Start your appropriate moderate to severe Alzheimer’s patients on NAMZARIC® to help improve cognition and global function1

In the overall study population

Demonstrated significantly superior improvement in cognition at 24 weeks using an LOCF* analysis2

NAMENDA XR® (memantine HCl) 28 mg+AChEI† vs placebo+AChEI treatment (P=0.001)2

  • Showed a 2.6 unit mean difference between treatment groups on the SIB at endpoint2
  • The SIB examines selected aspects of cognitive performance, including elements of attention, orientation, language, memory, visuospatial ability, construction, praxis, and social interaction. The SIB scoring range is from 0 to 100, with lower scores indicating greater cognitive impairment2

Please see Study Description below.

In the subset population, NAMZARIC (combination therapy with NAMENDA XR 28 mg+donepezil HCl 10 mg) demonstrated improvement in cognition (2.7 units)—similar to that observed in the overall study population (2.6 units) at 24 weeks.1

  • A pharmacokinetic study demonstrated the bioequivalence of NAMZARIC compared with coadministered NAMENDA XR 28 mg and donepezil HCl 10 mg1

Study Description: Results of a randomized, multicenter, double-blind, placebo-controlled, parallel-group, multinational study investigating the efficacy of NAMENDA XR 28 mg+AChEI in outpatients with moderate to severe AD. The study involved 677 patients with probable AD, ≥50 years of age, with a Mini-Mental State Examination (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. Approximately 68% of the patients received donepezil HCl (n=464) as the AChEI at baseline and throughout the study. Patients were randomized (1:1) to receive NAMENDA XR 28 mg (n=342; 28 mg QD) or placebo (n=335) for 24 weeks; 545 patients (273 memantine, 272 placebo) completed the study. Primary efficacy measures were changes from baseline on the SIB and the Clinician’s Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus). Primary data analyses were performed using the LOCF approach for missing data; results were also analyzed using the observed cases (OC) approach. The figure above shows the time course of the change from baseline in SIB score for patients completing 24 weeks of treatment.2,3

There is no evidence that NAMZARIC prevents or slows neurodegeneration in patients with AD.

*LOCF=last observation carried forward.

†AChEI=acetylcholinesterase inhibitor.

‡SIB=Severe Impairment Battery.

§SEM=Standard Error of the Mean.

Important Information About NAMENDA XR

  • NAMENDA XR (memantine HCl) is indicated for the treatment of moderate to severe Alzheimer’s disease.
  • NAMENDA XR is contraindicated in patients with a hypersensitivity to memantine HCl or any of its excipients. NAMENDA XR has not been systematically evaluated in patients with seizure disorders. Please see the following sections of the NAMZARIC Important Safety Information for additional Important Safety Information relating to NAMENDA XR (memantine HCl): Genitourinary Conditions under Warnings and Precautions; most common Adverse Reactions in patients taking memantine HCl; and Drug Interactions regarding alterations in urine pH and combined use of memantine HCl with other NMDA antagonists.
Please see full Prescribing Information for NAMENDA XR.

In the overall study population

Demonstrated significantly superior improvement in global function at 24 weeks using an LOCF* analysis2

NAMENDA XR® (memantine HCl) 28 mg+AChEI† vs placebo+AChEI treatment2

  • Statistically superior improvement in global function vs placebo+AChEI treatment at endpoint2
  • Showed a 0.3 unit mean difference between treatment groups on the CIBIC-Plus at endpoint2

  • More patients taking NAMENDA XR 28 mg+AChEI improved or had no change in global function vs patients taking placebo+AChEI2
  • CIBIC-Plus, a comprehensive evaluation of 4 domains: general, functional, cognitive, and behavioral, which includes caregiver input. The CIBIC-Plus measures clinically observable differences2

Please see Study Description below.

In the subset population, NAMZARIC (combination therapy with NAMENDA XR 28 mg+donepezil HCl 10 mg) demonstrated improvement in global function—similar to that observed in the overall study population (0.3 units) at 24 weeks.1

  • A pharmacokinetic study demonstrated the bioequivalence of NAMZARIC compared with coadministered NAMENDA XR 28 mg and donepezil HCl 10 mg1

Study Description: Results of a randomized, multicenter, double-blind, placebo-controlled, parallel-group, multinational study investigating the efficacy of NAMENDA XR 28 mg+AChEI 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. Approximately 68% of the patients randomized to receive either NAMENDA XR 28 mg or placebo were taking donepezil HCl (N=464) as the AChEI at baseline and throughout the study. Patients were randomized (1:1) to receive NAMENDA XR 28 mg (n=342; 28 mg QD) or placebo (n=335) for 24 weeks; 545 patients (273 memantine HCl, 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 first figure above shows the time course of the CIBIC-Plus score for patients completing 24 weeks of treatment. The second figure above shows the percent distribution of CIBIC-Plus ratings in patients who completed 24 weeks of treatment.2,3

There is no evidence that NAMZARIC prevents or slows neurodegeneration in patients with AD.

