Side effects of namenda

Namenda

Generic Name: memantine (meh MAN teen)
Brand Names: Namenda, Namenda XR

Medically reviewed by Sanjai Sinha, MD Last updated on Apr 11, 2019.

  • Overview
  • Side Effects
  • Dosage
  • Professional
  • Interactions
  • More

What is Namenda?

Namenda (memantine) reduces the actions of chemicals in the brain that may contribute to the symptoms of Alzheimer’s disease.

Namenda is used to treat moderate to severe dementia of the Alzheimer’s type.

Namenda may also be used for purposes not listed in this medication guide.

Important information

Before using Namenda, tell your doctor if you are allergic to any drugs, or if you have a seizure disorder, cataracts, liver or kidney disease, or a bladder or kidney infection.

Namenda can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert.

Before taking this medicine

You should not use Namenda if you are allergic to memantine.

To make sure Namenda is safe for you, tell your doctor if you have:

  • epilepsy or other seizure disorder;

  • liver disease;

  • kidney disease;

  • urination problems; or

  • a bladder or kidney infection.

Namenda is not expected to harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

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

How should I take Namenda?

Take Namenda exactly as it was prescribed for you. Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Namenda can be taken with or without food.

Do not crush, chew, break, or open an extended-release capsule. Swallow it whole.

To make swallowing easier, you may open the extended-release capsule and sprinkle the medicine into a spoonful of applesauce. Swallow right away without chewing. Do not save the mixture for later use.

Measure liquid medicine (oral solution) with the dosing syringe provided, or with a special dose-measuring spoon or medicine cup. If you do not have a dose-measuring device, ask your pharmacist for one.

Do not mix the oral solution with any other liquids.

Rinse the empty oral syringe with clean water and allow it to air dry after every use.

Use Namenda regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

Your doctor will need to check your progress while you are using Namenda.

Store Namenda at room temperature away from moisture and heat. Keep the liquid medicine bottle tightly closed with the cap provided. Do not store the bottle with the oral syringe in it.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Namenda dosing information

Usual Adult Dose for Alzheimer’s Disease:

IMMEDIATE-RELEASE:
Initial dose: 5 mg orally once a day, then titrated upwards by 5 mg per week
Maintenance dose: 5 mg once a day up to 10 mg twice a day
Maximum dose: 20 mg per day
EXTENDED-RELEASE:
Initial dose: 7 mg orally once a day, then titrated upwards by 7 mg per week
Maintenance dose: 7 mg once a day up to 28 mg once a day
Maximum dose: 28 mg orally once a day
Approved indication: For use in the treatment of moderate to severe dementia of the Alzheimer’s type.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

If you miss doses or forget to take your medicine for several days, call your doctor before starting the medicine again.

What happens if I overdose?

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

What should I avoid while taking Namenda?

Namenda can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert.

Namenda side effects

Get emergency medical help if you have signs of an allergic reaction to Namenda: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • severe headache, blurred vision, pounding in your neck or ears;

  • seizure (convulsions); or

  • unusual changes in mood or behavior.

Common Namenda side effects may include:

  • diarrhea;

  • dizziness; or

  • headache.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Namenda?

Tell your doctor about all your current medicines and any you start or stop using, especially:

  • amantadine;

  • zonisamide;

  • cough medicine that contains dextromethorphan (Delsym, Robitussin Maximum Strength, Vicks 44, and others);

  • medicines to make the urine alkaline – urine sodium bicarbonate, potassium citrate (K-Lyte, Urocit-K), sodium citrate and citric acid (Bicitra, Oracit), or sodium citrate and potassium (Citrolith, Polycitra); or

  • medicine to treat glaucoma or increased pressure inside the eyes – acetazolamide, methazolamide.

This list is not complete. Other drugs may interact with memantine, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Namenda only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Copyright 1996-2020 Cerner Multum, Inc. Version: 3.01.

