NDC 61919-608 Diclofenac Sodium E/r

Diclofenac Sodium

NDC Product Code 61919-608

NDC Code: 61919-608

Proprietary Name: Diclofenac Sodium E/r What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Diclofenac Sodium What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.

Product Characteristics

Color(s):
PINK (C48328)
Shape: ROUND (C48348)
Size(s):
9 MM
Imprint(s):
93;1041
Score: 1

NDC Code Structure

  • 61919 - Directrx
    • 61919-608 - Diclofenac Sodium

NDC 61919-608-60

Package Description: 60 TABLET, FILM COATED, EXTENDED RELEASE in 1 BOTTLE

NDC Product Information

Diclofenac Sodium E/r with NDC 61919-608 is a a human prescription drug product labeled by Directrx. The generic name of Diclofenac Sodium E/r is diclofenac sodium. The product's dosage form is tablet, film coated, extended release and is administered via oral form.

Labeler Name: Directrx

Dosage Form: Tablet, Film Coated, Extended Release - A solid dosage form that contains medicinal substances with or without suitable diluents and is coated with a thin layer of a water-insoluble or water-soluble polymer; the tablet is formulated in such manner as to make the contained medicament available over an extended period of time following ingestion.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Diclofenac Sodium E/r Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • DICLOFENAC SODIUM 100 mg/1

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
  • HYPROMELLOSES (UNII: 3NXW29V3WO)
  • ANHYDROUS LACTOSE (UNII: 3SY5LH9PMK)
  • MAGNESIUM STEARATE (UNII: 70097M6I30)
  • ANHYDROUS LACTOSE (UNII: 3SY5LH9PMK)
  • D&C RED NO. 27 (UNII: 2LRS185U6K)
  • POLYETHYLENE GLYCOL, UNSPECIFIED (UNII: 3WJQ0SDW1A)
  • HYDROXYETHYL CELLULOSE (4000 MPA.S AT 1%) (UNII: ZYD53NBL45)
  • ISOPROPYL ALCOHOL (UNII: ND2M416302)
  • POVIDONE (UNII: FZ989GH94E)
  • TALC (UNII: 7SEV7J4R1U)
  • TITANIUM DIOXIDE (UNII: 15FIX9V2JP)
  • TRIACETIN (UNII: XHX3C3X673)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Oral - Administration to or by way of the mouth.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Cyclooxygenase Inhibitors - [MoA] (Mechanism of Action)
  • Decreased Prostaglandin Production - [PE] (Physiologic Effect)
  • Anti-Inflammatory Agents -
  • Non-Steroidal - [CS]
  • Nonsteroidal Anti-inflammatory Drug - [EPC] (Established Pharmacologic Class)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Directrx
Labeler Code: 61919
FDA Application Number: ANDA075492 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: ANDA - A product marketed under an approved Abbreviated New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 04-04-2019 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2020 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

* Please review the disclaimer below.

Information for Patients

Diclofenac

Diclofenac is pronounced as (dye kloe' fen ak)

Why is diclofenac medication prescribed?
Diclofenac capsules (Zipsor, Zorvolex) and tablets (Cataflam) are used to relieve mild to moderate pain. Diclofenac extended-release tablets (Voltaren XR), tablets (Cata...
[Read More]

* Please review the disclaimer below.

Diclofenac Sodium E/r Product Label Images

Diclofenac Sodium E/r Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

Boxed Warning

Cardiovascular Risk - • NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be ...
Cardiovascular Risk•

NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk (see WARNINGS).



Diclofenac Sodium Extended-release Tablets are contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS).
Gastrointestinal Risk•

NSAIDs cause an increased risk of serious gastrointestinal adverse events including inflammation, 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 are at greater risk for serious gastrointestinal events (see WARNINGS).

Other

Rx only

Manufactured by:

Valeant Pharmaceuticals International, Inc.

