FDA

Memantine Hydrochloride

Approved 13 Oct 2015OralTablet

The FDA lists this product in 60 strengths and forms.

Indications

Memantine hydrochloride tablets are an N-methyl-D-asparate (NMDA) receptor antagonist indicated for the treatment of moderate to severe dementia of the Alzheimer's type. ( 1 ) Memantine hydrochloride tablets are indicated for the treatment of moderate to severe dementia of the Alzheimer's type.

Contraindications

Memantine hydrochloride tablets are contraindicated in patients with known hypersensitivity to memantine hydrochloride or to any excipients used in the formulation. ( 4 ) Memantine hydrochloride tablets are contraindicated in patients with known hypersensitivity to memantine hydrochloride or to any excipients used in the formulation.

Warnings and precautions

Conditions that raise urine pH may decrease the urinary elimination of memantine, resulting in increased plasma levels of memantine. ( 5.1 , 7.1 )

5.1Genitourinary Conditions

Conditions that raise urine pH may decrease the urinary elimination of memantine resulting in increased plasma levels of memantine [see Drug Interactions ( 7.1 )] .

Interactions

7.1 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.

7.2Use with Other N-methyl-D-aspartate (NMDA) Antagonists

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.

At a glance

Brand name: Memantine Hydrochloride
Route: Oral
Dosage form: Tablet
Applicant: Unichem
Status: Prescription
FDA approval: 13 Oct 2015
Application: ANDA200022-001

Contraindications

Warnings and precautions

Conditions that raise urine pH may decrease the urinary elimination of memantine, resulting in increased plasma levels of memantine. ( 5.1 , 7.1 )

5.1Genitourinary Conditions

Conditions that raise urine pH may decrease the urinary elimination of memantine resulting in increased plasma levels of memantine [see Drug Interactions ( 7.1 )] .

Interactions

Hence, memantine should be used with caution under these conditions.

7.2Use with Other N-methyl-D-aspartate (NMDA) Antagonists

Adverse reactions

Most common adverse reactions (≥ 5 % and greater than placebo) are dizziness, headache, confusion and constipation. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Unichem Pharmaceuticals (USA) Inc. at 1-866-562-4616 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials Experience

Memantine hydrochloride 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 memantine hydrochloride 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 memantine hydrochloride up to 20 mg/day, the likelihood of discontinuation because of an adverse reaction was the same in the memantine hydrochloride 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 memantine hydrochloride-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 memantine hydrochloride were dizziness, headache, confusion and constipation. Table 1 lists all adverse reactions that occurred in at least 2% of patients treated with memantine hydrochloride and at an incidence greater than placebo.

Table 1: Adverse Reactions Reported in Controlled Clinical Trials in at Least 2% of Patients Receiving Memantine Hydrochloride and at a Higher Frequency than Placebo-treated Patients Adverse Reaction Placebo Memantine hydrochloride (N = 922) (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 Memantine hydrochloride has not been systematically evaluated in patients with a seizure disorder. In clinical trials of memantine hydrochloride, seizures occurred in 0.2% of patients treated with memantine hydrochloride and 0.5% of patients treated with placebo.

6.2Postmarketing 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.

Memantine Hydrochloride

Indications

Contraindications

Warnings and precautions

5.1Genitourinary Conditions

Interactions

7.2Use with Other N-methyl-D-aspartate (NMDA) Antagonists

At a glance

Two medicines in one question?

Memantine Hydrochloride

Indications

Contraindications

Warnings and precautions

5.1Genitourinary Conditions

Interactions

7.2Use with Other N-methyl-D-aspartate (NMDA) Antagonists

At a glance

Two medicines in one question?

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

6.2Postmarketing Experience

Composition

Strengths and forms

Official product information