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Diclofenac Sodium/Misoprostol DICLOFENAC-SODIUM-MISOPROSTOL 75 mg; 200 ug Tablet, 90-count — NDC 42571-0134-90 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Diclofenac Sodium/Misoprostol DICLOFENAC-SODIUM-MISOPROSTOL 75 mg; 200 ug Tablet, 90-count — NDC 42571-134-90 (Billing 42571-0134-90)

by Micro Labs Limited · 90 TABLET in 1 BOTTLE

This is a package of 90 tablets of Diclofenac Sodium/Misoprostol DICLOFENAC-SODIUM-MISOPROSTOL 75 mg; 200 ug Tablet from Micro Labs Limited, marketed since Sep 2021 and currently FDA-listed.

NDC 42571-0134-90
🏷️ FDA NDC (as labeled) 42571-134-90 billing pads the product segment with a zero
This package
Contains90-count Pack sizes4 compare ↓
Also priced by: Part D plans $1.60/unit — full pricing hub ↓
Product page 42571-0134-60 Also comes in: 30 tablets 42571-134-30 60 tablets 42571-134-60 600 tablets 42571-134-29
Rx only Generic On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Oct 1, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

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

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 42571-134-90
Product NDC 42571-134
11-digit billing NDC 42571013490
RxCUI 857706, 1359105
UNII 0E43V0BB57, QTG126297Q
UPC 0342571133603, 0342571134600
Application # ANDA204355
SPL Set ID c61df58d-d6bb-4d3e-9ef8-60caa7d4e762
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 2021-09-01
Route ORAL
Dosage form TABLET
Substance DICLOFENAC SODIUM; MISOPROSTOL
TE code (Orange Book) AB · RLD · RS

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

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
Quick answers
  • GSN (GCN sequence number): 035737
  • GCN: 06263
  • GPI-14 (Medi-Span): 66109902200630
  • HICL (First Databank): 008302
  • AHFS class code: 28:08.04.04
  • RxCUI (RxNorm): 857706
Why two NDCs? The FDA registers this code as 42571-134-90 — 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 → 42571-0134-90. 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.

Clinical

Label name DICLOFENAC-MISOPROST 75-0.2 MG Ingredient Diclofenac Sodium/Misoprostol
📗 Our plain-language guide HelloPharmacist
  • It treats the signs and symptoms of osteoarthritis or rheumatoid arthritis in adults. It is for people at high risk of stomach or duodenal ulcers from NSAIDs. The misoprostol part...
  • Take it by mouth as prescribed, usually three or four times a day. Taking it with food can help cut down on diarrhea. Avoid magnesium-containing antacids, since they can make diarr...
  • Stomach upset is the most common, including belly pain, diarrhea, indigestion, nausea and gas. Diarrhea and pain often start early and usually pass in a few days. Call your doctor...
  • No. Misoprostol can cause miscarriage, premature birth, birth defects and uterine rupture. If you can become pregnant, your doctor will require a negative pregnancy test and reliab...
📖 Read our full Diclofenac and Misoprostol 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 eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · Q2 2026 $1.60 $144.14 / 90 tablets
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
42571-0134-29 42571-134-29 60 BLISTER PACK in 1 CARTON / 10 TABLET in 1 BLISTER PACK — — 2021-09-01 — Active
42571-0134-30 42571-134-30 30 TABLET in 1 BOTTLE — — 2021-09-01 — Active
42571-0134-60 42571-134-60 Main listing 60 TABLET in 1 BOTTLE $0.9662 / ea $57.97 2021-09-01 — Active
42571-0134-90 You're viewing this 90 TABLET in 1 BOTTLE — — 2021-09-01 — Active

This pack shows little to no recent Medicaid volume — the 60 tablets pack carries most fills. See all packs ↓

