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Diclofenac Sodium and Misoprostol 75 mg; 200 ug Tablet, Delayed Release, 60-count

by Amneal Pharmaceuticals LLC · 60 TABLET, DELAYED RELEASE in 1 BOTTLE (65162-438-06)

NDC 65162-0438-06

🏷️ FDA NDC (as labeled) 65162-438-06 billing pads the product segment with a zero

This package

Contains60-count Cost per ea$0.9418 NADAC Per package$56.51 / 60 tablets Pack sizes3 compare ↓

Also priced by: Medicaid pays $1.17/unit · Part D plans $1.60/unit — full pricing hub ↓

Also comes in: 30 tablets 65162-0438-03 100 tablets 65162-0438-10

Rx only Generic On market Non-controlled

🗂️ Data synced Sep 3, 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 Dr. Brian Staiger, PharmD

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

🆔 Identity & classification

FDA NDC (as labeled) 65162-438-06

Product NDC 65162-438

11-digit billing NDC 65162043806

NCPDP billing unit EA — each (per item)

RxCUI 857706, 1359105

UNII QTG126297Q, 0E43V0BB57

UPC 0365162438062, 0365162436068

Application # ANDA203995

SPL Set ID afd30051-8f59-474b-9972-962a5a871dfb

Established class (EPC) Prostaglandin E1 Analog

Chemical class Prostaglandins E, Synthetic

DEA schedule Non-controlled

Marketing category ANDA

Marketing status On market

FDA listing status Listed (active directory)

Marketing start 2016-12-01

Route ORAL

Dosage form TABLET, DELAYED RELEASE

Substance DICLOFENAC SODIUM; MISOPROSTOL

GPI-14 66109902200630

GPI class Diclofenac-miSOPROStol

GCN Seq No 035737

GCN 06263

HICL code 008302

Ingredient (HICL) Diclofenac Sodium/Misoprostol

HIC1 code S

Therapeutic class — broad (HIC1) Locomotor System

HIC2 code S2

Therapeutic class — intermediate (HIC2) Drugs Acting Principally On Joints

HIC3 code S2T

Therapeutic class — specific (HIC3) Nsaids(Cox Non-Spec.inhib)And Prostaglandin Analog

AHFS code 28:08.04.04

AHFS class Reversible Cox-1/Cox-2 Inhibitors

FDB label name DICLOFENAC-MISOPROST 75-0.2 MG

FDB brand name Diclofenac Sodium-Misoprostol

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 65162-438-06 — 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 → 65162-0438-06. 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 Nonsteroidal Anti-inflammatory Drug class.

Pharmacologic class Nonsteroidal Anti-inflammatory Drug

Drug family (ATC) Other dermatologicals, Acetic acid derivatives and related substances, Antiinflammatory preparations, non-steroids for topical use

How it works Cyclooxygenase 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

LabelerAmneal Pharmaceuticals LLC

Application holderAMNEAL PHARMACEUTICALS

FDA applicationANDA203995 (ANDA)

Labeler code65162

First marketedDec 2016

Product typeHuman Prescription Drug

Portfolio467 products on file

🔎 All NDCs from Amneal Pharmaceuticals LLC

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 DICLOFENAC-MISOPROST 75-0.2 MG Ingredient Diclofenac Sodium/Misoprostol

📖 What it is MedlinePlus · NLM

The combination of diclofenac and misoprostol is used to relieve the pain, tenderness, swelling, and stiffness caused by osteoarthritis (arthritis caused by a breakdown of the lining of the joints) and rheumatoid arthritis (arthritis caused by swelling of the lining of the joints) in patients who have a high risk of developing stomach ulcers. Diclofenac is in a class of medications called nonsteroidal anti-inflammatory drugs (NSAIDs). It works by stopping the body's production of a substance that causes pain and inflammation. Misoprostol is in a class of medications called prostaglandins. It p...

Read the full MedlinePlus article ↗

📗 Our plain-language guide HelloPharmacist

Great question. The diclofenac is the anti-inflammatory part — it relieves your arthritis pain and swelling. But NSAIDs like diclofenac can damage the lining of your stomach and th...
Why do I need two drugs in one pill? What does the misoprostol actually do?
Yes, stomach upset — especially diarrhea and abdominal cramping — is actually the most common side effect of this combination, mainly because of the misoprostol. The good news is t...
I'm getting diarrhea and stomach cramps. Is that normal, and will it go away?

📖 Read our full Diclofenac and Misoprostol guide →

Patient education

📘 MedlinePlus patient leaflet ↗

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

ShapeRound

ImprintAN;438

Size11 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 40UAA97IT9
Crospovidone is a synthetic polymer derived from povidone. It absorbs liquid quickly and swells, helping tablets and capsules break apart and dissolve faster in your stomach.
UNII ZF94AP8MEY
Hydrogenated castor oil is a processed plant oil made by adding hydrogen to castor oil. It's used as a binder to help hold tablet ingredients together and as a lubricant to prevent sticking 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 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 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
UNII XRK36F13ZZ
A synthetic polymer made from methacrylic acid and ethyl acrylate combined in a 1:2 ratio. It's used as a film-coating material to control how quickly the medicine dissolves and releases its active ingredients in the digestive system.
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 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 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 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 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.

13 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 system	Per ea	Per package
Retail pharmacies payNADAC · weekly	$0.942	$56.51 / 60 tablets
Medicaid paysCMS SDUD · 12 mo	$1.17	$70.38 / 60 tablets
Medicare drug plans payPart D · Q2 2026	$1.60	$96.09 / 60 tablets

NADAC price history (per ea) — tap or hover for the price & month

▼ Down 45% over the last 24 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.

🔁 Therapeutic equivalents

Product	Labeler	Pack	NADAC/unit	TE	Status	Price vs. this
Diclofenac Sodium and Misoprostol 75 mg/1; 200 ug 00591-0398-60	Actavis	60 tablets	$0.942	AB	Availability likely	—
Diclofenac sodium and Misoprostol 75 mg/1; 200 ug 59762-0029-01	Mylan	60 tablets	$0.942	AB	Availability likely	—
Diclofenac Sodium and Misoprostol 75 mg/1; 200 ugthis 65162-0438-06	Amneal	60 tablets	$0.942	AB	Availability likely	—
Diclofenac Sodium and Misoprostol 75 mg/1; 200 ug 68001-0232-06	BluePoint	60 tablets	$0.942	AB	Availability likely	—
Diclofenac Sodium Misoprostol 75 mg/1; 200 ug 75834-0265-60	Nivagen	60 tablets	$0.942	AB	Availability likely	—
Arthrotec 75 mg/1; 200 ug 00025-1421-60	Pfizer	60 tablets	$8.460	AB	Availability likely	+798%
Diclofenac Sodium and Misoprostol 75 mg/1; 200 ug 42291-0233-60	AvKARE	60 tablets	—	AB	FDA listed	—
Diclofenac Sodium/Misoprostol DICLOFENAC-SODIUM-MISOPROSTOL 75 mg/1; 200 ug 42571-0134-29	Micro	600 tablets	—	AB	FDA listed	—
Diclofenac Sodium Misoprostol 75 mg/1; 200 ug 71205-0866-00	Proficient	100 tablets	—	AB	FDA listed	—
Diclofenac Sodium and Misoprostol 75 mg/1; 200 ug 71335-1183-01	Bryant	20 tablets	—	AB	FDA listed	—
Diclofenac Sodium Misoprostol 75 mg/1; 200 ug 71335-2441-01	Bryant	20 tablets	—	AB	FDA listed	—
Diclofenac Sodium/Misoprostol DICLOFENAC-SODIUM-MISOPROSTOL 75 mg/1; 200 ug 71335-2603-01	Bryant	20 tablets	—	AB	FDA listed	—
Diclofenac Sodium Misoprostol 75 mg/1; 200 ug 72162-2519-06	Bryant	60 tablets	—	AB	FDA listed	—
Diclofenac sodium and Misoprostol DR 75 mg/1; 200 ug 80425-0272-01	Advanced	60 tablets	—	AB	FDA listed	—
DICLOENAC SODIUM and MISOPROSTOL DR 75 mg/1; 200 ug 80425-0273-01	Advanced	60 tablets	—	AB	FDA listed	—
Diclofenac Sodium/Misoprostol DICLOFENAC-SODIUM-MISOPROSTOL 75 mg/1; 200 ug 85766-0192-07	Sportpharm	7 tablets	—	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

