Namzaric 5 mg + 5 mg Capsules

Brand Name

This pharmaceutical product is marketed under the trade name Namzaric, a label commonly associated with advanced cognitive therapy.

International Non-Proprietary Name

The active components are identified globally as memantine and donepezil, adhering to the international nomenclature for medicinal substances.

Form of Release

The drug is available exclusively as extended-release capsules, designed for oral administration. It comes in combination strengths of 7 milligrams memantine with 10 milligrams donepezil, 14 milligrams memantine with 10 milligrams donepezil, 21 milligrams memantine with 10 milligrams donepezil, and 28 milligrams memantine with 10 milligrams donepezil, offering a range of options for tailored dosing.

Composition

The medication contains two active ingredients: memantine hydrochloride and donepezil hydrochloride, working synergistically to address neurological symptoms. The capsules include excipients such as microcrystalline cellulose, hypromellose, ethylcellulose, and magnesium stearate, forming a controlled-release matrix. Additional components like talc and lactose monohydrate ensure stability and consistent delivery of the active agents over time.

Pharmacologic Properties

Pharmacodynamics

This treatment combines two distinct mechanisms to manage cognitive decline. Memantine acts as an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, moderating glutamate activity to prevent excitotoxicity while preserving normal neuronal signaling. Donepezil functions as a reversible acetylcholinesterase inhibitor, increasing acetylcholine levels to enhance cholinergic transmission in the brain. Together, they target glutamate overstimulation and acetylcholine deficiency, key factors in neurodegenerative processes.

Clinical evidence suggests this dual approach stabilizes memory, reasoning, and daily functioning more effectively than either component alone. Memantine reduces neuronal damage in regions like the cortex, while donepezil boosts synaptic activity in the hippocampus and other cognitive centers. This synergy provides broader symptom relief, particularly in advanced stages of disease, without curing the underlying condition.

Pharmacokinetics

After oral intake, the medication releases its components gradually due to its extended-release design. Memantine reaches peak plasma levels in 9 to 12 hours, with nearly 100 percent bioavailability, while donepezil peaks in 3 to 4 hours, achieving close to full absorption. Food does not significantly alter uptake for either substance, allowing administration flexibility.

Memantine distributes widely, with a volume of distribution of 9 to 11 liters per kilogram, and binds to plasma proteins at about 45 percent. Donepezil has a smaller volume of distribution, around 12 liters per kilogram, and binds at 96 percent, primarily to albumin. Memantine undergoes minimal hepatic metabolism, producing three inactive metabolites, with a half-life of 60 to 100 hours. Donepezil is metabolized extensively by cytochrome P450 enzymes CYP2D6 and CYP3A4, with a half-life of approximately 70 hours, supporting once-daily dosing for both.

Excretion differs between the two. Memantine is primarily cleared unchanged through urine (over 80 percent), with renal function influencing its rate. Donepezil exits via urine (57 percent as metabolites) and feces (15 percent), with hepatic processing playing a larger role. This combined profile ensures prolonged activity tailored to their respective targets.

Indications for Use

Conditions and Disorders

The medication is indicated for moderate to severe Alzheimer’s disease, a progressive disorder marked by cognitive and functional decline. It is prescribed for patients already stabilized on separate memantine and donepezil therapies, combining them into a single formulation to improve memory, attention, and daily task performance. This approach addresses advanced symptoms like disorientation and behavioral changes.

Namzaric offers a streamlined option for managing complex dementia stages, enhancing patient adherence. Its use is specific to Alzheimer’s, with no formal approval for other conditions, though some clinicians may explore off-label applications in similar neurodegenerative states, pending further research.

Contraindications

Conditions Prohibiting Use

The drug is contraindicated in patients with hypersensitivity to memantine, donepezil, or piperidine derivatives, as reactions could range from skin irritation to severe anaphylaxis. Severe renal impairment (creatinine clearance below 5 milliliters per minute) prohibits its use due to memantine accumulation risks. Severe hepatic dysfunction also restricts administration, given donepezil’s reliance on liver metabolism.

It should not be used in patients with active gastrointestinal bleeding or untreated ulcers, as donepezil’s cholinergic effects may worsen these conditions. Uncontrolled asthma or chronic obstructive pulmonary disease precludes its use due to potential respiratory exacerbation. Cardiac issues like severe bradycardia or recent myocardial infarction further limit its application, reflecting combined risks from both components.

