Namzaric

Donepezil improves the function of nerve cells in the brain. It works by preventing the breakdown of a chemical called acetylcholine (ah SEET il KOE leen). People with dementia usually have lower levels of this chemical, which is important for the processes of memory, thinking, and reasoning.

Memantine reduces the actions of chemicals in the brain that may contribute to the symptoms of Alzheimer's disease.

Donepezil and memantine is a combination medicine used to treat moderate to severe dementia of the Alzheimer's type.

Donepezil and memantine is not a cure for Alzheimer's disease. This condition will progress over time, even in people who take donepezil.

Donepezil and memantine may also be used for purposes not listed in this medication guide.

Follow all directions on your medicine label and package. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

You should not use this medicine if you are allergic to donepezil or memantine.

To make sure donepezil and memantine is safe for you, tell your doctor if you have:

• asthma or other breathing disorder;
• heart disease, or heart rhythm disorder;
• a history of seizures;
• stomach ulcer, or a history of stomach or intestinal bleeding;
• bladder obstruction or other urination problems;
• liver disease; or
• kidney disease.

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether donepezil and memantine passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Take Namzaric exactly as prescribed.

Namzaric comes in an extended-release capsule form and is taken once a day in the evening before going to bed.

Do not change your dose or stop taking Namzaric without talking to your doctor.

Take Namzaric with or without food.

Namzaric capsules may be opened and sprinkled on applesauce before swallowing. Sprinkle all of the medicine in the capsule on the applesauce. Do not divide the dose.

If you do not open and sprinkle Namzaric capsules on applesauce, the Namzaric capsules must be swallowed whole. Do not divide, chew, or crush Namzaric capsules.

If you miss a dose take Namzaric at your next scheduled dose. Do not take two doses of Namzaric at the same time

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include severe dizziness, drowsiness, weakness, trouble walking, slow or fast heart rate, sweating, confusion, agitation, hallucinations, unusual thoughts or behavior, weak or shallow breathing, fainting, or seizure.

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

In the U.S.

• Namzaric
• Namzaric Titration Pack

Available Dosage Forms:

• Capsule, Extended Release
• Capsule, Delayed Release

Therapeutic Class: Central Nervous System Agent

Pharmacologic Class: Memantine

Namzaric is 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.

Use of Memantine with Drugs That Make the Urine Alkaline

The clearance of memantine was reduced by about 80% under alkaline urine conditions at pH 8. Therefore, alterations of urine pH towards the alkaline condition may lead to an accumulation of the drug with a possible increase in adverse reactions. Urine pH is altered by diet, drugs (e.g., carbonic anhydrase inhibitors, sodium bicarbonate) and clinical state of the patient (e.g., renal tubular acidosis or severe infections of the urinary tract). Hence, memantine should be used with caution under these conditions.

Use of Memantine with Other N-methyl-D-aspartate (NMDA) Antagonists

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.

Effect of Other Drugs on the Metabolism of Donepezil

Inhibitors of CYP3A4 (e.g., ketoconazole) and CYP2D6 (e.g., quinidine), inhibit donepezil metabolism in vitro. Whether there is a clinical effect of quinidine is not known.

Inducers of CYP3A4 (e.g., phenytoin, carbamazepine, dexamethasone, rifampin, and phenobarbital) could increase the rate of elimination of donepezil.

Use of Donepezil with Anticholinergics

Because of their mechanism of action, cholinesterase inhibitors, including donepezil hydrochloride, have the potential to interfere with the activity of anticholinergic medications.

Use of Donepezil with Cholinomimetics and Other Cholinesterase Inhibitors

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.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Memantine

There was no evidence of carcinogenicity in a 113-week oral study in mice at doses up to 40 mg/kg/day (7 times the dose of memantine at the maximum recommended human dose [MRHD] of Namzaric [28 mg/10 mg] on a mg/m2 basis). There was also no evidence of carcinogenicity in rats orally dosed at up to 40 mg/kg/day for 71 weeks followed by 20 mg/kg/day (14 and 7 times the MRHD on a mg/m2 basis, respectively) through 128 weeks.

Memantine produced no evidence of genotoxic potential when evaluated in the in vitro S. typhimurium or E. coli reverse mutation assay, an in vitro chromosomal aberration test in human lymphocytes, an in vivo cytogenetics assay for chromosome damage in rats, and the in vivo mouse micronucleus assay. The results were equivocal in an in vitro gene mutation assay using Chinese hamster V79 cells.

No impairment of fertility or reproductive performance was seen in rats administered up to 18 mg/kg/day (6 times the dose of memantine at the MRHD of Namzaric on a mg/m2 basis) orally from 14 days prior to mating through gestation and lactation in females, or for 60 days prior to mating in males.

Donepezil

No evidence of carcinogenic potential was obtained in an 88-week carcinogenicity study of donepezil conducted in mice at oral doses up to 180 mg/kg/day (approximately 90 times the dose of donepezil at the MRHD of Namzaric on a mg/m2 basis), or in a 104-week carcinogenicity study in rats at oral doses up to 30 mg/kg/day (approximately 30 times the dose of donepezil at the MRHD of Namzaric on a mg/m2 basis).