🏛️

2016

On the market since

Dec 2016

📍

2026

Currently FDA-listed

10 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.

🗺️ 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 65162-0438-06, 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 – Q4 2025 · 4 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

103

Units reimbursed last 4 qtrs

5.9K

Gross reimbursed last 4 qtrs

$6.9K

Avg / prescription

$66.98

Avg / unit

$1.1730

Latest quarter Q4 2025

18Rx

Medicaid pays / ea

$1.1730

gross reimbursed

NADAC / ea

$0.9418

acquisition cost

Spread

+$0.2312

+25% 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 ⓘ

63% FFS 37% MCO

Fee-for-service · 65 Rx Managed care · 38 Rx

State Medicaid map

Units reimbursed · per 100k residents

4.020.4

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 20.4 /100k

2 Ohio 5.7 /100k

3 Texas 4.0 /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.

60 tablets this page65162-0438-06 103 Rx · $6,898

30 tablets65162-0438-03 No Medicaid data

100 tablets65162-0438-10 No Medicaid data

Drug total (last 4 qtrs): 103 Rx · 5,881 units · $6,898 gross reimbursed

Tap a pack size to open its page. Source: CMS State Drug Utilization Data, last 4 quarters.

📦 Packaging — all sizes for this product

Package NDC	Description	Per unit	Per pack	Marketing start	Status
65162-0438-03	30 TABLET, DELAYED RELEASE in 1 BOTTLE (65162-438-03)	—	—	2016-12-01	Active
65162-0438-06 You're viewing this	60 TABLET, DELAYED RELEASE in 1 BOTTLE (65162-438-06)	$0.9418 / ea	$56.51	2016-12-01	Active
65162-0438-10	100 TABLET, DELAYED RELEASE in 1 BOTTLE (65162-438-10)	—	—	2016-12-01	Active

You're viewing one of 3 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 NDC 65162-0438-06?

NDC 65162-0438-06 is a 60-count package — 60 tablet, delayed release in 1 bottle.

What is the difference between NDC 65162-0438-06 and NDC 65162-0438-03?

Both are Diclofenac Sodium and Misoprostol 75 mg; 200 ug Tablet, Delayed Release — the drug itself is identical. NDC 65162-0438-06 is the 60-count package, while NDC 65162-0438-03 is the 30 tablets package.

What NDC number is used to bill for this package of Diclofenac Sodium and Misoprostol 75 mg; 200 ug Tablet, Delayed Release?

Bill NDC 65162-0438-06 — the 11-digit billing format is 65162043806. 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.

📄 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.

🚨 Boxed Warning 🎯 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 💬 Medication Guide

🚨 Boxed Warning ~2 min read ▾

WARNING: RISK OF UTERINE RUPTURE, ABORTION, PREMATURE BIRTH, BIRTH DEFECTS; SERIOUS CARDIOVASCULAR EVENTS; AND SERIOUS GASTROINTESTINAL EVENTS Uterine Rupture, Abortion, Premature Birth, and Birth Defects Administration of misoprostol, a component of diclofenac sodium and misoprostol delayed-release tablets, to pregnant women can cause uterine rupture, abortion, premature birth, or birth defects. Uterine rupture has occurred when misoprostol was administered in pregnant women to induce labor or an abortion [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1) ] .

Diclofenac sodium and misoprostol delayed-release tablets are contraindicated in pregnancy [see Contraindications (4) ] and not recommended in women of childbearing potential. Patients must be advised of the abortifacient property and warned not to give the drug to others [see Warnings and Precautions (5.1) ] . If diclofenac sodium and misoprostol delayed-release tablets are prescribed, verify the pregnancy status of females of reproductive potential prior to initiation of treatment and advise them to use effective contraception during treatment [see Use in Specific Populations (8.3) ] .

Cardiovascular Thrombotic Events NSAIDs cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use [see Warnings and Precautions (5.2) ] . Diclofenac sodium and misoprostol delayed-release tablets are contraindicated in the setting of coronary artery bypass graft (CABG) surgery [see Contraindications (4) and Warnings and Precautions (5.2) ] .

Gastrointestinal Bleeding, Ulceration, and Perforation NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events [see Warnings and Precautions (5.3) ] .

WARNING: RISK OF UTERINE RUPTURE, ABORTION, PREMATURE BIRTH, BIRTH DEFECTS; SERIOUS CARDIOVASCULAR EVENTS; AND SERIOUS GASTROINTESTINAL EVENTS See full prescribing information for complete boxed warning. Administration of misoprostol, a component of diclofenac sodium and misoprostol delayed-release tablets, to pregnant women can cause uterine rupture, abortion, premature birth, or birth defects. Uterine rupture has occurred when misoprostol was administered in pregnant women to induce labor or an abortion.

( 4 , 5.1 , 8.1 ) Diclofenac sodium and misoprostol delayed-release tablets are contraindicated in pregnancy and are not recommended in women of childbearing potential. Patients must be advised of the abortifacient property and warned not to give the drug to others. ( 5.1 , 8.3 ) Increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal.

( 5.2 ) Diclofenac sodium and misoprostol delayed-release tablets are contraindicated in the setting of coronary artery bypass graft (CABG) surgery. ( 4 , 5.2 ) Increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal and can occur at any time and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk.

( 5.3 )

🎯 Indications and Usage 121 words ▾

1 INDICATIONS AND USAGE Diclofenac sodium and misoprostol delayed-release tablets are indicated for treatment of the signs and symptoms of osteoarthritis or rheumatoid arthritis in adult patients at high risk of developing NSAID-induced gastric and duodenal ulcers and their complications. For a list of factors that may increase the risk of NSAID-induced gastric and duodenal ulcers and their complications [see Warnings and Precautions (5.3) ] . Diclofenac sodium and misoprostol delayed-release tablets are a combination of diclofenac sodium, a non-steroidal anti-inflammatory drug, and misoprostol, a prostaglandin-1 (PG E1) analog, indicated for the treatment of signs and symptoms of osteoarthritis or rheumatoid arthritis in adult patients at high risk of developing NSAID-induced gastric and duodenal ulcers and their complications.

( 1 )

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals. ( 2.1 ) Osteoarthritis: The recommended dosage for maximal GI protection is one tablet (containing 50 mg of diclofenac and 200 mcg of misoprostol) three times daily. A dosage of diclofenac higher than 150 mg/day is not recommended.

