memantine hydrochloride 28 mg Capsule, Extended Release, 1,000-count
Other active recalls for Memantine Hydrochloride (different manufacturers) — 1 · tap to view
🆔 Identity & classification
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🏭 Manufacturer & labeler
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🩺 Clinical
- Memantine helps manage the symptoms of moderate to severe Alzheimer's disease. It works by blocking certain brain receptors that are overstimulated in Alzheimer's, which is thought...
- What does memantine actually do for Alzheimer's disease?
- No — memantine can be taken with or without food, whichever is easier to stick with. For the extended-release capsule form, food does slightly affect the timing of when the drug pe...
- Just skip the missed dose and take your next dose at the regularly scheduled time. Never double up to make up for a missed one. If you've missed several days in a row, don't just r...
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💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII 5138Q19F1X
Ammonia is a colorless gas made from nitrogen and hydrogen. It's used in medicines as a pH buffer to maintain the correct acidity level and help keep the product stable.
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UNII 8PJ61P6TS3
Butyl alcohol is a clear liquid organic solvent derived from petroleum or natural sources. In medicines, it helps dissolve active ingredients and serves as a solvent in liquid formulations and some topical products.
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UNII 35SW5USQ3G
A synthetic yellow dye used to color medicines. It helps make tablets, capsules, and liquids visually distinct so patients can easily identify their medication.
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UNII 7Z8S9VYZ4B
Ethylcellulose is a plant-derived thickener and film-former made by chemically modifying cellulose. It's used as a binder to hold tablet ingredients together, a coating to control how quickly medicine is released, or a thickener in liquid formulations.
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UNII H3R47K3TBD
FD&C Blue No. 1 is a synthetic blue dye approved for use in foods and medicines. It serves as a colorant to give the medication its distinctive appearance and help with product identification.
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UNII H77VEI93A8
A synthetic yellow dye used to color medications. It helps identify the drug and make it visually distinctive, with no effect on how the medicine works.
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UNII XM0M87F357
A dark iron oxide compound that gives medicines their black or dark color. It's used as a colorant in tablets and capsules to help identify the product and make it visually distinctive.
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UNII 2G86QN327L
Gelatin is a protein derived from animal collagen, commonly used in medicines as a gelling agent and capsule material. It helps create soft or hard capsule shells that hold and release medication, and can also thicken liquid formulations.
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UNII 3NXW29V3WO
Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
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UNII NPU9M2E6L8
Methylcellulose is a plant-derived thickening agent made from cellulose. It acts as a binder to hold tablet ingredients together and a viscosity builder in liquid formulations.
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UNII 3WJQ0SDW1A
Polyethylene glycol is a synthetic liquid or solid polymer used in medicines as a solvent, lubricant, and humectant. It helps dissolve active ingredients, reduces friction during manufacturing, and retains moisture in the final product.
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UNII 6OZP39ZG8H
Polysorbate 80 is a synthetic emulsifier derived from sorbitol and oleic acid. It helps mix oil and water-based ingredients together in medications and improves how the product disperses in the body.
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UNII WZH3C48M4T
Potassium hydroxide is a strong alkaline chemical used in medicines to adjust and maintain the pH level of liquid formulations, helping keep the product stable and the active ingredients effective.
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UNII 6DC9Q167V3
Propylene glycol is a clear liquid derived from petroleum or vegetable sources. It acts as a solvent, humectant, and preservative in medicines, helping dissolve active ingredients and maintain product stability.
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UNII 46N107B71O
Shellac is a natural resin secreted by the lac beetle. It's used as a coating on tablets and capsules to control how quickly the medicine dissolves and to improve appearance and stability.
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UNII 368GB5141J
A detergent and foaming agent derived from coconut or palm oil. In medications, it helps break down and mix oil and water-based ingredients, aids in tablet disintegration, and improves how the drug dissolves and spreads in the mouth or digestive system.
