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Label Changes for:

Namzaric (memantine and donepezil hydrochlorides) Extended-release

July 2016

Changes have been made to the WARNINGS and PRECAUTIONS sections of the safety label.

Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)

July 2016

WARNINGS AND PRECAUTIONS

Anesthesia
Cardiovascular Conditions
  • donepezil hydrochloride, (addition of an active ingredient in NAMZARIC)

USE IN SPECIFIC POPULATIONS

PLLR Conversion:

Pregnancy
Risk Summary
  • There are no adequate data on the developmental risk associated with the use of NAMZARIC or its active ingredients (memantine hydrochloride and donepezil hydrochloride) in pregnant women.
  • Adverse developmental effects (mortality and decreased body weight and skeletal ossification) were observed in the offspring of rats administered memantine or donepezil during pregnancy at doses associated with minimal maternal toxicity. These doses are higher than those used in humans at the recommended daily dose of NAMZARIC.
  • In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.
Data
Animal Data
Memantine Hydrochloride
  • Oral administration of memantine (2, 6, or 18 mg/kg/day) to rats during the period of organogenesis resulted in decreased skeletal ossification in fetuses at the highest dose tested. The higher no-effect dose for adverse developmental effects (6 mg/kg) is 2 times the dose of memantine at the recommended human daily dose (RHD) of NAMZARIC (28 mg memantine/10 mg donepezil) on a body surface area (mg/m2) basis.
  • Oral administration of memantine to rabbits (3, 10, or 30 mg/kg/day) during the period of organogenesis resulted in no adverse developmental effects. The highest dose tested is approximately 20 times the dose of memantine at the RHD of NAMZARIC on a mg/m2 basis. In rats, memantine (2, 6, or 18 mg/kg/day) was administered orally prior to and throughout mating and, in females, through the period of organogenesis or continuing throughout lactation to weaning. Decreased skeletal ossification in fetuses and decreased body weight in pups were observed at the highest dose tested. The higher no-effect dose for adverse developmental effects (6 mg/kg/day) is 2 times the dose of memantine at the RHD of NAMZARIC on a mg/m2 basis.
  • Oral administration of memantine (2, 6, or 18 mg/kg/day) to rats from late gestation throughout lactation to weaning, resulted in decreased pup weights at the highest dose tested. The higher noeffect dose (6 mg/kg/day) is approximately 2 times the dose of memantine at the RHD of NAMZARIC on a mg/m2 basis.
Donepezil Hydrochloride
  • Oral administration of donepezil to rats and rabbits during the period of organogenesis resulted in no adverse developmental effects. The highest doses (16 and 10 mg/kg/day, respectively) were approximately 15 and 7 times, respectively, the dose of donepezil at the RHD of NAMZARIC on a mg/m2 basis.
  • Oral administration of donepezil (1, 3, or 10 mg/kg/day) to rats during late gestation and throughout lactation to weaning resulted in an increase in stillbirths and offspring mortality at the highest dose tested. The higher no-effect dose (3 mg/kg/day) is approximately 3 times the dose of donepezil at the RHD of NAMZARIC on a mg/m2 basis.
Lactation
Risk Summary
  • There are no data on the presence of memantine or donepezil in human milk, the effects on the breastfed infant, or the effects of NAMZARIC or its metabolites on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for NAMZARIC and any potential adverse effects on the breastfed infant from NAMZARIC or from the underlying maternal condition.
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