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Memantine and Donepezil 28 mg; 10 mg Capsule, Extended Release — NDC 33342-0313-56 package photo

Memantine and Donepezil 28 mg; 10 mg Capsule, Extended Release

by Macleods Pharmaceuticals Limited · 10 BLISTER PACK in 1 CARTON (33342-313-56) / 14 CAPSULE, EXTENDED RELEASE in 1 BLISTER PACK
NDC 33342-0313-56
🏷️ FDA NDC (as labeled) 33342-313-56 billing pads the product segment with a zero
This package
Contains14 capsule, extended release in 1 blister pack Pack sizes3 compare ↓
Also comes in: 30 capsules 33342-0313-07 90 capsules 33342-0313-10
Rx only Generic On market Non-controlled
🗂️ Data synced Sep 17, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

🆔 Identity & classification

FDA NDC (as labeled) 33342-313-56
Product NDC 33342-313
11-digit billing NDC 33342031356
RxCUI 1599803, 1599805
UNII JY0WD0UA60, 3O2T2PJ89D
UPC 0333342312075, 0333342312105, 0333342313072, 0333342313102
Application # ANDA208672
SPL Set ID 3d9a23dc-8cbe-47c3-a048-70d86cb9dc14
Established class (EPC) Cholinesterase Inhibitor; N-methyl-D-aspartate Receptor Antagonist
Mechanism of action Cholinesterase Inhibitors; NMDA Receptor Antagonists
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2025-07-15
Route ORAL
Dosage form CAPSULE, EXTENDED RELEASE
Substance MEMANTINE HYDROCHLORIDE; DONEPEZIL HYDROCHLORIDE
GPI-14 62059902507050
GCN Seq No 073815
GCN 38258
HICL code 041881
Ingredient (HICL) Memantine Hcl/Donepezil Hcl
HIC1 code H
Therapeutic class — broad (HIC1) Nervous System (Except Autonomic)
HIC2 code H1
Therapeutic class — intermediate (HIC2) Drugs Affecting Principally The Brain
HIC3 code H1C
Therapeutic class — specific (HIC3) Alzheimer's Thx,Nmda Receptor Antag-Cholines Inhib
AHFS code 12:04.00.00
AHFS class Parasympathomimetic (Cholinergic Agents)
FDB label name MEMANTINE-DONEPEZIL ER 28-10MG
FDB brand name Memantine Hcl-Donepezil Hcl Er
Legend status F — Federal legend — prescription drug or device
TE code (Orange Book) AB · RLD · RS
Why two NDCs? The FDA registers this code as 33342-313-56 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 33342-0313-56. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

🏷️ RxNorm drug class

This medicine belongs to the Cholinesterase Inhibitor class.

Pharmacologic class Cholinesterase Inhibitor
Drug family (ATC) Anticholinesterases
How it works Cholinesterase Inhibitors
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

🏭 Manufacturer & labeler

LabelerMacleods Pharmaceuticals Limited
Application holderMACLEODS PHARMACEUTICALS LTD
FDA applicationANDA208672 (ANDA)
Labeler code33342
First marketedJul 2025
Product typeHuman Prescription Drug
Portfolio385 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

🩺 Clinical

Label name MEMANTINE-DONEPEZIL ER 28-10MG Ingredient Memantine Hcl/Donepezil Hcl
📖 What it is MedlinePlus · NLM

Donepezil is used to treat Alzheimer's disease (AD; a brain disease that affects memory, thinking, and behavior). Donepezil is in a class of medications called cholinesterase inhibitors. It works by increasing the amount of a certain naturally occurring substance in the brain that play a role in mental function.

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • This combination medicine brings together two drugs that work in different ways to help manage the symptoms of moderate to severe Alzheimer's dementia. One ingredient, memantine, t...
  • What exactly does this medication do for Alzheimer's disease?
  • You take it once in the evening, every day. You can take it with or without food — whatever is easiest for you. If you or your loved one has trouble swallowing capsules, you can ca...
  • When and how should I take this capsule?
📖 Read our full Donepezil / Memantine guide →

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

💊 What it looks like

Color White / Orange
ShapeCapsule
Imprint185
Size19 mm
ScoringNot scored
One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.
Where does this data come from?
Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

🧪 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.

  • UNII OP1R32D61U
    Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
  • 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.
  • UNII 1K09F3G675
    Ferric oxide red is an inorganic iron compound used as a colorant in medicines. It gives tablets, capsules, or other dosage forms a red or reddish tint for identification and appearance.
  • 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.
  • 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.
  • 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.
  • UNII EWQ57Q8I5X
    Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
  • 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.
  • 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.
  • UNII MB5IUD6JUA
    Shellac is a natural resin secreted by lac beetles, purified and processed into a coating material. It seals and protects tablets and capsules, controls how quickly the medicine dissolves, and gives pills their glossy finish.
  • UNII ETJ7Z6XBU4
    Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
  • 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.
  • 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.
  • 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.
  • 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.

