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Memantine and Donepezil Hydrochlorides Extended-release 14 mg; 10 mg Capsule, Extended Release, 30-count — NDC 69238-1248-03 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Memantine and Donepezil Hydrochlorides Extended-release 14 mg; 10 mg Capsule, Extended Release, 30-count — NDC 69238-1248-3 (Billing 69238-1248-03)

by Amneal Pharmaceuticals NY LLC · 30 CAPSULE, EXTENDED RELEASE in 1 BOTTLE

This is a package of 30 capsules of Memantine and Donepezil Hydrochlorides Extended-release 14 mg; 10 mg Capsule, Extended Release from Amneal Pharmaceuticals NY LLC, marketed since Feb 2017 and currently FDA-listed; retail pharmacies pay about $6.49 per capsule (NADAC). It is the main listing for this product, which comes in 2 package sizes.

NDC 69238-1248-03
🏷️ FDA NDC (as labeled) 69238-1248-3 billing pads the package segment with a zero
This package
Contains30-count Cost per ea$6.49 NADAC Per package$194.65 / 30 capsules Pack sizes2 compare ↓
Also priced by: Medicaid pays $10.59/unit · Part D plans $13.64/unit — full pricing hub ↓
Main listing for product 69238-1248 · Also comes in: 90 capsules 69238-1248-9
Rx only Generic On market Non-controlled ⚠ On shortage ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed 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

NDC database record

One package, one record: these facts belong to NDC 69238-1248-3 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
69238 labeler · 1248 product · 3 package
Package marketed since
Feb 1, 2017
Sample package
No — commercial package
Listing certified through
Dec 31, 2026
Billing quantity
30 EA per package
Barcode (UPC)
0369238124897, 0369238155396, 0369238124798, 0369238155297
Medicaid fills, this package
106 prescriptions in the last four reported quarters
FDA record last changed
Sep 17, 2026
⚠️
Active FDA shortage. Donepezil Hydrochloride; Memantine Hydrochloride Capsule, Extended Release is currently reported in shortage by the FDA. Shortage details →

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 69238-1248-3
Product NDC 69238-1248
11-digit billing NDC 69238124803
NCPDP billing unit EA — each (per item)
RxCUI 1599803, 1599805, 1805420, 1805425
UNII JY0WD0UA60, 3O2T2PJ89D
UPC 0369238124897, 0369238155396, 0369238124798, 0369238155297
Application # ANDA208328
SPL Set ID 2335950c-be3b-4248-ad04-e9763aee47d2
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 2017-02-01
Route ORAL
Dosage form CAPSULE, EXTENDED RELEASE
Substance MEMANTINE HYDROCHLORIDE; DONEPEZIL HYDROCHLORIDE
TE code (Orange Book) AB · RLD · RS

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GPI-14 62059902507030
GCN Seq No 073814
GCN 38257
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 14-10MG
FDB brand name Memantine Hcl-Donepezil Hcl Er
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 073814
  • GCN: 38257
  • GPI-14 (Medi-Span): 62059902507030
  • HICL (First Databank): 041881
  • AHFS class code: 12:04.00.00
  • RxCUI (RxNorm): 1599803
Why two NDCs? The FDA registers this code as 69238-1248-3 — a 5-4-1 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 package segment → 69238-1248-03. 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.

Clinical

Label name MEMANTINE-DONEPEZIL ER 14-10MG 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
  • It treats moderate to severe dementia of the Alzheimer’s type in people already stabilized on donepezil. It combines two medicines that work in different ways on brain chemistry. I...
  • Take it once a day in the evening, with or without food. Swallow the capsule whole, or sprinkle the contents on applesauce. Please don’t chew, crush or divide it, and follow your p...
  • The most common are headache, diarrhea, dizziness, nausea, vomiting and loss of appetite. Stomach upset is most likely early on and often eases within a few weeks. Let your prescri...
  • Call for fainting, a very slow heartbeat, black or bloody stools, trouble passing urine, a seizure, or new breathing trouble. Also report a severe rash or blistering skin.
📖 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.

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 eaPer package
Retail pharmacies payNADAC · weekly $6.488 $194.65 / 30 capsules
Medicaid paysCMS SDUD · 12 mo $10.59 $317.63 / 30 capsules
Medicare drug plans payPart D · Q2 2026 $13.64 $409.19 / 30 capsules
NADAC price history (per ea) — tap or hover for the price & month
Dec 2025 Mar 2026 Jun 2026 Sep 2026 $14.843 $6.488
▼ Down 56% over the last 10 months.
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.