Medical Disclaimer

More about Namenda (memantine)

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Related treatment guides

  • Alzheimer’s Disease

SIDE EFFECTS

Clinical Trials Experience

NAMENDA was evaluated in eight double-blind placebo-controlled trials involving a total of 1862 dementia (Alzheimer’s disease, vascular dementia) patients (940 patients treated with NAMENDA and 922 patients treated with placebo) for a treatment period up to 28 weeks.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Adverse Events Leading to Discontinuation

In placebo-controlled trials in which dementia patients received doses of NAMENDA up to 20 mg/day, the likelihood of discontinuation because of an adverse reaction was the same in the NAMENDA group (10.1%) as in the placebo group (11.5%). No individual adverse reaction was associated with the discontinuation of treatment in 1% or more of NAMENDA-treated patients and at a rate greater than placebo.

Most Common Adverse Reactions

In double-blind placebo-controlled trials involving dementia patients, the most common adverse reactions (incidence ≥ 5% and higher than placebo) in patients treated with NAMENDA were dizziness, headache, confusion and constipation. Table 1 lists all adverse reactions that occurred in at least 2% of patients treated with NAMENDA and at an incidence greater than placebo.

Table 1: Adverse Reactions Reported in Controlled Clinical Trials in at Least 2% of Patients Receiving NAMENDA and at a Higher Frequency than Placebo-treated Patients

Adverse Reaction Placebo
(N = 922) %
NAMENDA
(N = 940) %
Body as a Whole
Fatigue 1 2
Pain 1 3
Cardiovascular System
Hypertension 2 4
Central and Peripheral Nervous System
Dizziness 5 7
Headache 3 6
Gastrointestinal System
Constipation 3 5
Vomiting 2 3
Musculoskeletal System
Back pain 2 3
Psychiatric Disorders
Confusion 5 6
Somnolence 2 3
Hallucination 2 3
Respiratory System
Coughing 3 4
Dyspnea 1 2

The overall profile of adverse reactions and the incidence rates for individual adverse reactions in the subpopulation of patients with moderate to severe Alzheimer’s disease were not different from the profile and incidence rates described above for the overall dementia population.

Seizures

NAMENDA has not been systematically evaluated in patients with a seizure disorder. In clinical trials of NAMENDA, seizures occurred in 0.2% of patients treated with NAMENDA and 0.5% of patients treated with placebo.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of memantine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These reactions include:

Blood and Lymphatic System Disorders -agranulocytosis, leukopenia (including neutropenia), pancytopenia, thrombocytopenia, thrombotic thrombocytopenic purpura.

Cardiac Disorders -cardiac failure congestive.

Gastrointestinal Disorders -pancreatitis.

Hepatobiliary Disorders – hepatitis.

Psychiatric Disorders -suicidal ideation.

Renal and Urinary Disorders -acute renal failure (including increased creatinine and renal insufficiency).

Skin Disorders -Stevens Johnson syndrome.

Read the entire FDA prescribing information for Namenda (Memantine HCL)

Namenda (also called Memantine) was approved by the FDA in 2003 for use in people with “moderate to severe” Alzheimer’s disease or other types of dementia. The FDA rejected the manufacturer’s application to expand approval to include mild Alzheimer’s or dementia. However, the drug is often prescribed “off-label” for patients with mild Alzheimer’s or dementia even though there is little evidence of its benefit at this stage of disease and other drugs, such as Aricept and Razadyne, are more effective. “Off- label” means that the use is not on the FDA-approved label for the drug, because of lack of proof that it is safe and effective for that use.

Although “Alzheimer’s disease” is the more common diagnosis, Alzheimer’s disease is just one type of dementia. It is currently impossible to be sure if the type of dementia is caused by Alzheimer’s disease until there is an autopsy. Doctors can make a probable diagnosis through additional lab tests. These tests cannot diagnose Alzheimer’s disease, but rule out other causes for dementia symptoms, some of which should be treated differently. These tests are expensive and can be very time consuming. For that reason, studies of “Alzheimer’s disease” are usually studies of people with multiple types of dementia, so we use the terms interchangeably in this article.