Pack size FAQ

What quantity is in this package?
This is a 90-count package — 90 tablet in 1 bottle.
How does this package differ from NDC 42571-0134-30?
Both are Diclofenac Sodium/Misoprostol DICLOFENAC-SODIUM-MISOPROSTOL 75 mg; 200 ug Tablet — the drug itself is identical. This page's package is the 90-count one, while NDC 42571-0134-30 is the 30 tablets package.
What NDC number is used to bill for this package of Diclofenac Sodium/Misoprostol DICLOFENAC-SODIUM-MISOPROSTOL 75 mg; 200 ug Tablet?
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
Diclofenac Sodium and Misoprostol 75 mg/1; 200 ug 00591-0398-60 Actavis 60 tablets $0.966 AB Availability likely —
Diclofenac sodium and Misoprostol 75 mg/1; 200 ug 59762-0029-01 Mylan 60 tablets $0.966 AB Availability likely —
Diclofenac Sodium and Misoprostol 75 mg/1; 200 ug 68001-0232-06 BluePoint 60 tablets $0.966 AB Availability likely —
Diclofenac Sodium Misoprostol 75 mg/1; 200 ug 75834-0265-60 Nivagen 60 tablets $0.966 AB Availability likely —
Arthrotec 75 mg/1; 200 ug 00025-1421-60 Pfizer 60 tablets $8.475 AB Availability likely —
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 ugthis 42571-0134-90 Micro 90 tablets — AB FDA listed —
Diclofenac Sodium and Misoprostol 75 mg/1; 200 ug 65162-0438-03 Amneal 30 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

🏛️
2021
On the market since
Sep 2021
📍
2026
Currently FDA-listed
5 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 white
ShapeRound
ImprintD75M
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.

Loading inactive ingredients from the official FDA label in the background. No external source is being called by this page request.
Where does this data come from?
Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

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

LabelerMicro Labs Limited
Application holderMICRO LABS LTD
FDA applicationANDA204355 (ANDA)
Labeler code42571
First marketedSep 2021
Product typeHuman Prescription Drug
Portfolio190 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

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.
🚨 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 🍼 Nursing Mothers 🧬 Pharmacokinetics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🚨 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 is 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 (PGE1) 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/200 mcg (50 mg diclofenac sodium and 200 mcg misoprostol) or diclofenac sodium and misoprostol delayed-release tablets 75 mg/200 mcg (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 and misoprostol delayed-release tablets 50 mg/200 mcg three times a day. For patients who experience intolerance, diclofenac sodium and misoprostol delayed-release tablets 75 mg/200 mcg two times a day or diclofenac sodium and misoprostol delayed-release tablets 50 mg/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 and misoprostol delayed-release tablets 50 mg/200 mcg three times a day two times a day* 150 100 600 400 Diclofenac sodium and misoprostol delayed-release tablets 75 mg/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 and misoprostol delayed-release tablets 50 mg/200 mcg three or four times a day. For patients who experience intolerance, diclofenac sodium and misoprostol delayed-release tablets 75 mg/200 mcg two times a day or diclofenac sodium and misoprostol delayed-release tablets 50 mg/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 and misoprostol delayed-release tablets 50 mg/200 mcg four times a day three times a day two times a day* 200 150 100 800 600 400 Diclofenac sodium and misoprostol delayed-release tablets 75 mg/200 mcg two times a day* 150 400 * For patients who experience intolerance; these dosages are less effective in preventing ulcers 2.4… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 114 words ▾

3 DOSAGE FORMS AND STRENGTHS Diclofenac sodium and misoprostol delayed-release tablets, USP are supplied as a uncoated tablets in dosage strengths of either 50 mg diclofenac sodium/200 mcg misoprostol or 75 mg diclofenac sodium/200 mcg misoprostol. 50 mg/200 mcg dosage strength is a white to off-white, round, biconvex uncoated tablet, debossed with “D 50 M” on one side and plain on other side. 75 mg/200 mcg dosage strength is a white to off-white, round, biconvex uncoated tablet, debossed with “D 75 M” on one side and plain on other side.