( 2.2 ) Rheumatoid Arthritis: The recommended dosage for maximal GI protection is one tablet (containing 50 mg of diclofenac and 200 mcg of misoprostol) three or four times daily. A dosage of diclofenac higher than 200 mg/day is not recommended. ( 2.3 ) For dosage modifications due to intolerance, see the full Prescribing Information.

( 2.2 , 2.3 )

2.1Important Dosage Information Carefully consider the potential benefits and risks of diclofenac sodium and misoprostol delayed-release tablets and other treatment options before deciding to use diclofenac sodium and misoprostol delayed-release tablets. Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see Warnings and Precautions (5) ] . After observing the response to initial therapy with diclofenac sodium and misoprostol delayed-release tablets, the dose and frequency should be adjusted to suit an individual patient’s needs.

Diclofenac sodium and misoprostol delayed-release tablets are not recommended for patients who would not receive the appropriate dosage of both active ingredients. Diclofenac sodium and misoprostol delayed-release tablets, a fixed combination product, is administered as diclofenac sodium and misoprostol delayed-release tablets (50 mg diclofenac sodium and 200 mcg misoprostol) or diclofenac sodium and misoprostol delayed-release tablets (75 mg diclofenac sodium and 200 mcg misoprostol).

2.2Recommended Dosage in Patients with Osteoarthritis The recommended dosage for the treatment of osteoarthritis for maximal GI mucosal protection is diclofenac sodium 50 mg and misoprostol 200 mcg three times a day. For patients who experience intolerance, diclofenac sodium 75 mg and misoprostol 200 mcg two times a day or diclofenac sodium 50 mg and misoprostol 200 mcg two times a day can be used, but these dosages are less effective in preventing ulcers. A daily dosage of diclofenac sodium greater than 150 mg/day is not recommended.

Daily doses of the components delivered with these regimens are as follows: Osteoarthritis Regimen Diclofenac sodium (mg/day) Misoprostol (mcg/day) diclofenac sodium 50 mg and misoprostol 200 mcg three times a day two times a day * 150 100 600 400 diclofenac sodium 75 mg and misoprostol 200 mcg two times a day * 150 400 * For patients who experience intolerance; these dosages are less effective in preventing ulcers

2.3Recommended Dosage in Patients with Rheumatoid Arthritis The recommended dosage for the treatment of rheumatoid arthritis is diclofenac sodium 50 mg and misoprostol 200 mcg three or four times a day. For patients who experience intolerance, diclofenac sodium 75 mg and misoprostol 200 mcg two times a day or diclofenac sodium 50 mg and misoprostol 200 mcg two times a day can be used, but are less effective in preventing ulcers. A daily dosage of diclofenac sodium greater than 200 mg/day is not recommended.

Daily doses of the components delivered with these regimens are as follows: Rheumatoid Arthritis Regimen Diclofenac sodium (mg/day) Misoprostol (mcg/day) diclofenac sodium 50 mg and misoprostol 200 mcg four times a day three times a day two times a day * 200 150 100 800 600 400 diclofenac sodium 75 mg and misoprostol 200 mcg two times a day * 150 400 * For patients who experience intolerance; these dosages are less effective in preventing ulcers

2.4Additional Dosage Recommendations Diclofenac sodium and misoprostol delayed-release tablets contain misoprostol, which provides protection against gastric and duodenal ulcers [see Clinical Studies (14) ] . For gastric ulcer prevention, the 200 mcg four and three…

💊 Dosage Forms and Strengths 85 words ▾

3 DOSAGE FORMS AND STRENGTHS Delayed-release tablets: 50 mg diclofenac sodium and 200 mcg misoprostol as white to off-white, round shaped, biconvex, debossed with “AN” on one side and “436” on the other side. 75 mg diclofenac sodium and 200 mcg misoprostol as white to off-white, round shaped, biconvex, debossed with “AN” on one side and “438” on the other side. Delayed-release tablets: 50 mg diclofenac sodium and 200 mcg misoprostol ( 3 ) 75 mg diclofenac sodium and 200 mcg misoprostol ( 3 )

⛔ Contraindications 205 words ▾

4 CONTRAINDICATIONS Diclofenac sodium and misoprostol delayed-release tablets are contraindicated in the following patients: Pregnancy. Use of misoprostol, a component of diclofenac sodium and misoprostol delayed-release tablets, during pregnancy can result in maternal and fetal harm, including uterine rupture, abortion, premature birth, or birth defects [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1) ] . In the setting of coronary artery bypass graft (CABG) surgery [see Warnings and Precautions (5.2) ] .

Active gastrointestinal bleeding [see Warnings and Precautions (5.3) ] . History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients [see Warnings and Precautions (5.8 , 5.9) ] .

Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to diclofenac sodium and misoprostol, other prostaglandins, or any components of the drug product [see Warnings and Precautions (5.8 , 5.10) ] . Pregnancy ( 4 ) In the setting of CABG surgery ( 4 ) Active gastrointestinal bleeding ( 4 ) History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs ( 4 ) Known hypersensitivity to diclofenac sodium, misoprostol, or any components of the drug product ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Embryo-Fetal Toxicity with NSAIDs: Use of NSAIDs, including diclofenac in women at about 20 weeks gestation and later in pregnancy may cause oligohydramnios/fetal renal dysfunction and premature closure of the fetal ductus arteriosus. ( 4 , 5.1 , 8.1 ) Hepatotoxicity: Inform patients of warning signs and symptoms of hepatotoxicity. Discontinue if abnormal liver tests persist or worsen or if clinical signs and symptoms of liver disease develop.

( 5.4 ) Hypertension: Patients taking some antihypertensive medications may have impaired response to these therapies when taking NSAIDs. Monitor blood pressure. ( 5.5 , 7 ) Heart Failure and Edema: Avoid in patients with severe heart failure unless benefits are expected to outweigh risk of worsening heart failure.

( 5.6 ) Renal Toxicity: Monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia. Avoid in patients with advanced renal disease unless benefits are expected to outweigh risk of worsening renal function. ( 5.7 ) Anaphylactic Reactions: Seek emergency help if an anaphylactic reaction occurs.

( 5.8 ) Exacerbation of Asthma Related to Aspirin Sensitivity: Contraindicated in patients with aspirin-sensitive asthma. Monitor patients with preexisting asthma (without aspirin sensitivity). ( 5.9 ) Serious Skin Reactions: Discontinue at first appearance of skin rash or other signs of hypersensitivity.

( 5.10 ) Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) : Discontinue and evaluate clinically. ( 5.11 ) Hematologic Toxicity: Monitor hemoglobin or hematocrit in patients with any signs or symptoms of anemia. ( 5.12 , 7 )

5.1Uterine Rupture, Abortion, Premature Birth, or Birth Defects with Misoprostol and Embryo-Fetal Toxicity with NSAIDs Misoprostol Administration of misoprostol, a component of diclofenac sodium and misoprostol delayed-release tablets, to pregnant women can cause uterine rupture, abortion, premature birth, or birth defects. Uterine rupture has occurred when misoprostol was administered to pregnant women to induce labor or an abortion. Diclofenac sodium and misoprostol delayed-release tablets are contraindicated in pregnant women.