The severity of dementia is usually diagnosed using a test called the Mini-Mental State Examination (MMSE). A score of around 20-23 usually indicates mild disease; 10-19 indicates moderate to moderately severe disease; and less than 10 is considered severe disease.

Depending on which drug they are taking, patients are usually prescribed between 3mg-20mg each day. The cost of a generic version of Namenda (20mg/day) is typically a little more than of the generic version of Aricept (10mg/day), and seems to be less effective for most patients. The generic versions of Razadyne and Exelon are usually more expensive, but this varies depending on insurance coverage and where the drugs are purchased. Aricept, Razadyne, and Exelon work in the same way in the brain, while Namenda works through a different system. That is why doctors sometimes hope that adding Namenda to Aricept or the other drugs might have an added benefit for patients with moderate or severe dementia.

There is no cure for most types of dementia and treatments are not very effective. Current drugs merely delay decline and help reduce symptoms. Patients with mild Alzheimer’s disease won’t benefit from Namenda but will cost them money and could cause side effects. Some side effects of Namenda are dizziness, confusion, headache, sleepiness, constipation, vomiting, pain (especially in the back), and coughing. More serious side effects are rare but include shortness of breath and hallucination.

A study by Lon Schneider and his colleagues from the University of Southern California Keck School of Medicine examined available evidence on the effectiveness of Namenda in patients with mild Alzheimer’s disease. The researchers conducted a meta-analysis, meaning they pooled and analyzed data available from several different clinical trials, in order to evaluate a larger number of people. They analyzed data from three clinical trials that included 431 patients with mild Alzheimer’s disease and 697 patients with moderate Alzheimer’s.

All three clinical trials randomly assigned patients to either receive Namenda or a placebo, and neither patients nor investigators were aware of who was receiving the drug and who was not. This is called a “double-blind” study and it prevents bias based on expectations that a drug will improve the outcome being measured. In this case, investigators measured patient’s cognitive functioning, behavior, and ability to perform activities of daily living. They also measured “impression of change” in the patient according to the patient’s clinician and caregiver. Four different scales were used to measure these outcomes and then scores were compared between the Namenda and placebo groups.

The study concluded that Namenda was not effective in patients with mild dementia. This was true when they looked at each trial separately and also when they pooled data from the three studies and analyzed that.

Among patients with moderate Alzheimer’s disease, the effect of Namenda was very small.3 Looking at the trials separately, only one of the three trials found any statistically significant improvement for patients taking Namenda compared to patients taking placebo. Even that improvement was for only one measure – a subjective measure of the doctor or caregiver’s impressions of the patients’ behavior. When the data were combined, there was a statistically significant effect on cognitive functioning and impression of change. However, these differences were small—about half the impact of drugs like Aricept, Exelon, or Razadyne, which are commonly prescribed to treat Alzheimer’s symptoms.

A 2014 study found that male military veterans with mild or moderate dementia did not benefit from Namenda, whether taken alone or together with vitamin E. However, vitamin E taken alone did slow the progression of mild to moderate Alzheimer’s. Several other studies have also suggested that vitamin E can provide a moderate benefit for Alzheimer’s patients. However, high levels of vitamin E may be dangerous, sometimes increasing the chances of heart failure and death. For more information on vitamin E, please visit here.

More recent meta-analyses have evaluated Namenda for dementia ranging from mild to severe, based on randomized controlled trials. These have found a significant benefit of Namenda compared to placebo for patients with dementia ranging from moderate to severe for cognitive function, behavioral disturbances, and ability to function in activities related to daily life dementia, but not for patients with milder dementia.

None of the current treatments for dementia will radically improve patients’ memory or thinking, nor will they stop the progression of the disease. However, Namenda may help moderate or severe dementia, while Aricept, Razadyne, or Exelon may help patients with dementia ranging from mild to severe.

All articles are reviewed and approved by Dr. Diana Zuckerman and other senior staff.