Packaging — all sizes for this product

Package NDCDescription Per unit Per pack Marketing startMarketing endStatus
69238-1248-03 You're viewing this Main listing 30 CAPSULE, EXTENDED RELEASE in 1 BOTTLE $6.49 / ea $194.65 2017-02-01 — Active
69238-1248-09 69238-1248-9 90 CAPSULE, EXTENDED RELEASE in 1 BOTTLE — — 2017-02-01 — Active

You're viewing the smallest of 2 pack sizes for this product.

In Medicaid, this is the most-dispensed pack of this product — about 100% of fills over the last four reported quarters. See all packs ↓

Pack size FAQ

What quantity is in this package?
This is a 30-count package — 30 capsule, extended release in 1 bottle.
How does this package differ from NDC 69238-1248-09?
Both are Memantine and Donepezil Hydrochlorides Extended-release 14 mg; 10 mg Capsule, Extended Release — the drug itself is identical. This page's package is the 30-count one, while NDC 69238-1248-09 is the 90 capsules package.
What NDC number is used to bill for this package of Memantine and Donepezil Hydrochlorides Extended-release 14 mg; 10 mg Capsule, Extended Release?
Use the 11-digit billing form listed in the identifiers section of this page. 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.

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Memantine and Donepezil 14 mg/1; 10 mg 33342-0312-07 Macleods 30 capsules $6.488 AB Availability likely —
Memantine and Donepezil Hydrochlorides Extended-release 14 mg/1; 10 mgthis 69238-1248-03 Amneal 30 capsules $6.488 AB Availability likely —
memantine hydrochloride and donepezil hydrochloride 14 mg/1; 10 mg 69680-0183-30 Vitruvias 30 capsules $6.488 AB Availability likely —
Namzaric 14 mg/1; 10 mg 00456-1214-11 Allergan, 10 capsules — AB Discontinued —
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

🏛️
2017
On the market since
Feb 2017
📍
2026
Currently FDA-listed
9 years 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.

What it looks like

Color green / yellow / white
ShapeCapsule
ImprintAN;1553
Size2 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 3K9958V90M
    A liquid solvent derived from fermentation or chemical synthesis. In medicines, alcohol dissolves active ingredients, helps preserve the product, and improves how the body absorbs certain drugs.
  • 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.
  • 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.
  • 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 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.
  • 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 2165RE0K14
    A plant-based thickener made from cellulose that helps control how quickly the medicine dissolves and releases its active ingredient. It also binds ingredients together and improves the tablet's texture and handling during manufacturing.
  • 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 ND2M416302
    Isopropyl alcohol is a clear liquid solvent derived from petroleum. In medicines, it dissolves active ingredients and other components, helps the product flow smoothly, and aids in sterilization during manufacturing.
  • UNII FZ989GH94E
    Povidone is a synthetic polymer made from a plastic-like material. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in your stomach so the medicine can be absorbed.
  • 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 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.
  • 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 55X04QC32I
    A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during 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 O8232NY3SJ
    A plant-based carbohydrate derived from corn kernels. It acts as a filler to add bulk, a binder to hold ingredients together, and a disintegrant to help the tablet break apart in your stomach for absorption.
  • 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.
  • 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.

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.

Manufacturer & labeler

LabelerAmneal Pharmaceuticals NY LLC
Application holderAMNEAL PHARMACEUTICALS LLC
FDA applicationANDA208328 (ANDA)
Labeler code69238
First marketedFeb 2017
Product typeHuman Prescription Drug
Portfolio372 products on file

More NDCs from Amneal Pharmaceuticals NY LLC labeler code 69238

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.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). 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 🧬 Pharmacokinetics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Patient Package Insert 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 82 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 increments 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 and donepezil hydrochlorides extended-release 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 capsule 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 to 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 impairment,… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths ~1 min read ▾

3 DOSAGE FORMS AND STRENGTHS Memantine and donepezil hydrochlorides extended-release capsules: 7 mg memantine hydrochloride extended-release/10 mg donepezil hydrochloride capsules: Two piece hard gelatin capsules with green opaque cap and white opaque body filled with white to off- white pellets. Imprinted in black ink AN on the cap and imprinted in black ink 1552 on the body. 14 mg memantine hydrochloride extended-release/10 mg donepezil hydrochloride capsules: Two-piece hard gelatin capsules with green opaque cap and green opaque body filled with white to off-white pellets.