15 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — 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

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

💲 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 systemPer eachPer 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.
ℹ️
No price is published for this exact package yet. CMS surveys NADAC per package size, so a different pack of the same drug often has one.
Try another pack size: 30 capsules 90 capsules
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Memantine and Donepezil Hydrochlorides Extended-release 28 mg/1; 10 mg 69238-1247-03 Amneal 30 capsules $9.448 AB Availability likely —
memantine hydrochloride and donepezil hydrochloride 28 mg/1; 10 mg 69680-0185-30 Vitruvias 30 capsules $9.448 AB Availability likely —
Namzaric 28 mg/1; 10 mg 00456-1228-11 Allergan, 10 capsules — AB Discontinued —
Memantine and Donepezil 28 mg/1; 10 mgthis 33342-0313-56 Macleods 14 capsules — AB FDA listed —
Memantine and Donepezil Hydrochlorides Extended-release 28 mg/1; 10 mg 73190-0004-30 AvKARE 30 capsules — AB FDA listed —
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

⏳ Availability & generic status

🏛️
2025
On the market since
Jul 2025
📍
2026
Currently FDA-listed
1 year listed
🔓
·
Generic on the market
this product is a generic
✅This is a generic drug

This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

🔬 Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for Memantine and Donepezil — the ingredient across all brands.

Top reported reactions

Interstitial Lung Disease1
Pleural Effusion1
Pulmonary Oedema1
Pulmonary Toxicity1

Reporter sex

1 reports
Female · 100%
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

📦 Packaging — all sizes for this product

Package NDCDescription Per unit Per pack Marketing startStatus
33342-0313-07 30 CAPSULE, EXTENDED RELEASE in 1 BOTTLE (33342-313-07) $9.45 / ea $283.44 2025-07-15 Active
33342-0313-10 90 CAPSULE, EXTENDED RELEASE in 1 BOTTLE (33342-313-10) — — 2025-07-15 Active
33342-0313-56 You're viewing this 10 BLISTER PACK in 1 CARTON (33342-313-56) / 14 CAPSULE, EXTENDED RELEASE in 1 BLISTER PACK — — 2025-07-15 Active

Pack size FAQ

What quantity is in NDC 33342-0313-56?
NDC 33342-0313-56 is listed by the FDA — 10 blister pack in 1 carton / 14 capsule, extended release in 1 blister pack.
What NDC number is used to bill for this package of Memantine and Donepezil 28 mg; 10 mg Capsule, Extended Release?
Bill NDC 33342-0313-56 — the 11-digit billing format is 33342031356. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.

🧭 About this NDC listing & data coverage

Finished prescription product
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 ✓ Available
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.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The FDA registers it as 33342-313-56, which is what is printed on the packaging and shown on DailyMed. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero: 33342-0313-56, written without dashes as 33342031356. The Identity section at the top of this page lists every form of this code.
What do the three segments of this NDC mean?
In 33342-0313-56, the first segment (33342) is the labeler code FDA assigned to Macleods Pharmaceuticals Limited; the middle segment (0313) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (56) identifies this exact package size and type. Together they name one specific package of one specific product.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Macleods Pharmaceuticals Limited. Listing status can change — the directory data on this page refreshes weekly.
Does this product come in other package sizes?
Yes — the FDA directory lists 2 other package presentations of this same product, including 30 capsules (33342-0313-07), 90 capsules (33342-0313-10). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
Macleods Pharmaceuticals Limited is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients
🎯 Indications and Usage 84 words ▾

1 INDICATIONS AND USAGE Memantine and donepezil hydrochlorides extended-release capsules are indicated for the treatment of moderate to severe dementia of the Alzheimer’s type in patients stabilized on 10 mg of donepezil hydrochloride once daily. Memantine and donepezil hydrochlorides extended-release capsules are a combination of memantine hydrochloride, an NMDA receptor antagonist, and donepezil hydrochloride, an acetylcholinesterase inhibitor, indicated for the treatment of moderate to severe dementia of the Alzheimer’s type in patients stabilized on 10 mg of donepezil hydrochloride once daily.