  1. Forest Receives Non-Approvable Letter for Expanded Namenda Indication. Drug Industry Daily, Vol. 4 No. 145. July 26, 2005.
  2. National Library of Medicine. Medline Plus. Memantine. nlm.nih.gov/medlineplus/druginfo/meds/a604006
  3. Schneider LS, Dagerman KS, Higgins JP, McShane R (2011). Lack of Evidence for the Efficacy of Memantine in Mild Alzheimer Disease. Arch Neurol. 68(8):991-998.
  4. Di Santo SG, Princelli F, Adorni F, Caltagirone C, & Musicco M (2013). A meta-analysis of the efficacy of donepezil, rivastigmine, galantamine, and memantine in relation to severity of Alzheimer’s disease. Journal of Alzheimer’s Disease.35:349-361.
  5. La Fata G, Weber P, & Mohajeri MH (2014). Effects of Vitamin E on Cognitive Performance during Ageing and in Alzheimer’s Disease. Nutrients. 6:5453-547.
  6. American Psychiatric Association (2010). Practice guideline for the treatment of patients with Alzheimer’s Disease and other dementias. Second edition.
  7. Matsunaga S, Kishi T, & Iwata N (2015). Memantine monotherapy for Alzheimer’s disease: A systematic review and meta-analysis. PLoS ONE. 10(4):e0123289.
  8. Di Santo SG, Princelli F, Adorni F, Caltagirone C, & Musicco M (2013). A meta-analysis of the efficacy of donepezil, rivastigmine, galantamine, and memantine in relation to severity of Alzheimer’s disease. Journal of Alzheimer’s Disease.35:349-361.
  9. Rive B, Gauthier S, Costello S, Marre C, & Francois C (2013). Synthesis and comparison of the meta-analyses evaluating the efficacy of memantine in moderate to severe stages of Alzheimer’s disease. CNS Drugs. 27:573-582.

Namenda Side Effects

Generic Name: memantine

Medically reviewed by Drugs.com. Last updated on Nov 4, 2018.

  • Overview
  • Side Effects
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Note: This document contains side effect information about memantine. Some of the dosage forms listed on this page may not apply to the brand name Namenda.

In Summary

More frequent side effects include: constipation, headache, and hypertension. See below for a comprehensive list of adverse effects.

For the Consumer

Applies to memantine: oral capsule extended release, oral solution, oral tablet

Along with its needed effects, memantine (the active ingredient contained in Namenda) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking memantine:

Less common

  • Bloating or swelling of the face, arms, hands, lower legs, or feet
  • blurred vision
  • dizziness
  • headache
  • nervousness
  • pounding in the ears
  • rapid weight gain
  • slow or fast heartbeat
  • tingling of the hands or feet
  • unusual weight gain or loss

Incidence not known

  • Abdominal or stomach pain
  • agitation
  • black, tarry stools
  • bleeding gums
  • blistering, peeling, or loosening of the skin
  • blood in the urine or stools
  • chest pain
  • coma
  • constipation
  • continuing vomiting
  • convulsions
  • dark-colored urine
  • decreased urine output
  • depression
  • fainting
  • fast, pounding, or irregular heartbeat or pulse
  • general feeling of tiredness or weakness
  • high fever
  • high or low blood pressure
  • hostility
  • increased sweating
  • indigestion
  • infection from breathing foreign substances into the lungs
  • itching
  • lethargy
  • light-colored stools
  • lip smacking or puckering
  • loss of consciousness
  • muscle twitching
  • no blood pressure
  • no breathing
  • no pulse
  • numbness or tingling in the face, arms, or legs
  • pain in the stomach, side, or abdomen, possibly radiating to the back
  • pain or swelling in the arms or legs without any injury
  • pain, tension, and weakness upon walking that subsides during periods of rest
  • pinpoint red spots on the skin
  • pounding, slow heartbeat
  • puffing of the cheeks
  • rapid or worm-like movements of the tongue
  • rapid weight gain
  • recurrent fainting
  • red irritated eyes
  • red skin lesions, often with a purple center
  • seizures
  • severe constipation
  • severe headache
  • severe muscle stiffness
  • severe vomiting
  • sores, ulcers, or white spots in the mouth or on the lips
  • stupor
  • sudden severe weakness
  • swelling of the face, ankles, or hands
  • total body jerking
  • trouble with speaking or walking
  • troubled breathing
  • twitching, twisting, or uncontrolled repetitive movements of the tongue, lips, face, arms, or legs
  • uncontrolled chewing movements
  • unusual bleeding or bruising
  • unusually pale skin
  • vomiting
  • yellow eyes and skin