Delayed-release tablets: 50 mg diclofenac sodium and 200 mcg misoprostol ( 3 ) 75 mg diclofenac sodium and 200 mcg misoprostol ( 3 )

⛔ Contraindications 207 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 nonselec… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 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 Micro Labs USA Inc. at 1-855-839-8195 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 delayed-release tablets is derived from multinational controlled clinical trials in over 2,000 patients receiving diclofenac sodium and misoprostol delayed-release tablets 50 mg/200 mcg or diclofenac sodium and misoprostol delayed-release tablets 75 mg/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 delayed-release tablets. These events were generally minor, but led to discontinuation of therapy in 9% of patients on diclofenac sodium and misoprostol delayed-release tablets and 5% of patients on diclofenac sodium. For GI ulcer rates, [see Clinical Studies ( 14 )].

GI disorder Diclofenac Sodium and Misoprostol Delayed-Release Tablets Diclofenac Sodium Abdominal pain 21% 15% Diarrhea 19% 11% Dyspepsia 14% 11% Nausea 11% 6% Flatulence 9% 4% Diclofenac sodium and misoprostol delayed-release tablets 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 delayed-release tablets are prescribed. The incidence of diarrhea can be minimized by administering diclofenac sodium and misoprostol delayed-release tablets 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 delayed-release tablets (see below).

Postmenopausal vaginal bleeding may be related to administration of diclofenac sodium and misoprostol delayed-release tablets. 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 delayed-release tablets, diclofenac or other NSAIDs, or misoprostol are: Body as a whole: asthenia, fatigue, malaise.

Central and peripheral nervous system: dizziness, drowsiness, headache, insomnia, par… [Excerpted — this section continues on DailyMed.]

🔄 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 delayed-release tablets 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 delayed-release tablets 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 delayed-release tablets are 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 delayed-release tablets 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 delayed-release tablets 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 delayed-release tablets 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 delayed-release tablets and digoxin, monitor serum digoxin levels. Lithium Clinical Impact: NSAIDs have produced elevations… [Excerpted — this section continues on DailyMed.]

👥 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 delayed-release tablets 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. Dic… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~3 min read ▾

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 delayed-release tablets 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 misoprostol delayed-release tablets are contraindicated in pregnant women [see Contraindications ( 4 )].

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… [Excerpted — this section continues on DailyMed.]

🧒 Pediatric Use 20 words ▾

8.4Pediatric Use Safety and effectiveness of diclofenac sodium and misoprostol delayed-release tablets 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 delayed-release tablets 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 delayed-release tablets, especially in patients with concomitant use of ACE inhibitors or ARBs .

Of the 2,184 patients in clinical studies with diclofenac sodium and misoprostol delayed-release tablets, 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 delayed-release tablets 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. Diclo fenac Sodium and Misoprostol Delayed-Release Tablets Symptoms of acute overdosage with diclofenac sodium and misoprostol delayed-release tablets 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 are 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 mcg to 400 mcg. Neither diclofenac nor misoprostol accumulated in plasma following repeated doses of diclofenac sodium and misoprostol delayed-release tablets given every 12 hours under fasted conditions. Table 2: Pharmacokinetic Parameters of Diclofenac and Misoprostol Acid… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action ~2 min read ▾

12.1Mechanism of Action Diclofenac sodium and misoprostol delayed-release tablets are 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.

📦 How Supplied / Storage and Handling 163 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Diclofenac sodium and misoprostol delayed-release tablets, USP are supplied as a uncoated tablets in dosage strengths of either 50 mg diclofenac sodium/200 mcg misoprostol or 75 mg diclofenac sodium/200 mcg misoprostol. 50 mg/200 mcg dosage strength is a white to off-white, round, biconvex uncoated tablet, debossed with “D 50 M” on one side and plain on other side. 75 mg/200 mcg dosage strength is a white to off-white, round, biconvex uncoated tablet, debossed with “D 75 M” on one side and plain on other side.