Diclofenac sodium and misoprostol delayed-release tablets are not recommended in women of childbearing potential. Patients must be advised of the abortifacient property and warned not to give the drug to others [see Use in Specific Populations (8.1) ] . If diclofenac sodium and misoprostol delayed-release tablets are prescribed, verify the pregnancy status of females of reproductive potential prior to initiation of treatment and advise the use effective contraception during treatment with diclofenac sodium and misoprostol delayed-release tablets [see Use in Specific Populations (8.3) ] .

Diclofenac Premature Closure of Fetal Ductus Arteriosus NSAIDs, including diclofenac, a component of diclofenac sodium and misoprostol delayed-release tablets, increase the risk of premature closure of the fetal ductus arteriosus at about 30 weeks of gestation and later. Oligohydramnios/Neonatal Renal Impairment Use of NSAIDs, including diclofenac, at about 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation.

Oligohydramnios is often, but not always, reversible with treatment discontinuation. Complications of prolonged oligohydramnios may, for example, include limb contractures and delayed lung maturation. In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required [see Use in Specific Populations (8.1) ] .

5.2Cardiovascular Thrombotic Events Clinical trials of several cyclooxygenase-2 (COX-2) selective and nonselectiv…

🤒 Adverse Reactions ~2 min read ▾

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: Cardiovascular Thrombotic Events [see Warnings and Precautions (5.2) ] GI Bleeding, Ulceration and Perforation [see Warnings and Precautions (5.3) ] Hepatotoxicity [see Warnings and Precautions (5.4) ] Hypertension [see Warnings and Precautions (5.5) ] Heart Failure and Edema [see Warnings and Precautions (5.6) ] Renal Toxicity and Hyperkalemia [see Warnings and Precautions (5.7) ] Anaphylactic Reactions [see Warnings and Precautions (5.8) ] Serious Skin Reactions [see Warnings and Precautions (5.10) ] Hematologic Toxicity [see Warnings and Precautions (5.12) ] Most common adverse reactions (> 2%) are: abdominal pain, diarrhea, dyspepsia, nausea, flatulence, gastritis, vomiting, constipation, headache, dizziness, alanine aminotransferase increased, hematocrit decreased.

( 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. Adverse reaction information for diclofenac sodium and misoprostol is derived from multinational controlled clinical trials in over 2,000 patients receiving diclofenac sodium 50 mg and misoprostol 200 mcg or diclofenac sodium 75 mg and misoprostol 200 mcg, as well as from blinded, controlled trials of diclofenac sodium delayed-release tablets and misoprostol tablets.

Gastrointestinal GI disorders had the highest reported incidence of adverse reactions for patients receiving diclofenac sodium and misoprostol. These events were generally minor, but led to discontinuation of therapy in 9% of patients on diclofenac sodium and misoprostol and 5% of patients on diclofenac sodium. For GI ulcer rates, [see Clinical Studies (14) ] .

GI disorder Diclofenac Sodium and Misoprostol Diclofenac Sodium Abdominal pain 21% 15% Diarrhea 19% 11% Dyspepsia 14% 11% Nausea 11% 6% Flatulence 9% 4% Diclofenac sodium and misoprostol can cause more abdominal pain, diarrhea, and other GI symptoms than diclofenac alone. Diarrhea and abdominal pain developed early in the course of therapy, and were usually self-limited (resolved after 2 to 7 days). Rare instances of profound diarrhea leading to severe dehydration have been reported in patients receiving misoprostol.

Patients with an underlying condition such as inflammatory bowel disease, or those in whom dehydration, were it to occur, would be dangerous, should be monitored carefully if diclofenac sodium and misoprostol is prescribed. The incidence of diarrhea can be minimized by administering diclofenac sodium and misoprostol with food and by avoiding co-administration with magnesium-containing antacids. Gynecological Gynecological disorders previously reported with misoprostol use have also been reported for women receiving diclofenac sodium and misoprostol (see below).

Postmenopausal vaginal bleeding may be related to administration of diclofenac sodium and misoprostol. If it occurs, diagnostic workup should be undertaken to rule out gynecological pathology [see Boxed Warnings , Contraindications (4) and Warnings and Precautions (5) ] . Other adverse experiences reported occasionally with diclofenac sodium and misoprostol, diclofenac or other NSAIDs, or misoprostol are: Body as a whole: asthenia, fatigue, malaise.

Central and peripheral nervous system: dizziness, drowsiness, headache, insomnia, paresthesia, vertigo. Digestive: anorexia, appetite changes, constipation, dry mouth, dysphagia, esophageal ulceration, esophagitis, eructation, gastritis, gastroesophageal reflux, GI neoplasm benign, peptic ulcer, tenesmus, vomiting. Female reproductive disorders: breast pain, dysmenorrhea, menst…

🔄 Drug Interactions ~3 min read ▾

7 DRUG INTERACTIONS See Table 1 for clinically significant drug interactions with diclofenac and misoprostol. Table 1: Clinically Significant Drug Interactions with Diclofenac and Misoprostol Drugs That Interfere with Hemostasis Clinical Impact: Diclofenac and anticoagulants such as warfarin have a synergistic effect on bleeding. The concomitant use of diclofenac and anticoagulants have an increased risk of serious bleeding compared to the use of either drug alone.

Serotonin release by platelets plays an important role in hemostasis. Case-control and cohort epidemiological studies showed that concomitant use of drugs that interfere with serotonin reuptake and an NSAID may potentiate the risk of bleeding more than an NSAID alone. Intervention: Monitor patients with concomitant use of diclofenac sodium and misoprostol with anticoagulants (e.g., warfarin), antiplatelet drugs (e.g., aspirin), SSRIs, and SNRIs for signs of bleeding [see Warnings and Precautions (5.12) ] .

Aspirin Clinical Impact: Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone [see Warnings and Precautions (5.3)] . Intervention: Concomitant use of diclofenac sodium and misoprostol and analgesic doses of aspirin is not generally recommended because of the increased risk of bleeding [see Warnings and Precautions (5.12) ] .

Diclofenac sodium and misoprostol is not a substitute for low dose aspirin for cardiovascular protection. ACE Inhibitors, Angiotensin Receptor Blockers, and Beta-Blockers Clinical Impact: NSAIDs may diminish the antihypertensive effect of ACE inhibitors, ARBs, or beta-blockers (including propranolol). In patients who are elderly, volume-depleted (including those on diuretic therapy), or have renal impairment, co-administration of an NSAID with ACE inhibitors or ARBs may result in deterioration of renal function, including possible acute renal failure.

These effects are usually reversible. Intervention: The concomitant administration of these drugs should be done with caution. Patients should be adequately hydrated and the clinical need to monitor the renal function should be assessed at the beginning of the concomitant treatment and periodically thereafter.

During concomitant use of diclofenac sodium and misoprostol and ACE inhibitors, ARBs, or beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained. During concomitant use of diclofenac sodium and misoprostol and ACE inhibitors or ARBs in patients who are elderly, volume-depleted, or have impaired renal function, monitor for signs of worsening renal function [see Warnings and Precautions (5.7) ] . Diuretics Clinical Impact: Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients.

This effect has been attributed to the NSAID inhibition of renal prostaglandin synthesis. Intervention: During concomitant use of diclofenac sodium and misoprostol with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions (5.7) ] . Digoxin Clinical Impact: The concomitant use of diclofenac with digoxin has been reported to increase the serum concentration and prolong the half-life of digoxin.