Some side effects of memantine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

  • Confusion

Less common

  • Anxiety
  • back pain
  • bladder pain
  • bloody or cloudy urine
  • change in walking and balance
  • chills
  • clumsiness or unsteadiness
  • cough producing mucus
  • coughing
  • diarrhea
  • difficult, burning, or painful urination
  • difficulty with breathing
  • difficulty with moving
  • discouragement
  • dry mouth
  • fear
  • feeling sad or empty
  • fever
  • frequent urge to urinate
  • general feeling of discomfort or illness
  • hyperventilation
  • insomnia
  • irritability
  • joint pain
  • loss of appetite
  • loss of bladder control
  • loss of interest or pleasure
  • lower back or side pain
  • muscle pain or stiffness
  • nausea
  • nervousness
  • pain
  • pain in the joints
  • restlessness
  • seeing, hearing, or feeling things that are not there
  • shortness of breath
  • sleepiness or unusual drowsiness
  • sore throat
  • tightness in the chest
  • tiredness
  • trouble with concentrating
  • trouble with sleeping
  • unusual tiredness or weakness
  • vomiting
  • wheezing

Incidence not known

  • Burning feeling in the chest or stomach
  • burning, numbness, pain, or tingling in all fingers except smallest finger
  • cold sweats
  • cool pale skin
  • decreased interest in sexual intercourse
  • difficulty with swallowing
  • general feeling of discomfort or illness
  • heartburn
  • inability to have or keep an erection
  • increased hunger
  • large amounts of fat in the blood
  • loss in sexual ability, desire, drive, or performance
  • nightmares
  • shakiness
  • slurred speech
  • stomach cramps
  • stomach upset
  • tenderness in the stomach area
  • watery or bloody diarrhea

For Healthcare Professionals

Applies to memantine: oral capsule extended release, oral kit, oral solution, oral tablet

General

The most common adverse reactions (frequency of at least 5% and higher than placebo) were dizziness, headache, confusion, constipation, and diarrhea.

Cardiovascular

Uncommon (0.1% to 1%): Cardiac failure, venous thrombosis/thromboembolism

Dermatologic

Common (1% to 10%): Purpura, rash, basal cell carcinoma

Frequency not reported: Dermatitis, skin disorder, skin ulceration, bullous eruption, pruritus, increased sweating

Postmarketing reports: Stevens Johnson syndrome

Endocrine

Common (1% to 10%): Hyperglycemia, diabetes mellitus

Frequency not reported: Aggravated diabetes mellitus

Gastrointestinal

Common (1% to 10%): Constipation, diarrhea, abdominal pain, vomiting, nausea, gastroenteritis

Frequency not reported: Diverticulitis, dyspepsia, hemorrhoids, gastric ulcer, ileus

Postmarketing reports: Pancreatitis

Genitourinary

Common (1% to 10%): Urinary incontinence, fecal incontinence, urinary tract infection, hyperuricemia, micturition frequency

Frequency not reported: Cystitis, pyuria, hematuria

Hepatic

Common (1% to 10%): Increased ALT, increased AST, increased gamma-glutamyl transferase (GGT), increased phosphatase alkaline, elevated liver function test

Postmarketing reports: Hepatitis, bilirubinemia

Hypersensitivity

Common (1% to 10%): Drug hypersensitivity

Metabolic

Common (1% to 10%): Increased weight, decreased weight, anorexia, dehydration, hypokalemia

