MEMANTINE HYDROCHLORIDE capsule, extended release

Land: Vereinigte Staaten

Sprache: Englisch

Quelle: NLM (National Library of Medicine)

Wirkstoff:

MEMANTINE HYDROCHLORIDE (UNII: JY0WD0UA60) (MEMANTINE - UNII:W8O17SJF3T)

Verfügbar ab:

Slate Run Pharmaceuticals, LLC

Verabreichungsweg:

ORAL

Verschreibungstyp:

PRESCRIPTION DRUG

Anwendungsgebiete:

Memantine Hydrochloride Extended-Release Capsules are indicated for the treatment of moderate to severe dementia of the Alzheimer’s type. Memantine Hydrochloride Extended-Release Capsules are contraindicated in patients with known hypersensitivity to memantine hydrochloride or to any excipients used in the formulation . Risk  Summary There are no adequate data on the developmental risk associated with the use of memantine hydrochloride extended-release capsules in pregnant women.  Adverse developmental effects (decreased body weight and skeletal ossification) were observed in the offspring of rats administered memantine during pregnancy at doses associated with minimal maternal toxicity. These doses are higher than those used in humans at the maximum recommended daily dose of memantine hydrochloride extended-release capsules  [see  Data]. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal  Data Oral administration of memantine (0, 2, 6, or 18 mg/kg/day) to rats during the period of organogenesis resulted in decreased skeletal ossificationin fetuses at the highest dose tested. The higher no-effect dose for adverse developmental effects (6 mg/kg) is 2 times the maximum recommended human daily dose (MRHD) of memantine hydrochloride extended-release capsules (28 mg) on a body surface area (mg/m 2 ) basis.  Oral administration of memantine to rabbits (0, 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 MRHD of memantine hydrochloride extended-release capsules on a mg/m 2  basis. In rats, memantine (0, 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 MRHD of memantine hydrochloride extended-release capsules on a mg/m 2  basis. Oral administration of memantine (0, 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 no-effect dose (6 mg/kg/day) is approximately 2 times the MRHD of memantine hydrochloride extended-release capsules on a mg/m 2  basis. Risk  Summary There are no data on the presence of memantine in human milk, the effects on the breastfed infant, or the effects of memantine hydrochloride extended-release capsules on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for memantine hydrochloride extended-release capsules and any potential adverse effects on the breastfed infant from memantine hydrochloride extended-release capsules or from the underlying maternal condition. Safety and effectiveness in pediatric patients have not been established. Memantine failed to demonstrate efficacy in two 12-week controlled clinical studies of 578 pediatric patients aged 6 to 12 years with autism spectrum disorders (ASD), including autism, Asperger’s disorder and Pervasive Development Disorder-Not Otherwise Specified (PDD-NOS).Memantine has not been studied in pediatric patients under 6 years of age or over 12 years of age. Memantine treatment was initiated at 3 mg/day and the dose was escalated to the target dose (weight-based) by week 6. Oral doses of memantine 3, 6, 9, or 15 mg extended-release capsules were administered once daily to patients with weights <20 kg, 20 to 39 kg, 40 to 59 kg and ≥60 kg, respectively. In a randomized, 12-week double-blind, placebo-controlled parallel study (Study A) in patients with autism, there was no statistically significant difference in the Social Responsiveness Scale (SRS) total raw score between patients randomized to memantine (n=54) and those randomized to placebo (n=53). In a 12-week responder-enriched randomized withdrawal study (Study B) in 471 patients with ASD, there was no statistically significant difference in the loss of therapeutic response rates between patients randomized to remain on full-dose memantine (n=153) and those randomized to switch to placebo (n=158). The overall safety profile of memantine in pediatric patients was generally consistent with the known safety profile in adults [see Adverse Reactions ( 6.1 )] . In Study A, the adverse reactions in the memantine group (n=56) that were reported in at least 5% of patients and at least twice the frequency of the placebo group (N=58) are listed in Table 2. The adverse reactions that were reported in at least 5% of patients in the 12 to 48 week open-label study to identify responders to enroll in Study B are listed in Table 3. In the randomized withdrawal study (Study B), the adverse reaction in patients randomized to placebo (n=160) and reported in at least 5% of patients and twice that of the full-dose memantine treatment group (n=157) was irritability (5.0% vs 2.5%). Juvenile Animal Study In a juvenile animal study, male and female juvenile rats were administered memantine (15, 30, and 45 mg/kg/day) starting on postnatal day (PND) 14 through PND 70. Body weights were reduced at 45 mg/kg/day. Delays in sexual maturation were noted in male and female rats at doses ≥30 mg/kg/day. Memantine induced neuronal lesions in several areas of the brain on PND 15 and 17 at doses ≥30 mg/kg/day. Behavioral toxicity (decrease percent of auditory startle habituation) was noted for animals in the 45 mg/kg/day dose group. The 15 mg/kg/day dose was considered the No-Observed-Adverse-Effect-Level (NOAEL) for this study. In a second juvenile rat toxicity study, male and female juvenile rats were administered memantine (1, 3, 8, 15, 30, and 45 mg/kg/day) starting on postnatal day (PND) 7 through PND 70.  Due to early memantine-related mortality, the 30 and 45 mg/kg/day dose groups were terminated without further evaluation. Memantine induced apoptosis or neuronal degeneration in several areas of the brain on PND 8, 10, and 17 at a dose of 15 mg/kg/day. The NOAEL for apoptosis and neuronal degeneration was 8 mg/kg/day. Behavioral toxicity (effects on motor activity, auditory startle habituation, and learning and memory) was noted at doses ≥3 mg/kg/day during treatment, but was not seen after drug discontinuation. Therefore, the 1 mg/kg/day dose was considered the NOAEL for the neurobehavioral effect in this study. The majority of people with Alzheimer’s disease are 65 years of age and older. In the clinical study of memantine hydrochloride extended-release, the mean age of patients was approximately 77 years; over 91% of patients were 65 years and older, 67% were 75 years and older, and 14% were at or above 85 years of age. The efficacy and safety data presented in the clinical trial sections were obtained from these patients. There were no clinically meaningful differences in most adverse reactions reported by patient groups ≥65 years old and <65 years old. No dosage adjustment is needed in patients with mild or moderate renal impairment. A dosage reduction is recommended in patients with severe renal impairment [see Dosage and Administration ( 2.3 ) and Clinical Pharmacology ( 12.3 )] . No dosage adjustment is needed in patients with mild or moderate hepatic impairment. Memantine hydrochloride extended-release capsules were not studied in patients with severe hepatic impairment  [see Clinical Pharmacology ( 12.3 )] .