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UNII C151H8M554
A natural sugar derived from sugar cane or sugar beets. It's used as a sweetener, filler, and binder to improve taste, add bulk, and help hold tablet or capsule ingredients together.
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UNII 7SEV7J4R1U
A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
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UNII 8Z96QXD6UM
Triethyl citrate is a clear liquid derived from citric acid. It acts as a plasticizer and solvent in tablet coatings and film formulations, helping the coating remain flexible and adhere properly to the medicine.
20 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| memantine hydrochloride 28 mgthis 47335-0034-18 | Sun | 1000 capsules | — | — | Discontinued | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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🔬 Reported adverse events (FAERS)
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 47335-0034-18 You're viewing this | 1000 CAPSULE, EXTENDED RELEASE in 1 BOTTLE (47335-034-18) | 2013-06-14 | Inactivated by FDA |
| 47335-0034-81 | 90 CAPSULE, EXTENDED RELEASE in 1 BOTTLE (47335-034-81) | 2013-06-14 | Inactivated by FDA |
| 47335-0034-83 | 30 CAPSULE, EXTENDED RELEASE in 1 BOTTLE (47335-034-83) | 2013-06-14 | Inactivated by FDA |
You're viewing the largest of 3 pack sizes for this product.
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🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | — Not published for this NDC Applies only to products approved under an NDA/ANDA; many listings are out of scope. |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Memantine hydrochloride extended-release capsules are indicated for the treatment of moderate to severe dementia of the Alzheimer’s type. Memantine hydrochloride, is a N-methyl-D-aspartate (NMDA) receptor antagonist indicated for the treatment of moderate to severe dementia of the Alzheimer’s type. ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION The recommended starting dose of memantine hydrochloride extended-release capsules is 7 mg once daily; the dose should be increased in 7 mg increments to the recommended maintenance dose of 28 mg once daily; the minimum recommended interval between dose increases is one week. ( 2.1 ) Patients with severe renal impairment: the recommended maintenance dose of memantine hydrochloride extended-release capsules is 14 mg once daily. ( 2.3 )
2.1Recommended Dosing The dosage of memantine hydrochloride extended-release capsules shown to be effective in a controlled clinical trial is 28 mg once daily. The recommended starting dose of memantine hydrochloride extended-release capsules is 7 mg once daily. The dose should be increased in 7 mg increments to the recommended maintenance dose of 28 mg once daily.
The minimum recommended interval between dose increases is one week. The dose should only be increased if the previous dose has been well tolerated. The maximum recommended dose is 28 mg once daily.
Memantine hydrochloride extended-release capsules can be taken with or without food. Memantine hydrochloride extended-release capsules can be taken intact or may be opened, sprinkled on applesauce, and thereby swallowed. The entire contents of each memantine hydrochloride extended-release capsule should be consumed; the dose should not be divided.
Except when opened and sprinkled on applesauce, as described above, memantine hydrochloride extended-release capsules should be swallowed whole. Memantine hydrochloride extended-release capsules should not be divided, chewed, or crushed. If a patient misses a single dose of memantine hydrochloride extended-release capsules, that patient should not double up on the next dose.
The next dose should be taken as scheduled. If a patient fails to take memantine hydrochloride extended-release capsules for several days, dosing may need to be resumed at lower doses and retitrated as described above.
2.2Switching from Memantine Hydrochloride Tablets to Memantine Hydrochloride Extended-Release Capsules Patients treated with memantine hydrochloride tablets may be switched to memantine hydrochloride extended-release capsules as follows: It is recommended that a patient who is on a regimen of 10 mg twice daily of memantine hydrochloride tablets be switched to memantine hydrochloride extended-release capsules 28 mg once daily capsules the day following the last dose of 10 mg memantine hydrochloride tablet. There is no study addressing the comparative efficacy of these 2 regimens.
In a patient with severe renal impairment, it is recommended that a patient who is on a regimen of 5 mg twice daily of memantine hydrochloride tablets be switched to memantine hydrochloride extended-release capsules 14 mg once daily capsules the day following the last dose of 5 mg memantine hydrochloride tablet.
