Memantine/donepezil ER 21mg/10mg CP
It is used to treat dementia in people with Alzheimer's disease.
Drug Class
Agents for Alzheimer's Disease
Pharmacologic Class
N-methyl-D-aspartate (NMDA) receptor antagonist; Acetylcholinesterase inhibitor
Pregnancy Category
Category C
FDA Approved
Apr 2014
DEA Schedule
Not Controlled
Overview
What is this medicine?
This medication is a combination of two drugs, memantine and donepezil, used to treat moderate to severe Alzheimer's disease. It works by affecting different chemicals in the brain to help improve memory, awareness, and the ability to perform daily activities.
How to Use This Medicine
Taking Your Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. Take your dose in the evening, with or without food. Swallow the capsule whole - do not chew or crush it. If you notice any capsules that appear abnormal or are damaged, do not take them.
If you have difficulty swallowing the capsule whole, you can sprinkle its contents onto applesauce. If you choose to do this, swallow the mixture immediately without chewing.
Continue taking your medication as directed by your doctor or healthcare provider, even if you start feeling well.
Storing and Disposing of Your Medication
Keep your medication at room temperature in a dry location, avoiding storage in a bathroom. Store it in its original container or in a container that protects it from light.
What to Do If You Miss a Dose
If you miss a dose, skip it and resume your normal dosing schedule. Do not take two doses at the same time or take extra doses to make up for the missed one.
To use this medication correctly, follow your doctor's instructions and read all the information provided. Take your dose in the evening, with or without food. Swallow the capsule whole - do not chew or crush it. If you notice any capsules that appear abnormal or are damaged, do not take them.
If you have difficulty swallowing the capsule whole, you can sprinkle its contents onto applesauce. If you choose to do this, swallow the mixture immediately without chewing.
Continue taking your medication as directed by your doctor or healthcare provider, even if you start feeling well.
Storing and Disposing of Your Medication
Keep your medication at room temperature in a dry location, avoiding storage in a bathroom. Store it in its original container or in a container that protects it from light.
What to Do If You Miss a Dose
If you miss a dose, skip it and resume your normal dosing schedule. Do not take two doses at the same time or take extra doses to make up for the missed one.
Lifestyle & Tips
- Take this medication once daily, usually in the evening, with or without food.
- Swallow the capsule whole. Do not crush, chew, or divide the capsule.
- If you have difficulty swallowing, the capsule may be opened and the entire contents sprinkled on a small amount of applesauce. Swallow the mixture immediately without chewing.
- Take the medication at the same time each day to help you remember.
- Do not stop taking this medication suddenly without consulting your doctor, as it may worsen symptoms.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
21 mg memantine ER / 10 mg donepezil once daily (as a titration step or maintenance dose)
Dose Range:
14 - 28 mg
Condition-Specific Dosing:
Initial:
Patients stabilized on donepezil 10 mg once daily can be switched to Namzaric 14 mg/10 mg once daily.
Titration:
After 1 week, the dose can be increased to 21 mg/10 mg once daily. After another week, the dose can be increased to 28 mg/10 mg once daily (maximum recommended dose).
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
No adjustment needed (CrCl 50-80 mL/min)
Moderate:
Maximum recommended dose of memantine component is 14 mg/day (e.g., Namzaric 14 mg/10 mg once daily) (CrCl 30-49 mL/min)
Severe:
Not recommended for Namzaric; if individual components are used, memantine dose should be reduced to 7 mg/day (CrCl 5-29 mL/min)
Dialysis:
Not studied; generally not recommended for combination product.
Hepatic Impairment:
Mild:
No adjustment needed
Moderate:
No adjustment needed for memantine; Donepezil component: use with caution, monitor for adverse effects.
Severe:
Not studied for memantine; Donepezil component: use with caution, monitor for adverse effects, consider dose reduction.
Pharmacology
Mechanism of Action
Memantine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist. It binds to the NMDA receptor-operated cation channels, blocking the effects of excessive levels of glutamate, which is thought to contribute to the symptoms of Alzheimer's disease. Donepezil is a reversible acetylcholinesterase inhibitor. It enhances cholinergic function by increasing the concentration of acetylcholine at cholinergic synapses in the central nervous system.
Pharmacokinetics
Absorption:
Bioavailability:
Memantine: ~100%; Donepezil: ~100%
Tmax:
Memantine ER: 3-7 hours; Donepezil: 3-5 hours
FoodEffect:
No significant food effect for either component.