Imprinted in white ink AN on the cap and imprinted in white ink 1248 on the body. 21 mg memantine hydrochloride extended-release/10 mg donepezil hydrochloride capsules: Two piece hard gelatin capsules with yellow opaque cap and white opaque body filled with white to off-white pellets. Imprinted in black ink AN on the cap and imprinted in black ink 1553 on the body.

28 mg memantine hydrochloride extended-release/10 mg donepezil hydrochloride capsules: Two-piece hard gelatin capsules with yellow opaque cap and yellow opaque body filled with white to off-white pellets. Imprinted in black ink AN on the cap and imprinted in black ink 1247 on the body. Memantine and donepezil hydrochlorides extended-release capsules: 7 mg memantine hydrochloride and 10 mg donepezil hydrochloride (3) 14 mg memantine hydrochloride and 10 mg donepezil hydrochloride (3) 21 mg memantine hydrochloride and 10 mg donepezil hydrochloride (3) 28 mg memantine hydrochloride and 10 mg donepezil hydrochloride (3)

⛔ Contraindications 59 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 is likely to exaggerate succinylcholine-type muscle relaxation during anesthesia. (5.1) Memantine and donepezil hydrochlorides extended-release 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 can cause diarrhea, nausea, and vomiting. (5.4) Memantine and donepezil hydrochlorides extended-release 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 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, 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 and at twice or more the placebo rate, include diarrhea, anorexia, vomiting, nausea, and ecchymosis. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-835-5472 or 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 with placebo.

The most common adverse reactions leading to discontinua… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~1 min read ▾

7 DRUG INTERACTIONS Combined use with NMDA antagonists: use with caution. (7.2) Memantine and donepezil hydrochlorides extended-release 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 [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 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 (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 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 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 on a mg/m 2 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 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 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 hydrochlorides extended-release capsules or from the un… [Excerpted — this section continues on DailyMed.]

🤰 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 [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 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 (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 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 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 on a mg/m 2 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 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 on a mg/m 2 basis.

🧒 Pediatric Use ~3 min read ▾

8.4Pediatric Use Safety and effectiveness of memantine and donepezil hydrochlorides extended-release 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, 6, 9, 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 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% Nasopharyngitis 6.3% Pyrexia 5.8% Irritability 5.4% Discontinuations due to adverse reactions a Irritability 1.2% Aggression 1% 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% 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 degeneration in se… [Excerpted — this section continues on DailyMed.]

🧓 Geriatric Use 177 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 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. 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 to 2 mg IV with subsequent doses based upon clinical response. Atypical responses in blood pressure and heart rate have been reported with other cholinomimetics when co-administered 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 extended-release 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 Memantine and donepezil hydrochlorides extended-release was 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 administration in the fed or fasted state was similar. Further, exposure of memantine and donepezil following memantine and donepezil hydrochlorides extended-release 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 AUC 0-24 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 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 ad… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 181 words ▾

12.1Mechanism of Action Memantine and donepezil hydrochlorides extended-release capsules contain two approved medications: memantine hydrochloride extended-release 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 ~1 min read ▾

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1How Supplied Memantine and donepezil hydrochlorides extended-release capsules, 7 mg/10 mg , are supplied as two-piece hard gelatin capsules with green opaque cap and white opaque body filled with white to off-white pellets. Imprinted in black ink AN on the cap and imprinted in black ink 1552 on the body. They are available as follows: Bottles of 30: NDC 69238-1552-3 Bottles of 90: NDC 69238-1552-9 Memantine and donepezil hydrochlorides extended-release capsules, 14 mg/10 mg , are supplied as two-piece hard gelatin capsules with green opaque cap and green opaque body filled with white to off-white pellets.

Imprinted in white ink AN on the cap and imprinted in white ink 1248 on the body. They are available as follows: Bottle of 30: NDC 69238-1248-3 Bottle of 90: NDC 69238-1248-9 Memantine and donepezil hydrochlorides extended-release capsules, 21 mg/10 mg , are supplied as two-piece hard gelatin capsules with yellow opaque cap and white opaque body filled with white to off-white pellets. Imprinted in black ink AN on the cap and imprinted in black ink 1553 on the body.