The dosage strengths are supplied in: Strength NDC Number Size 50 mg/200 mcg 42571-133-30 Bottle of 30 Tablets 42571-133-60 Bottle of 60 Tablets 42571-133-90 Bottle of 90 Tablets 42571-133-29 Carton of 60 (6X10) unit-dose Tablets 75 mg/200 mcg 42571-134-30 Bottle of 30 Tablets 42571-134-60 Bottle of 60 Tablets 42571-134-90 Bottle of 90 Tablets 42571-134-29 Carton of 60 (6X10) unit-dose Tablets Store at 20° to 25°C (68° to 77°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, 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 (diclofenac sodium and misoprostol delayed-release tablets 50 mg/200 mcg) or 75 mg (diclofenac sodium and misoprostol delayed-release tablets 75 mg/200 mcg) of diclofenac sodium (equivalent to 46.39 mg or 69.58 mg of diclofenac, respectively) surrounded by an outer mantle containing 200 mcg misoprostol.

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 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 include: colloidal silicon dioxide; corn starch; crospovidone; hydrogenated castor oil; hypromellose; lactose monohydrate; magnesium stearate; methacrylic acid copolymer; microcrystalline cellulose; povidone; sodium hydroxide; talc; triethyl citrate. FDA approved dissolution test specifications differ from USP

💬 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 )].

Aler… [Excerpted — this section continues on DailyMed.]

🍼 Nursing Mothers ~2 min read ▾

8.3Females and Males of Reproductive Potential Diclofenac sodium and misoprostol delayed-release tablets are not recommended in women of childbearing potential [see Warnings and Precautions ( 5.1 )] . If diclofenac sodium and misoprostol delayed-release tablets are prescribed, patients must be advised of the abortifacient property and warned not to give the drug to others. Pregnancy Testing Verify pregnancy status for females of reproductive potential within 2 weeks prior to initiating diclofenac sodium and misoprostol delayed-release tablets.

Contraception Females Diclofenac sodium and misoprostol delayed-release tablets can cause fetal harm when administered to a pregnant woman [see Contraindications ( 4 ) and Use in Specific Populations ( 8.1 )]. Advise females of reproductive potential to use effective contraception during treatment with diclofenac sodium and misoprostol delayed-release tablets. Diclofenac sodium and misoprostol delayed-release tablets may be prescribed if the patient: has had a negative serum pregnancy test within 2 weeks prior to beginning therapy. is capable of complying with effective contraceptive measures. has received both oral and written warnings of the hazards of misoprostol, the risk of possible contraception failure, and the danger to other women of childbearing potential should the drug be taken by mistake. will begin diclofenac sodium and misoprostol delayed-release tablets only on the second or third day of the next normal menstrual period .

Advise females to inform their healthcare provider of a known or suspected pregnancy. Infertility Females Based on the mechanism of action, the use of prostaglandin-mediated NSAIDs, including diclofenac, a component of 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 Clinical Pharmacology ( 12.1 )]. Published animal studies have shown that administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation.

Small studies in women treated with NSAIDs have also shown a reversible delay in ovulation. Consider withdrawal of NSAIDs, including diclofenac sodium and misoprostol delayed-release tablets, in women who have difficulties conceiving or who are undergoing investigation of infertility.

🧬 Pharmacokinetics ~3 min read ▾

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 mcg to 400 mcg. Neither diclofenac nor misoprostol accumulated in plasma following repeated doses of diclofenac sodium and misoprostol delayed-release tablets given every 12 hours under fasted conditions. Table 2: Pharmacokinetic Parameters of Diclofenac and Misoprostol Acid Following Single Oral Doses of Diclo fenac Sodium and Misoprostol Delayed-Release Tablets or Separate Products in Healthy Subjects MISOPROSTOL ACID Mean (SD) Treatment (n=36) C max (pg/mL) T max (hr) AUC (0 to 4h) (pg ● hr/mL) Diclofenac sodium and misoprostol delayed-release tablets 50 mg/200 mcg Misoprostol 441 (137) 478 (201) 0.30 (0.13) 0.30 (0.10) 266 (95) 295 (143) Diclofenac sodium and misoprostol delayed-release tablets 75 mg/200 mcg Misoprostol 304 (110) 290 (130) 0.26 (0.09) 0.35 (0.12) 117 (49) 176 (58) DICLOFENAC Mean (SD) Treatment (n=36) C max (ng/mL) T max (hr) AUC (0 to 12h) (ng●hr/mL) Diclofenac sodium and misoprostol delayed-release tablets 50 mg/200 mcg Diclofenac Sodium 1207 (364) 1298 (441) 2.4 (1.0) 2.4 (1.0) 1380 (272) 1357 (290) Diclofenac sodium and misoprostol delayed-release tablets 75 mg/200 mcg Diclofenac Sodium 2025 (2005) 2367 (1318) 2.0 (1.4) 1.9 (0.7) 2773 (1347) 2609 (1185) SD: Standard deviation of the mean; AUC: Area under the curve; C max : Peak concentration; T max : Time to peak concentration Absorption Diclofenac : Diclofenac is completely absorbed from the GI tract after oral administration under fasted condition, and peak plasma levels are achieved in 2 hours (range 1 to 4 hours), and the area under the plasma concentration curve (AUC) is dose-proportional within the range of 25 mg to 150 mg.