Distribution:
Vd:
Memantine: 9-11 L/kg; Donepezil: ~12 L/kg
ProteinBinding:
Memantine: ~45%; Donepezil: 96% (primarily to albumin and alpha1-acid glycoprotein)
CnssPenetration:
Yes
Elimination:
HalfLife:
Memantine ER: 60-80 hours; Donepezil: ~70 hours
Clearance:
Not available
ExcretionRoute:
Memantine: Renal; Donepezil: Renal and Fecal
Unchanged:
Memantine: 75-90% (renal); Donepezil: ~17% (renal), ~50% (fecal)
Pharmacodynamics
OnsetOfAction:
Weeks for clinical effect for both components.
PeakEffect:
Donepezil: 3-4 weeks; Memantine: Several weeks
DurationOfAction:
Once daily dosing due to long half-lives.
Safety & Warnings
Side Effects
Serious Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor immediately or seek emergency medical attention:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Urination problems
Severe dizziness or fainting
Fever, chills, or sore throat
New or worsening breathing difficulties
Seizures
Stomach pain or heartburn
Black, tarry, or bloody stools
Vomiting blood or coffee ground-like material
Slow heartbeat
Abnormal heartbeat
Bruising
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other symptoms that bother you or persist, contact your doctor:
Diarrhea
Upset stomach or vomiting
Decreased appetite
Dizziness or headache
Muscle cramps
Fatigue or weakness
* Sleep disturbances
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor immediately or seek emergency medical attention:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Urination problems
Severe dizziness or fainting
Fever, chills, or sore throat
New or worsening breathing difficulties
Seizures
Stomach pain or heartburn
Black, tarry, or bloody stools
Vomiting blood or coffee ground-like material
Slow heartbeat
Abnormal heartbeat
Bruising
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other symptoms that bother you or persist, contact your doctor:
Diarrhea
Upset stomach or vomiting
Decreased appetite
Dizziness or headache
Muscle cramps
Fatigue or weakness
* Sleep disturbances
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Severe or persistent nausea, vomiting, or diarrhea
- Slow or irregular heartbeat (bradycardia)
- Fainting spells or severe dizziness
- Seizures
- Severe confusion or agitation
- Unusual muscle weakness or cramps
- Dark-colored urine (rhabdomyolysis, rare)
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced as a result of the allergy.
All medications you are currently taking, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins. This information will help your doctor and pharmacist assess potential interactions between this medication and other substances you are taking.
* Any existing health problems, as this medication may interact with certain conditions.
To ensure your safety, it is crucial to verify that it is safe to take this medication with all your current medications and health conditions. Never start, stop, or change the dose of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced as a result of the allergy.
All medications you are currently taking, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins. This information will help your doctor and pharmacist assess potential interactions between this medication and other substances you are taking.
* Any existing health problems, as this medication may interact with certain conditions.
To ensure your safety, it is crucial to verify that it is safe to take this medication with all your current medications and health conditions. Never start, stop, or change the dose of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all of your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. While this drug can help manage symptoms, it is not a cure for Alzheimer's disease, and you should continue to receive regular care from your doctor. If you are pregnant, planning to become pregnant, or are breastfeeding, be sure to discuss this with your doctor, as you will need to carefully weigh the potential benefits and risks of this medication to both you and your baby.
Overdose Information
Overdose Symptoms:
- Severe cholinergic symptoms (e.g., severe nausea, vomiting, salivation, sweating, bradycardia, hypotension, collapse, convulsions)
- Severe CNS effects (e.g., agitation, hallucinations, stupor, coma)
- Severe dizziness
- Lethargy
- Vertigo
- Ataxia
- Vomiting
- Diarrhea
What to Do:
Seek immediate medical attention. Call 911 or your local poison control center (1-800-222-1222 in the US). Treatment is supportive. Atropine may be used for cholinergic crisis. Dialysis may be considered for memantine overdose.
Drug Interactions
Major Interactions
- Other NMDA antagonists (e.g., amantadine, ketamine, dextromethorphan) - increased risk of CNS toxicity.
- Cholinomimetics (e.g., bethanechol, succinylcholine) - increased cholinergic effects.
Moderate Interactions
- Drugs that increase urine pH (e.g., carbonic anhydrase inhibitors, sodium bicarbonate) - decreased memantine renal clearance.
- CYP3A4/2D6 inhibitors (e.g., ketoconazole, quinidine, fluoxetine, paroxetine) - may increase donepezil levels.
- CYP3A4/2D6 inducers (e.g., rifampin, phenytoin, carbamazepine, phenobarbital) - may decrease donepezil levels.
- Anticholinergics (e.g., atropine, scopolamine) - antagonistic effects with donepezil.
- Beta-blockers - increased risk of bradycardia with donepezil.