They are available as follows: Bottles of 30: NDC 69238-1553-3 Bottles of 90: NDC 69238-1553-9 Memantine and donepezil hydrochlorides extended-release capsules, 28 mg/10 mg , are supplied as two-piece hard gelatin capsules with yellow opaque cap and yellow opaque body filled with white to off-white pellets. Imprinted in black ink AN on the cap and imprinted in black ink 1247 on the body. They are available as follows: Bottle of 30: NDC 69238-1247-3 Bottle of 90: NDC 69238-1247-9

16.2Storage and Handling Store at 20º to 25°C (68º to 77°F); excursions permitted between 15° to 30ºC (59°F to 86°F) [see USP Controlled Room Temperature]. Dispense in a tight, light-resistant container, as defined in the USP.

📋 Description ~2 min read ▾

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, USP The chemical name for memantine hydrochloride, USP 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, USP occurs as a fine white to off-white powder.

Donepezil Hydrochloride, USP The chemical name for donepezil hydrochloride, USP is (±)-2-[(1-benzyl- 4-piperidyl) methyl]-5,6-dimethoxy-1-indanone hydrochloride The molecular formula is C 24 H 29 NO 3 •HCl and the molecular weight is 415.95. Donepezil hydrochloride, USP is off white to cream coloured powder. Memantine and donepezil hydrochlorides extended-release capsules contain 7 mg memantine hydrochloride extended-release and 10 mg donepezil hydrochloride (7 mg/10 mg), 14 mg memantine hydrochloride extended-release and 10 mg donepezil hydrochloride (14 mg/10 mg), 21 mg memantine hydrochloride extended-release and 10 mg donepezil hydrochloride (21 mg/10 mg) or 28 mg memantine hydrochloride extended-release and 10 mg donepezil hydrochloride (28 mg/10 mg).

Memantine and donepezil hydrochlorides extended-release capsules (7 mg/10 mg) contain the following inactive ingredients: colloidal silicon dioxide, ethyl cellulose, hydroxypropyl cellulose, hypromellose, sugar spheres (corn starch, sucrose), talc and triethyl citrate. The hard gelatin capsules contain D&C yellow no. 10, FD&C blue no.

1, gelatin, sodium lauryl sulfate and titanium dioxide. The black monogramming ink contains black iron oxide, butyl alcohol, dehydrated alcohol, isopropyl alcohol, potassium hydroxide, propylene glycol, shellac, strong ammonia solution and purified water. Memantine and donepezil hydrochlorides extended-release capsules ( 14 mg/10 mg) contain the following inactive ingredients: colloidal silicon dioxide, ethyl cellulose, hydroxypropyl cellulose, hypromellose, sugar spheres (corn starch, sucrose), talc and triethyl citrate.

The hard gelatin capsules contain D&C yellow no.10, FD&C blue no. 1, gelatin, sodium lauryl sulfate and titanium dioxide. The white monogramming ink contains butyl alcohol, dehydrated alcohol, isopropyl alcohol, sodium hydroxide, propylene glycol, povidone, shellac and titanium dioxide.

Memantine and donepezil hydrochlorides extended-release capsules (21 mg/10 mg) contain the following inactive ingredients: colloidal silicon dioxide, ethyl cellulose, hydroxypropyl cellulose, hypromellose, sugar spheres (corn starch, sucrose), talc and triethyl citrate. The hard gelatin capsules contain D&C yellow no. 10, FD&C red no.

40, gelatin, sodium lauryl sulfate and titanium dioxide. The black monogramming ink contains black iron oxide, butyl alcohol, dehydrated alcohol, isopropyl alcohol, potassium hydroxide, propylene glycol, shellac, strong ammonia solution and purified water. Memantine and donepezil hydrochlorides extended-release capsules (28 mg/10 mg ) contain the following inactive ingredients: colloidal silicon dioxide, ethyl cellulose, hydroxypropyl cellulose, hypromellose, sugar spheres (corn starch, sucrose), talc and triethyl citrate.

The hard gelatin capsules contain D&C yellow no.10, FD&C red no. 40, gelatin, sodium lauryl sulfate and titanium dioxide. The black monogramming ink contains black iron oxide, butyl alcohol, dehydrated alcohol, isopropyl alcohol, potassium hydroxide, propylene glycol, purified water, shellac and strong ammonia solution. chem structure 1 chem structure 2

💬 Information for Patients 195 words ▾

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 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, 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 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 may cause headache, diarrhea, dizziness, anorexia, vomiting, nausea, and ecchymosis [see Adverse Reactions (6.1)] .