( 1 )

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION • For patients on donepezil hydrochloride 10 mg only, the recommended starting dose of memantine and donepezil hydrochlorides extended-release capsules is 7 mg/10 mg, taken once daily in the evening. The dose should be increased in 7 mg increment to the recommended maintenance dose of 28 mg /10 mg. the minimum recommended interval between dose increases is one week. ( 2.1 ) • Patients on memantine hydrochloride (10 mg twice daily or 28 mg extended-release once daily) and donepezil hydrochloride 10 mg once daily can be switched to memantine and donepezil hydrochlorides extended-release capsules 28 mg/10 mg, taken once daily in the evening ( 2.1 ) • Memantine and donepezil hydrochlorides extended-release capsules can be taken with or without food, whole or sprinkled on applesauce; do not divide, chew, or crush ( 2.2 ) • Severe renal impairment: the recommended maintenance dose for memantine and donepezil hydrochlorides extended-release capsules is 14 mg/10 mg once daily in the evening.

( 2.3 )

2.1Recommended Dosing The recommended dose of memantine and donepezil hydrochlorides extended-release capsules is 28 mg/10 mg once daily. For patients stabilized on donepezil and not currently on memantine: For patients stabilized on donepezil hydrochloride 10 mg and not currently on memantine hydrochloride, the recommended starting dose of memantine and donepezil hydrochlorides extended-release capsules is 7 mg/10 mg, taken once a day in the evening. The dose should be increased in 7 mg increments of the memantine hydrochloride component to the recommended maintenance dose of 28 mg/10 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 dose is 28 mg /10 mg once daily.

For patients stabilized on both donepezil and memantine: Patients stabilized on memantine hydrochloride (10 mg twice daily or 28 mg extended-release once daily) and donepezil hydrochloride 10 mg once daily can be switched to memantine and donepezil hydrochlorides extended-release capsules 28 mg/10 mg, taken once a day in the evening. Patients should start memantine and donepezil hydrochlorides extended-release capsules the day following the last dose of memantine hydrochloride and donepezil hydrochloride administered separately.

If a patient misses a single dose of memantine and donepezil hydrochlorides extended-release capsules, the next dose should be taken as scheduled, without doubling up the dose.

2.2Administration Information Memantine and donepezil hydrochlorides extended-release capsules can be taken with or without food. Memantine and donepezil hydrochlorides extended-release capsules can be taken intact or may be opened, sprinkled on applesauce, and swallowed without chewing. The entire contents of each memantine and donepezil hydrochlorides extended-release capsules should be consumed; the dose should not be divided.

Except when opened and sprinkled on applesauce, as described above, memantine and donepezil hydrochlorides extended-release capsules should be swallowed whole. Memantine and donepezil hydrochlorides extended-release capsules should not be divided, chewed, or crushed.

2.3Dosing in Patients with Severe Renal Impairment For patients stabilized on donepezil and not currently on memantine: For patients with severe renal impairment (creatinine clearance 5-29 mL/min, based on the Cockcroft-Gault equation) stabilized on donepezil hydrochloride 10 mg once daily and not currently on memantine hydrochloride, the recommended starting dose of memantine and donepezil hydrochlorides extended-release capsules is 7 mg/10 mg taken once a day in the evening. The dose should be increased to the recommended maintenance dose of 14 mg/10 mg once daily in the evening after a minimum of one week [ see Use in Specific Populations (8.6) ].

For patients stabilized on both donepezil and memantine: Patients with severe renal imp…

💊 Dosage Forms and Strengths 94 words ▾

3 DOSAGE FORMS AND STRENGTHS Memantine and donepezil hydrochlorides extended-release capsules: • 14 mg memantine hydrochloride extended-release/10 mg donepezil hydrochloride capsules are white capsules imprinted with “184” on cap with black ink and plain body. • 28 mg memantine hydrochloride extended-release/10 mg donepezil hydrochloride capsules are light orange cap, white body imprinted with “185” on cap with black ink and plain body. Memantine and donepezil hydrochlorides extended-release capsules: • 14 mg memantine hydrochloride and 10 mg donepezil hydrochloride ( 3 ) • 28 mg memantine hydrochloride and 10 mg donepezil hydrochloride ( 3 )

⛔ Contraindications 61 words ▾

4 CONTRAINDICATIONS Memantine and donepezil hydrochlorides extended-release capsules are contraindicated in patients with known hypersensitivity to memantine hydrochloride, donepezil hydrochloride, piperidine derivatives, or to any excipients used in the formulation. Memantine and donepezil hydrochlorides extended-release capsules are contraindicated in patients with known hypersensitivity to memantine hydrochloride, donepezil hydrochloride, piperidine derivatives, or to any excipients used in the formulation. ( 4 )

⚠️ Warnings and Cautions ~2 min read ▾

5 WARNINGS AND PRECAUTIONS • Memantine and donepezil hydrochlorides extended-release capsules are likely to exaggerate succinylcholine-type muscle relaxation during anesthesia. ( 5.1 ) • Memantine and donepezil hydrochlorides extended-release capsules may have vagotonic effects on the sinoatrial and atrioventricular nodes manifesting as bradycardia or heart block. ( 5.2 ) • Monitor patients for symptoms of active or occult gastrointestinal bleeding, especially those at increased risk for developing ulcers.