Steinbach, MB R5G 1Z7

Canada
Distributed by:

Oceanside Pharmaceuticals, a division of

Valeant Pharmaceuticals North America LLC

Bridgewater, NJ 08807 USA
©Valeant Pharmaceuticals North America LLC9493401 20001557Rev. 07/2016

Description

Diclofenac Sodium Extended-release Tablets are a benzeneacetic acid derivative. The chemical name is 2-[(2,6-dichlorophenyl)amino] benzeneacetic acid, monosodium salt. The molecular weight is 318.13. Its molecular formula is C14H10Cl2NNaO2, and it has the following structural formula:[Chemical Structure]Each extended-release tablet for oral administration contains 100 mg of diclofenac sodium, USP. In addition, each tablet contains the following inactive ingredients: anhydrous lactose, colloidal silicon dioxide, D & C Red # 27 (phloxine aluminum lake), hydroxyethyl cellulose, hypromellose, isopropyl alcohol, lactose monohydrate, magnesium stearate, polyethylene glycol, povidone, talc, titanium dioxide, and triacetin.

Clinical Pharmacology

PharmacodynamicsDiclofenac Sodium Extended-release Tablets are a nonsteroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, analgesic, and antipyretic activities in animal models. The mechanism of action of Diclofenac Sodium Extended-release Tablets, like that of other NSAIDs, is not completely understood but may be related to prostaglandin synthetase inhibition.PharmacokineticsAbsorptionDiclofenac is 100% absorbed after oral administration compared to IV administration as measured by urine recovery. However, due to first-pass metabolism, only about 50% of the absorbed dose is systemically available (see Table 1). When Diclofenac Sodium Extended-release Tablets are taken with food, there is a delay of 1 to 2 hours in the Tmax and a two-fold increase in Cmax values. The extent of absorption of diclofenac, however, is not significantly affected by food intake.Table 1. Pharmacokinetic Parameters for Diclofenac

PK Parameter Normal Healthy Adults

(18 to 48 yrs.)

Mean Coefficient of Variation (%)
Absolute

Bioavailability (%)
[N = 7]5540Tmax (hr) [N = 12]5.328Oral Clearance(CL/F; mL/min)

[N = 12]
89556Renal Clearance

(% unchanged drug in urine)

[N = 7]
<1–Apparent Volume of Distribution

(V/F; L/kg) [N = 56]
1.458Terminal Half-life(hr) [N = 56]2.348DistributionThe apparent volume of distribution (V/F) of diclofenac sodium is 1.4 L/kg. Diclofenac is more than 99% bound to human serum proteins, primarily to albumin. Serum protein binding is constant over the concentration range (0.15 to 105 mcg/mL) achieved with recommended doses.Diclofenac diffuses into and out of the synovial fluid. Diffusion into the joint occurs when plasma levels are higher than those in the synovial fluid, after which the process reverses and synovial fluid levels are higher than plasma levels. It is not known whether diffusion into the joint plays a role in the effectiveness of diclofenac.MetabolismFive diclofenac metabolites have been identified in human plasma and urine. The metabolites include 4'-hydroxy-, 5-hydroxy-, 3'-hydroxy-, 4',5-dihydroxy- and 3'-hydroxy-4'-methoxy-diclofenac. The major diclofenac metabolite, 4'-hydroxy-diclofenac, has very weak pharmacologic activity. The formation of 4'-hydroxy diclofenac is primarily mediated by CPY2C9. Both diclofenac and its oxidative metabolites undergo glucuronidation or sulfation followed by biliary excretion. Acylglucuronidation mediated by UGT2B7 and oxidation mediated by CPY2C8 may also play a role in diclofenac metabolism. CYP3A4 is responsible for the formation of minor metabolites, 5-hydroxy- and 3'-hydroxy-diclofenac. In patients with renal dysfunction, peak concentrations of metabolites 4'-hydroxy- and 5-hydroxy-diclofenac were approximately 50% and 4% of the parent compound after single oral dosing compared to 27% and 1% in normal healthy subjects.ExcretionDiclofenac is eliminated through metabolism and subsequent urinary and biliary excretion of the glucuronide and the sulfate conjugates of the metabolites. Little or no free unchanged diclofenac is excreted in the urine. Approximately 65% of the dose is excreted in the urine and approximately 35% in the bile as conjugates of unchanged diclofenac plus metabolites. Because renal elimination is not a significant pathway of elimination for unchanged diclofenac, dosing adjustment in patients with mild to moderate renal dysfunction is not necessary. The terminal half-life of unchanged diclofenac is approximately 2 hours.Drug InteractionsWhen coadministered with voriconazole (inhibitor of CYP2C9, 2C19, and 3A4 enzyme), the Cmax and AUC of diclofenac increased by 114% and 78%, respectively (see PRECAUTIONS, Drug Interactions).Special PopulationsPediatric: The pharmacokinetics of Diclofenac Sodium Extended-release Tablets have not been investigated in pediatric patients.Race: Pharmacokinetic differences due to race have not been identified.Hepatic Insufficiency: Hepatic metabolism accounts for almost 100% of Diclofenac Sodium Extended-release Tablets elimination, so patients with hepatic disease may require reduced doses of Diclofenac Sodium Extended-release Tablets compared to patients with normal hepatic function.Renal Insufficiency: Diclofenac pharmacokinetics has been investigated in subjects with renal insufficiency. No differences in the pharmacokinetics of diclofenac have been detected in studies of patients with renal impairment. In patients with renal impairment (inulin clearance 60 to 90, 30 to 60, and <30 mL/min; N=6 in each group), AUC values and elimination rate were comparable to those in healthy subjects.

