Efficacy: NAMENDA XR 28 mg+AChEI

Significant improvement in global function

Combination therapy with NAMENDA XR 28 mg+AChEI demonstrated greater improvement in global function vs placebo+AChEI treatment at 24 weeks, using an LOCF analysis1


global-function-improvement-chart-1

Study Description: Results of a randomized, multicenter, double-blind, placebo-controlled, parallel-group, multinational study investigating the efficacy of NAMENDA XR in outpatients with moderate to severe AD. The study involved 677 patients with probable AD, ≥50 years of age, with an MMSE score of ≥3 to ≤14 points, who were on a stable dose of an AChEI (donepezil, rivastigmine, or galantamine) for a minimum of 3 months prior to study entry and should have remained on the same dose throughout the study. Patients were randomized (1:1) to receive NAMENDA XR (n=342; 28 mg QD) or placebo (n=335) for 24 weeks; 545 patients (273 NAMENDA XR, 272 placebo) completed the study. Primary efficacy measures were changes from baseline on the SIB and the CIBIC-Plus. Primary data analyses were performed using the LOCF approach for missing data; results were also analyzed using the OC approach. The figure above shows the time course of the CIBIC-Plus score for patients completing 24 weeks of treatment.2

CIBIC-Plus—a comprehensive evaluation of 4 domains: general, functional, cognitive, and behavioral1

  • CIBIC-Plus=Clinician's Interview-Based Impression of Change Plus Caregiver Input. CIBIC-Plus instrument used in this trial evaluated 4 domains: general (overall clinical status), functional (including activities of daily living), cognitive, and behavioral. Scoring is based on a 7-point categorical rating, ranging from a score of 1 (marked improvement), to a score of 4 (no change), to a score of 7 (marked worsening). The CIBIC-Plus is not a single, standardized instrument. Results reflect clinical experience only from the trial in which it was used and cannot be compared directly with CIBIC-Plus results from other clinical trials.1,3
  • SEM=Standard Error of the Mean.

NAMENDA XR 28 mg+AChEI was statistically significantly superior to treatment with placebo+AChEI at endpoint, using an LOCF§ analysis1,2


global-function-improvement-chart-2

Study Description: Results of a randomized, multicenter, double-blind, placebo-controlled, parallel-group, multinational study investigating the efficacy of NAMENDA XR in outpatients with moderate to severe AD. The study involved 677 patients with probable AD, ≥50 years of age, with an MMSE score of ≥3 to ≤14 points, who were on a stable dose of an AChEI (donepezil, rivastigmine, or galantamine) for a minimum of 3 months prior to study entry and should have remained on the same dose throughout the study. Patients were randomized (1:1) to receive NAMENDA XR (n=342; 28 mg QD) or placebo (n=335) for 24 weeks; 545 patients (273 NAMENDA XR, 272 placebo) completed the study. Primary efficacy measures were changes from baseline on the SIB and the CIBIC-Plus. Primary data analyses were performed using the LOCF approach for missing data; results were also analyzed using the OC approach.2

  • At endpoint, there was a 0.3 unit mean difference between treatment groups on the CIBIC-Plus1

73% of patients treated with NAMENDA XR 28 mg+AChEI demonstrated improvement or no change in global function at endpoint vs 67% of patients in the placebo+AChEI arm, using an LOCF analysis2


global-function-improvement-chart-3

Study Description: Results of a randomized, multicenter, double-blind, placebo-controlled, parallel-group, multinational study investigating the efficacy of NAMENDA XR in outpatients with moderate to severe AD. The study involved 677 patients with probable AD, ≥50 years of age, with an MMSE score of ≥3 to ≤14 points, who were on a stable dose of an AChEI (donepezil, rivastigmine, or galantamine) for a minimum of 3 months prior to study entry and should have remained on the same dose throughout the study. Patients were randomized (1:1) to receive NAMENDA XR (n=342; 28 mg QD) or placebo (n=335) for 24 weeks; 545 patients (273 NAMENDA XR, 272 placebo) completed the study. Primary efficacy measures were changes from baseline on the SIB and the CIBIC-Plus. Primary data analyses were performed using the LOCF approach for missing data; results were also analyzed using the OC approach. The figure above shows the percent distribution of CIBIC-Plus ratings in patients who completed 24 weeks of treatment.2

  • AChEI=acetylcholinesterase inhibitor.
  • LOCF=last observation carried forward.

Review efficacy in cognition with NAMENDA XR 28 mg

View side effects and pharmacokinetic drug interactions

References:

  1. NAMENDA XR (memantine HCl) extended-release Prescribing Information. Cincinnati, OH: Forest Pharmaceuticals, Inc.; 2014.
  2. Data on file. Forest Laboratories, LLC
  3. Schneider LS, Olin JT, Doody RS, et al. Validity and reliability of the Alzheimer's Disease Cooperative Study–Clinical Global Impression of Change. Alzheimer Dis Assoc Disord. 1997;11(suppl 2):S22-S32.

NAMENDA XR® (memantine hydrochloride) extended-release capsules are indicated for the treatment of moderate to severe dementia of the Alzheimer’s type.

Important Safety Information

Contraindications

  • NAMENDA XR is contraindicated in patients with known hypersensitivity to memantine hydrochloride or to any excipients used in the formulation.

Warnings and Precautions

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

Adverse Reactions

  • The most commonly observed adverse reactions in patients administered NAMENDA XR (28 mg/day) in a 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 (6% vs 5%), diarrhea (5% vs 4%), and dizziness (5% vs 1%).
  • NAMENDA XR has not been systematically evaluated in patients with a seizure disorder.

Drug Interactions

  • Alterations of urine pH toward the alkaline condition may lead to an accumulation of memantine with a possible increase in adverse reactions. NAMENDA XR should be used with caution under conditions that may be associated with increased urine pH including alterations by diet, drugs, and the clinical state of the patient.
  • No drug-drug interaction studies have been conducted with NAMENDA XR, specifically. The combined use of NAMENDA XR with other NMDA antagonists (amantadine, ketamine, or dextromethorphan) has not been systematically evaluated and such use should be approached with caution.

Dosage and Administration

  • 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.
  • 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.
  • It is recommended that a patient with severe renal impairment 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

  • NAMENDA XR should be administered with caution to patients with severe hepatic 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 Cockcroft-Gault equation).