Peak plasma levels are less than dose-proportional and are approximately 1.5 and 2 mcg/mL for 50 mg and 75 mg doses, respectively. The diclofenac in diclofenac sodium and misoprostol delayed-release tablets is in a pharmaceutical formulation that resists dissolution in the low pH of gastric fluid but allows a rapid release of drug in the higher pH environment of the duodenum. Only 50% of the absorbed dose is systemically available due to first pass metabolism (i.e., oral bioavailability is 50%).

Misoprostol : Misoprostol is rapidly absorbed following oral administration of diclofenac sodium and misoprostol delayed-release tablets, and misoprostol acid (active metabolite) reaches a maximum plasma concentration in approximately 20 minutes. Maximum plasma concentrations of misoprostol acid are diminished when the dose is taken with food, and total availability of misoprostol acid is reduced by use of concomitant antacid. Clinical trials were conducted with concomitant antacid; this effect does not appear to be clinically important.

Food decreases the multiple-dose bioavailability profile of diclofenac sodium and misoprostol delayed-release tablets 50 mg/200 mcg and diclofenac sodium and misoprostol delayed-release tablets 75 mg/200 mcg. Distribution Diclofenac : The volume of distribution of diclofenac is approximately

0.55L/kg. More than 99% of diclofenac is bound to plasma albumin. Misoprostol : The plasma protein binding of misoprostol acid is less than 90% and is concentration-independent in the therapeutic range. After a single oral dose of misoprostol to nursing mothers, misoprostol acid was excreted in breast milk. The maximum concentration of misoprostol acid in… [Excerpted — this section continues on DailyMed.]

🔬 Clinical Studies ~2 min read ▾

14 CLINICAL STUDIES Osteoarthritis Diclofenac sodium, as a single ingredient or in combination with misoprostol, has been shown to be effective in the management of the signs and symptoms of osteoarthritis. Rheumatoid Arthritis Diclofenac sodium, as a single ingredient or in combination with misoprostol, has been shown to be effective in the management of the signs and symptoms of rheumatoid arthritis. Upper Gastrointestinal Safety Diclofenac, and other NSAIDs, have caused serious gastrointestinal toxicity, such as bleeding, ulceration, and perforation of the stomach, small intestine or large intestine.

Misoprostol has been shown to reduce the incidence of endoscopically diagnosed NSAID-induced gastric and duodenal ulcers. In a 12-week, randomized, double-blind, dose-response study, misoprostol 200 mcg administered four, three or two times a day, was significantly more effective than placebo in reducing the incidence of gastric ulcer in osteoarthritis and rheumatoid arthritis patients using a variety of NSAIDs. The three times a day regimen was therapeutically equivalent to misoprostol 200 mcg four times a day with respect to the prevention of gastric ulcers.

Misoprostol 200 mcg given two times a day was less effective than 200 mcg given three or four times a day. The incidence of NSAID-induced duodenal ulcer was also significantly reduced with all three regimens of misoprostol compared to placebo (see Table 3). Table 3 Misoprostol 200 mcg Dosage Regimen Placebo two times a day three times a day four times a day Gastric ulcer 11% 6%* 3%* 3%* Duodenal ulcer 6% 2%* 3%* 1%* N=1623; 12 weeks *Misoprostol significantly different from placebo (p<0.05) Results of a study in 572 patients with osteoarthritis demonstrate that patients receiving diclofenac sodium and misoprostol delayed-release tablets have a lower incidence of endoscopically defined gastric ulcers compared to patients receiving diclofenac sodium (see Table 4).