Indications & Usage

Carefully consider the potential benefits and risks of Diclofenac Sodium Extended-release Tablets and other treatment options before deciding to use Diclofenac Sodium Extended-release Tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).Diclofenac Sodium Extended-release Tablets are indicated:•

For relief of the signs and symptoms of osteoarthritis



For relief of the signs and symptoms of rheumatoid arthritis

Contraindications

Diclofenac Sodium Extended-release Tablets are contraindicated in patients with known hypersensitivity to diclofenac.Diclofenac Sodium Extended-release Tablets should not be given to patients who have experienced asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients (see WARNINGS, Anaphylactic Reactions, and PRECAUTIONS, Preexisting Asthma).Diclofenac Sodium Extended-release Tablets are contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS).

Warnings

Cardiovascular EffectsCardiovascular Thrombotic EventsClinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal. All NSAIDs, both COX-2 selective and nonselective, may have a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with an NSAID, the lowest effective dose should be used for the shortest duration possible. Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms. Patients should be informed about the signs and/or symptoms of serious CV events and the steps to take if they occur.There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID does increase the risk of serious gastrointestinal events (see WARNINGS, Gastrointestinal (GI) Effects: Risk of GI Ulceration, Bleeding, and Perforation).Two large, controlled, clinical trials of COX-2 selective NSAID for the treatment of pain in the first 10 to14 days following CABG surgery found an increased incidence of myocardial infarction and stroke (see CONTRAINDICATIONS).HypertensionNSAIDs can lead to onset of new hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including Diclofenac Sodium Extended-release Tablets, should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.Congestive Heart Failure and EdemaFluid retention and edema have been observed in some patients taking NSAIDs. Diclofenac Sodium Extended-release Tablets should be used with caution in patients with fluid retention or heart failure.Gastrointestinal (GI) Effects: Risk of GI Ulceration, Bleeding, and PerforationNSAIDs, including Diclofenac Sodium Extended-release Tablets, can cause serious GI adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients, who develop a serious upper GI adverse event on NSAID therapy, is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3 to 6 months and in about 2 to 4% of patients treated for one year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk.NSAIDs should be prescribed with extreme caution in those with a prior history of ulcer disease or gastrointestinal bleeding. Patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding who use NSAIDs have a greater than 10-fold increased risk for developing a GI bleed compared to patients with neither of these risk factors. Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. Most spontaneous reports of fatal GI events are in elderly or debilitated patients and, therefore, special care should be taken in treating this population.To minimize the potential risk for an adverse GI event in patients treated with an NSAID, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of the NSAID until a serious GI adverse event is ruled out. For high risk patients, alternate therapies that do not involve NSAIDs should be considered.Renal EffectsCaution should be used when initiating treatment with Diclofenac Sodium Extended-release Tablets in patients with considerable dehydration.Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a nonsteroidal anti-inflammatory drug may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly. Discontinuation of non-steroidal anti-inflammatory drug (NSAID) therapy is usually followed by recovery to the pretreatment state.Advanced Renal DiseaseNo information is available from controlled clinical studies regarding the use of Diclofenac Sodium Extended-release Tablets in patients with advanced renal disease. Therefore, treatment with Diclofenac Sodium Extended-release Tablets is not recommended in these patients with advanced renal disease. If Diclofenac Sodium Extended-release Tablets therapy must be initiated, close monitoring of the patient's renal function is advisable.Hepatic EffectsElevations of one or more liver tests may occur during therapy with Diclofenac Sodium Extended-release Tablets. These laboratory