( 5.3 ) • Memantine and donepezil hydrochlorides extended-release capsules can cause diarrhea, nausea, and vomiting. ( 5.4 ) • Memantine and donepezil hydrochlorides extended-release capsules may cause bladder outflow obstructions. ( 5.5 ) • Conditions that raise urine pH may decrease the urinary elimination of memantine, resulting in increased plasma levels of memantine.

( 5.5 , 7.1 )

5.1Anesthesia Donepezil hydrochloride, an active ingredient in memantine and donepezil hydrochlorides extended-release capsules, as a cholinesterase inhibitor, is likely to exaggerate succinylcholine-type muscle relaxation during anesthesia.

5.2Cardiovascular Conditions Because of their pharmacological action, cholinesterase inhibitors may have vagotonic effects on the sinoatrial and atrioventricular nodes. This effect may manifest as bradycardia or heart block in patients both with and without known underlying cardiac conduction abnormalities. Syncopal episodes have been reported in association with the use of donepezil hydrochloride, an active ingredient in memantine and donepezil hydrochlorides extended-release capsules.

5.3Peptic Ulcer Disease and Gastrointestinal Bleeding Through their primary action, cholinesterase inhibitors may be expected to increase gastric acid secretion due to increased cholinergic activity. Clinical studies of donepezil hydrochloride in a dose of 5 mg/day to 10 mg/day have shown no increase, relative to placebo, in the incidence of either peptic ulcer disease or gastrointestinal bleeding. Patients treated with memantine and donepezil hydrochlorides extended-release capsules should be monitored closely for symptoms of active or occult gastrointestinal bleeding, especially those at increased risk for developing ulcers, e.g., those with a history of ulcer disease or those receiving concurrent nonsteroidal anti-inflammatory drugs (NSAIDs).

5.4Nausea and Vomiting Donepezil hydrochloride, an active ingredient in memantine and donepezil hydrochlorides extended-release capsules, when initiated, as a predictable consequence of its pharmacological properties, has been shown to produce diarrhea, nausea, and vomiting. Although in most cases, these effects have been mild and transient, sometimes lasting one to three weeks, and have resolved during continued use of donepezil hydrochloride, patients should be observed closely at the initiation of treatment.

5.5Genitourinary Conditions Although not observed in clinical trials of donepezil hydrochloride, an active ingredient in memantine and donepezil hydrochlorides extended-release capsules, cholinomimetics may cause bladder outflow obstruction. Conditions that raise urine pH may decrease the urinary elimination of memantine, an active ingredient in memantine and donepezil hydrochlorides extended-release capsules, resulting in increased plasma levels of memantine [ see Drug Interactions (7.1) ].

5.6Seizures Cholinomimetics, including donepezil hydrochloride, an active ingredient in memantine and donepezil hydrochlorides extended-release capsules, are believed to have some potential to cause generalized convulsions. However, seizure activity also may be a manifestation of Alzheimer’s disease.

5.7Pulmonary Conditions Because of their cholinomimetic actions, cholinesterase inhibitors should be prescribed with care to patients with a history of asthma or obstructive pulmonary disease.

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following serious adverse reactions are discussed below and elsewhere in the labeling. • Cardiovascular Conditions [ see Warnings and Precautions ( 5.2 ) ] • Peptic Ulcer Disease and Gastrointestinal Bleeding [ see Warnings and Precautions ( 5.3 ) ] • Nausea and Vomiting [ see Warnings and Precautions ( 5.4 ) ] • Genitourinary Conditions [ see Warnings and Precautions ( 5.5 ) ] • Seizures [ see Warnings and Precautions ( 5.6 ) ] • Pulmonary Conditions [ see Warnings and Precautions ( 5.7 ) ] • The most common adverse reactions, occurring at a frequency of at least 5% and greater than placebo with memantine hydrochloride extended-release 28 mg/day, were headache, diarrhea, and dizziness.