Distributed by: Amneal Pharmaceuticals Bridgewater, NJ 08807 Rev. 12-2024-01

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics Memantine and donepezil hydrochlorides extended-release Memantine and donepezil hydrochlorides extended-release was 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 administration in the fed or fasted state was similar. Further, exposure of memantine and donepezil following memantine and donepezil hydrochlorides extended-release 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 AUC 0-24 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 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. Pharmacokinetics in Special Populations 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 to 80 mL/min), 8 subjects with moderate renal impairment (CLcr 30 to 49 mL/min), 7 subjects with severe renal impairment (CLcr 5 to 29 mL/min) and 8 healthy subjects (CLcr > 80 mL/min) matched as closely as possible by age, weight and gender to the subjects with renal impairment.

Mean AUC 0-∞ increased by 4%, 60%, and 115% in subjects with mild, moderate, and severe renal impairment, respectively, compared to healthy subjects. The terminal elimination half-life increased by 18%, 41%, and 95% in subjects with mild, moderate, and severe renal impairment, respectively, compared to healthy subjects [see Dosage and Administration (2.3) and Use in Specific Populations (8.6) ] . Hepatic Impairment Memantine pharmacokinetics were evaluated following the administration of single oral doses of 20 mg in 8 subjects with moderate hepatic impairment (Child-Pugh Class B, score 7 to 9) and 8 subjects who were age-, gender-, and weight-matched to the hepatically-impaired s… [Excerpted — this section continues on DailyMed.]

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES The effectiveness of memantine and donepezil hydrochlorides extended-release as a treatment for patients with moderate to severe Alzheimer’s disease was established by demonstrating the bioequivalence of memantine and donepezil hydrochlorides extended-release with co-administered memantine and donepezil hydrochlorides extended-release [see Clinical Pharmacology (12.3) ] . Memantine Hydrochloride The effectiveness of memantine hydrochloride extended-release as a treatment for patients with moderate to severe Alzheimer’s disease when co-administered with acetylcholinesterase inhibitors, including donepezil hydrochloride, was based on the results of a double-blind, placebo-controlled trial.

24-week Study of Memantine Hydrochloride Extended-Release This was a randomized, double-blind clinical investigation in 677 outpatients with moderate to severe Alzheimer’s disease (diagnosed by DSM-IV criteria and NINCDS-ADRDA criteria for AD with a Mini Mental State Examination [MMSE] score ≥ 3 and ≤ 14 at Screening and Baseline) receiving acetylcholinesterase inhibitor (AChEI) therapy at a stable dose for 3 months prior to screening. Approximately 68% of the patients received donepezil as the AChEI. The mean age of patients participating in this trial was 76.5 years, with a range of 49 to 97 years.

Approximately 72% of patients were female and 94% were Caucasian. Study Outcome Measures The effectiveness of memantine hydrochloride extended-release was evaluated in this study using the co-primary efficacy parameters of Severe Impairment Battery (SIB) and the Clinician’s Interview-Based Impression of Change (CIBIC-Plus). The ability of memantine hydrochloride extended-release to improve cognitive performance was assessed with the Severe Impairment Battery (SIB), a multi-item instrument that has been validated for the evaluation of cognitive function in patients with moderate to severe dementia.

The SIB examines selected aspects of cognitive performance, including elements of attention, orientation, language, memory, visuospatial ability, construction, praxis, and social interaction. The SIB scoring range is from 0 to 100, with lower scores indicating greater cognitive impairment. The ability of memantine hydrochloride extended-release to produce an overall clinical effect was assessed using a Clinician’s Interview Based Impression of Change that required the use of caregiver information, the CIBIC-Plus.

The CIBIC-Plus is not a single instrument and is not a standardized instrument like the ADCS-ADL or SIB. Clinical trials for investigational drugs have used a variety of CIBIC formats, each different in terms of depth and structure. As such, results from a CIBIC-Plus reflect clinical experience from the trial or trials in which it was used and cannot be compared directly with the results of CIBIC-Plus evaluations from other clinical trials.

The CIBIC-Plus used in this trial was a structured instrument based on a comprehensive evaluation at baseline and subsequent time points of four domains: general (overall clinical status), functional (including activities of daily living), cognitive, and behavioral. It represents the assessment of a skilled clinician using validated scales based on his/her observation during an interview with the patient, in combination with information supplied by a caregiver familiar with the behavior of the patient over the interval rated.

