Diclofenac Sodium

INDICATIONS AND USAGE Carefully consider the potential benefits and risks of diclofenac sodium extended release tablets, USP 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; Gastrointestinal Bleeding, Ulceration, and Perforation ) . 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

DOSAGE AND ADMINISTRATION Carefully consider the potential benefits and risks of diclofenac sodium extended-release tablets, USP 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 daily. For the relief of rheumatoid arthritis, the recommended dosage is 100 mg daily. In the rare patient where diclofenac sodium extended-release tablets 100 mg/day are unsatisfactory, the dose may be increased to 100 mg twice a day 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, USP, diclofenac potassium immediate-release tablets) are not necessarily bioequivalent even if the milligram strength is the same.

CONTRAINDICATIONS Diclofenac sodium extended-release tablets, USP are contraindicated in the following patients: • Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to diclofenac or any components of the drug product ( see WARNINGS; Anaphylactic Reactions, Serious Skin Reactions ). • History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactice reactions to NSAIDs have been reported in such patients ( see WARNINGS; Anaphylactic Reactions , PRECAUTIONS; Exacerbation of Asthma Related to Aspirin Sensitivity ) . • In the setting of coronary artery bypass graft (CABG) surgery ( see WARNINGS; Cardiovascular Thrombotic Events ).

ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: • Cardiovascular Thrombotic Events (see WARNINGS ) • GI Bleeding, Ulceration and Perforation (see WARNINGS ) • Hepatotoxicity (see WARNINGS ) • Hypertension (see WARNINGS ) • Heart Failure and Edema (see WARNINGS ) • Renal Toxicity and Hyperkalemia (see WARNINGS ) • Anaphylactic Reactions (see WARNINGS ) • Serious Skin Reactions (see WARNINGS ) • Hematologic Toxicity (see WARNINGS ) Clinical 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. In patients taking diclofenac sodium extended-release tablets, USP 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, sepsis Cardiovascular System: congestive heart failure, hypertension, tachycardia, syncope Digestive System: dry mouth, esophagitis, gastric/peptic ulcers, gastritis, gastrointestinal bleeding, glossitis, hematemesis, hepatitis, jaundice Hemic and Lymphatic System: ecchymosis, eosinophilia, leukopenia, melena, purpura, rectal bleeding, stomatitis, thrombocytopenia Metabolic and Nutritional: weight changes Nervous System: anxiety, asthenia, confusion, depression, dream abnormalities, drowsiness, insomnia, malaise, nervousness, paresthesia, somnolence, tremors, vertigo Respiratory System: asthma, dyspnea Skin and Appendages: alopecia, photosensitivity, sweating increased Special Senses: blurred vision Urogenital System: cystitis, dysuria, hematuria, interstitial nephritis, oliguria/polyuria, proteinuria, renal failure. Other adverse reactions, which occur rarely are: Body as a Whole: anaphylactic reactions, appetite changes, death Cardiovascular System: arrhythmia, hypotension, myocardial infarction, palpitations, vasculitis Digestive System: colitis, eructation, fulminant hepatitis with and without jaundice, liver failure, liver necrosis, pancreatitis Hemic and Lymphatic System: agranulocytosis, hemolytic anemia, aplastic anemia, lymphadenopathy, pancytopenia Metabolic and Nutritional: hyperglycemia Nervous System: convulsions, coma, hallucinations, meningitis Respiratory System: respiratory depression, pneumonia Skin and Appendages: angioedema, toxic epidermal necrolysis, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, fixed drug eruption (FDE), urticaria Special Senses: conjunctivitis, hearing impairment. To report SUSPECTED ADVERSE EVENTS, contact Edenbridge Pharmaceuticals, LLC at 877-381-3336 or FDA at 1-800-FDA- 1088 or http://www.fda.gov/medwatch for voluntary reporting of adverse reactions.

Drug Interactions See Table 2 for clinically significant drug interactions with diclofenac. Table 2. Clinically Significant Drug Interactions with Diclofenac 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 extended-release tablets with anticoagulants (e.g., warfarin), antiplatelet agents (e.g., aspirin), selective serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs) for signs of bleeding (see WARNINGS; Hematological Toxicity ) . 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; Gastrointestinal Bleeding, Ulceration, and Perforation ) . Intervention: Concomitant use of diclofenac sodium extended-release tablets and analgesic doses of aspirin is not generally recommended because of the increased risk of bleeding (see WARNINGS; Hematological Toxicity ) . Diclofenac sodium extended-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 angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or beta-blockers (including propranolol). • In patients who are elderly, volume-depleted (including those on diuretic therapy), or have renal impairment, coadministration 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: • During concomitant use of diclofenac sodium extended-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 extended-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; Renal Toxicity and Hyperkalemia ) . • When these drugs are administered concomitantly, patients should be adequately hydrated. Assess renal function at the beginning of the concomitant treatment and periodically thereafter. 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 NSAIDinhibition of renal prostaglandin synthesis. Intervention: During concomitant use of diclofenac sodium extended-release tablets with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy, including antihypertensive effects (see WARNINGS; Renal Toxicity and Hyperkalemia ) . 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 extended-release tablets and digoxin, monitor serum digoxin levels. Lithium Clinical Impact: NSAIDs have produced elevat …

DESCRIPTION Diclofenac sodium extended-release tablets, USP is a benzeneacetic acid derivative. Diclofenac sodium extended-release tablets of 100 mg (pink) are available for oral administration. Diclofenac sodium is a white or slightly yellowish crystalline powder and is sparingly soluble in water at 25°C. The chemical name is 2-[(2,6-dichlorophenyl)amino] benzeneacetic acid, monosodium salt. The molecular weight is 318.14. Its molecular formula is C 14 H 10 Cl 2 NNaO 2, and it has the following structural formula: The inactive ingredients in diclofenac sodium extended-release tablets include: carnauba wax, cetostearyl alcohol, colloidal silicon dioxide, compressible sugar, copovidone, gum acacia, hydroxypropyl methylcellulose, iron oxide red, magnesium stearate, polyethylene glycol, povidone, sugar, talc, titanium dioxide. Meets USP Dissolution Test 2. Structural Formula

OVERDOSAGE 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; Cardiovascular Thrombotic Events, Gastrointestinal Bleeding, Ulceration, and Perforation, Hypertension, Renal Toxicity and Hyperkalemia ) . Manage patients with symptomatic and supportive care following an NSAID overdosage. There are no specific antidotes. Consider emesis and/or activated charcoal (60 to 100 grams in adults, 1 to 2 grams per kg in pediatric patients) and/or osmotic cathartic in symptomatic patients seen within four hours of ingestion or in patients with a large overdose (5 to 10 times the recommended dosage). Forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion may not be useful due to high protein binding. For additional information about overdosage treatment contact a poison control center (1-800-222-1222).

HOW SUPPLIED Diclofenac sodium extended-release tablets, USP 100 mg - Pink round convex film coated tablet debossed with DX 41 on one side. Bottle of 100 NDC 42799-953-01. Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Protect from moisture. Dispense in tight container (USP). Manufactured for: Edenbridge Pharmaceuticals, LLC DBA Dexcel Pharma USA Parsippany, NJ 07054 877-381-3336 Manufactured by: Dexcel Pharma Technologies Ltd., Israel Revised: 02/2025