( 6.1 ) • The most common adverse reactions, occurring at a frequency of at least 5% in patients receiving donepezil hydrochloride and at twice or more the placebo rate, include diarrhea, anorexia, vomiting, nausea, and ecchymosis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Macleods Pharma USA, Inc. at 1-888-943-3210 or 1-855-926-3384 FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials Experience 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. Memantine Hydrochloride Memantine hydrochloride extended-release was evaluated in a double-blind, placebo-controlled trial in 676 patients with moderate to severe dementia of the Alzheimer’s type (341 patients treated with memantine 28 mg/day dose and 335 patients treated with placebo) for a treatment period up to 24 weeks.

Of the patients randomized, 236 treated with memantine 28 mg/day and 227 treated with placebo were on a stable dose of donepezil for 3 months prior to screening. Adverse Reactions Leading to Discontinuation with Memantine Hydrochloride In the placebo-controlled clinical trial of memantine hydrochloride extended-release, the proportion of patients in the memantine hydrochloride extended-release 28 mg/day dose group and in the placebo group who discontinued treatment due to adverse reactions was 10% and 6%, respectively.

The most common adverse reaction in the memantine hydrochloride extended-release treated group that led to treatment discontinuation was dizziness, at a rate of 1.5%. Most Common Adverse Reactions with Memantine Hydrochloride The most common adverse reactions with memantine hydrochloride extended-release in patients with moderate to severe Alzheimer’s disease, defined as those occurring at a frequency of at least 5% in the memantine hydrochloride extended-release group and at a higher frequency than placebo, were headache, diarrhea, and dizziness.

Table 1 lists adverse reactions that occurred at an incidence of ≥ 2% in the memantine hydrochloride extended-release treated group and occurred at a rate greater than placebo. Table 1: Adverse reactions with memantine hydrochloride extended-release in patients with moderate to severe Alzheimer’s disease Adverse Reaction Placebo (n = 335) % Memantine hydrochloride extended-release 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 Increased weight 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 Donepezil hydrochloride Adverse Reactions Leading to Discontinuation with Donepezil Hydrochloride In controlled clinical trials of donepezil hydrochloride, the rate of discontinuation due to adverse reactions for patients treated with donepezil hydrochloride was approximately 12%, compared to 7% for patients treated…

🔄 Drug Interactions ~1 min read ▾

7 DRUG INTERACTIONS • Combined use with NMDA antagonists: use with caution. ( 7.2 ) • Memantine and donepezil hydrochlorides extended-release capsules may interfere with anticholinergic medications. ( 7.4 ) • Concomitant administration of succinylcholine, similar neuromuscular blocking agents, or cholinergic agonists may lead to synergistic effect. ( 7.5 )

7.1Use of Memantine with 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 reactions. 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 of Memantine 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.

7.3Effect of Other Drugs on the Metabolism of Donepezil Inhibitors of CYP3A4 (e.g., ketoconazole) and CYP2D6 (e.g., quinidine), inhibit donepezil metabolism in vitro. Whether there is a clinical effect of quinidine is not known. Inducers of CYP3A4 (e.g., phenytoin, carbamazepine, dexamethasone, rifampin, and phenobarbital) could increase the rate of elimination of donepezil.

7.4Use of Donepezil with Anticholinergics Because of their mechanism of action, cholinesterase inhibitors, including donepezil hydrochloride, have the potential to interfere with the activity of anticholinergic medications.

7.5Use of Donepezil with Cholinomimetics and Other Cholinesterase Inhibitors A synergistic effect may be expected when cholinesterase inhibitors, including donepezil hydrochloride, are given concurrently with succinylcholine, similar neuromuscular blocking agents, or cholinergic agonists such as bethanechol.

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS

8.1Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of memantine and donepezil hydrochlorides extended-release capsules or its active ingredients (memantine hydrochloride and donepezil hydrochloride) in pregnant women. Adverse developmental effects (mortality and decreased body weight and skeletal ossification) were observed in the offspring of rats administered memantine or donepezil during pregnancy at doses associated with minimal maternal toxicity. These doses are higher than those used in humans at the recommended daily dose of memantine and donepezil hydrochlorides 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 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data Memantine Hydrochloride Oral administration of memantine (2, 6, 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 dose of memantine at the recommended human daily dose (RHD) of memantine and donepezil hydrochlorides extended-release capsules (28 mg memantine/10 mg donepezil) on a body surface area (mg/m 2 ) basis. Oral administration of memantine to rabbits (3, 10, 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 dose of memantine at the RHD of memantine and donepezil hydrochlorides extended-release capsules on a mg/m 2 basis.

In rats, memantine (2, 6, 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 dose of memantine at the RHD of memantine and donepezil hydrochlorides extended-release capsules on a mg/m 2 basis.