The CIBIC-Plus is scored as a seven point categorical rating, ranging from a score of 1, indicating “marked improvement” to a score of 4, indicating “no change” to a score of 7, indicating “marked worsening.” The CIBIC-Plus has not been systematically compared directly to assessments not using information from caregivers (CIBIC) or other global methods. Study Results In this study, 677 patients were randomized to one of the following 2 treatments: memantine hydrochloride extended-release 28 mg/day or placebo, while still receiving an AChEI (either donepezil, galantami… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology ~2 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Memantine There was no evidence of carcinogenicity in a 113-week oral study in mice at doses up to 40 mg/kg/day (7 times the dose of memantine at the maximum recommended human dose [MRHD] of memantine and donepezil hydrochlorides extended-release [28 mg/10 mg] on a mg/m 2 basis). There was also no evidence of carcinogenicity in rats orally dosed at up to 40 mg/kg/day for 71 weeks followed by 20 mg/kg/day (14 and 7 times the MRHD on a mg/m 2 basis, respectively) through 128 weeks.

Memantine produced no evidence of genotoxic potential when evaluated in the in vitro S. typhimurium or E. coli reverse mutation assay, an in vitro chromosomal aberration test in human lymphocytes, an in vivo cytogenetics assay for chromosome damage in rats, and the in vivo mouse micronucleus assay. The results were equivocal in an in vitro gene mutation assay using Chinese hamster V79 cells. No impairment of fertility or reproductive performance was seen in rats administered up to 18 mg/kg/day (6 times the dose of memantine at the MRHD of memantine and donepezil hydrochlorides extended-release on a mg/m 2 basis) orally from 14 days prior to mating through gestation and lactation in females, or for 60 days prior to mating in males.

Donepezil No evidence of carcinogenic potential was obtained in an 88-week carcinogenicity study of donepezil conducted in mice at oral doses up to 180 mg/kg/day (approximately 90 times the dose of donepezil at the MRHD of memantine and donepezil hydrochlorides extended-release on a mg/m 2 basis), or in a 104-week carcinogenicity study in rats at oral doses up to 30 mg/kg/day (approximately 30 times the dose of donepezil at the MRHD of memantine and donepezil hydrochlorides extended-release on a mg/m 2 basis). Donepezil was negative in a battery of genotoxicity assays ( in vitro bacterial reverse mutation, in vitro mouse lymphoma tk , in vitro chromosomal aberration, and in vivo mouse micronucleus).

Donepezil had no effect on fertility in rats at oral doses up to 10 mg/kg/day (approximately 10 times the dose of donepezil at the MRHD of memantine and donepezil hydrochlorides extended-release on a mg/m 2 basis) when administered to males and females prior to and during mating and continuing in females through implantation.

13.2Animal Toxicology and/or Pharmacology Memantine induced neuronal lesions (vacuolation and necrosis) in the multipolar and pyramidal cells in cortical layers III and IV of the posterior cingulate and retrosplenial neocortices in rats, similar to those which are known to occur in rodents administered other NMDA receptor antagonists. Lesions were seen after a single dose of memantine. In a study in which rats were given daily oral doses of memantine for 14 days, the no-effect dose for neuronal necrosis was 4 times the dose of memantine at the MRHD of memantine and donepezil hydrochlorides extended-release on a mg/m 2 basis.

In acute and repeat-dose neurotoxicity studies in female rats, oral administration of memantine and donepezil in combination resulted in increased incidence, severity, and distribution of neurodegeneration compared with memantine alone. The no-effect levels of the combination were associated with clinically relevant plasma memantine and donepezil exposures. The relevance of these findings to humans is unknown.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ~2 min read ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Memantine There was no evidence of carcinogenicity in a 113-week oral study in mice at doses up to 40 mg/kg/day (7 times the dose of memantine at the maximum recommended human dose [MRHD] of memantine and donepezil hydrochlorides extended-release [28 mg/10 mg] on a mg/m 2 basis). There was also no evidence of carcinogenicity in rats orally dosed at up to 40 mg/kg/day for 71 weeks followed by 20 mg/kg/day (14 and 7 times the MRHD on a mg/m 2 basis, respectively) through 128 weeks.

