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
- 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
- NAMZARIC is likely to exaggerate succinylcholine-type muscle relaxation during anesthesia.
- 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.
- 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.
- 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.
- Cholinesterase inhibitors should be prescribed with care to patients with a history of asthma or obstructive pulmonary disease.
- 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%).
- 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.
- 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/10mg 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.