2.3Dosing in Patients with Renal Impairment In patients with severe renal impairment (creatinine clearance of 5 mL/min to 29 mL/min, based on the Cockcroft-Gault equation), the recommended maintenance dose (and maximum recommended dose) is 14 mg/day [see Clinical Pharmacology (1 2.3 )] .
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Each capsule contains 7 mg, 14 mg, 21 mg, or 28 mg of memantine hydrochloride. The 7 mg capsules are size #4 hard gelatin capsules, yellow colored cap and body with “031” imprinted in black ink on cap and body containing white to off white pellets. The 14 mg capsules are size #4 hard gelatin capsules, yellow colored cap and dark green colored body with “032” imprinted in black ink on cap and body containing white to off white pellets.
The 21 mg capsules are size #3 hard gelatin capsules, white to off white colored cap and dark green colored body with “033” imprinted in black ink on cap and body containing white to off white pellets. The 28 mg capsules are size #2 hard gelatin capsules, dark green colored cap and body with “034” imprinted in black ink on cap and body containing white to off white pellets. Memantine hydrochloride extended-release capsules are available as extended-release capsule in the following strengths: 7 mg, 14 mg, 21 mg, 28 mg ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Memantine hydrochloride extended-release capsules are contraindicated in patients with known hypersensitivity to memantine hydrochloride or to any excipients used in the formulation. Memantine hydrochloride extended-release capsules are contraindicated in patients with known hypersensitivity to memantine hydrochloride or to any excipients used in the formulation. ( 4 )
⚠️ Warnings and Cautions ▾
5 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 )] .
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The most commonly observed adverse reactions occurring at a frequency of at least 5% and greater than placebo with administration of memantine hydrochloride extended-release capsules 28 mg/day were headache, diarrhea and dizziness. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc. at 1-800-818-4555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials Experience Memantine hydrochloride extended-release capsules were evaluated in a double-blind placebo-controlled trial in which a total of 676 patients with moderate to severe dementia of the Alzheimer’s type (341 patients on memantine hydrochloride extended-release capsules 28 mg/day and 335 patients on placebo) were treated for up to 24 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 practice.
Adverse Reactions Leading to Discontinuation In the placebo-controlled clinical trial of memantine hydrochloride extended-release capsules, the proportion of patients in the memantine hydrochloride extended-release capsules group and the placebo group who discontinued treatment due to adverse reactions was 10% and 6%, respectively. The most common adverse reaction that led to treatment discontinuation in the memantine hydrochloride extended-release capsules group was dizziness, at a rate of 1.5%. Most Common Adverse Reactions The most commonly observed adverse reactions seen in patients administered memantine hydrochloride extended-release capsules in the controlled clinical trial, defined as those occurring at a frequency of at least 5% in the memantine hydrochloride extended-release capsules group and at a frequency higher than placebo, were headache, diarrhea and dizziness.
Table 1 lists adverse reactions that were observed at an incidence of ≥ 2% in the memantine hydrochloride extended-release capsules group and occurred at a rate greater than placebo. Table 1: Adverse Reactions Observed with a Frequency of ≥ 2% in the Memantine Hydrochloride Extended-Release Capsules Group and at a Rate Greater than Placebo Adverse Reaction Placebo (n = 335) % Memantine Hydrochloride Extended-Release Capsules 28 mg (n = 341) % Gastrointestinal Disorders Diarrhea 4 5 Constipation 1 3 Abdominal pain 1 2 Vomiting 1 2 Infections and Infestations Influenza 3 4 Investigations Weight, increased 1 3 Musculoskeletal and Connective Tissue Disorders Back pain 1 3 Nervous System Disorders Headache 5 6 Dizziness 1 5 Somnolence 1 3 Psychiatric Disorders Anxiety 3 4 Depression 1 3 Aggression 1 2 Renal and Urinary Disorders Urinary incontinence 1 2 Vascular Disorders Hypertension 2 4 Hypotension 1 2 Seizure Memantine has not been systematically evaluated in patients with a seizure disorder.