Frequency not reported: Increased appetite, hypernatremia, hyponatremia

Musculoskeletal

Common (1% to 10%): Back pain, arthralgia, leg pain, hypertonia, arthrosis, muscle weakness, myalgia, skeletal pain

Nervous system

Common (1% to 10%): Dizziness, headache, somnolence, balance disorders, abnormal gait, syncope, coma

Uncommon (0.1% to 1%): Seizures

Frequency not reported: Aphasia, speech disorder, hyperkinesia, dyskinesia, dementia, partial epileptic seizure, convulsions, tremor, extrapyramidal disorder, transient ischemic attack, vertigo, numbness, paresthesia, stupor, cerebrovascular disorder, intracranial hemorrhage

Ocular

Common (1% to 10%): Cataract, conjunctivitis

Other

Uncommon (0.1% to 1%): Fungal infections

Frequency not reported: Fever, asthenia, tiredness, chest pain, menstrual disorder

Psychiatric

Frequency not reported: Increased libido, mental status changes, nervousness, excitation/mania, suicide attempt, psychotic reactions

Postmarketing reports: Suicidal ideation, suicide, psychotic reactions

Respiratory

Common (1% to 10%): Coughing, dyspnea, bronchitis, pneumonia, upper respiratory tract infection, apnea, rhinitis

Frequency not reported: Atelectasis

Hematologic

Frequency not reported: Anemia

Postmarketing reports: Agranulocytosis, leukopenia (including neutropenia), pancytopenia, thrombocytopenia, thrombotic thrombocytopenic purpura, increased erythrocyte sedimentation rate (ESR), leucocytosis

Renal

Frequency not reported: Abnormal renal function, renal calculus

Postmarketing reports: Acute renal failure (including increased creatinine, renal insufficiency)

1. Cerner Multum, Inc. “Australian Product Information.” O 0

2. “Product Information. Namenda XR (memantine).” Forest Pharmaceuticals, St. Louis, MO.

3. “Product Information. Namenda (memantine).” Forest Pharmaceuticals, St. Louis, MO.

4. Cerner Multum, Inc. “UK Summary of Product Characteristics.” O 0

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.

Medical Disclaimer

Incidence not known

Abdominal or stomach pain

agitation

black, tarry stools

bleeding gums

blistering, peeling, or loosening of the skin

blood in the urine or stools

chest pain

coma

constipation

continuing vomiting

convulsions

dark-colored urine

decreased urine output

depression

fainting

fast, pounding, or irregular heartbeat or pulse

general feeling of tiredness or weakness

high fever

high or low blood pressure

hostility

increased sweating

indigestion

infection from breathing foreign substances into the lungs

itching

lethargy

light-colored stools

lip smacking or puckering

loss of consciousness

muscle twitching

no blood pressure

no breathing

no pulse

numbness or tingling in the face, arms, or legs

pain in the stomach, side, or abdomen, possibly radiating to the back

pain or swelling in the arms or legs without any injury

pain, tension, and weakness upon walking that subsides during periods of rest

pinpoint red spots on the skin

pounding, slow heartbeat

puffing of the cheeks

rapid or worm-like movements of the tongue

rapid weight gain

recurrent fainting

red irritated eyes

red skin lesions, often with a purple center

seizures

severe constipation

severe headache

severe muscle stiffness

severe vomiting

sores, ulcers, or white spots in the mouth or on the lips

stupor

sudden severe weakness

swelling of the face, ankles, or hands

total body jerking

trouble with speaking or walking

troubled breathing

twitching, twisting, or uncontrolled repetitive movements of the tongue, lips, face, arms, or legs

uncontrolled chewing movements

unusual bleeding or bruising

unusually pale skin

vomiting

yellow eyes and skin

What should I discuss with my healthcare provider before taking memantine (Namenda, Namenda XR)?

You should not use memantine if you are allergic to it.

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

  • epilepsy or other seizure disorder;
  • liver disease;
  • kidney disease;
  • urination problems; or
  • a bladder or kidney infection.