abnormalities may progress, may remain unchanged, or may be transient with continued therapy. Borderline elevations (i.e., less than 3 times the ULN [ULN = the Upper Limit of the Normal range]), or greater elevations of transaminases occurred in about 15% of diclofenac-treated patients. Of the markers of hepatic function, ALT (SGPT) is recommended for the monitoring of liver injury.In clinical trials, meaningful elevations (i.e., more than 3 times the ULN) of AST (GOT) (ALT was not measured in all studies) occurred in about 2% of approximately 5,700 patients at some time during diclofenac treatment. In a large, open-label, controlled trial of 3,700 patients treated for 2 to 6 months, patients were monitored first at 8 weeks and 1,200 patients were monitored again at 24 weeks. Meaningful elevations of ALT and/or AST occurred in about 4% of patients and included marked elevations (i.e., more than 8 times the ULN) in about 1% of the 3,700 patients. In that open-label study, a higher incidence of borderline (less than 3 times the ULN), moderate (3 to 8 times the ULN), and marked (>8 times the ULN) elevations of ALT or AST was observed in patients receiving diclofenac when compared to other NSAIDs. Elevations in transaminases were seen more frequently in patients with osteoarthritis than in those with rheumatoid arthritis.Almost all meaningful elevations in transaminases were detected before patients became symptomatic. Abnormal tests occurred during the first 2 months of therapy with diclofenac in 42 of the 51 patients in all trials who developed marked transaminase elevations.In postmarketing reports, cases of drug-induced hepatotoxicity have been reported in the first month, and in some cases, the first 2 months of therapy, but can occur at any time during treatment with diclofenac. Postmarketing surveillance has reported cases of severe hepatic reactions, including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure. Some of these reported cases resulted in fatalities or liver transplantation.Physicians should measure transaminases periodically in patients receiving long-term therapy with diclofenac, because severe hepatotoxicity may develop without a prodrome of distinguishing symptoms. The optimum times for making the first and subsequent transaminase measurements are not known. Based on clinical trial data, and postmarketing experiences, transaminases should be monitored within 4 to 8 weeks after initiating treatment with diclofenac. However, severe hepatic reactions can occur at any time during treatment with diclofenac.If abnormal liver tests persist or worsen, if clinical signs and/or symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, abdominal pain, diarrhea, dark urine, etc.), Diclofenac Sodium Extended-release Tablets should be discontinued immediately.To minimize the possibility that hepatic injury will become severe between transaminase measurements, physicians should inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, diarrhea, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms), and the appropriate action patients should take if these signs and symptoms appear.To minimize the potential risk for an adverse liver related event in patients treated with Diclofenac Sodium Extended-release Tablets, the lowest effective dose should be used for the shortest duration possible. Caution should be exercised in prescribing Diclofenac Sodium Extended-release Tablets with concomitant drugs that are known to be potentially hepatotoxic (e.g., antibiotics, anti-epileptics).Anaphylactic ReactionsAs with other NSAIDs, anaphylactic reactions may occur both in patients with the aspirin triad and in patients without known sensitivity to NSAIDs or known prior exposure to Diclofenac Sodium Extended-release Tablets. Diclofenac Sodium Extended-release Tablets should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs (see CONTRAINDICATIONS and PRECAUTIONS, Preexisting Asthma). Anaphylaxis-type reactions have been reported with NSAID products, including with diclofenac products, such as Diclofenac Sodium Extended-release Tablets. Emergency help should be sought in cases where an anaphylactic reaction occurs.Skin ReactionsNSAIDs, including Diclofenac Sodium Extended-release Tablets, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Patients should be informed about the signs and symptoms of serious skin manifestations and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.PregnancyIn late pregnancy, as with other NSAIDs, Diclofenac Sodium Extended-release Tablets should be avoided because it may cause premature closure of the ductus arteriosus.