Intervention: During concomitant use of diclofenac sodium and misoprostol and digoxin, monitor serum digoxin levels. Lithium Clinical Impact: NSAIDs have produced elevations in plasma lithium levels and reductions in renal lithium clearance. The mean minimum lithium concentration increased 15%, and the renal clearance decreased by approximately 2…

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Reversible Infertility: Consider withdrawal in women who have difficulties conceiving. ( 8.3 ) Geriatric Patients: Avoid use in patients with cardiovascular and/or renal risk factors. ( 8.5 ) Renal Impairment : Avoid use in patients with advanced renal disease. ( 8.6 )

8.1Pregnancy Risk Summary Diclofenac sodium and misoprostol delayed-release tablets are contraindicated in pregnant women [see Contraindications (4) ] . If a woman becomes pregnant while taking diclofenac sodium and misoprostol delayed-release tablets, discontinue the drug and advise the woman of the potential risks to her and to a fetus. There are no adequate and well-controlled studies of diclofenac sodium and misoprostol in pregnant women; however, there is information available about the active drug components of diclofenac sodium and misoprostol delayed-release tablets, diclofenac sodium and misoprostol.

Administration of misoprostol to pregnant women can cause uterine rupture, abortion, premature birth, or birth defects [see Warnings and Precautions (5.1) ] . Congenital anomalies sometimes associated with fetal death have been reported subsequent to the unsuccessful use of misoprostol as an abortifacient, but the drug’s teratogenic mechanism has not been demonstrated. Use of NSAIDS, including diclofenac a component of diclofenac sodium and misoprostol delayed-release tablets, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment (see Data) .

There are clinical considerations when misoprostol and diclofenac are used in pregnant women (see Clinical Considerations) . In reproduction studies with pregnant rabbits, there were no skeletal or visceral malformations when the combination of diclofenac sodium and misoprostol was administered during organogenesis at doses less than the maximum recommended human doses (MRHD); however, embryotoxicity was observed at this exposure (see Data) . Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization.

In animal studies, administration of prostaglandin synthesis inhibitors such as diclofenac, resulted in increased pre- and post-implantation loss. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

The estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Maternal Adverse Reactions Misoprostol may produce uterine contractions, uterine bleeding, and expulsion of the products of conception. Misoprostol has been used to ripen the cervix, to induce labor, and to treat postpartum hemorrhage, outside of its approved indication.

A major adverse effect of these uses is hyperstimulation of the uterus. Uterine rupture, amniotic fluid embolism, severe bleeding, shock, and maternal death have been reported when misoprostol was administered to pregnant women to induce labor to induce abortion beyond the eighth week of pregnancy. Higher doses of misoprostol, including the 100 mcg tablet, may increase the risk of complications from uterine hyperstimulation.

Diclofenac sodium and misoprostol delayed-release tablets, which contains 200 mcg of misoprostol, is likely to have a greater risk of uterine hyperstimulation than the 100 mcg tablet of misoprostol. Abortions caused by misoprostol may be incomplete. Cases of amniotic fluid embolism, which resulted in maternal and fetal death, have been reported with use of misoprostol during pregnancy.

Severe vaginal bleeding, retained placenta, shock, and pelvic pain have also been reported. These women were administered misoprostol vaginally and/or orally over a range of doses. Diclofenac sodium and misopr…

🤰 Pregnancy ~3 min read ▾

If a woman is or becomes pregnant while taking this drug, the drug should be discontinued and the patient apprised of the potential hazard to the fetus. Fetal/Neonatal Adverse Reactions Misoprostol Misoprostol may endanger pre…

🧒 Pediatric Use 18 words ▾

8.4Pediatric Use Safety and effectiveness of diclofenac sodium and misoprostol in pediatric patients have not been established.

🧓 Geriatric Use ~1 min read ▾

8.5Geriatric Use Geriatric patients (those 65 years of age and older), compared to younger adult patients, are at greater risk for NSAID-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions [ see Warnings and Precautions (5.2 , 5.3 , 5.7 )] . In addition, the risk of diclofenac-associated adverse reactions may be greater in geriatric patients with renal impairment or those taking concomitant ACE inhibitors or ARBs [see Drug Interactions (7) and Use in Specific Populations (8.6) ] . Avoid use of diclofenac sodium and misoprostol in geriatric patients with cardiovascular and/or renal risk factors.

If use cannot be avoided, use the lowest recommended dosage for the shortest duration and monitor for cardiac and renal adverse reactions [see Dosage and Administration (2.1) ] . Monitor renal function in geriatric patients during treatment with diclofenac sodium and misoprostol, especially in patients with concomitant use of ACE inhibitors or ARBs . Of the 2,184 patients in clinical studies with diclofenac sodium and misoprostol, 557 (25.5%) were 65 years of age and over.

No overall differences in effectiveness were observed between these patients and younger adult patients, and other reported clinical experience has not identified differences in effectiveness between geriatric patients and younger adult patients, but greater sensitivity of some older individuals cannot be ruled out. No clinically meaningful differences in the pharmacokinetics of diclofenac and misoprostol were observed in geriatric patients compared to younger adult patients [see Clinical Pharmacology (12.3) ].

🆘 Overdosage ~2 min read ▾

10 OVERDOSAGE Manage patients with symptomatic and supportive care following an acute NSAID overdosage. There are no specific antidotes. It is advisable to contact a poison control center (1-800-222-1222) to determine the latest recommendations because strategies for the management of overdose are continually evolving.

The toxic dose of diclofenac sodium and misoprostol has not been determined. However, signs of overdosage from the components of the product have been described. Diclofenac Symptoms following acute NSAID overdosages have been typically limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which have been generally reversible with supportive care.

Gastrointestinal bleeding has occurred. Hypertension, acute renal failure, respiratory depression, and coma have occurred, but were rare [see Warnings and Precautions (5.2 , 5.3 , 5.5 , 5.7) ] . Clinical signs that may suggest diclofenac sodium overdose include GI complaints, confusion, drowsiness, or general hypotonia.

If gastric decontamination may be potentially beneficial to the patient, e.g., short time since ingestion or a large overdosage (5 to 10 times the recommended dosage), consider emesis and/or activated charcoal (60 grams to 100 grams in adults, 1 gram to 2 grams per kg of body weight in pediatric patients) and/or an osmotic cathartic in symptomatic patients. Forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion may not be useful due to high protein binding. Misoprostol The toxic dose of misoprostol in humans has not been determined.

Cumulative total daily doses of 1600 mcg have been tolerated, with only symptoms of GI discomfort being reported. Clinical signs that may indicate an overdose are sedation, tremor, convulsions, dyspnea, abdominal pain, diarrhea, fever, palpitations, hypotension, or bradycardia. Diclofenac Sodium and Misoprostol Symptoms of acute overdosage with diclofenac sodium and misoprostol should be treated with supportive and symptomatic therapy.

There are no specific antidotes. In case of acute overdosage, emesisis and/or gastric lavage may be considered dependent upon amount ingested and time since ingestion. The use of oral activated charcoal may help to reduce the absorption of diclofenac sodium and misoprostol.

Induced diuresis may be beneficial because diclofenac sodium and misoprostol metabolites are excreted in the urine. The effect of dialysis or hemoperfusion on the elimination of diclofenac sodium (99% protein bound) and misoprostol acid remains unproven.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Diclofenac sodium and misoprostol delayed-release tablets is a combination product containing diclofenac sodium, an NSAID with analgesic, anti-inflammatory and antipyretic properties, and misoprostol, a GI mucosal protective prostaglandin-1 (PGE1) analog. Diclofenac The mechanism of action of diclofenac, like that of other NSAIDs, is not completely understood but involves inhibition of cyclooxygenase (COX-1 and COX-2). Diclofenac is a potent inhibitor of prostaglandin (PG) synthesis in vitro .