This medicine is not expected to harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

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

How should I take memantine (Namenda, Namenda XR)?

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Memantine can be taken with or without food.

Do not crush, chew, break, or open an extended-release capsule. Swallow it whole.

To make swallowing easier, you may open the extended-release capsule and sprinkle the medicine into a spoonful of applesauce. Swallow right away without chewing. Do not save the mixture for later use.

Measure liquid medicine (oral solution) with the dosing syringe provided, or with a special dose-measuring spoon or medicine cup. If you do not have a dose-measuring device, ask your pharmacist for one.

Do not mix the oral solution with any other liquids.

Rinse the empty oral syringe with clean water and allow it to air dry after every use.

Use memantine regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

Your doctor will need to check your progress while you are using memantine.

Store memantine at room temperature away from moisture and heat. Keep the liquid medicine bottle tightly closed with the cap provided. Do not store the bottle with the oral syringe in it.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Though approved for use in patients with mild to moderate AD, both rivastigmine and galantamine are currently prescribed off-label for moderate to severe AD. There are no published prospective controlled trials for use of rivastigmine in moderate to severe AD. A single controlled trial of galantamine in patients with severe AD found a significant benefit vs placebo for cognition on the SIB scale.17

ChEI: Adverse Effects

ChEIs are associated with a well-defined adverse effect profile; gastrointestinal problems such as nausea, diarrhea, and less commonly vomiting, are the primary adverse events observed early in therapy (Table 1). Gastrointestinal adverse effects are generally most problematic when treatment is initiated or following a dose increase. Patients who are debilitated, or those who weigh <50 kg, may be more likely to experience adverse effects and significant weight loss on ChEI therapy. These patients should be closely monitored, particularly when rivastigmine is prescribed or when titrating to donepezil 23mg.18 Other less frequently reported adverse effects associated with ChEI therapy include bradycardia, syncope, muscle cramps, weakness, insomnia, and nightmares.

Donepezil
Individuals with moderate to severe Alzheimer’s disease who were titrated to donepezil 23mg may experience cognitive benefits compared to individuals who were maintained on donepezil 10mg. With this dose increase, patients may also experience more adverse events. The most common adverse events associated with this dose-related increase include gastrointestinal side effects, such as nausea, vomiting, and diarrhea. Additional side effects that are less common include exacerbation of asthma symptoms; anorexia and weight loss; peptic ulcer disease and gastrointestinal (GI) bleeding; and dizziness and syncope related to bradycardia.

Strategies to reduce preventable adverse events for patients on high-dose donepezil:

  • Adverse events may be impacted by the rate of dose increase. Titration to donepezil 23 mg should only occur in patients who have been on donepezil 10 mg for at least 3 months.
  • Donepezil, at any dose, should be swallowed whole.
  • Cholinesterase inhibitors can be given with food to decrease the risk of GI side effects.
  • Donepezil 23 mg should be used with caution in patients with bradycardia or heart block, those at risk of peptic ulcer disease and GI bleeding, and those <50 kg.
  • Concurrent use of non-steroidal anti-inflammatory agents should also be avoided.

NMDA Receptor Antagonist

Memantine, a low-to-moderate affinity noncompetitive NMDA glutamate receptor antagonist, blocks excitotoxic neuronal toxicity associated with excessive release of glutamates. The postulated mechanism of action of memantine in AD may relate to inhibition of glutamatergic excitotoxicity and/or neuronal activity in the hippocampus.19

Use of Memantine for Moderate to Severe AD

Memantine was approved by the FDA in 2003 for the treatment of moderate to severe AD. Clinical data has demonstrated that memantine monotherapy modestly improves cognition, function, and behavior in patients with moderate to severe AD and may slow the rate of decline in one or more of these domains over time. Memantine is often used in combination with cholinesterase inhibitors; the combination of memantine and donepezil was found to offer greater benefit in cognitive, functional, neuropsychiatric, and global outcomes than donepezil alone in a 6-month placebo-controlled trial of patients with moderate to severe AD.20,21 To date, no head-to-head trials, comparing memantine monotherapy with ChEI therapy in AD have been conducted.