Method of Administration and Dosage

Administration Guidelines

The medication is taken orally once daily, preferably in the evening, with or without food, offering dosing convenience. Capsules should be swallowed whole with water and not crushed or chewed to maintain the extended-release profile. Consistent timing enhances its steady-state effects on brain function.

Dosage for Adults and Children

For adults with moderate to severe Alzheimer’s, therapy typically starts with 7 milligrams memantine and 10 milligrams donepezil daily, increasing weekly by 7 milligrams of memantine (keeping donepezil at 10 milligrams) to a maximum of 28 milligrams memantine and 10 milligrams donepezil, if tolerated. Patients must already be on 10 milligrams donepezil daily before switching. Pediatric use is not approved, as safety and efficacy in children remain unstudied.

Dose Adjustments for Specific Conditions

In moderate renal impairment (creatinine clearance 30 to 49 milliliters per minute), the maximum dose is 14 milligrams memantine with 10 milligrams donepezil daily. Severe renal impairment (5 to 29 milliliters per minute) limits it to 7 milligrams memantine with 10 milligrams donepezil. Mild to moderate hepatic impairment allows standard dosing with caution, but severe liver issues contraindicate use due to donepezil metabolism concerns.

Side Effects

Potential Adverse Reactions

Common effects include nausea, diarrhea, and headache, often linked to donepezil’s cholinergic action or memantine’s neurological adjustment. Dizziness, fatigue, and insomnia may occur, particularly during dose escalation, typically subsiding with time. Some patients experience muscle cramps or appetite loss, reflecting combined receptor effects.

Less frequent reactions involve confusion, agitation, or hypertension, which may overlap with disease progression. Rarely, hallucinations, seizures, or urinary issues emerge, especially in advanced stages or with renal compromise. Severe abdominal pain, fainting, or allergic responses require immediate medical evaluation.

Overdose

Symptoms of Excessive Intake

Overdosing may combine cholinergic and NMDA-related effects, including vomiting, sweating, slowed heart rate, and agitation. Severe cases can lead to seizures, psychosis, or coma, with respiratory depression or blood pressure spikes posing significant risks. Symptoms depend on the dominant component in excess and patient condition.

First Aid Measures

Stop the drug and seek emergency care immediately. Activated charcoal may reduce absorption if given soon after ingestion, provided the patient is conscious. Atropine could address donepezil-related cholinergic symptoms, while supportive care manages memantine effects like sedation or hypertension. Professional monitoring is critical to stabilize vital functions.

Drug Interactions

Effects on Other Medications

The medication can amplify cholinergic agents’ effects, like bethanechol, increasing gastrointestinal or cardiac risks due to donepezil. Memantine may alter clearance of drugs using renal tubular secretion, such as ranitidine, by competition. CYP2D6 or CYP3A4 inhibitors, like fluoxetine, could elevate donepezil levels, while urine alkalinizers, like acetazolamide, might raise memantine concentrations.

Namzaric may enhance sedation with central nervous system depressants, such as opioids, or increase dyskinesia risk with dopaminergic drugs like levodopa. Anticholinergics, like scopolamine, could see reduced efficacy due to donepezil’s opposing action, requiring careful co-administration planning.

Compatibility with Alcohol and Food

Alcohol may worsen dizziness or confusion, so limited intake is advised. Food does not affect absorption significantly, allowing administration with meals for comfort if desired. No specific dietary restrictions apply, though monitoring for gastrointestinal upset is prudent.

Special Precautions

Use During Pregnancy and Breastfeeding

Data on pregnancy use are limited, with no clear human evidence of safety or risk for either component. Animal studies suggest minimal fetal harm, but use should be restricted to cases where benefits outweigh uncertainties, under strict oversight. Both agents may enter breast milk in small amounts, so nursing mothers should consult a doctor, potentially halting breastfeeding during therapy.

Impact on Driving and Machinery Operation

The medication may cause drowsiness, dizziness, or balance issues, especially early on or with dose changes. Patients should test their tolerance before driving or operating machinery, avoiding these tasks if affected. Caregivers may need to assist those with significant cognitive or motor impairments.

Considerations for Elderly and Pediatric Patients

Elderly patients, the primary users due to Alzheimer’s prevalence, generally manage it well, though renal or hepatic decline may necessitate dose adjustments in moderate to severe cases. Namzaric is not approved for children, as its role in pediatric conditions lacks evidence, confining use to adults.