*LOCF=last observation carried forward.

†AChEI=acetylcholinesterase inhibitor.

‡CIBIC-Plus=Clinician’s Interview-Based Impression of Change Plus Caregiver Input. 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.

§SEM=Standard Error of the Mean.

Important Information About NAMENDA XR

  • NAMENDA XR (memantine HCl) is indicated for the treatment of moderate to severe Alzheimer’s disease.
  • NAMENDA XR is contraindicated in patients with a hypersensitivity to memantine HCl or any of its excipients. NAMENDA XR has not been systematically evaluated in patients with seizure disorders. Please see the following sections of the NAMZARIC Important Safety Information for additional Important Safety Information relating to NAMENDA XR (memantine HCl): Genitourinary Conditions under Warnings and Precautions; most common Adverse Reactions in patients taking memantine HCl; and Drug Interactions regarding alterations in urine pH and combined use of memantine HCl with other NMDA antagonists.
Please see full Prescribing Information for NAMENDA XR.
Learn about the safety profile of NAMZARIC

References:

  1. NAMZARIC (memantine and donepezil hydrochlorides) extended-release Prescribing Information. Irvine, CA: Allergan USA, Inc.; 2016.
  2. NAMENDA XR (memantine hydrochloride) extended-release Prescribing Information. St. Louis, MO: Forest Pharmaceuticals, Inc.; 2014.
  3. Saxton J, McGonigle KL, Swihart AA, Boller F. The Severe Impairment Battery. Bury St Edmunds: Thames Valley Test Company; 1993.
INDICATIONS AND USAGE

NAMZARIC (memantine and donepezil hydrochlorides) extended-release capsules are indicated for the treatment of moderate to severe dementia of the Alzheimer’s type in patients stabilized on 10 mg of donepezil hydrochloride once-daily.