Memantine: Adverse Effects

Memantine is notably well tolerated in clinical trials and post-marketing surveillance. The most frequently occurring adverse reactions reported in pooled clinical trial data include dizziness, confusion, headache, fatigue, somnolence, and constipation. Clinical trials demonstrated a decrease in symptoms of behavioral disturbance for patients taking memantine; however, there are anecdotal reports of mild increases in behavioral symptoms since memantine became widely available in the United States in 2004. It has been reported that memantine may mitigate adverse effects associated with ChEI therapy in combination therapy.

Strategies to prevent adverse events with memantine:

  • Follow the titration schedule by starting a patient on 5 mg every day and increase the dose by 5 mg every week until a maximum dose of 10 mg BID is reached. If side effects are noted, the titration schedule can be slowed.
  • Memantine tablets should not be crushed or chewed as this may increase the rate of absorption. For patients who have dysphagia, memantine should be administered as an oral solution rather than the tablet
  • Because memantine is cleared by the kidneys, it should be given at a lower dose in patients with creatinine clearance <30 ml/min. The maximum dose for these patients should be 10 mg/day.22

Table. 1 Available Medications for Alzheimer’s Disease

Drug Name Recommended Dosage Adverse Effects Indication
Donepezil

Tablet: Initial dose of 5 mg daily

May increase dose to 10 mg daily after 4-6 weeks if well tolerated

May increase to 23 mg tablet daily after minimum of 3 months of donepezil 10 mg daily for patients with moderate to severe AD

Other Dosage Form: Donepezil ODT (Orally Disintegrating Tablet), 5 and 10 mg

Nausea, vomiting, diarrhea, leg cramps All stages for AD Higher dose indicated only for moderate to severe AD
Rivastigmine

Capsule: Initial dose of 3 mg/day (1.5 mg bid)
May increase dose to 6 mg/day (3 mg bid), 9 mg (4.5 mg bid), and 12 mg/day (6 mg bid) at minimum 2-week intervals (usual titration in practice is at monthly) if well tolerated

If more than several days of treatment are missed, must re-titrate from lowest dose to avoid severe GI adverse effects

Patch: Initial dose of 4.6 mg daily; may increase to 9.5 mg daily after minimum of 4 weeks if well tolerated

Patients weighing <50 kg should be monitored closely after therapy is initiated as they may be at higher risk of developing gastrointestinal adverse effects and clinically significant weight loss

If more than several days of therapy (capsules or patch) re-titration from the starting dose is recommended to avoid severe GI adverse effects.
Also available as oral solution; same dosage as capsule

Nausea, vomiting, diarrhea, weight loss, loss of appetite, muscle weakness

mild to moderate AD

Galantamine

Tablet: Initial dose of 8 mg/day (4 mg bid)
May increase dose to 16 mg/day (8 mg bid) and 24 mg/day (12 mg bid) at minimum 4-week intervals if well tolerated

Extended-release capsule: Same daily dosage as above but taken once a day

Also available as oral solution; same dosage as above

Nausea, vomiting, diarrhea, weight loss, anorexia

mild to moderate AD

Memantine

Tablet: Initial dose is 5mg daily

Increase dose to 10 mg/day (5 mg bid), 15 mg/day (5 mg and 10 mg as separate doses), and 20 mg/day (10 mg bid) at minimum 1-week intervals if well tolerated: (Maximum dose of 5 mg BID is recommended in patients with severe renal impairment )

Also available as oral solution; same dosage as above

Approved in June 2010, but not yet available; XR 7 and 28 mg

Capsules: Initial dose is 7mg daily

Increase dose to 14 mg/day, 21 mg/day, and 28 mg/d at minimum 1-week intervals if well tolerated. (Maximum dose of 14 mg/day is recommended in patients with severe renal impairment (creatinine clearance of 5 – 29 mL/min)

Dizziness, headache, constipation, confusion

moderate to severe AD

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