Table 4 Osteoarthritis patients with history of ulcer or erosive disease (N=572), 6 weeks Incidence of ulcers Gastric Duodenal Diclofenac sodium and misoprostol delayed-release tablets 50 mg/200 mcg three times a day 3%* 6% Diclofenac sodium and misoprostol delayed-release tablets 75 mg/200 mcg two times a day 4%* 3% Diclofenac sodium 75 mg two times a day 11% 7% Placebo 3% 1% *Statistically significantly different from diclofenac (p<0.05)

🧪 Nonclinical Toxicology ~2 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Long-term animal studies to evaluate the potential for carcinogenesis and animal studies to evaluate the effects on fertility have been performed with each component of diclofenac sodium and misoprostol delayed-release tablets given alone. In a 24 month rat carcinogenicity study, misoprostol administered orally at doses up to 2.4 mg/kg/day (14.4 mg/m 2 /day, 24 times the MRHD of 0.6 mg/m 2 /day) was not tumorigenic. In a 21-month mouse carcinogenicity study, misoprostol administered orally at doses up to 16 mg/kg/day (48 mg/m 2 /day), 80 times the MRHD based on body surface area, was not tumorigenic.

In a 24-month rat carcinogenicity study, diclofenac sodium administered orally at up to 2 mg/kg/day (12 mg/m 2 /day) was not tumorigenic. In a 24-month mouse carcinogenicity study, oral diclofenac sodium at doses up to 0.3 mg/kg/day (0.9 mg/m 2 /day, 0.006 times the MRHD based on body surface area) in males and 1 mg/kg/day (3 mg/m 2 /day, 0.02 times the MRHD based on body surface area) in females was not tumorigenic. Mutagenesis Diclofenac sodium and misoprostol combination in 250:1 ratio was not genotoxic in the Ames test, the Chinese hamster ovary cell (CHO/HGPRT) forward mutation test, the rat lymphocyte chromosome aberration test, or the mouse bone marrow micronucleus test.

Impairment of Fertility The effects of diclofenac sodium and misoprostol on male or female fertility have not been studied in animals; however, there are data with diclofenac sodium and misoprostol given alone. Misoprostol, when administered to male and female breeding rats in an oral dose range of 0.1 to 10 mg/kg/day (0.6 to 60 mg/m 2 /day, 1 to 100 times the MRHD based on body surface area) produced dose-related pre-and post-implantation losses and a significant decrease in the number of live pups born at the highest dose (60 mg/m 2 /day, 100 times the MRHD based on body surface area).

Diclofenac sodium at oral doses up to 4 mg/kg/day (24 mg/m 2 /day, 0.16 times the MRHD based on body surface area) was found to have no effect on fertility and reproductive performance of male and female rats.

13.2Animal Toxicology A reversible increase in the number of normal surface gastric epithelial cells occurred in the dog, rat, and mouse during long-term toxicology studies with misoprostol. No such increase has been observed in humans administered misoprostol for up to 1 year. An apparent response of the female mouse to misoprostol in long-term studies at 100 to 1000 times the human dose was hyperostosis, mainly of the medulla of sternebrae.

Hyperostosis did not occur in long-term studies in the dog and rat and has not been seen in humans treated with misoprostol.

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

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Long-term animal studies to evaluate the potential for carcinogenesis and animal studies to evaluate the effects on fertility have been performed with each component of diclofenac sodium and misoprostol delayed-release tablets given alone. In a 24 month rat carcinogenicity study, misoprostol administered orally at doses up to 2.4 mg/kg/day (14.4 mg/m 2 /day, 24 times the MRHD of 0.6 mg/m 2 /day) was not tumorigenic. In a 21-month mouse carcinogenicity study, misoprostol administered orally at doses up to 16 mg/kg/day (48 mg/m 2 /day), 80 times the MRHD based on body surface area, was not tumorigenic.