Important Safety Information
CONTRAINDICATIONS
  • NAMZARIC is contraindicated in patients with known hypersensitivity to memantine hydrochloride, donepezil hydrochloride, piperidine derivatives, or to any excipients used in the formulation.
Warnings and Precautions
Anesthesia
  • NAMZARIC is likely to exaggerate succinylcholine-type muscle relaxation during anesthesia.
Cardiovascular Conditions
  • NAMZARIC may have vagotonic effects on the sinoatrial and atrioventricular nodes manifesting as bradycardia or heart block. Bradycardia or heart block may manifest in patients both with and without known underlying cardiac conduction abnormalities. Syncopal episodes have been reported in association with the use of donepezil hydrochloride, an active ingredient in NAMZARIC.
Peptic Ulcer Disease and Gastrointestinal Bleeding
  • Patients treated with NAMZARIC should be monitored closely for symptoms of active or occult gastrointestinal bleeding, especially those at increased risk for developing ulcers, those with a history of ulcer disease, or those receiving concurrent nonsteroidal anti-inflammatory drugs (NSAIDs).
Nausea and Vomiting
  • NAMZARIC can cause diarrhea, nausea, and vomiting. Although in most cases these effects have been mild and transient, sometimes lasting one to three weeks, and have resolved during continued use of donepezil hydrochloride, patients should be observed closely at the initiation of treatment.
Genitourinary Conditions
  • NAMZARIC may cause bladder outflow obstructions. Conditions that raise urine pH may decrease the urinary elimination of memantine, an active ingredient in NAMZARIC, resulting in increased plasma levels of memantine.
Seizures
  • Cholinomimetics, including donepezil hydrochloride, are believed to have some potential to cause generalized convulsions. However, seizure activity also may be a manifestation of Alzheimer’s disease.
Pulmonary Conditions
  • Cholinesterase inhibitors should be prescribed with care to patients with a history of asthma or obstructive pulmonary disease.
ADVERSE REACTIONS
  • The most common adverse reactions, occurring at a frequency of at least 5% in patients taking memantine hydrochloride extended-release 28 mg/day, and greater than placebo, were headache (6% vs 5%), diarrhea (5% vs 4%), and dizziness (5% vs 1%).
  • The most common adverse reactions, occurring at a frequency of at least 5% in patients taking donepezil, and at twice or more the rate of placebo, were diarrhea (10% vs 4%), anorexia (8% vs 4%), vomiting (8% vs 4%), nausea (6% vs 2%), and ecchymosis (5% vs 2%).
Drug Interactions
  • Alterations of urine pH toward the alkaline condition may lead to an accumulation of memantine with a possible increase in adverse reactions. NAMZARIC 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.
  • The combined use of memantine hydrochloride with other NMDA antagonists (amantadine, ketamine, and dextromethorphan) has not been systematically evaluated and such use should be approached with caution.
  • Inhibitors of CYP450, 3A4 (eg, ketoconazole) and 2D6 (eg, quinidine), inhibit donepezil metabolism in vitro. Whether there is a clinical effect of quinidine is not known.
  • Inducers of CYP3A4 (eg, phenytoin, carbamazepine, dexamethasone, rifampin, and phenobarbital) could increase the rate of elimination of donepezil.
  • Cholinesterase inhibitors, including donepezil hydrochloride, have the potential to interfere with the activity of anticholinergic medications.
  • A synergistic effect may be expected when cholinesterase inhibitors, including donepezil hydrochloride, are given concurrently with succinylcholine, similar neuromuscular blocking agents, or cholinergic agonists such as bethanechol.
DOSAGE AND ADMINISTRATION
For patients stabilized on donepezil and not currently on memantine:
  • For patients stabilized on donepezil hydrochloride 10 mg and not currently on memantine hydrochloride, the recommended starting dose of NAMZARIC is 7 mg/10 mg, taken once a day in the evening. The dose should be increased in 7 mg increments of the memantine hydrochloride component to the recommended maintenance dose of 28 mg/10 mg once daily. The minimum recommended interval between dose increases is one week. The dose should only be increased if the previous dose has been well tolerated. The maximum dose is 28 mg/10 mg once daily.
  • For patients with severe renal impairment (creatinine clearance 5-29 mL/min, based on the Cockcroft-Gault equation) stabilized on donepezil hydrochloride 10 mg once daily and not currently on memantine hydrochloride, the recommended starting dose of NAMZARIC is 7 mg/10 mg taken once a day in the evening. The dose should be increased to the recommended maintenance dose of 14 mg/10 mg once daily in the evening after a minimum of one week.
For patients stabilized on both donepezil and memantine:
  • Patients stabilized on memantine hydrochloride (10 mg twice daily or 28 mg extended-release once daily) and donepezil hydrochloride 10 mg once daily can be switched to NAMZARIC 28 mg/10 mg, taken once a day in the evening. Patients should start NAMZARIC the day following the last dose of memantine hydrochloride and donepezil hydrochloride administered separately.
  • Patients with severe renal impairment, stabilized on memantine hydrochloride (5 mg twice daily or 14 mg extended-release once daily) and donepezil hydrochloride 10 mg once daily, can be switched to NAMZARIC 14 mg/10 mg, taken once daily in the evening.

Please see accompanying full Prescribing Information.

This site is intended for U.S. healthcare professionals only. The products discussed on this site may have different product labeling outside of the United States.
NAMZARIC®, NAMENDA XR®, NAMENDA® and their designs are registered trademarks of Merz Pharma GmbH & Co. KGaA.
All other trademarks and product names are the property of their respective owners.
© 2023 AbbVie. All rights reserved.
NMZ108265    06/17

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INDICATIONS AND USAGE

NAMZARIC (memantine and donepezil hydrochlorides) extended-release capsules are indicated for the treatment of moderate to severe dementia of the Alzheimer’s type in patients stabilized on 10 mg of donepezil hydrochloride once-daily.