Diclofenac concentrations reached during therapy have produced in vivo effects. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Prostaglandins are mediators of inflammation.

Because diclofenac is an inhibitor of prostaglandin synthesis, its mode of action may be due to a decrease of prostaglandins in peripheral tissues. Misoprostol Misoprostol is a synthetic PGE1 analog with gastric antisecretory and mucosal protective properties. NSAIDs inhibit prostaglandin synthesis.

A deficiency of prostaglandins within the gastric and duodenal mucosa may lead to diminishing bicarbonate and mucus secretion and may contribute to the mucosal damage caused by NSAIDs. Misoprostol can increase bicarbonate and mucus production, but it has been shown at doses 200 mcg and above that are also antisecretory. It is therefore not possible to differentiate whether the ability of misoprostol to reduce the risk of gastric and duodenal ulcers is the result of its antisecretory effect, its mucosal protective effect, or both.

In vitro studies on canine parietal cells using titrated misoprostol acid as the ligand have led to the identification and characterization of specific prostaglandin receptors. Receptor binding is saturable, reversible, and stereo-specific. The sites have a high affinity for misoprostol, for its acid metabolite, and for other E type prostaglandins, but not for F or I prostaglandins and other unrelated compounds, such as histamine or cimetidine.

Receptor-site affinity for misoprostol correlates well with an indirect index of antisecretory activity. It is likely that these specific receptors allow misoprostol taken with food to be effective topically, despite the lower serum concentrations attained. Misoprostol, over the range of 50 mcg to 200 mcg, inhibits basal and nocturnal gastric acid secretion, and acid secretion in response to a variety of stimuli, including meals, histamine, pentagastrin, and coffee.

Activity is apparent 30 minutes after oral administration and persists for at least 3 hours. In general, the effects of 50 mcg were modest and shorter-lived, and only the 200 mcg dose had substantial effects on nocturnal secretion or on histamine- and meal-stimulated secretion. Misoprostol also produces a moderate decrease in pepsin concentration during basal conditions, but not during histamine stimulation.

It has no significant effect on fasting or postprandial gastrin nor intrinsic factor output.

12.3Pharmacokinetics General Pharmacokinetic Characteristics The pharmacokinetic profiles of diclofenac and misoprostol administered as the fixed combination (diclofenac sodium and misoprostol delayed-release tablets 50 mg/200 mcg or 75 mg/200 mcg) are similar to the profiles when the two drugs are administered as separate tablets (see Table 2). No pharmacokinetic interaction between the two drugs has been observed following multiple dosing. The diclofenac total exposure [area under the curve (AUC)] is dose-proportional within the range of 25 mg to 150 mg.

Approximately dose-proportional increase in misoprostol exposure was also observed within the range of 200 to 400 mcg. Neither diclofenac nor misoprostol accumulated in plasma following repeated doses of diclofenac sodium and misoprostol given every 12 hours under fasted conditions. Table 2: Pharmacokinetic Parameters of Diclofenac and Misoprostol Acid Following Single Oral Doses…

🧬 Mechanism of Action ~2 min read ▾

It has no significant effect on fasting or postprandial gastrin nor intrinsic factor output.

📦 How Supplied / Storage and Handling 162 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Diclofenac sodium and misoprostol delayed-release tablets, USP are supplied as a tablet in dosage strengths of either 50 mg diclofenac sodium, USP/200 mcg misoprostol, USP or 75 mg diclofenac sodium, USP/200 mcg misoprostol, USP. The 50 mg/200 mcg dosage strength is supplied as white to off-white, round shaped, biconvex tablets debossed with “AN” on one side and “436” on the other side. They are available as follows: Bottles of 30: NDC 65162-436-03 Bottles of 60 NDC 65162-436-06 Bottles of 90 NDC 65162-436-09 Bottles of 100: NDC 65162-436-10 The 75 mg/200 mcg dosage strength is supplied as white to off-white, round shaped, biconvex tablets debossed with “AN” on one side and “438” on the other side.

They are available as follows: Bottles of 30: NDC 65162-438-03 Bottles of 60: NDC 65162-438-06 Bottles of 100: NDC 65162-438-10 Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

📋 Description ~1 min read ▾

11 DESCRIPTION Diclofenac sodium and misoprostol delayed-release tablets, USP is a combination product containing diclofenac sodium, USP, an NSAID with analgesic properties, and misoprostol, a gastrointestinal (GI) mucosal protective prostaglandin-1 (PGE1) analog. Diclofenac sodium and misoprostol delayed-release tablets are white to off-white, round, biconvex, and approximately 11 mm in diameter. Each tablet consists of an enteric-coated core containing 50 mg or 75 mg of diclofenac sodium, USP (equivalent to 46.39 mg or 69.58 mg of diclofenac, respectively) surrounded by an outer mantle containing 200 mcg misoprostol, USP.

Diclofenac sodium, USP is a phenylacetic acid derivative that is a white to off-white, virtually odorless, crystalline powder. Diclofenac sodium, USP is freely soluble in methanol, soluble in ethanol, and practically insoluble in chloroform and in dilute acid. Diclofenac sodium, USP is sparingly soluble in water.

Its chemical formula and name are: C 14 H 10 Cl 2 NO 2 Na [M.W. = 318.14] 2-[(2,6-dichlorophenyl) amino] benzeneacetic acid, monosodium salt. Misoprostol, USP is a water-soluble, viscous liquid that contains approximately equal amounts of two diastereomers. Its chemical formula and name are: C 22 H 38 O 5 [M.W. = 382.54] (±) methyl 11α,16-dihydroxy-16-methyl-9-oxoprost-13E-en-1-oate.

Inactive ingredients in diclofenac sodium and misoprostol delayed-release tablets, USP include: colloidal silicon dioxide, corn starch, crospovidone, hydrogenated castor oil, hypromellose, lactose monohydrate, magnesium stearate, methacrylic acid and ethyl acrylate copolymer dispersion, microcrystalline cellulose, povidone, sodium hydroxide, talc, and triethyl citrate.

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Inform patients, families, or their caregivers of the following information before initiating therapy with diclofenac sodium and misoprostol delayed-release tablets and periodically during the course of ongoing therapy. Uterine Rupture, Abortion, Premature Birth, or Birth Defects with Misoprostol and Embryo-Fetal Toxicity with NSAIDs Advise females that diclofenac sodium and misoprostol delayed-release tablets are contraindicated in pregnant women.

Use of misoprostol, a component of diclofenac sodium and misoprostol delayed-release tablets during pregnancy can result in maternal and fetal harm, including uterine rupture, abortion, premature birth, or birth defects. Use of diclofenac may cause oligohydramnios/fetal renal dysfunction and premature closure of the fetal ductus arteriosus. Advise patients not to give diclofenac sodium and misoprostol delayed-release tablets to others.

Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment with diclofenac sodium and misoprostol delayed-release tablets. Advise females to inform their healthcare provider of a known or suspected pregnancy [see Contraindications (4) , Warnings and Precautions (5.1) , and Use in Specific Populations (8.1 , 8.3) ] . Infertility Advise females of reproductive potential that diclofenac sodium and misoprostol delayed-release tablets may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women [see Use in Specific Populations (8.3) ] .

