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.
There is no evidence that NAMZARIC prevents or slows neurodegeneration in patients with AD.
Important Safety Information
CONTRAINDICATIONS
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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
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NAMZARIC is likely to exaggerate succinylcholine-type muscle relaxation during anesthesia.
Cardiovascular Conditions
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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
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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
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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
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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
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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
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Cholinesterase inhibitors should be prescribed with care to patients with a history of asthma or obstructive pulmonary disease.
ADVERSE REACTIONS
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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%).
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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
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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.
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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.
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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.
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Inducers of CYP3A4 (eg, phenytoin, carbamazepine, dexamethasone, rifampin, and
phenobarbital) could increase the rate of elimination of donepezil.
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Cholinesterase inhibitors, including donepezil hydrochloride, have the potential
to interfere with the activity of anticholinergic medications.
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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:
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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.
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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:
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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.
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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.