These highlights do not include all the information needed to use NAMENDA XR capsules safely and effectively. See full prescribing information for NAMENDA XR capsules.
NAMENDA XR ® (memantine hydrochloride) extended release capsules
Initial U.S. Approval: 2003
INDICATIONS AND USAGE
NAMENDA XR contains memantine HCl, an NMDA receptor antagonist indicated for the treatment of moderate to severe dementia of the Alzheimer's type. (1) DOSAGE AND ADMINISTRATION
Maintenance Dose 28 mg NAMENDA XR once daily (2.1)
A minimum of 1 week of treatment with the previous dose should be observed before increasing the dose. (2.1)
A target dose of 14 mg once daily is recommended in patients with severe renal impairment. (2.1)
DOSAGE FORMS AND STRENGTHS
NAMENDA XR is available as an extended-release capsule (3.1) in the following strengths: 7 mg, 14 mg, 21 mg, 28 mg (3.1, 3.2)
CONTRAINDICATIONS
NAMENDA XR is contraindicated in patients with known hypersensitivity to memantine hydrochloride or to any excipients used in the formulation. (4.1)
WARNINGS AND PRECAUTIONS
Conditions that raise urine pH may decrease the urinary elimination of memantine resulting in increased plasma levels of memantine. (5.1)
ADVERSE REACTIONS
The most commonly observed adverse reactions occurring at a frequency of at least 5% and greater than placebo with administration of NAMENDA XR 28 mg/day were headache, diarrhea and dizziness. Other less common and sometimes serious adverse events have been reported. (6)
To report SUSPECTED ADVERSE REACTIONS, Contact Forest Laboratories, Inc. at 1-800-678-1605 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
DRUG INTERACTIONS
Use with other NMDA antagonists (amantadine, ketamine, and dextromethorphan) has not been systematically eva luated and such use should be approached with caution. (7.1)
USE IN SPECIFIC POPULATIONS
Pediatric Use: The safety and effectiveness of NAMENDA XR in pediatric patients have not been established. (8.4)
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
Sections or subsections omitted from the full prescribing information are not listed.
1 INDICATIONS AND USAGE
NAMENDA XR (memantine hydrochloride) extended-release capsules are indicated for the treatment of moderate to severe dementia of the Alzheimer's type.
2 DOSAGE AND ADMINISTRATION
2.1 Recommended Dosing
The dosage of NAMENDA XR shown to be effective in a controlled clinical trial is 28 mg once daily.
The recommended starting dose of NAMENDA XR is 7 mg once daily. The recommended target dose is 28 mg once daily. The dose should be increased in 7 mg increments to 28 mg once daily. The minimum recommended interval between dose increases is one week, and only if the previous dose has been well tolerated. The maximum recommended dose is 28 mg once daily.
NAMENDA XR can be taken with or without food. NAMENDA XR capsules can be taken intact or may be opened, sprinkled on applesauce, and thereby swallowed. The entire contents of each NAMENDA XR capsule should be consumed; the dose should not be divided.
Except when opened and sprinkled on applesauce, as described above, NAMENDA XR should be swallowed whole. NAMENDA XR capsules should not be divided, chewed, or crushed.
Switching from NAMENDA Tablets to NAMENDA XR Capsules:
Patients treated with NAMENDA tablets may be switched to NAMENDA XR capsules as follows:
It is recommended that a patient who is on a regimen of 10 mg twice daily of NAMENDA tablets be switched to NAMENDA XR 28 mg once daily capsules the day following the last dose of a 10 mg NAMENDA tablet. There is no study addressing the comparative efficacy of these 2 regimens.
In a patient with severe renal impairment, it is recommended that a patient who is on a regimen of 5 mg twice daily of NAMENDA tablets be switched to NAMENDA XR 14 mg once daily capsules the day following the last dose of a 5 mg NAMENDA tablet.
Special Populations:
Hepatic Impairment
No dosage adjustment is recommended in patients with mild or moderate hepatic impairment. NAMENDA XR should be administered with caution to patients with severe hepatic impairment.
Renal Impairment
No dosage adjustment is recommended in patients with mild or moderate renal impairment.
A target dose of 14 mg/day is recommended in patients with severe renal impairment (creatinine clearance of 5 – 29 mL/min, based on the Cockroft-Gault equation).
3 DOSAGE FORMS AND STRENGTHS
3.1 Dosage Form
Capsule:
Each capsule contains 7 mg, 14 mg, 21 mg or 28 mg of memantine HCl.
The 7 mg capsules are a yellow opaque #4 size capsule, with “FLI 7 mg” black imprint.
The 14 mg capsules are a yellow cap and dark green opaque body #4 size capsule, with “FLI 14 mg” black imprint on the yellow cap.
The 21 mg capsules are a white to off-white cap and dark green opaque body #4 size capsule, with “FLI 21 mg” black imprint on the white to off-white cap.