Cardiovascular Thrombotic Events Advise patients to be alert for the symptoms of cardiovascular thrombotic events, including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their health care provider immediately [see Warnings and Precautions (5.2) ] . Gastrointestinal Bleeding, Ulceration, and Perforation Advise patients to report symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis to their health care provider. In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, inform patients of the increased risk for and the signs and symptoms of GI bleeding [see Warnings and Precautions (5.3) ] .

Hepatotoxicity Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, diarrhea, jaundice, right upper quadrant tenderness, and “flu-like” symptoms). If these occur, instruct patients to stop diclofenac sodium and misoprostol delayed-release tablets and seek immediate medical therapy [see Warnings and Precautions (5.4) ] . Heart Failure and Edema Advise patients to be alert for the symptoms of congestive heart failure including shortness of breath, unexplained weight gain, or edema and to contact their healthcare provider if such symptoms occur [see Warnings and Precautions (5.6) ] .

Anaphylactic Reactions Inform patients of the signs of an anaphylactic reaction (e.g., difficulty breathing, swelling of the face or throat). Instruct patients to seek immediate emergency help if these occur [see Contraindications (4) and Warnings and Precautions (5.8) ] . Serious Skin Reactions , including DRESS Advise patients to stop taking diclofenac sodium and misoprostol delayed-release tablets immediately if they develop any type of rash or fever and contact their healthcare provider as soon as possible [see Warnings and Precautions (5.10 , 5.11) ] .

Avoid Concomitant Use of NSAIDs Inform patients that the concomitant use of diclofenac sodium and misoprostol delayed-release tablets with other NSAIDs or salicylates (e.g., diflunisal, salsalate) is not recommended due to the increased risk of gastrointestinal toxicity, and little or no increase in efficacy [see Warnings and Precautions (5.3) and Drug Interactions (7) ] . Alert patients tha…

💬 Medication Guide ~3 min read ▾

Medication Guide for Diclofenac Sodium and Misoprostol Delayed-release Tablets, USP Diclofenac Sodium (dye kloe' fen ak soe' dee um) and Misoprostol (mye'' soe pros' tol) Delayed-Release Tablets, USP for oral use What is the most important information I should know about diclofenac sodium and misoprostol delayed-release tablets? Diclofenac sodium and misoprostol delayed-release tablets contains diclofenac (a nonsteroidal anti-inflammatory drug (NSAID)) and misoprostol, and can cause uterus to tear (uterine rupture), abortion, premature birth, or birth defects.

The risk of uterine rupture increases as your pregnancy advances, if you have given birth to 5 or more children, and if you have had surgery on the uterus, such as a cesarean delivery. Do not take diclofenac sodium and misoprostol delayed-release tablets if you are pregnant . Tell your healthcare provider if you become pregnant or think you may be pregnant during treatment with diclofenac sodium and misoprostol delayed-release tablets.

If you are able to become pregnant, your healthcare provider should do a pregnancy test before you start treatment with diclofenac sodium and misoprostol delayed-release tablets. Females who are able to become pregnant should use an effective form of birth control (contraception) during treatment with diclofenac sodium and misoprostol delayed-release tablets. What is the most important information I should know about medicines containing Nonsteroidal Anti-inflammatory Drugs (NSAIDs)?

NSAIDs can cause serious side effects, including: Increased risk of a heart attack or stroke that can lead to death. This risk may happen early in treatment and may increase: with increasing doses of NSAIDs with longer use of NSAIDs Do not take NSAID containing medicines right before or after a heart surgery called a “coronary artery bypass graft (CABG)." Avoid taking NSAID containing medicines after a recent heart attack, unless your healthcare provider tells you to. You may have an increased risk of another heart attack if you take NSAIDs after a recent heart attack.

Increased risk of bleeding, ulcers, and tears (perforation) of the esophagus (tube leading from the mouth to the stomach), stomach and intestines: anytime during use without warning symptoms that may cause death The risk of getting an ulcer or bleeding increases with: past history of stomach ulcers, or stomach or intestinal bleeding with use of NSAIDs taking medicines called “corticosteroids”, “antiplatelet drugs”, “anticoagulants”, “SSRIs”, or “SNRIs” increasing doses of NSAIDs longer use of NSAIDs smoking drinking alcohol older age poor health advanced liver disease bleeding problems NSAID containing medicines should only be used: exactly as prescribed at the lowest dose possible for your treatment for the shortest time needed What are diclofenac sodium and misoprostol delayed-release tablets?

Diclofenac sodium and misoprostol delayed-release tablet contains 2 medicines: 1. Diclofenac is a non-steroidal anti-inflammatory drug (NSAID). See “What is the most important information I should know about medicines called Nonsteroidal Anti-inflammatory Drugs (NSAIDs)?” 2.

Misoprostol is a medicine used to protect the lining of the esophagus, stomach and intestines while taking diclofenac. Diclofenac sodium and misoprostol delayed-release tablets are a prescription medicine used to treat: symptoms of osteoarthritis or rheumatoid arthritis in adults at high risk of developing stomach (gastric) and intestinal (duodenal) ulcers while taking NSAIDs. It is not known if diclofenac sodium and misoprostol delayed-release tablets are safe and effective for use in children.

What are NSAIDs? NSAIDs are used to treat pain and redness, swelling, and heat (inflammation) from medical conditions such as different types of arthritis. Who should not take diclofenac sodium and misoprostol delayed-release tablets?

Do not take diclofenac sodium and misoprostol delayed-release tablets: if you are pregnant. right before or a…

Glossary — plain-language definitions of medical terms used in this label:

antiplatelet: A medicine that makes platelets, the blood cells that start a clot, less likely to clump together.

contraindicated: Should not be used in that situation, because the risk is considered too high.

exacerbation: A flare-up or worsening of a condition.

in vitro: In a laboratory dish or test tube rather than in a living person or animal; results may not carry over to people.

in vivo: In a living person or animal rather than in a laboratory dish.

synergistic: When two things taken together produce a larger effect than adding their separate effects would predict.

abdominal pain: Pain, cramping, or discomfort felt anywhere in the belly area.

Absorption: How a medicine moves from where it is taken, such as the stomach or gut, into the bloodstream.

adverse reaction: An unwanted or harmful effect that a medicine causes in the body.

Adverse Reactions: Unwanted or harmful effects that people experienced while taking a medicine, listed on its official label.

anemia: A low level of red blood cells or the oxygen-carrying protein inside them, which can cause tiredness, weakness, and paleness.

anorexia: Loss of appetite, or not feeling hungry (on a drug label this means reduced appetite, not the eating disorder).

asthenia: Unusual weakness or lack of physical strength and energy.

AUC: A measure of total drug exposure over time, showing how much medicine the blood is exposed to overall.

Boxed Warning: The strongest safety warning the FDA can require, set inside a bold black border because the risk it describes can be very serious.

bradycardia: A slower-than-normal heart rate, usually under 60 beats per minute.

clearance: How quickly the body removes a medicine from the blood, usually through the liver and kidneys.

Clinical Pharmacology: The label section explaining how a medicine works in the body and how the body processes it.

Clinical Studies: The label section summarizing the research trials used to show that a medicine works and is acceptably safe.

constipation: Having bowel movements less often than usual, or passing stools that are hard, dry, and difficult to move.

contraception: Methods used to prevent pregnancy, such as birth control pills, condoms, or an intrauterine device.