Memantine produced no evidence of genotoxic potential when evaluated in the in vitro S. typhimurium or E. coli reverse mutation assay, an in vitro chromosomal aberration test in human lymphocytes, an in vivo cytogenetics assay for chromosome damage in rats, and the in vivo mouse micronucleus assay. The results were equivocal in an in vitro gene mutation assay using Chinese hamster V79 cells. No impairment of fertility or reproductive performance was seen in rats administered up to 18 mg/kg/day (6 times the dose of memantine at the MRHD of memantine and donepezil hydrochlorides extended-release on a mg/m 2 basis) orally from 14 days prior to mating through gestation and lactation in females, or for 60 days prior to mating in males.

Donepezil No evidence of carcinogenic potential was obtained in an 88-week carcinogenicity study of donepezil conducted in mice at oral doses up to 180 mg/kg/day (approximately 90 times the dose of donepezil at the MRHD of memantine and donepezil hydrochlorides extended-release on a mg/m 2 basis), or in a 104-week carcinogenicity study in rats at oral doses up to 30 mg/kg/day (approximately 30 times the dose of donepezil at the MRHD of memantine and donepezil hydrochlorides extended-release on a mg/m 2 basis). Donepezil was negative in a battery of genotoxicity assays ( in vitro bacterial reverse mutation, in vitro mouse lymphoma tk , in vitro chromosomal aberration, and in vivo mouse micronucleus).

Donepezil had no effect on fertility in rats at oral doses up to 10 mg/kg/day (approximately 10 times the dose of donepezil at the MRHD of memantine and donepezil hydrochlorides extended-release on a mg/m 2 basis) when administered to males and females prior to and during mating and continuing in females through implantation.

📄 Patient Package Insert ~2 min read ▾

PATIENT INFORMATION Memantine (meh-MAN-teen) and Donepezil (doe-NEP-e-zil) Hydrochlorides Extended-release Capsules What are memantine and donepezil hydrochlorides extended-release capsules? Memantine and donepezil hydrochlorides extended-release capsules is a prescription medicine used to treat moderate to severe dementia in people with Alzheimer’s disease. Memantine and donepezil hydrochlorides extended-release capsules contain 2 medicines, memantine HCl, an NMDA receptor antagonist, and donepezil HCl, an acetylcholinesterase inhibitor.

Memantine and donepezil hydrochlorides extended-release capsules are for people who are taking donepezil HCl 10 mg. It is not known if memantine and donepezil hydrochlorides extended-release capsules are safe and effective in children. Do not take memantine and donepezil hydrochlorides extended-release capsules if you have an allergy to memantine HCl, donepezil HCl, medicines that contains piperidines, or any of the ingredients in memantine and donepezil hydrochlorides extended-release capsules.

See the end of this leaflet for a complete list of ingredients in memantine and donepezil hydrochlorides extended-release capsules. Before taking memantine and donepezil hydrochlorides extended-release capsules, tell your doctor about all of your medical conditions, including if you: have heart problems including an irregular, slow, or fast heartbeat. have asthma or lung problems. have seizures. have stomach ulcers. have bladder or kidney problems. have liver problems. have surgical, dental, or other medical procedures scheduled and anesthesia may be used. are pregnant or plan to become pregnant.

It is not known if memantine and donepezil hydrochlorides extended-release capsules can harm an unborn baby. are breast-feeding or plan to breastfeed. It is not known if memantine hydrochloride and donepezil hydrochloride passes into breast milk. Talk to your doctor about the best way to feed your baby if you take memantine and donepezil hydrochlorides extended-release capsules.

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. How should I take memantine and donepezil hydrochlorides extended-release capsules? Take memantine and donepezil hydrochlorides extended-release capsules exactly as your doctor tells you to take it.

Do not change your dose or stop taking memantine and donepezil hydrochlorides extended-release capsules without talking to your doctor. Take memantine and donepezil hydrochlorides extended-release capsules by mouth 1 time each evening before going to bed. Take memantine and donepezil hydrochlorides extended-release capsules with or without food.

Memantine and donepezil hydrochlorides extended-release capsules may be opened and sprinkled on applesauce before swallowing. Sprinkle all of the medicine in the capsule on the applesauce. Do not divide the dose.

If you do not open and sprinkle memantine and donepezil hydrochlorides extended-release capsules on applesauce, the memantine and donepezil hydrochlorides extended-release capsules must be swallowed whole. Do not divide, chew, or crush memantine and donepezil hydrochlorides extended-release capsules. If you miss a dose take memantine and donepezil hydrochlorides extended-release capsules at your next scheduled dose.