In a 24-month rat carcinogenicity study, diclofenac sodium administered orally at up to 2 mg/kg/day (12 mg/m 2 /day) was not tumorigenic. In a 24-month mouse carcinogenicity study, oral diclofenac sodium at doses up to 0.3 mg/kg/day (0.9 mg/m 2 /day, 0.006 times the MRHD based on body surface area) in males and 1 mg/kg/day (3 mg/m 2 /day, 0.02 times the MRHD based on body surface area) in females was not tumorigenic. Mutagenesis Diclofenac sodium and misoprostol combination in 250:1 ratio was not genotoxic in the Ames test, the Chinese hamster ovary cell (CHO/HGPRT) forward mutation test, the rat lymphocyte chromosome aberration test, or the mouse bone marrow micronucleus test.

Impairment of Fertility The effects of diclofenac sodium and misoprostol on male or female fertility have not been studied in animals; however, there are data with diclofenac sodium and misoprostol given alone. Misoprostol, when administered to male and female breeding rats in an oral dose range of 0.1 to 10 mg/kg/day (0.6 to 60 mg/m 2 /day, 1 to 100 times the MRHD based on body surface area) produced dose-related pre-and post-implantation losses and a significant decrease in the number of live pups born at the highest dose (60 mg/m 2 /day, 100 times the MRHD based on body surface area).

Diclofenac sodium at oral doses up to 4 mg/kg/day (24 mg/m 2 /day, 0.16 times the MRHD based on body surface area) was found to have no effect on fertility and reproductive performance of male and female rats.

📄 Recent Major Changes 8 words ▾

Warnings and Precautions, Serious Skin Reactions (5.10) 11/2024

📄 Package Label / Principal Display Panel 65 words ▾

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL NDC 42571-133-60 Rx Only Diclofenac Sodium and Misoprostol Delayed- Release Tablets, USP 50 mg/ 200 mcg Pharmacist: Dispense the enclosed Medication Guide to each patient. 60 Tablets MICRO LABS LIMITED NDC 42571-134-60 Rx Only Diclofenac Sodium and Misoprostol Delayed- Release Tablets, USP 75 mg/ 200 mcg Pharmacist: Dispense the enclosed Medication Guide to each patient. 60Tablets MICRO LABS LIMITED diclo-labla.jpg diclo-lablb.jpg

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

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 tablets42571-0134-60 326 Rx · $24,854
10 tablets42571-0134-29 No Medicaid data
30 tablets42571-0134-30 No Medicaid data
90 tablets this page42571-0134-90 No Medicaid data
Drug total (last 4 qtrs): 326 Rx · 20,937 units · $24,854 gross reimbursed
Tap a pack size to open its page. Source: CMS State Drug Utilization Data, last 4 quarters.

Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Diclofenac Sodium-Misoprostol (matched by generic name) — the program that covers self-administered drugs. 6 manufacturers.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Diclofenac Sodium-Misoprostol. CMS lists 3 products for this generic; we show the highest-spend one. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$958.3K
Claims incl. refills
6.8K
Beneficiaries
4.7K
Spend / beneficiary
$203.59
Spend / claim
$141.40
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

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 Diclofenac Sodium/Misoprostol — the ingredient across all brands.

Top reported reactions

Nausea99
Drug Hypersensitivity98
Fatigue89
Arthralgia85
Malaise85
Pain84
Pain In Extremity84

Age at onset

Child1
Adult46
Elderly25

Reporter sex

436 reports
Male · 14%
Female · 84%
Unknown · 2%

Serious outcomes

Hospitalization109
Life-threatening37
Reports over time (by year) — tap or hover for the count & year
2020 2022 2024 2026 78 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.

About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available.
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Micro Labs Limited. Listing status can change — the directory data on this page refreshes weekly.
Does this product come in other package sizes?
Yes — the FDA directory lists 3 other package presentations of this same product, including 30 tablets (42571-0134-30), 60 tablets (42571-0134-60), 600 tablets (42571-0134-29). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
Micro Labs Limited is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 42571-0133-29 · Micro 42571-0137-25 · Micro →
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.