Contraindications: A list of situations or health conditions in which a medicine should not be used because the chance of harm is too high.

delayed-release: A pill coated so it does not release its medicine until after it has passed through the stomach.

depression: A lasting low mood with loss of interest that affects everyday life.

diarrhea: Loose, watery bowel movements that happen more often than normal.

Dosage and Administration: The label section explaining how much of a medicine to use and how to take or give it.

Drug Interactions: The label section listing other medicines, foods, or substances that can change how a medicine works or raise the chance of side effects.

dyspepsia: Discomfort, fullness, or a burning feeling in the upper belly, commonly called indigestion.

dysphagia: Trouble or discomfort swallowing food, liquids, or pills.

dyspnea: The medical word for shortness of breath, or the feeling that you cannot get enough air.

edema: Swelling caused by extra fluid trapped in the body's tissues.

efficacy: How well a treatment works under the controlled conditions of a clinical study.

Elimination: The overall removal of a medicine from the body by breaking it down and passing it out.

embolism: A blockage of a blood vessel by a clot or other material that has traveled from elsewhere in the body.

embryo-fetal toxicity: Harm to a developing baby in the womb, such as birth defects, slowed growth, or loss of the pregnancy.

emesis: The medical word for vomiting, or bringing up the contents of the stomach through the mouth.

enteric-coated: A special coating that keeps a pill from dissolving in the stomach, so it opens up further along in the intestine.

eosinophilia: A higher-than-normal level of eosinophils, a type of white blood cell often linked to allergies or drug reactions.

eructation: The medical word for burping, or releasing gas from the stomach up through the mouth.

esophagitis: Swelling and irritation of the lining of the food pipe, or esophagus.

estimated background risk: The normal chance that any pregnancy will have a birth defect or problem, even without taking any medicine.

fetal harm: Injury or damage to a developing baby while it is growing inside the womb.

flatulence: Passing gas from the bowel; feeling bloated or gassy.

Full Prescribing Information: The complete, detailed label for a prescription medicine that follows the summary highlights.

gastritis: Swelling or irritation of the lining of the stomach.

gastrointestinal bleeding: Bleeding anywhere along the digestive tract, from the food pipe down to the bowel.

Half-life: The time it takes for the amount of medicine in the blood to drop by half.

heart failure: A condition in which the heart cannot pump blood as well as it should, causing tiredness, breathlessness, and swelling.

hematemesis: Vomiting blood, which may look bright red or like dark coffee grounds.

hematocrit: A blood test showing what share of your blood is made up of red blood cells.

hemodialysis: A treatment that uses a machine to filter waste and extra fluid from the blood when the kidneys cannot.

hemoglobin: The iron-containing protein inside red blood cells that carries oxygen throughout the body.

hemorrhage: Bleeding, especially heavy or uncontrolled bleeding, either inside the body or from an outside wound.

hepatic impairment: Reduced liver function, meaning the liver does not work as well as normal at processing substances, including medicines.

hepatotoxicity: Damage to the liver caused by a medicine or other substance.

How Supplied/Storage and Handling: The label section describing the forms and strengths a medicine comes in and how to store it properly.

hyperkalemia: A higher-than-normal level of potassium, an important mineral, in the blood.

hypersensitivity: An overreaction of the body's defense system to a substance, causing symptoms such as rash, swelling, or trouble breathing.

hypertension: Blood pressure that stays higher than normal, commonly called high blood pressure.

hypotension: Blood pressure that is lower than normal, which can cause dizziness or fainting.

incidence: How often a new event, such as a side effect, happens in a group of people over a set period of time.

Indications and Usage: The label section stating which medical conditions the FDA has officially approved the medicine to treat, prevent, or manage.

inhibitor: A substance that blocks an enzyme or transporter, which can raise the levels of drugs it normally handles.

insomnia: Trouble falling asleep, staying asleep, or getting restful sleep.

jaundice: Yellowing of the skin and the whites of the eyes caused by too much bilirubin in the blood.

lethargy: A state of tiredness and sluggishness, often with slowed thinking or movement.

malaise: A general feeling of being unwell, uneasy, or low on energy, without one clear symptom.

Mechanism of Action: How a medicine produces its effect in the body, described at the level of cells or body chemistry.

Medication Guide: An FDA-approved handout written for patients that explains important safety information about certain medicines in plain language.

melena: Black, sticky, tar-like stools caused by blood that has been digested higher up in the gut.

metabolite: A new substance formed when the body breaks a medicine down.

myocardial infarction: The medical term for a heart attack, when blood flow to part of the heart muscle is blocked.

NDC: A unique number that identifies a specific medicine, its maker, strength, and package size.

neonatal: Relating to a newborn baby during its first four weeks of life.

organogenesis: The early stage of pregnancy when the developing baby's organs are first forming.

Overdosage: The label section describing what can happen if too much of a medicine is taken and how it may be treated.

palpitations: The feeling that your heart is racing, pounding, fluttering, or skipping beats.

paresthesia: A tingling, prickling, or "pins and needles" feeling in the skin, often in the hands or feet.

Patient Counseling Information: The label section telling health professionals what to explain to patients about using a medicine safely.

perforation: A hole that forms all the way through the wall of the stomach or intestine.

pharmacokinetic interaction: When one medicine changes how the body absorbs, spreads, breaks down, or removes another, altering its level in the blood.

Pharmacokinetics: The study of how the body takes in a medicine, spreads it around, breaks it down, and removes it over time.

postpartum: The period of time right after a woman gives birth.

potentiate: To make the effect of one medicine stronger by taking another substance along with it.

Prescribing Information: The official, detailed document approved by the FDA that tells health professionals how to use a prescription medicine.

prophylaxis: Treatment given to prevent an infection or illness before it starts, rather than to treat one that is already present.

protein binding: How much of a medicine sticks to proteins in the blood instead of moving freely through the body.

pruritus: Itching of the skin.

receptor: A special docking spot on a cell that a medicine or natural body chemical attaches to in order to trigger an effect.

renal impairment: Reduced kidney function, meaning the kidneys do not filter waste and fluid from the blood as well as normal.

reproductive potential: The ability to have children, meaning a person who could become pregnant or could father a child.

respiratory depression: Breathing that becomes too slow or too shallow to move enough air, so the body may not get enough oxygen.

sedation: A calm, sleepy, slowed-down state caused by a medicine that relaxes the brain and body.

synergistic effect: When two medicines taken together produce a combined effect that is greater than simply adding their separate effects.

teratogenic: Able to cause physical birth defects in a developing baby when a medicine is taken during pregnancy.

tremor: Shaking or trembling of part of the body, such as the hands, that a person cannot control.

ulceration: The forming of an open sore on the skin or on a lining inside the body, such as the stomach.

urticaria: Raised, itchy welts on the skin, commonly called hives.

Use in Specific Populations: The label section describing how a medicine affects particular groups, such as pregnant people, children, or older adults.

vertigo: A spinning sensation that makes you feel like you or the room around you is moving.

Warnings and Precautions: The label section describing serious risks to know about and safety steps to follow while using a medicine.

withdrawal: Uncomfortable physical or mental symptoms that appear when a medicine the body has gotten used to is reduced or stopped.

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

← 65162-0436-03 · Amneal 65162-0441-03 · 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.

Diclofenac Sodium and Misoprostol 75 mg; 200 ug Tablet, Delayed Release, 60-count

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