Do not take 2 doses of memantine and donepezil hydrochlorides extended-release capsules at the same time. Do not use any memantine and donepezil hydrochlorides extended-release capsules that are damaged or show signs of tampering. If you take too much memantine and donepezil hydrochlorides extended-release capsules, call Poison Control Center at 1-800-222-1222, or go to the nearest hospital emergency room right away.

What are the possible side effects of memantine and donepezil hydrochlorides extended-release capsules? Memantine and donepezil hydrochlorides extended-release capsules may cause serious side effects, including: muscle problems… [Excerpted — this section continues on DailyMed.]

📄 Recent Major Changes 14 words ▾

RECENT MAJOR CHANGES Indications and Usage (1) 07/2016 Dosage and Administration (2.1, 2.3) 07/2016

📄 Package Label / Principal Display Panel 8 words ▾

PRINCIPAL DISPLAY PANEL 7mg

14mg

21 mg

28mg

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for this package alone, not the drug overall. Other pack sizes report separately.
💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.
📅 Q1 2025 – Q1 2026 · 5 quarters of data
ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.
Prescriptions last 4 qtrs
106
Units reimbursed last 4 qtrs
3.4K
Gross reimbursed last 4 qtrs
$36.5K
Avg / prescription
$344.20
Avg / unit
$10.5878
Latest quarter Q1 2026
49Rx
Medicaid pays / ea
$10.5878
gross reimbursed
vs
NADAC / ea
$6.4882
acquisition cost
=
Spread
+$4.0996
+63% vs cost
What Medicaid paid per ea (before rebates; includes the pharmacy’s dispensing fee) compared with NADAC — the average price pharmacies pay to buy the drug. A positive spread means Medicaid reimbursed more than the purchase price, before manufacturer rebates.
Fee-for-service vs managed care ⓘ
100% FFS
Fee-for-service · 106 Rx Managed care · 0 Rx
State Medicaid map
Alaska: no data reported AK Maine: no data reported ME Washington: no data reported WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: no data reported MN Wisconsin: no data reported WI Michigan: no data reported MI New York: 3,446 units · 17.6 per 100k residents NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: no data reported OR Nevada: no data reported NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: no data reported IA Illinois: no data reported IL Indiana: no data reported IN Ohio: no data reported OH Pennsylvania: no data reported PA New Jersey: no data reported NJ Massachusetts: no data reported MA California: no data reported CA Utah: no data reported UT Colorado: no data reported CO Nebraska: no data reported NE Missouri: no data reported MO Kentucky: no data reported KY West Virginia: no data reported WV Virginia: no data reported VA Maryland: no data reported MD Connecticut: no data reported CT Rhode Island: no data reported RI Arizona: no data reported AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: no data reported AR Tennessee: no data reported TN North Carolina: no data reported NC South Carolina: no data reported SC Delaware: no data reported DE Oklahoma: no data reported OK Louisiana: no data reported LA Mississippi: no data reported MS Alabama: no data reported AL Georgia: no data reported GA D.C.: no data reported DC Hawaii: no data reported HI Texas: no data reported TX Florida: no data reported FL
Units reimbursed · per 100k residents
17.617.6
gray = no data reported ⓘ
Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.
Tap or hover a state
…for its Medicaid breakdown
🏆 Top states by units · per 100k residents
1 New York 17.6 /100k
National units — by quarter
💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

Medicaid utilization by pack size

Medicaid (SDUD) totals over the four most recent reported quarters for every package size of this drug — handy when a specific package (e.g. a starter/titration pack) carries little or no Medicaid volume on its own.
30 capsules this page69238-1248-03 106 Rx · $36,485
90 capsules69238-1248-09 No Medicaid data
Drug total (last 4 qtrs): 106 Rx · 3,446 units · $36,485 gross reimbursed
Tap a pack size to open its page. Source: CMS State Drug Utilization Data, last 4 quarters.

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 Hydrochlorides Extended-release (this brand).

Top reported reactions

Interstitial Lung Disease1
Pleural Effusion1
Pulmonary Oedema1
Pulmonary Toxicity1

Reporter sex

1 reports
Reports over time (by year) — tap or hover for the count & year
2023 2024 2025 2026 1 0
Most recent year is provisional (FAERS lags ~3 months).
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.
← 69238-1247-03 · Amneal 69238-1250-01 · Amneal →
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.