MEMANTINE HYDROCHLORIDE capsule, extended release

Pays: États-Unis

Langue: anglais

Source: NLM (National Library of Medicine)

Ingrédients actifs:

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

Disponible depuis:

Lupin Pharmaceuticals, Inc.

DCI (Dénomination commune internationale):

MEMANTINE HYDROCHLORIDE

Composition:

MEMANTINE HYDROCHLORIDE 7 mg

Mode d'administration:

ORAL

Type d'ordonnance:

PRESCRIPTION DRUG

indications thérapeutiques:

Memantine hydrochloride extended-release capsules are indicated for the treatment of moderate to severe dementia of the Alzheimer's type. Memantine hydrochloride extended-release is 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 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 [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 ossification in 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 (28 mg) on a body surface area (mg/m2 ) 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 on a mg/m2 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 on a mg/m2 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 on a mg/m2 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 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 and any potential adverse effects on the breastfed infant from memantine hydrochloride extended release 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 was not studied in patients with severe hepatic impairment [see CLINICAL PHARMACOLOGY (12.3)].

Descriptif du produit:

7 mg Capsule Size '4' hard gelatin yellow capsule with yellow opaque cap and yellow opaque body, with black imprint "LU" on cap and "O61" on body. Bottle of 30:                                                    NDC 68180-246-06 Bottle of 90:                                                    NDC 68180-246-09 Bottle of 500:                                                  NDC 68180-246-02 14 mg Capsule Size '4' hard gelatin capsule with yellow opaque cap and dark green opaque body, with black imprint "LU" on cap and "O62" on body. Bottle of 30:                                                    NDC 68180-247-06 Bottle of 90:                                                    NDC 68180-247-09 Bottle of 500:                                                  NDC 68180-247-02 Blister of 10 X 10 Unit-Dose:                        NDC 68180-247-13 21 mg Capsule Size '4' hard gelatin capsule with white opaque cap and dark green opaque body, with black imprint "LU" on cap and "O63" on body. Bottle of 30:                                                    NDC 68180-248-06 Bottle of 90:                                                    NDC 68180-248-09 Bottle of 500:                                                  NDC 68180-248-02 28 mg Capsule Size '3' hard gelatin dark green capsule with black imprint "LU" on cap and "O64" on body. Bottle of 30:                                                    NDC 68180-249-06 Bottle of 90:                                                    NDC 68180-249-09 Bottle of 500:                                                  NDC 68180-249-02 Blister of 10 X 10 Unit-Dose:                        NDC 68180-249-13 Storage Store memantine hydrochloride extended-release at 25°C (77°F); excursions permitted to 15 to 30°C (59 to 86°F) [see USP Controlled Room Temperature].

Statut de autorisation:

Abbreviated New Drug Application

Notice patient

Lupin Pharmaceuticals, Inc.
----------
PATIENT INFORMATION
Memantine Hydrochloride Extended-release Capsules
[me-MAN-teen HYE-droe-KLOR-ide]
Rx Only
Read this Patient Information that comes with memantine hydrochloride
extended-release capsules before
you start taking it and each time you get a refill. There may be new
information. This information does not
take the place of talking to your doctor about your medical condition
or your treatment.
What are memantine hydrochloride extended-release capsules?
Memantine hydrochloride extended-release capsule is a prescription
medicine used for the treatment of
moderate to severe dementia in people with Alzheimer's disease.
Memantine hydrochloride extended-release
capsule belongs to a class of medicines called NMDA
(N-methyl-D-aspartate) inhibitors.
It is not known if memantine hydrochloride extended-release capsule is
safe and effective in children.
Who should not take memantine hydrochloride extended-release capsules?
Do not take memantine hydrochloride extended-release capsules if you
are allergic to memantine or any of
the other ingredients in memantine hydrochloride extended-release
capsules. See the end of this leaflet for a
complete list of ingredients in memantine hydrochloride
extended-release capsules.
What should I tell my doctor before taking memantine hydrochloride
extended-release capsules?
Before you take memantine hydrochloride extended-release capsules,
tell your doctor if you:
•
have or have had seizures
•
have or have had problems passing urine
•
have or have had bladder or kidney problems
•
have liver problems
•
have any other medical conditions
•
are pregnant or plan to become pregnant. It is not known if memantine
hydrochloride extended-
release will harm your unborn baby.
•
are breastfeeding or plan to breastfeed. It is not known if memantine
hydrochloride extended-release
passes into your breast milk. You and your doctor should decide if you
will take memantine
hydrochloride extended-release or breastfeed.
Tell your doctor about all

Résumé des caractéristiques du produit

MEMANTINE HYDROCHLORIDE- MEMANTINE HYDROCHLORIDE CAPSULE, EXTENDED
RELEASE
LUPIN PHARMACEUTICALS, INC.
----------
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 capsule is available as an
extended-release capsule in the
following strengths: 7 mg, 14 mg, 21 mg, 28 mg (3)
CONTRAINDICATIONS
Memantine hydrochloride extended-release is 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 28 mg/day were headache,
diarrhea and dizziness. (6.1)
TO REPORT SUSPECTED ADVERSE REACTIONS, CONTACT LUPIN PHARMACEUTICALS,
INC. AT 1-800-
399-2561 OR FDA AT 1-800-FDA-