Oral administration of memantine (2, 6, 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 dose of memantine at the RHD of memantine and donepezil hydrochlorides extended-release capsules on a mg/m2 basis. Donepezil Hydrochloride Oral administration of donepezil to rats and rabbits during the period of organogenesis resulted in no adverse developmental effects.

The highest doses (16 and 10 mg/kg/day, respectively) were approximately 15 and 7 times, respectively, the dose of donepezil at the RHD of memantine and donepezil hydrochlorides extended-release capsules on a mg/m 2 basis. Oral administration of donepezil (1, 3, or 10 mg/kg/day) to rats during late gestation and throughout lactation to weaning resulted in an increase in stillbirths and offspring mortality at the highest dose tested. The higher no-effect dose (3 mg/kg/day) is approximately 3 times the dose of donepezil at the RHD of memantine and donepezil hydrochlorides extended-release capsules on a mg/m 2 basis.

8.2Lactation Risk Summary There are no data on the presence of memantine or donepezil in human milk, the effects on the breastfed infant, or the effects of memantine and donepezil hydrochlorides extended-release capsules or its metabolites on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for memantine and donepezil hydrochlorides extended-release capsules and any potential adverse effects on the breastfed infant from memantine and donepezil…

🤰 Pregnancy ~2 min read ▾

8.1Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of memantine and donepezil hydrochlorides extended-release capsules or its active ingredients (memantine hydrochloride and donepezil hydrochloride) in pregnant women. Adverse developmental effects (mortality and decreased body weight and skeletal ossification) were observed in the offspring of rats administered memantine or donepezil during pregnancy at doses associated with minimal maternal toxicity. These doses are higher than those used in humans at the recommended daily dose of memantine and donepezil hydrochlorides 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 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data Memantine Hydrochloride Oral administration of memantine (2, 6, 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 dose of memantine at the recommended human daily dose (RHD) of memantine and donepezil hydrochlorides extended-release capsules (28 mg memantine/10 mg donepezil) on a body surface area (mg/m 2 ) basis. Oral administration of memantine to rabbits (3, 10, 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 dose of memantine at the RHD of memantine and donepezil hydrochlorides extended-release capsules on a mg/m 2 basis.

In rats, memantine (2, 6, 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 dose of memantine at the RHD of memantine and donepezil hydrochlorides extended-release capsules on a mg/m 2 basis.

Oral administration of memantine (2, 6, 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 dose of memantine at the RHD of memantine and donepezil hydrochlorides extended-release capsules on a mg/m2 basis. Donepezil Hydrochloride Oral administration of donepezil to rats and rabbits during the period of organogenesis resulted in no adverse developmental effects.

The highest doses (16 and 10 mg/kg/day, respectively) were approximately 15 and 7 times, respectively, the dose of donepezil at the RHD of memantine and donepezil hydrochlorides extended-release capsules on a mg/m 2 basis. Oral administration of donepezil (1, 3, or 10 mg/kg/day) to rats during late gestation and throughout lactation to weaning resulted in an increase in stillbirths and offspring mortality at the highest dose tested. The higher no-effect dose (3 mg/kg/day) is approximately 3 times the dose of donepezil at the RHD of memantine and donepezil hydrochlorides extended-release capsules on a mg/m 2 basis.

🧒 Pediatric Use ~3 min read ▾

8.4Pediatric Use Safety and effectiveness of memantine and donepezil hydrochlorides extended-release capsules in pediatric patients have not been established. Memantine failed to demonstrate efficacy in two 12-week controlled clinical studies of 578 pediatric patients aged 6-12 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, 6, 9, or 15 mg extended-release capsules were administered once daily to patients with weights < 20 kg, 20-39 kg, 40-59 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 risk profile of memantine in pediatric patients was generally consistent with the known risk 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 3: Table 3: 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 4: Table 4: 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 at twice the frequency of the full-dose memantine treatment group (n=157) was irritability (5.0% vs 2.5%). In a juvenile animal study, male and female juvenile rats were administered memantine (15, 30, 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, 3, 8, 15, 30, and 45 mg/kg/day) starting on postnatal day (PND) 7 through PND 70. Due to early memantine-related mortality, the 30 and 45 mg/kg/day dose groups were terminated without further evaluation.

Memantine induced apoptosis or neuronal degeneratio…

🧓 Geriatric Use 178 words ▾

8.5Geriatric Use Memantine Hydrochloride The majority of people with Alzheimer’s disease are 65 years 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 of age and older, 67% were 75 years of age and older, and 14% were 85 years of age and older. The efficacy and safety data presented in the clinical trials section were obtained from these patients.