In clinical trials of memantine, seizures occurred in 0.3% of patients treated with memantine and 0.6% 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.
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS
7.1Drugs That Make 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 extended-release capsules with other NMDA antagonists (amantadine, ketamine, and dextromethorphan) has not been systematically evaluated and such use should be approached with caution.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of memantine hydrochloride extended-release capsules in pregnant women. Adverse developmental effects (decreased body weight and skeletal ossification) were observed in the offspring of rats administered memantine during pregnancy at doses associated with minimal maternal toxicity. These doses are higher than those used in humans at the maximum recommended daily dose of memantine hydrochloride extended-release capsules [see Data].
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data Oral administration of memantine (0 mg/kg/day, 2 mg/kg/day, 6 mg/kg/day, or 18 mg/kg/day) to rats during the period of organogenesis resulted in decreased skeletal ossification in fetuses at the highest dose tested.
The higher no-effect dose for adverse developmental effects (6 mg/kg) is 2 times the maximum recommended human daily dose (MRHD) of memantine hydrochloride extended-release capsules (28 mg) on a body surface area (mg/m 2 ) basis. Oral administration of memantine to rabbits (0 mg/kg/day, 3 mg/kg/day, 10 mg/kg/day, or 30 mg/kg/day) during the period of organogenesis resulted in no adverse developmental effects. The highest dose tested is approximately 20 times the MRHD of memantine hydrochloride extended-release capsules on a mg/m 2 basis.
In rats, memantine (0 mg/kg/day, 2 mg/kg/day, 6 mg/kg/day, or 18 mg/kg/day) was administered orally prior to and throughout mating and, in females, through the period of organogenesis or continuing throughout lactation to weaning. Decreased skeletal ossification in fetuses and decreased body weight in pups were observed at the highest dose tested. The higher no-effect dose for adverse developmental effects (6 mg/kg/day) is 2 times the MRHD of memantine hydrochloride extended-release capsules on a mg/m 2 basis.
Oral administration of memantine (0 mg/kg/day, 2 mg/kg/day, 6 mg/kg/day, or 18 mg/kg/day) to rats from late gestation throughout lactation to weaning, resulted in decreased pup weights at the highest dose tested. The higher no-effect dose (6 mg/kg/day) is approximately 2 times the MRHD of memantine hydrochloride extended-release capsules on a mg/m 2 basis.
8.2Lactation Risk Summary There are no data on the presence of memantine in human milk, the effects on the breastfed infant, or the effects of memantine hydrochloride extended-release capsules on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for memantine hydrochloride extended-release capsules and any potential adverse effects on the breastfed infant from memantine hydrochloride extended-release capsules or from the underlying maternal condition.
8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established. Memantine failed to demonstrate efficacy in two 12-week controlled clinical studies of 578 pediatric patients aged 6 to 12 years with autism spectrum disorders (ASD), including autism, Asperger’s disorder and Pervasive Development Disorder - Not Otherwise Specified (PDD-NOS). Memantine has not been studied in pediatric patients under 6 years of age or over 12 years of age.
Memantine treatment was initiated at 3 mg/day and the dose was escalated to the target dose (weight-based) by week 6. Oral doses of memantine 3 mg, 6 mg, 9 mg, or 15 mg extended-release capsules were administered once daily to patients with weights < 20 kg, 20 to 39 kg, 40 to 59 kg and ≥ 60 kg, respectively. In a randomized, 12-week double-blind, placebo-controlled parallel study (Study A) in patients with autism, there was no statistically significant difference in the Social Responsiven…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of memantine hydrochloride extended-release capsules in pregnant women. Adverse developmental effects (decreased body weight and skeletal ossification) were observed in the offspring of rats administered memantine during pregnancy at doses associated with minimal maternal toxicity. These doses are higher than those used in humans at the maximum recommended daily dose of memantine hydrochloride extended-release capsules [see Data].