Important Safety Information
CONTRAINDICATIONS
  • NAMZARIC is contraindicated in patients with known hypersensitivity to memantine hydrochloride, donepezil hydrochloride, piperidine derivatives, or to any excipients used in the formulation.
Warnings and Precautions
Anesthesia
  • NAMZARIC is likely to exaggerate succinylcholine-type muscle relaxation during anesthesia.
Cardiovascular Conditions
  • NAMZARIC may have vagotonic effects on the sinoatrial and atrioventricular nodes manifesting as bradycardia or heart block. Bradycardia or heart block may manifest in patients both with and without known underlying cardiac conduction abnormalities. Syncopal episodes have been reported in association with the use of donepezil hydrochloride, an active ingredient in NAMZARIC.
Peptic Ulcer Disease and Gastrointestinal Bleeding
  • Patients treated with NAMZARIC should be monitored closely for symptoms of active or occult gastrointestinal bleeding, especially those at increased risk for developing ulcers, those with a history of ulcer disease, or those receiving concurrent nonsteroidal anti-inflammatory drugs (NSAIDs).
Nausea and Vomiting
  • NAMZARIC can cause diarrhea, nausea, and vomiting. Although in most cases these effects have been mild and transient, sometimes lasting one to three weeks, and have resolved during continued use of donepezil hydrochloride, patients should be observed closely at the initiation of treatment.
Genitourinary Conditions
  • NAMZARIC may cause bladder outflow obstructions. Conditions that raise urine pH may decrease the urinary elimination of memantine, an active ingredient in NAMZARIC, resulting in increased plasma levels of memantine.
Seizures
  • Cholinomimetics, including donepezil hydrochloride, are believed to have some potential to cause generalized convulsions. However, seizure activity also may be a manifestation of Alzheimer’s disease.
Pulmonary Conditions
  • Cholinesterase inhibitors should be prescribed with care to patients with a history of asthma or obstructive pulmonary disease.
ADVERSE REACTIONS
  • The most common adverse reactions, occurring at a frequency of at least 5% in patients taking memantine hydrochloride extended-release 28 mg/day, and greater than placebo, were headache (6% vs 5%), diarrhea (5% vs 4%), and dizziness (5% vs 1%).
  • The most common adverse reactions, occurring at a frequency of at least 5% in patients taking donepezil, and at twice or more the rate of placebo, were diarrhea (10% vs 4%), anorexia (8% vs 4%), vomiting (8% vs 4%), nausea (6% vs 2%), and ecchymosis (5% vs 2%).
Drug Interactions
  • Alterations of urine pH toward the alkaline condition may lead to an accumulation of memantine with a possible increase in adverse reactions. NAMZARIC 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.
  • The combined use of memantine hydrochloride with other NMDA antagonists (amantadine, ketamine, and dextromethorphan) has not been systematically evaluated and such use should be approached with caution.
  • Inhibitors of CYP450, 3A4 (eg, ketoconazole) and 2D6 (eg, quinidine), inhibit donepezil metabolism in vitro. Whether there is a clinical effect of quinidine is not known.
  • Inducers of CYP3A4 (eg, phenytoin, carbamazepine, dexamethasone, rifampin, and phenobarbital) could increase the rate of elimination of donepezil.
  • Cholinesterase inhibitors, including donepezil hydrochloride, have the potential to interfere with the activity of anticholinergic medications.
  • A synergistic effect may be expected when cholinesterase inhibitors, including donepezil hydrochloride, are given concurrently with succinylcholine, similar neuromuscular blocking agents, or cholinergic agonists such as bethanechol.
DOSAGE AND ADMINISTRATION
For patients stabilized on donepezil and not currently on memantine:
  • For patients stabilized on donepezil hydrochloride 10 mg and not currently on memantine hydrochloride, the recommended starting dose of NAMZARIC is 7 mg/10 mg, taken once a day in the evening. The dose should be increased in 7 mg increments of the memantine hydrochloride component to the recommended maintenance dose of 28 mg/10 mg once daily. The minimum recommended interval between dose increases is one week. The dose should only be increased if the previous dose has been well tolerated. The maximum dose is 28 mg/10 mg once daily.
  • For patients with severe renal impairment (creatinine clearance 5-29 mL/min, based on the Cockcroft-Gault equation) stabilized on donepezil hydrochloride 10 mg once daily and not currently on memantine hydrochloride, the recommended starting dose of NAMZARIC is 7 mg/10 mg taken once a day in the evening. The dose should be increased to the recommended maintenance dose of 14 mg/10 mg once daily in the evening after a minimum of one week.
For patients stabilized on both donepezil and memantine:
  • Patients stabilized on memantine hydrochloride (10 mg twice daily or 28 mg extended-release once daily) and donepezil hydrochloride 10 mg once daily can be switched to NAMZARIC 28 mg/10 mg, taken once a day in the evening. Patients should start NAMZARIC the day following the last dose of memantine hydrochloride and donepezil hydrochloride administered separately.
  • Patients with severe renal impairment, stabilized on memantine hydrochloride (5 mg twice daily or 14 mg extended-release once daily) and donepezil hydrochloride 10 mg once daily, can be switched to NAMZARIC 14 mg/10 mg, taken once daily in the evening.

Please see accompanying full Prescribing Information.

Indication

NAMZARIC (memantine and donepezil hydrochlorides) extended-release capsules are indicated for the treatment of moderate to severe dementia of the Alzheimer’s type in patients stabilized on 10 mg of donepezil hydrochloride once-daily.