Precautions

GeneralDiclofenac Sodium Extended-release Tablets cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids.The pharmacological activity of Diclofenac Sodium Extended-release Tablets in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions.Hematological EffectsAnemia is sometimes seen in patients receiving NSAIDs, including Diclofenac Sodium Extended-release Tablets. This may be due to fluid retention, occult or gross GI blood loss, or an incompletely described effect upon erythropoiesis. Patients on long-term treatment with NSAIDs, including Diclofenac Sodium Extended-release Tablets, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia.NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively less, of shorter duration, and reversible. Patients receiving Diclofenac Sodium Extended-release Tablets who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored.Preexisting AsthmaPatients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bronchospasm which can be fatal. Since cross-reactivity, including bronchospasm, between aspirin and other nonsteroidal anti-inflammatory drugs has been reported in such aspirin-sensitive patients, Diclofenac Sodium Extended-release Tablets should not be administered to patients with this form of aspirin sensitivity and should be used with caution in all patients with preexisting asthma.Information for PatientsPatients should be informed of the following information before initiating therapy with an NSAID and periodically during the course of ongoing therapy. Patients should also be encouraged to read the NSAID Medication Guide that accompanies each prescription dispensed.1.

Diclofenac Sodium Extended-release Tablets, like other NSAIDs, may cause serious CV side effects, such as MI or stroke, which may result in hospitalization and even death. Although serious CV events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, weakness, slurring of speech, and should ask for medical advice when observing any indicative sign or symptoms. Patients should be apprised of the importance of this follow-up (see WARNINGS, Cardiovascular Effects).

2.

Diclofenac Sodium Extended-release Tablets, like other NSAIDs, can cause GI discomfort and, rarely, more serious GI side effects, such as ulcers and bleeding, which may result in hospitalization and even death. Although serious GI tract ulcerations and bleeding can occur without warning symptoms, patients should be alert for the signs and symptoms of ulcerations and bleeding, and should ask for medical advice when observing any indicative sign or symptoms including epigastric pain, dyspepsia, melena, and hematemesis. Patients should be apprised of the importance of this follow-up (see WARNINGS, Gastrointestinal (GI) Effects: Risk of GI Ulceration, Bleeding, and Perforation).

3.

Diclofenac Sodium Extended-release Tablets, like other NSAIDS, can cause serious skin side effects such as exfoliative dermatitis, SJS, and TEN, which may result in hospitalizations and even death. Although serious skin reactions may occur without warning, patients should be alert for the signs and symptoms of skin rash and blisters, fever, or other signs of hypersensitivity such as itching, and should ask for medical advice when observing any indicative signs or symptoms. Patients should be advised to stop the drug immediately if they develop any type of rash and contact their physicians as soon as possible.

4.

Patients should promptly report signs or symptoms of unexplained weight gain or edema to their physicians.

5.

Patients should be informed of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). If these occur, patients should be instructed to stop therapy and seek immediate medical therapy (see WARNINGS, Hepatic Effects).

6.

Patients should be informed of the signs of an anaphylactic reaction (e.g., difficulty breathing, swelling of the face or throat). If these occur, patients should be instructed to seek immediate emergency help (see WARNINGS, Anaphylactic Reactions).

7.

