence of carcinogenicity in rats orally dosed at up to 40 mg/kg/day for 71 weeks followed by 20 mg/kg/day (20 and 10 times the MRHD on a mg/m² basis, respectively) through 128 weeks.

Memantine produced no evidence of genotoxic potential when evaluated in the in vitro S. typhimurium or E. coli reverse mutation assay, an in vitro chromosomal aberration test in human lymphocytes, an in vivo cytogenetics assay for 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.

No impairment of fertility or reproductive performance was seen in rats administered up to 18 mg/kg/day (9 times the MRHD on a mg/m² basis) orally from 14 days prior to mating through gestation and lactation in females, or for 60 days prior to mating in males.

Pregnancy Category B: Memantine given orally to pregnant rats and pregnant rabbits during the period of organogenesis was not teratogenic up to the highest doses tested (18 mg/kg/day in rats and 30 mg/kg/day in rabbits, which are 9 and 30 times, respectively, the maximum recommended human dose [MRHD] on a mg/m² basis).

Slight maternal toxicity, decreased pup weights and an increased incidence of non-ossified cervical vertebrae were seen at an oral dose of 18 mg/kg/day in a study in which rats were given oral memantine beginning pre-mating and continuing through the postpartum period. Slight maternal toxicity and decreased pup weights were also seen at this dose in a study in which rats were treated from day 15 of gestation through the postpartum period. The no-effect dose for these effects was 6 mg/kg, which is 3 times the MRHD on a mg/m² basis.

There are no adequate and well-controlled studies of memantine in pregnant women. Memantine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

It is not known whether memantine is excreted in human breast milk. Because many drugs are excreted in human milk, caution should be exercised when memantine is administered to a nursing mother.

There are no adequate and well-controlled trials documenting the safety and efficacy of memantine in any illness occurring in children.