Donepezil was negative in a battery of genotoxicity assays (in vitro bacterial reverse mutation, in vitro mouse lymphoma tk, in vitro chromosomal aberration, and in vivo mouse micronucleus).

Donepezil had no effect on fertility in rats at oral doses up to 10 mg/kg/day (approximately 10 times the dose of donepezil at the MRHD of Namzaric on a mg/m2 basis) when administered to males and females prior to and during mating and continuing in females through implantation.

Animal Toxicology and/or Pharmacology

Memantine induced neuronal lesions (vacuolation and necrosis) in the multipolar and pyramidal cells in cortical layers III and IV of the posterior cingulate and retrosplenial neocortices in rats, similar to those which are known to occur in rodents administered other NMDA receptor antagonists. Lesions were seen after a single dose of memantine. In a study in which rats were given daily oral doses of memantine for 14 days, the no-effect dose for neuronal necrosis was 4 times the dose of memantine at the MRHD of Namzaric on a mg/m2 basis.

In acute and repeat-dose neurotoxicity studies in female rats, oral administration of memantine and donepezil in combination resulted in increased incidence, severity, and distribution of neurodegeneration compared with memantine alone. The no-effect levels of the combination were associated with clinically relevant plasma memantine and donepezil exposures.

The relevance of these findings to humans is unknown.

Rx only NDC 0456-1214-30

30 capsules

Namzaric®

(memantine and donepezil
hydrochlorides) extended-
release capsules

14 mg/10 mg per capsule

AllerganTM

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Common side effects of Namzaric include: diarrhea. Other side effects include: dizziness, nausea, vomiting, anorexia, and ecchymoses. See below for a comprehensive list of adverse effects.

Applies to donepezil / memantine: oral capsule extended release, oral kit

Cardiovascular

Memantine:
Common (1% to 10%): Hypertension, hypotension
Postmarketing reports: Congestive cardiac failure

Donepezil:
Common (1% to 10%): Hypertension, hemorrhage, syncope
Postmarketing reports: Heart block (all types)[Ref]

Nervous system

Memantine:
Common (1% to 10%): Headache, dizziness, somnolence

Donepezil:
Common (1% to 10%): Headache, dizziness, somnolence
Postmarketing reports: Convulsions, neuroleptic malignant syndrome[Ref]

Gastrointestinal

Memantine:
Common (1% to 10%): Diarrhea, constipation, abdominal pain, vomiting
Postmarketing reports: Pancreatitis

Donepezil:
Very common (10% or more): Diarrhea (10%)
Common (1% to 10%): Vomiting, anorexia, nausea
Postmarketing reports: Abdominal pain, pancreatitis[Ref]

Respiratory

Memantine:
Common (1% to 10%): Influenza[Ref]

General

The most common adverse reactions in patients receiving memantine ER were headache, diarrhea, and dizziness. The most common adverse reactions in patients receiving donepezil were diarrhea, anorexia, vomiting, nausea, and ecchymosis.[Ref]

Dermatologic

Memantine:
Postmarketing reports: Stevens Johnson Syndrome

Donepezil:
Common (1% to 10%): Eczema
Postmarketing reports: Rash[Ref]

Hematologic

Memantine:
Postmarketing reports: Agranulocytosis, leukopenia (including neutropenia), pancytopenia, thrombocytopenia, thrombotic thrombocytopenic purpura

Donepezil:
Common (1% to 10%): Ecchymosis
Postmarketing reports: Hemolytic anemia[Ref]

Hepatic

Memantine:
Postmarketing reports: Hepatitis

Donepezil:
Postmarketing reports: Cholecystitis, hepatitis[Ref]

Metabolic

Donepezil:
Common (1% to 10%): Increased creatinine phosphokinase, dehydration, hyperlipidemia
Postmarketing reports: Hyponatremia[Ref]

Musculoskeletal

Memantine:
Common (1% to 10%): Back pain

Donepezil:
Common (1% to 10%): Back pain[Ref]

Other

Memantine:
Common (1% to 10%): Increased weight

Donepezil:
Very common (10% or more): Accident (13%), infection (11%)
Common (1% to 10%): Fever, pain, chest pain[Ref]

Psychiatric

Memantine:
Common (1% to 10%): Anxiety, depression, aggression
Postmarketing reports: Suicidal ideation

Donepezil:
Common (1% to 10%): Insomnia, nervousness, hallucinations, hostility, depression, confusion, emotional lability, personality disorder
Postmarketing reports: Agitation, confusion, hallucinations[Ref]

Renal

Memantine:
Common (1% to 10%): Urinary incontinence
Postmarketing reports: Acute renal failure

Donepezil:
Common (1% to 10%): Urinary incontinence[Ref]

Some side effects of Namzaric may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.