In late pregnancy, as with other NSAIDs, Diclofenac Sodium Extended-release Tablets should be avoided because it will cause premature closure of the ductus arteriosus.
Laboratory TestsBecause serious GI tract ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms of GI bleeding. In patients on long-term treatment with NSAIDs, including Diclofenac Sodium Extended-release Tablets, the CBC and a chemistry profile (including transaminase levels) should be checked periodically. If clinical signs and symptoms consistent with liver or renal disease develop, systemic manifestations occur (e.g., eosinophilia, rash, etc.) or if abnormal liver tests persist or worsen, Diclofenac Sodium Extended-release Tablets should be discontinued.Drug InteractionsAspirin: When Diclofenac Sodium Extended-release Tablets are administered with aspirin, its protein binding is reduced. The clinical significance of this interaction is not known; however, as with other NSAIDs, concomitant administration of diclofenac and aspirin is not generally recommended because of the potential of increased adverse effects.Methotrexate: NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. This may indicate that they could enhance the toxicity of methotrexate. Caution should be used when NSAIDs are administered concomitantly with methotrexate.Cyclosporine: Diclofenac Sodium Extended-release Tablets, like other NSAIDs, may affect renal prostaglandins and increase the toxicity of certain drugs. Therefore, concomitant therapy with Diclofenac Sodium Extended-release Tablets may increase cyclosporine's nephrotoxicity. Caution should be used when Diclofenac Sodium Extended-release Tablets are administered concomitantly with cyclosporine.ACE Inhibitors: Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE inhibitors. This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE inhibitors.Furosemide: Clinical studies, as well as postmarketing observations, have shown that Diclofenac Sodium Extended-release Tablets can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition or renal prostaglandin synthesis. During concomitant therapy with NSAIDs, the patient should be observed closely for signs of renal failure (see WARNINGS, Renal Effects), as well as to assure diuretic efficacy.Lithium: NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. The mean minimum lithium concentration increased 15% and the renal clearance was decreased by approximately 20%. These effects have been attributed to inhibition of renal prostaglandin synthesis by the NSAID. Thus, when NSAIDs and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity.Warfarin: The effects of warfarin and NSAIDs on GI bleeding are synergistic, such that users of both drugs together have a risk of serious GI bleeding higher than users of either drug alone.CYP2C9 Inhibitors or Inducers: Diclofenac is metabolized by cytochrome P450 enzymes, predominantly by CYP2C9. Coadministration of diclofenac with CYP2C9 inhibitors (e.g. voriconazole) may enhance the exposure and toxicity of diclofenac whereas coadministration with CYP2C9 inducers (e.g. rifampin) may lead to compromised efficacy of diclofenac. Use caution when dosing diclofenac with CYP2C9 inhibitors or inducers, a dosage adjustment may be warranted (see CLINICAL PHARMACOLOGY, Pharmacokinetics, Drug Interactions).PregnancyTeratogenic Effects: Pregnancy Category CReproductive studies conducted in rats and rabbits have not demonstrated evidence of developmental abnormalities. However, animal reproduction studies are not always predictive of human response. There are no adequate and well-controlled studies in pregnant women.Nonteratogenic EffectsBecause of the known effects of nonsteroidal anti-inflammatory drugs on the fetal cardiovascular system (closure of ductus arteriosus), use during pregnancy (particularly late pregnancy) should be avoided.Labor and DeliveryIn rat studies with NSAIDs, as with other drugs known to inhibit prostaglandin synthesis, an increased incidence of dystocia, delayed parturition, and decreased pup survival occurred. The effects of Diclofenac Sodium Extended-release Tablets on labor and delivery in pregnant women are unknown.Nursing MothersIt is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Diclofenac Sodium Extended-release Tablets, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.Pediatric UseSafety and effectiveness in pediatric patients have not been established.Geriatric UseAs with any NSAIDs, caution should be exercised in treating the elderly (65 years and older).