Minor Interactions
- Cimetidine, ranitidine, quinidine, nicotine - may increase memantine levels by inhibiting renal tubular secretion.
- Hydrochlorothiazide - may decrease memantine levels.
Monitoring
Baseline Monitoring
Cognitive function assessment (e.g., MMSE, ADAS-Cog)
Rationale: To establish baseline cognitive status and monitor disease progression/response to therapy.
Timing: Prior to initiation of therapy
Vital Signs (Heart Rate, Blood Pressure)
Rationale: Donepezil can cause bradycardia and syncope.
Timing: Prior to initiation of therapy
ECG
Rationale: Consider for patients with pre-existing cardiac conduction abnormalities or those at risk for bradycardia (due to donepezil).
Timing: Prior to initiation of therapy (if indicated)
Routine Monitoring
Cognitive function assessment
Frequency: Every 6-12 months or as clinically indicated
Target: Improvement or stabilization of cognitive scores
Action Threshold: Significant decline may warrant re-evaluation of therapy.
Adverse effects monitoring (e.g., GI upset, dizziness, headache, bradycardia, syncope)
Frequency: Regularly, especially during titration and dose changes
Target: Minimization of side effects
Action Threshold: Persistent or severe adverse effects may require dose reduction or discontinuation.
Vital Signs (Heart Rate, Blood Pressure)
Frequency: Periodically, or if symptoms of bradycardia/hypotension occur
Target: Within normal limits for the patient
Action Threshold: Significant bradycardia or hypotension may require intervention.
Symptom Monitoring
- Nausea
- Vomiting
- Diarrhea
- Dizziness
- Headache
- Confusion
- Agitation
- Hallucinations
- Bradycardia (slow heart rate)
- Syncope (fainting)
- Muscle cramps
- Fatigue
Special Patient Groups
Pregnancy
Category C. There are no adequate and well-controlled studies of Memantine/donepezil in pregnant women. Use only if the potential benefit justifies the potential risk to the fetus.
Trimester-Specific Risks:
First Trimester:
Potential risk, but human data are limited.
Second Trimester:
Potential risk, but human data are limited.
Third Trimester:
Potential risk, but human data are limited.
Lactation
It is not known whether memantine or donepezil are excreted in human milk. Donepezil is excreted in the milk of rats. Caution should be exercised when administered to a nursing mother.
Infant Risk:
Not available; potential for adverse effects on the infant due to drug excretion in milk.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established. This drug is not indicated for use in pediatric populations.
Geriatric Use
Alzheimer's disease primarily affects the geriatric population. No specific dose adjustment is generally required based on age alone, but elderly patients may be more susceptible to adverse effects (e.g., bradycardia, syncope, GI upset) and should be monitored closely.
Clinical Information
Clinical Pearls
- Memantine/donepezil ER is a fixed-dose combination indicated for the treatment of moderate to severe Alzheimer's disease in patients already stabilized on donepezil 10 mg.
- The extended-release formulation allows for once-daily dosing, which may improve patient adherence and reduce peak-related side effects compared to immediate-release formulations.
- Capsules can be opened and sprinkled on applesauce for patients with swallowing difficulties, but the beads must not be chewed.
- Titration is crucial to minimize gastrointestinal side effects (nausea, vomiting, diarrhea) and other adverse events like dizziness and bradycardia.
- Monitor for signs of bradycardia or syncope, especially in patients with pre-existing cardiac conditions.
- This medication treats symptoms but does not cure Alzheimer's disease or stop its progression.
Alternative Therapies
- Other cholinesterase inhibitors (e.g., rivastigmine, galantamine)
- Other NMDA receptor antagonists (no other approved for AD)
Cost & Coverage
Average Cost:
Highly variable, typically $300-$600+ per 30 tablets
Insurance Coverage:
Tier 2 or Tier 3 (Specialty/Non-preferred Brand)
General Drug Facts
If your symptoms or health problems persist or worsen, it is essential to contact your doctor promptly. To ensure safe use, never share your medication with others or take someone else's medication. Store all medications in a secure location, out of reach of children and pets, to prevent accidental ingestion. Dispose of unused or expired medications properly; do not flush them down the toilet or pour them down the drain unless instructed to do so by a healthcare professional. If you are unsure about the proper disposal method, consult your pharmacist, who can also inform you about potential drug take-back programs in your area. Some medications may come with an additional patient information leaflet, which your pharmacist can provide. If you have any questions or concerns about your medication, discuss them with your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately contact your local poison control center or seek emergency medical attention. Be prepared to provide information about the medication taken, the quantity, and the time of the incident.