Does Namenda (memantine) cause side effects?

Namenda (memantine) is an orally active NMDA receptor antagonist used to treat moderate to severe dementia associated with Alzheimer's disease. 

Other medications used for Alzheimer's disease affect acetylcholine, one of the neurotransmitter chemicals that nerve cells in the brain use to communicate with one another. Those drugs inhibit the enzyme acetylcholinesterase that destroys acetylcholine and thereby increase the effects of acetylcholine. 

Namenda’s effects are independent of acetylcholine and acetylcholinesterase. Glutamate is the main excitatory neurotransmitter in the brain. It is believed that too much stimulation of nerve cells by glutamate may be responsible for the degeneration of nerves that occurs in some neurological diseases such as Alzheimer's disease.

Like other neurotransmitters, glutamate is produced and released by nerve cells in the brain. The released glutamate then travels to nearby nerve cells where it attaches to a receptor on the surface of the cells called the N-methyl-D-aspartate (NMDA) receptor. 

Namenda blocks this receptor and thereby decreases the effects of glutamate. It is thought that by blocking the NMDA receptor and the effects of glutamate, Namenda may protect nerve cells from excess stimulation by glutamate.

Common side effects of Namenda include

Serious side effects of Namenda include

Drug interactions of Namenda include medicines that make the urine more alkaline (for example, carbonic anhydrase inhibitors such as acetazolamide and sodium bicarbonate) because they reduce the elimination of Namenda by the kidneys and might increase the blood levels and the risk of side effects of Namenda. 

Combining Namenda with other NMDA receptor antagonists (for example, amantadine, ketamine, and dextromethorphan) has not been evaluated and should be done cautiously. Studies of Namenda have not been conducted in pregnant women. 

Namenda should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. 

It is unknown if Namenda is excreted into breast milk. Consult your doctor before breastfeeding.

What are the important side effects of Namenda (memantine)?

The most common side effects of memantine are:

Memantine may cause a serious skin reaction called Stevens-Johnson syndrome.

Other potential serious side effects include:

Namenda (memantine) side effects list for healthcare professionals

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

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 ReactionPlacebo
(N = 922) %
Namenda
(N = 940) %
Body as a Whole
  Fatigue12
  Pain13
Cardiovascular System
  Hypertension24
Central and Peripheral Nervous System
  Dizziness57
  Headache36
Gastrointestinal System
  Constipation35
  Vomiting23
Musculoskeletal System
  Back pain23
Psychiatric Disorders
  Confusion56
  Somnolence23
  Hallucination  23
Respiratory System
  Coughing34
  Dyspnea12

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.

What drugs interact with Namenda (memantine)?

Drugs That Make The Urine Alkaline

The clearance of memantine was reduced by about 80% under alkaline urine conditions at pH 8. Therefore, alterations of urine pH towards the alkaline condition may lead to an accumulation of the drug with a possible increase in adverse effects.

Urine pH is altered by diet, drugs (e.g. carbonic anhydrase inhibitors, sodium bicarbonate) and clinical state of the patient (e.g. renal tubular acidosis or severe infections of the urinary tract). Hence, memantine should be used with caution under these conditions.

Use With Other N-methyl-D-aspartate (NMDA) Antagonists

The combined use of Namenda with other NMDA antagonists (amantadine, ketamine, and dextromethorphan) has not been systematically evaluated and such use should be approached with caution.

Summary

Namenda (memantine) is an orally active NMDA receptor antagonist used to treat moderate to severe dementia associated with Alzheimer's disease. Common side effects of Namenda include fatigue, pain, increased blood pressure, dizziness, headache, constipation, vomiting, back pain, confusion, sleepiness, hallucinations, coughing, and difficulty breathing. Namenda should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. It is unknown if Namenda is excreted into breast milk.

Treatment & Diagnosis

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Medically Reviewed on 9/24/2020
References
FDA Prescribing Information

Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.
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