Adverse Reactions

In patients taking Diclofenac Sodium Extended-release Tablets or other NSAIDs, the most frequently reported adverse experiences occurring in approximately 1% to 10% of patients are:Gastrointestinal experiences including: abdominal pain, constipation, diarrhea, dyspepsia, flatulence, gross bleeding/perforation, heartburn, nausea, GI ulcers (gastric/duodenal) and vomiting.Abnormal renal function, anemia, dizziness, edema, elevated liver enzymes, headaches, increased bleeding time, pruritus, rashes and tinnitus.Additional adverse experiences reported occasionally include:Body as a Whole: fever, infection, sepsisCardiovascular System: congestive heart failure, hypertension, tachycardia, syncopeDigestive System: dry mouth, esophagitis, gastric/peptic ulcers, gastritis, gastrointestinal bleeding, glossitis, hematemesis, hepatitis, jaundiceHemic and Lymphatic System: ecchymosis, eosinophilia, leukopenia, melena, purpura, rectal bleeding, stomatitis, thrombocytopeniaMetabolic and Nutritional: weight changesNervous System: anxiety, asthenia, confusion, depression, dream abnormalities, drowsiness, insomnia, malaise, nervousness, paresthesia, somnolence, tremors, vertigoRespiratory System: asthma, dyspneaSkin and Appendages: alopecia, photosensitivity, sweating increasedSpecial Senses: blurred visionUrogenital System: cystitis, dysuria, hematuria, interstitial nephritis, oliguria/polyuria, proteinuria, renal failureOther adverse reactions, which occur rarely are:Body as a Whole: anaphylactic reactions, appetite changes, deathCardiovascular System: arrhythmia, hypotension, myocardial infarction, palpitations, vasculitisDigestive System: colitis, eructation, fulminant hepatitis with and without jaundice, liver failure, liver necrosis, pancreatitisHemic and Lymphatic System: agranulocytosis, hemolytic anemia, aplastic anemia, lymphadenopathy, pancytopeniaMetabolic and Nutritional: hyperglycemiaNervous System: convulsions, coma, hallucinations, meningitisRespiratory System: respiratory depression, pneumoniaSkin and Appendages: angioedema, toxic epidermal necrolysis, erythema multiforme, exfoliative dermatitis, Stevens-Johnson Syndrome, urticariaSpecial Senses: conjunctivitis, hearing impairmentTo report SUSPECTED ADVERSE REACTIONS, contact Oceanside Pharmaceuticals, a division of Valeant Pharmaceuticals North America LLC, at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Overdosage

Symptoms following acute NSAID overdoses are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which are generally reversible with supportive care. Gastrointestinal bleeding can occur. Hypertension, acute renal failure, respiratory depression and coma may occur, but are rare. Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDs, and may occur following an overdose.Patients should be managed by symptomatic and supportive care following a NSAID overdose. There are no specific antidotes. Emesis and/or activated charcoal (60 to 100 g in adults, 1 to 2 g/kg in children) and/or osmotic cathartic may be indicated in patients seen within 4 hours of ingestion with symptoms or following a large overdose (5 to 10 times the usual dose). Forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion may not be useful due to high protein binding.

Dosage & Administration

Carefully consider the potential benefits and risks of Diclofenac Sodium Extended-release Tablets and other treatment options before deciding to use Diclofenac Sodium Extended-release Tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).After observing the response to initial therapy with Diclofenac Sodium Extended-release Tablets, the dose and frequency should be adjusted to suit an individual patient's needs.For the relief of osteoarthritis, the recommended dosage is 100 mg q.d.For the relief of rheumatoid arthritis, the recommended dosage is 100 mg q.d. In the rare patient where Diclofenac Sodium Extended-release Tablets 100 mg/day is unsatisfactory, the dose may be increased to 100 mg b.i.d. if the benefits outweigh the clinical risks of increased side effects.Different formulations of diclofenac [diclofenac sodium enteric-coated tablets; diclofenac sodium extended-release tablets; diclofenac potassium immediate-release tablets] are not necessarily bioequivalent even if the milligram strength is the same.

How Supplied

Diclofenac Sodium Extended-release Tablets

100 mg - unscored, pink, round film coated tablets, engraved with "93" on one side and "1041" on the other side.
NDC 68682-103-01 – Bottles of 100Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].Protect from moisture.Dispense in tight container (USP).