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data Oral administration of memantine (0 mg/kg/day, 2 mg/kg/day, 6 mg/kg/day, or 18 mg/kg/day) to rats during the period of organogenesis resulted in decreased skeletal ossification in fetuses at the highest dose tested.
The higher no-effect dose for adverse developmental effects (6 mg/kg) is 2 times the maximum recommended human daily dose (MRHD) of memantine hydrochloride extended-release capsules (28 mg) on a body surface area (mg/m 2 ) basis. Oral administration of memantine to rabbits (0 mg/kg/day, 3 mg/kg/day, 10 mg/kg/day, or 30 mg/kg/day) during the period of organogenesis resulted in no adverse developmental effects. The highest dose tested is approximately 20 times the MRHD of memantine hydrochloride extended-release capsules on a mg/m 2 basis.
In rats, memantine (0 mg/kg/day, 2 mg/kg/day, 6 mg/kg/day, or 18 mg/kg/day) was administered orally prior to and throughout mating and, in females, through the period of organogenesis or continuing throughout lactation to weaning. Decreased skeletal ossification in fetuses and decreased body weight in pups were observed at the highest dose tested. The higher no-effect dose for adverse developmental effects (6 mg/kg/day) is 2 times the MRHD of memantine hydrochloride extended-release capsules on a mg/m 2 basis.
Oral administration of memantine (0 mg/kg/day, 2 mg/kg/day, 6 mg/kg/day, or 18 mg/kg/day) to rats from late gestation throughout lactation to weaning, resulted in decreased pup weights at the highest dose tested. The higher no-effect dose (6 mg/kg/day) is approximately 2 times the MRHD of memantine hydrochloride extended-release capsules on a mg/m 2 basis.
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established. Memantine failed to demonstrate efficacy in two 12-week controlled clinical studies of 578 pediatric patients aged 6 to 12 years with autism spectrum disorders (ASD), including autism, Asperger’s disorder and Pervasive Development Disorder - Not Otherwise Specified (PDD-NOS). Memantine has not been studied in pediatric patients under 6 years of age or over 12 years of age.
Memantine treatment was initiated at 3 mg/day and the dose was escalated to the target dose (weight-based) by week 6. Oral doses of memantine 3 mg, 6 mg, 9 mg, or 15 mg extended-release capsules were administered once daily to patients with weights < 20 kg, 20 to 39 kg, 40 to 59 kg and ≥ 60 kg, respectively. In a randomized, 12-week double-blind, placebo-controlled parallel study (Study A) in patients with autism, there was no statistically significant difference in the Social Responsiveness Scale (SRS) total raw score between patients randomized to memantine (n=54) and those randomized to placebo (n=53).
In a 12-week responder-enriched randomized withdrawal study (Study B) in 471 patients with ASD, there was no statistically significant difference in the loss of therapeutic response rates between patients randomized to remain on full-dose memantine (n=153) and those randomized to switch to placebo (n=158). The overall safety profile of memantine in pediatric patients was generally consistent with the known safety profile in adults [see Adverse Reactions (6.1)] . In Study A, the adverse reactions in the memantine group (n=56) that were reported in at least 5% of patients and at least twice the frequency of the placebo group (N=58) are listed in Table 2.
Table 2: Study A Commonly Reported Adverse Reactions with a Frequency ≥ 5% and Twice That of Placebo Adverse Reaction Memantine N=56 Placebo N=58 Cough 8.9% 3.4% Influenza 7.1% 3.4% Rhinorrhea 5.4% 0% Agitation 5.4% 1.7% Discontinuations due to Adverse Reactions a Aggression 3.6% 1.7% Irritability 1.8% 3.4% a Reported adverse reactions leading to discontinuation in more than one patient in either treatment group. The adverse reactions that were reported in at least 5% of patients in the 12 to 48 week open-label study to identify responders to enroll in Study B are listed in Table 3: Table 3: 12 to 48 Week Open Label Lead-In study to Study B Commonly Reported Adverse Reactions with a Frequency ≥ 5% Adverse Reaction Memantine N=903 Headache 8.0% Nasopharyngitis 6.3% Pyrexia 5.8% Irritability 5.4% Discontinuations due to Adverse Reactions a Irritability 1.2% Aggression 1.0% a At least 1% incidence of adverse reactions leading to premature discontinuation.