There were no clinically meaningful differences in most adverse events reported by patients ≥ 65 years old and < 65 years old. Donepezil Hydrochloride The mean age of patients enrolled in the clinical studies with donepezil hydrochloride was 73 years; 80% of these patients were between 65 and 84 years of age, and 49% of patients 75 years of age and older. The efficacy and safety data presented in the clinical trials section were obtained from these patients.

There were no clinically significant differences in most adverse events reported by patients ≥ 65 years old and < 65 years old.

🆘 Overdosage ~2 min read ▾

10 OVERDOSAGE Memantine hydrochloride and donepezil hydrochloride are the two active ingredients of memantine and donepezil hydrochlorides extended-release capsules. No specific antidote for memantine hydrochloride overdose is known; however, elimination of memantine can be increased by acidification of the urine. Tertiary anticholinergics such as atropine may be used as an antidote for donepezil hydrochloride overdose.

In managing cases of overdose, consider the possibility of multiple drug involvement. In case of overdose, call Poison Control Center at 1-800-222-1222 for the latest recommendation. In general, supportive measures should be utilized, and treatment should be symptomatic.

Memantine Hydrochloride 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 an individual who took memantine in conjunction with unspecified antidiabetic medications.

This person experienced coma, diplopia, and agitation, but subsequently recovered. One patient participating in a memantine hydrochloride extended-release clinical trial unintentionally took 112 mg of memantine hydrochloride extended-release daily for 31 days and experienced an elevated serum uric acid, elevated serum alkaline phosphatase, and low platelet count. No fatalities have been noted with overdoses of memantine alone.

A fatal outcome has very rarely been reported when memantine has been ingested as part of overdosing with multiple drugs; in those instances, the relationship between memantine and a fatal outcome has been unclear. Donepezil Hydrochloride Overdosage with cholinesterase inhibitors can result in cholinergic crisis characterized by severe nausea, vomiting, salivation, sweating, bradycardia, hypotension, respiratory depression, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved.

Tertiary anticholinergics such as atropine may be used as an antidote for donepezil hydrochloride overdosage. Intravenous atropine sulfate titrated to effect is recommended: an initial dose of 1.0 to 2.0 mg IV with subsequent doses based upon clinical response. Atypical responses in blood pressure and heart rate have been reported with other cholinomimetics when coadministered with quaternary anticholinergics such as glycopyrrolate.

It is not known whether donepezil hydrochloride and/or its metabolites can be removed by dialysis (hemodialysis, peritoneal dialysis, or hemofiltration). Dose-related signs of toxicity in animals included reduced spontaneous movement, prone position, staggering gait, lacrimation, clonic convulsions, depressed respiration, salivation, miosis, tremors, fasciculation, and lower body surface temperature.

🧬 Clinical Pharmacology ~2 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Memantine and donepezil hydrochlorides extended-release capsules contain two approved medications: memantine hydrochloride and donepezil hydrochloride. Each of those medications is postulated to have a different mechanism in Alzheimer’s disease. Memantine Persistent activation of central nervous system 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. Donepezil Current theories on the pathogenesis of the cognitive signs and symptoms of Alzheimer’s disease attribute some of them to a deficiency of cholinergic neurotransmission.

Donepezil is postulated to exert its therapeutic effect by enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine in the central nervous system through reversible inhibition of its hydrolysis by acetylcholinesterase. There is no evidence that donepezil prevents or slows neurodegeneration in patients with Alzheimer’s disease.

12.3Pharmacokinetics Memantine and donepezil hydrochlorides extended-release capsules Memantine and donepezil hydrochlorides extended-release capsules were bioequivalent to co-administration of individual memantine hydrochloride extended-release and donepezil hydrochloride. Exposure (AUC and C max ) of memantine and donepezil following memantine and donepezil hydrochlorides extended-release capsules administration in the fed or fasted state was similar. Further, exposure of memantine and donepezil following memantine and donepezil hydrochlorides extended-release capsules administration as intact capsule or capsule contents sprinkled on applesauce was similar in healthy subjects.

Memantine Hydrochloride 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 to 10 mg twice-daily memantine hydrochloride, C max and AUC0-24 values were 48% and 33% higher for the memantine hydrochloride extended-release dosage regimen, respectively.

Absorption After multiple dose administration of memantine hydrochloride extended-release, memantine peak concentrations occur around 9 to 12 hours postdose. There is no difference in the absorption of memantine hydrochloride extended-release when the capsule is taken intact or when the contents are sprinkled on applesauce. After single-dose administration, there is no difference in memantine exposure, based on C max or AUC, for memantine hydrochloride extended-release when the 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 to 11 L/kg and the plasma protein binding is low (45%). Metabolism Memantine undergoes partial hepatic metabolism.