Spl Medguide

DICLOFENAC (dye-KLOE-fen-ak)(See the end of this Medication Guide for a list of prescription NSAID medicines.)What is the most important information I should know about medicines called Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?NSAID medicines may increase the chance of a heart attack or stroke that can lead to death. This chance increases:•

with longer use of NSAID medicines



in people who have heart disease
NSAID medicines should never be used right before or after a heart surgery called a "coronary artery bypass graft (CABG)."NSAID medicines can cause ulcers and bleeding in the stomach and intestines at any time during treatment. Ulcers and bleeding:•

can happen without warning symptoms



may cause death
The chance of a person getting an ulcer or bleeding increases with:•

taking medicines called "corticosteroids" and "anticoagulants"



longer use



smoking



drinking alcohol



older age



having poor health
NSAID medicines should only be used:•

exactly as prescribed



at the lowest dose possible for your treatment



for the shortest time needed
What are Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?NSAID medicines are used to treat pain and redness, swelling, and heat (inflammation) from medical conditions such as:•

different types of arthritis



menstrual cramps and other types of short-term pain
Who should not take a Non-Steroidal Anti-Inflammatory Drug (NSAID)?Do not take an NSAID medicine:•

if you had an asthma attack, hives, or other allergic reaction with aspirin or any other NSAID medicine



for pain right before or after heart bypass surgery
Tell your healthcare provider:•

about all your medical conditions.



about all of the medicines you take. NSAIDs and some other medicines can interact with each other and cause serious side effects. Keep a list of your medicines to show to your healthcare provider and pharmacist.



if you are pregnant. NSAID medicines should not be used by pregnant women late in their pregnancy.



if you are breastfeeding. Talk to your doctor.
What are the possible side effects of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?Serious side effects include:•

heart attack



stroke



high blood pressure



heart failure from body swelling (fluid retention)



kidney problems including kidney failure



bleeding and ulcers in the stomach and intestine



low red blood cells (anemia)



life-threatening skin reactions



life-threatening allergic reactions



liver problems including liver failure



asthma attacks in people who have asthma
Other side effects include:•

stomach pain



constipation



diarrhea



gas



heartburn



nausea



vomiting



dizziness
Get emergency help right away if you have any of the following symptoms:•

shortness of breath or trouble breathing



chest pain



weakness in one part or side of your body



slurred speech



swelling of the face or throat
Stop your NSAID medicine and call your healthcare provider right away if you have any of the following symptoms:•

nausea



more tired or weaker than usual



itching



your skin or eyes look yellow



stomach pain



flu-like symptoms



vomit blood



there is blood in your bowel movement or it is black and sticky like tar



unusual weight gain



skin rash or blisters with fever



swelling of the arms and legs, hands and feet
These are not all the side effects with NSAID medicines. Talk to your healthcare provider or pharmacist for more information about NSAID medicines. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.Other information about Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)•

Aspirin is an NSAID medicine but it does not increase the chance of a heart attack. Aspirin can cause bleeding in the brain, stomach, and intestines. Aspirin can also cause ulcers in the stomach and intestines.



Some of these NSAID medicines are sold in lower doses without a prescription (over-the-counter). Talk to your healthcare provider before using over-the-counter NSAIDs for more than 10 days.
NSAID medicines that need a prescriptionGeneric Name Tradename*

Vicoprofen contains the same dose of ibuprofen as over-the-counter (OTC) NSAIDs, and is usually used for less than 10 days to treat pain. The OTC NSAID label warns that long-term continuous use may increase the risk for heart attack or stroke.
CelecoxibCelebrexDiclofenacCataflam, Voltaren, Arthrotec (combined with misoprostol)DiflunisalDolobidEtodolacLodine, Lodine XLFenoprofenNalfon, Nalfon 200FlurbiprofenAnsaidIbuprofenMotrin, Tab-Profen, Vicoprofen* (combined with hydrocodone), Combunox (combined with oxycodone)IndomethacinIndocin, Indocin SR, Indo-Lemmon, IndomethaganKetoprofenOruvailKetorolacToradolMefenamic AcidPonstelMeloxicamMobicNabumetoneRelafenNaproxenNaprosyn, Anaprox, Anaprox DS, EC-Naprosyn, Naprelan, Naprapac (copackaged with lansoprazole)OxaprozinDayproPiroxicamFeldeneSulindacClinorilTolmetinTolectin, Tolectin DS, Tolectin 600This Medication Guide has been approved by the U.S. Food and Drug Administration.All other product/brand names are trademarks of their respective owners.Revised: 07/2016

* Please review the disclaimer below.

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