In the randomized withdrawal study (Study B), the adverse reaction in patients randomized to placebo (n=160) and reported in at least 5% of patients and twice that of the full-dose memantine treatment group (n=157) was irritability (5.0% vs 2.5%). Juvenile Animal Study In a juvenile animal study, male and female juvenile rats were administered memantine (15 mg/kg/day, 30 mg/kg/day, and 45 mg/kg/day) starting on postnatal day (PND) 14 through PND 70. Body weights were reduced at 45 mg/kg/day.
Delays in sexual maturation were noted in male and female rats at doses ≥ 30 mg/kg/day. Memantine induced neuronal lesions in several areas of the brain on PND 15 and 17 at doses ≥ 30 mg/kg/day. Behavioral toxicity (decrease percent of auditory startle habituation) was noted for animals in the 45 mg/kg/day dose group.
The 15 mg/kg/day dose was considered the No-Observed-Adverse-Effect-Level (NOAEL) for this study. In a second juvenile rat toxicity study, male and female juvenile rats were administered memantine (1 mg/kg/day, 3 mg/kg/day, 8 mg/kg/day, 15 mg/kg/day, 30 mg/kg/day, and 45 mg/kg/day) starting on postnatal day (PND) 7 through PND 70. Due to early memantine-related mortality, the 30 mg/kg/day and 45 mg/kg/day dose groups were terminated without further evaluation.
Memantine…
🧓 Geriatric Use ▾
8.5Geriatric Use The majority of people with Alzheimer’s disease are 65 years of age and older. In the clinical study of memantine hydrochloride extended-release, the mean age of patients was approximately 77 years; over 91% of patients were 65 years and older, 67% were 75 years and older, and 14% were at or above 85 years of age. The efficacy and safety data presented in the clinical trial sections were obtained from these patients.
There were no clinically meaningful differences in most adverse reactions reported by patient groups ≥ 65 years old and < 65 years old.
🆘 Overdosage ▾
10 OVERDOSAGE Signs and symptoms most often accompanying overdosage with other formulations of memantine in clinical trials and from worldwide marketing experience, alone or in combination with other drugs and/or alcohol, include agitation, asthenia, bradycardia, confusion, coma, dizziness, ECG changes, increased blood pressure, lethargy, loss of consciousness, psychosis, restlessness, slowed movement, somnolence, stupor, unsteady gait, visual hallucinations, vertigo, vomiting, and weakness. The largest known ingestion of memantine worldwide was 2 grams in a patient who took memantine in conjunction with unspecified antidiabetic medications.
This patient experienced coma, diplopia, and agitation, but subsequently recovered. One patient participating in a memantine hydrochloride extended-release capsules clinical trial unintentionally took 112 mg of memantine hydrochloride extended-release capsules daily for 31 days and experienced an elevated serum uric acid, elevated serum alkaline phosphatase, and low platelet count. Fatal outcome has been very rarely reported with memantine, and the relationship to memantine was unclear.
Because strategies for the management of overdose are continually evolving, it is advisable to contact a poison control center to determine the latest recommendations for the management of an overdose of any drug. As in any cases of overdose, general supportive measures should be utilized, and treatment should be symptomatic. Elimination of memantine can be enhanced by acidification of urine.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Persistent activation of central nervous system N-methyl-D-aspartate (NMDA) receptors by the excitatory amino acid glutamate has been hypothesized to contribute to the symptomatology of Alzheimer’s disease. Memantine is postulated to exert its therapeutic effect through its action as a low to moderate affinity uncompetitive (open-channel) NMDA receptor antagonist which binds preferentially to the NMDA receptor-operated cation channels. There is no evidence that memantine prevents or slows neurodegeneration in patients with Alzheimer’s disease.