The 28 mg capsules are a dark green opaque #3 size capsule, with “FLI 28 mg” white imprint.
3.2 Dosage Strengths
Each 7 mg capsule contains 7 mg memantine HCl.
Each 14 mg capsule contains 14 mg memantine HCl.
Each 21 mg capsule contains 21 mg memantine HCl.
Each 28 mg capsule contains 28 mg memantine HCl.
For a full list of excipients, see Description (11).
4 CONTRAINDICATIONS
4.1 Hypersensitivity
NAMENDA XR is contraindicated in patients with known hypersensitivity to memantine hydrochloride or to any excipients used in the formulation [See Description (11)].
5 WARNINGS AND PRECAUTIONS
5.1 Genitourinary Conditions
Conditions that raise urine pH may decrease the urinary elimination of memantine resulting in increased plasma levels of memantine.
5.2 Seizures
NAMENDA XR has not been systematically eva luated in patients with a seizure disorder. In clinical trials of memantine, seizures occurred in 0.3% of patients treated with memantine and 0.6% of patients treated with placebo.
6 ADVERSE REACTIONS
6.1 Clinical Trial Data Sources
NAMENDA XR was eva luated in a double-blind placebo-controlled trial treating a total of 676 patients with moderate to severe dementia of the Alzheimer's type (341 patients treated with NAMENDA XR 28 mg/day dose and 335 patients treated with placebo) for a treatment period up to 24 weeks.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
6.2 Adverse Reactions Leading to Discontinuation
In the placebo-controlled clinical trial of NAMENDA XR [See Clinical Studies (14)], which treated a total of 676 patients, the proportion of patients in the NAMENDA XR 28 mg/day dose and placebo groups who discontinued treatment due to adverse events were 10.0% and 6.3%, respectively. The most common adverse reaction in the NAMENDA XR treated group that led to treatment discontinuation in this study was dizziness at a rate of 1.5%.
6.3 Most Common Adverse Reactions
The most commonly observed adverse reactions seen in patients administered NAMENDA XR in the controlled clinical trial, defined as those occurring at a frequency of at least 5% in the NAMENDA XR group and at a higher frequency than placebo were headache, diarrhea and dizziness.
Table 1 lists treatment-emergent adverse reactions that were observed at an incidence of ≥ 2% in the NAMENDA XR treated group and occurred at a rate greater than placebo.
Table 1: Adverse reactions observed with a frequency of ≥ 2% and occurring with a rate greater than placebo
Adverse reaction
Placebo (n = 335) %
NAMENDA XR 28mg (n = 341) %
Gastrointestinal Disorders
Diarrhea
4
5
Constipation
1
3
Abdominal pain
1
2
Vomiting
1
2
Infections and infestations
Influenza
3
4
Investigations
Weight, increased
1
3
Musculoskeletal and connective tissue disorders
Back pain
1
3
Nervous system disorders
Headache
5
6
Dizziness
1
5
Somnolence
1
3
Psychiatric disorders
Anxiety
3
4
Depression
1
3
Aggression
1
2
Renal and urinary disorders
Urinary incontinence
1
2
Vascular disorders
Hypertension
2
4
Hypotension
1
2
6.4 Vital Sign Changes
NAMENDA XR and placebo groups were compared with respect to (1) mean change from baseline in vital signs (pulse, systolic blood pressure, diastolic blood pressure, and weight) and (2) the incidence of patients meeting criteria for potentially clinically significant changes from baseline in these variables. There were no clinically important changes in vital signs in patients treated with NAMENDA XR. A comparison of supine and standing vital sign measures for NAMENDA XR and placebo in Alzheimer's patients indicated that NAMENDA XR treatment is not associated with orthostatic changes.
6.5 Laboratory Changes
NAMENDA XR and placebo groups were compared with respect to (1) mean change from baseline in various serum chemistry, hematology, and urinalysis variables and (2) the incidence of patients meeting criteria for potentially clinically significant changes from baseline in these variables. These analyses revealed no clinically important changes in laboratory test parameters associated with NAMENDA XR treatment.
6.6 ECG Changes
NAMENDA XR and placebo groups were compared with respect to (1) mean change from baseline in various ECG parameters and (2) the incidence of patients meeting criteria for potentially clinically significant changes from baseline in these variables. These analyses revealed no clinically important changes in ECG parameters associated with NAMENDA XR treatment.
6.7 Other Adverse Reactions Observed During Clinical Trials of NAMENDA XR
Following is a list of treatment-emergent adverse reactions reported from 750 patients treated with NAMENDA XR for periods up to 52 weeks in double-blind or open-label clinical trials. The listing does not include those events already listed in Table 1, those events for which a drug cause was remote, those events for which descriptive terms were so lacking in specificity as to be uninformative, and those events reported only once which did not have a substantial probability of being immediately life threatening. Events are categorized by body system.