The hepatic microsomal CYP450 enzyme system does not play a significant role in the metabolism of memantine. Elimination Memantine is excreted predominantly in the urine, unchanged, and has a terminal elimination half-life of about 60-80 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…

🧬 Mechanism of Action 180 words ▾

12.1Mechanism of Action Memantine and donepezil hydrochlorides extended-release capsules contain two approved medications: memantine hydrochloride and donepezil hydrochloride. Each of those medications is postulated to have a different mechanism in Alzheimer’s disease. Memantine Persistent activation of central nervous system 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. Donepezil Current theories on the pathogenesis of the cognitive signs and symptoms of Alzheimer’s disease attribute some of them to a deficiency of cholinergic neurotransmission.

Donepezil is postulated to exert its therapeutic effect by enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine in the central nervous system through reversible inhibition of its hydrolysis by acetylcholinesterase. There is no evidence that donepezil prevents or slows neurodegeneration in patients with Alzheimer’s disease.

📦 How Supplied / Storage and Handling 112 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1How Supplied Memantine and donepezil hydrochlorides extended-release capsules, 14 mg/10 mg: White capsules imprinted with “184” on cap with black ink and plain body. Bottle of 30s: NDC 33342-312-07 Bottle of 90s: NDC 33342-312-10 100 Capsules (10×10s): NDC 33342-312-12 Memantine and donepezil hydrochlorides extended-release capsules, 28 mg/10 mg: Light orange cap, white body imprinted with “185” on cap with black ink and plain body. Bottle of 30s: NDC 33342-313-07 Bottle of 90s: NDC 33342-313-10 140 Capsules (10×14s): NDC 33342-313-56

16.2Storage and Handling Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86° F). [See USP Controlled Room Temperature].

📋 Description 213 words ▾

11 DESCRIPTION Memantine and donepezil hydrochlorides extended-release capsules contain memantine, an orally active NMDA receptor antagonist, as the hydrochloride salt and donepezil, a reversible inhibitor of the enzyme acetylcholinesterase, as the hydrochloride salt. Memantine Hydrochloride 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.

Donepezil Hydrochloride The chemical name for donepezil hydrochloride is 2,3-dihydro-5,6-dimethoxy-2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-inden-1-one hydrochloride. The molecular formula is C 24 H 29 NO 3 •HCl and the molecular weight is 415.96. Donepezil hydrochloride is a white crystalline powder.

Memantine and donepezil hydrochlorides extended-release capsules Memantine and donepezil hydrochlorides extended-release capsules for oral administration, containing 14 mg memantine hydrochloride extended-release and 10 mg donepezil hydrochloride (14 mg/10 mg) or 28 mg memantine hydrochloride extended-release and 10 mg donepezil hydrochloride (28 mg/10 mg). All doses of memantine and donepezil hydrochlorides extended-release capsules contain the following inactive ingredients: colloidal silicon dioxide, ethyl cellulose, hydroxypropylmethyl cellulose, lactose monohydrate, microcrystalline cellulose, sugar sphere, talc.

The hard gelatin capsules contain gelatin, sodium lauryl sulfate and titanium dioxide; colorants are iron oxide red (28 mg/10 mg). The black ink contains black iron oxide, propylene glycol and shellac. str str

💬 Information for Patients ~1 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Dosing Information • Instruct patients and caregivers to take memantine and donepezil hydrochlorides extended-release capsules only once daily in the evening, as prescribed [ see Dosage and Administration ( 2.1 ) ]. • If a patient misses a single dose of memantine and donepezil hydrochlorides extended-release capsules, that patient should not double up on the next dose. The next dose should be taken as scheduled [ see Dosage and Administration ( 2.1 ) ]. • Instruct patients and caregivers that memantine and donepezil hydrochlorides extended-release capsules should be swallowed whole.

Alternatively, memantine and donepezil hydrochlorides 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 and caregivers not to use any capsules of memantine and donepezil hydrochlorides extended-release capsules that are damaged or show signs of tampering [ see Dosage and Administration ( 2.2 ) ].

Common Adverse Reactions Advise patients and caregivers that memantine and donepezil hydrochlorides extended-release capsules may cause headache, diarrhea, dizziness, anorexia, vomiting, nausea, and ecchymosis [ see Adverse Reactions ( 6.1 ) ]. Manufactured for: Macleods Pharma USA, Inc. Princeton, NJ 08540 Manufactured by: Macleods Pharmaceuticals Ltd.

Baddi, Himachal Pradesh, INDIA Trademarks are the property of their respective owners. Revised: April 2025

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗
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For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.