12.2Pharmacodynamics Memantine showed low to negligible affinity for GABA, benzodiazepine, dopamine, adrenergic, histamine and glycine receptors and for voltage-dependent Ca 2+ , Na + or K + channels. Memantine also showed antagonistic effects at the 5HT 3 receptor with a potency similar to that for the NMDA receptor and blocked nicotinic acetylcholine receptors with one-sixth to one-tenth the potency. In vitro studies have shown that memantine does not affect the reversible inhibition of acetylcholinesterase by donepezil, galantamine, or tacrine.
12.3Pharmacokinetics Memantine is well absorbed after oral administration and has linear pharmacokinetics over the therapeutic dose range. It is excreted predominantly unchanged in urine and has a terminal elimination half-life of about 60 to 80 hours. In a study comparing 28 mg once daily memantine hydrochloride extended-release capsules to 10 mg twice daily memantine hydrochloride tablets, the C max and AUC 0-24 values were 48% and 33% higher for the XR dosage regimen, respectively.
Absorption After multiple dose administration of memantine hydrochloride extended-release capsules, memantine peak concentrations occur around 9 to 12 hours post-dose. There is no difference in the absorption of memantine hydrochloride extended-release capsules when the capsule is taken intact or when the contents are sprinkled on applesauce. There is no difference in memantine exposure, based on C max or AUC, for memantine hydrochloride extended-release capsules whether that drug product is administered with food or on an empty stomach.
However, peak plasma concentrations are achieved about 18 hours after administration with food versus approximately 25 hours after administration on an empty stomach. Distribution The mean volume of distribution of memantine is 9 L/kg to 11 L/kg and the plasma protein binding is low (45%). Elimination Metabolism Memantine undergoes partial hepatic metabolism.
The hepatic microsomal CYP450 enzyme system does not play a significant role in the metabolism of memantine. Excretion Memantine is excreted predominantly unchanged in the urine and has a terminal elimination half-life of about 60 to 80 hours. About 48% of administered drug is excreted unchanged in urine; the remainder is converted primarily to three polar metabolites which possess minimal NMDA receptor antagonistic activity: the N-glucuronide conjugate, 6-hydroxy-memantine, and 1-nitroso-deaminated memantine.
A total of 74% of the administered dose is excreted as the sum of the parent drug and the N-glucuronide conjugate. Renal clearance involves active tubular secretion moderated by pH dependent tubular reabsorption. Specific Populations Elderly The pharmacokinetics of memantine in young and elderly subjects are similar.
Gender Following multiple dose administration of memantine hydrochloride 20 mg daily, females had about 45% higher exposure than males, but there was no difference in exposure when body weight was taken into account. Renal Impairment Memantine pharmacokinetics were evaluated following single oral administration of 20 mg memantine hydrochloride in 8 subjects with mild renal impairment (creatinine clearance, CLcr, > 50 mL/min to 80 mL/min), 8 subjects with moderate renal impairment (CLcr 30 mL/min to 49 mL/min), 7 subjects with severe renal impairment (CLcr 5 mL/min to 29 mL/min) and 8 healthy subjects (CLc…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Persistent activation of central nervous system N-methyl-D-aspartate (NMDA) receptors by the excitatory amino acid glutamate has been hypothesized to contribute to the symptomatology of Alzheimer’s disease. Memantine is postulated to exert its therapeutic effect through its action as a low to moderate affinity uncompetitive (open-channel) NMDA receptor antagonist which binds preferentially to the NMDA receptor-operated cation channels. There is no evidence that memantine prevents or slows neurodegeneration in patients with Alzheimer’s disease.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING 7 mg capsule: Size #4 hard gelatin capsules, yellow colored cap and body with “031” imprinted in black ink on cap and body containing white to off white pellets. Bottles of 30’s with Child Resistant Cap…………....……........................... NDC 47335-031-83 Bottles of 90’s with Child Resistant Cap.......................................................