Produktbesonderheiten:

Memantine Hydrochloride Extended-Release Capsules contain 7 mg, 14 mg, 21 mg or 28 mg of memantine hydrochloride, USP. 7 mg Capsule Opaque buff capsule, with “YH” black imprint on the cap and “123” black imprint on the body. Bottle of 30 capsules with a child-resistant closure: NDC 70436-054-04 14 mg Capsule Opaque buff cap and opaque dark green body capsule, with “YH” black imprint on the cap and “124” black imprint on the body. Bottle of 30 capsules with a child-resistant closure: NDC 70436-055-04 Bottle of 90 capsules with a child-resistant closure: NDC 70436-055-06 21 mg Capsule Opaque white cap and opaque dark green body capsule, with “YH” black imprint on the cap and “125” black imprint on the body. Bottle of 30 capsules with a child-resistant closure: NDC 70436-056-04 28 mg Capsule Dark green opaque capsule, with “YH” white imprint on the cap and “126” white imprint on the body. Bottle of 30 capsules with a child-resistant closure: NDC 70436-057-04 Bottle of 90 capsules with a child-resistant closure: NDC 70436-057-06 Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Dispense in a tightly closed container as defined in the USP with a child-resistant closure. Keep Memantine Hydrochloride Extended-Release Capsules and all medicines out of the reach of children.

Berechtigungsstatus:

Abbreviated New Drug Application

Fachinformation

MEMANTINE HYDROCHLORIDE- MEMANTINE HYDROCHLORIDE CAPSULE, EXTENDED
RELEASE
SLATE RUN PHARMACEUTICALS, LLC
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
MEMANTINE
HYDROCHLORIDE EXTENDED-RELEASE CAPSULES SAFELY AND EFFECTIVELY. SEE
FULL PRESCRIBING
INFORMATION FOR MEMANTINE HYDROCHLORIDE EXTENDED-RELEASE CAPSULES.
MEMANTINE HYDROCHLORIDE EXTENDED-RELEASE CAPSULES, FOR ORAL USE
INITIAL U.S. APPROVAL: 2003
INDICATIONS AND USAGE
Memantine Hydrochloride Extended-Release Capsules are a
N-methyl-D-aspartate (NMDA) receptor
antagonist indicated for the treatment of moderate to severe dementia
of the Alzheimer’s type. ( 1)
DOSAGE AND ADMINISTRATION
The recommended starting dose of memantine hydrochloride
extended-release capsules is 7 mg once
daily; the dose should be increased in 7 mg increments to the
recommended maintenance dose of 28
mg once daily; the minimum recommended interval between dose increases
is one week. ( 2.1)
Patients with severe renal impairment: the recommended maintenance
dose of memantine
hydrochloride extended-release capsules is 14 mg once daily. ( 2.3)
DOSAGE FORMS AND STRENGTHS
Memantine hydrochloride extended-release capsules are available as an
extended-release capsule in
the following strengths: 7 mg, 14 mg, 21 mg, 28 mg ( 3)
CONTRAINDICATIONS
Memantine Hydrochloride Extended-Release Capsules are contraindicated
in patients with known
hypersensitivity to memantine hydrochloride or to any excipients used
in the formulation. ( 4)
WARNINGS AND PRECAUTIONS
Conditions that raise urine pH may decrease the urinary elimination of
memantine resulting in
increased plasma levels of memantine. ( 5.1, 7.1)
ADVERSE REACTIONS
The most commonly observed adverse reactions occurring at a frequency
of at least 5% and greater than
placebo with administration of memantine hydrochloride
extended-release capsules 28 mg/day were
headache, diarrhea and dizziness. ( 6.1)
TO REPORT SUSPECTED ADVERSE REACTIONS, CONTACT SLATE RUN
PHARMACEUTICALS, LLC AT