NDC 47335-031-81 Bottles of 1000’s .................................................…….…........................... NDC 47335-031-18 14 mg capsule: Size #4 hard gelatin capsules, yellow colored cap and dark green colored body with “032” imprinted in black ink on cap and body containing white to off white pellets. Bottles of 30's with Child Resistant Cap..................................…………..
NDC 47335-032-83 Bottles of 90's with Child Resistant Cap..................................………..… NDC 47335-032-81 Bottles of 1000's ....................................................................….…......... NDC 47335-032-18 21 mg capsule: Size #3 hard gelatin capsules, white to off white colored cap and dark green colored body with “033” imprinted in black ink on cap and body containing white to off white pellets. Bottles of 30's with Child Resistant Cap.............................………………..
NDC 47335-033-83 Bottles of 90's with Child Resistant Cap………………............................... NDC 47335-033-81 Bottles of 1000's ..............................................……….…........................... NDC 47335-033-18 28 mg capsule: Size #2 hard gelatin capsules, dark green colored cap and body with “034” imprinted in black ink on cap and body containing white to off white pellets.
Bottles of 30’s with Child Resistant Cap………………....................….. NDC 47335-034-83 Bottles of 90’s with Child Resistant Cap………………......................… NDC 47335-034-81 Bottles of 1000’s ..............................................……....................….…. NDC 47335-034-18 Store memantine hydrochloride extended-release capsules at 20° to 25°C (68° to 77°F); excursions permitted between 15° and 30°C (59° and 86°F) [see USP Controlled Room Temperature].
Keep this and all medicines out of reach of children.
📋 Description ▾
11 DESCRIPTION Memantine hydrochloride extended-release capsules are orally active NMDA receptor antagonist. The chemical name for memantine hydrochloride is 1-amino-3,5-dimethyladamantane hydrochloride with the following structural formula: The molecular formula is C 12 H 21 N•HCl and the molecular weight is 215.76. Memantine hydrochloride occurs as a fine white to off-white powder and is soluble in water.
Memantine hydrochloride extended-release capsules are supplied for oral administration as 7 mg, 14 mg, 21 mg, and 28 mg capsules. Each capsule contains extended-release pellets with the labeled amount of memantine hydrochloride and the following inactive ingredients: sugar spheres, talc, hypromellose, polyethylene glycol, methyl cellulose, polysorbate 80, ethyl cellulose and triethyl citrate. The capsule shell contains gelatin, sodium lauryl sulfate, titanium dioxide, iron oxide yellow (7 mg, 14 mg), FD&C Blue #1 (14 mg, 21 mg, 28 mg), FD&C yellow #6 (14 mg, 21 mg, 28 mg) and D&C yellow #10 (14 mg, 21 mg, 28 mg).
The imprinting ink contains shellac, butyl alcohol, propylene glycol, strong ammonia solution, black iron oxide and potassium hydroxide. chemical-structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). To assure safe and effective use of memantine hydrochloride extended-release capsules, the information and instructions provided in the patient information section should be discussed with patients and caregivers. Instruct patients and caregivers to take memantine hydrochloride extended-release capsules only once per day, as prescribed.
Instruct patients and caregivers that memantine hydrochloride extended-release capsules be swallowed whole. Alternatively, memantine hydrochloride extended-release capsules may be opened and sprinkled on applesauce and the entire contents should be consumed. The capsules should not be divided, chewed or crushed.
Warn patients not to use any capsules of memantine hydrochloride extended-release that are damaged or show signs of tampering. If a patient misses a single dose of memantine hydrochloride extended-release capsules, that patient should not double up on the next dose. The next dose should be taken as scheduled.
If a patient fails to take memantine hydrochloride extended-release capsulesfor several days, dosing should not be resumed without consulting that patient’s healthcare professional. Advise patients and caregivers that memantine hydrochloride extended-release capsules may cause headache, diarrhea, and dizziness.