SULINDAC

INDICATIONS AND USAGE Carefully consider the potential benefits and risks of sulindac and other treatment options before deciding to use sulindac. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS ). Sulindac is indicated for acute or long-term use in the relief of signs and symptoms of the following: 1. Osteoarthritis 2. Rheumatoid arthritis** 3. Ankylosing spondylitis 4. Acute painful shoulder (Acute subacromial bursitis/supraspinatus tendinitis) 5. Acute gouty arthritis **The safety and effectiveness of sulindac tablets USP have not been established in rheumatoid arthritis patients who are designated in the American Rheumatism Association classification as Functional Class IV (incapacitated, largely or wholly bedridden, or confined to wheelchair, little or no self-care).

DOSAGE AND ADMINISTRATION Carefully consider the potential benefits and risks of sulindac tablets and other treatment options before deciding to use sulindac 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 sulindac tablets, the dose and frequency should be adjusted to suit an individual patient's needs. Sulindac tablets should be administered orally twice a day with food. The maximum dosage is 400 mg per day. Dosages above 400 mg per day are not recommended. In osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis, the recommended starting dosage is 150 mg twice a day. The dosage may be lowered or raised depending on the response. A prompt response (within one week) can be expected in about one-half of patients with osteoarthritis, ankylosing spondylitis, and rheumatoid arthritis. Others may require longer to respond. In acute painful shoulder (acute subacromial bursitis/supraspinatus tendinitis) and acute gouty arthritis, the recommended dosage is 200 mg twice a day. After a satisfactory response has been achieved, the dosage may be reduced according to the response. In acute painful shoulder, therapy for 7–14 days is usually adequate. In acute gouty arthritis, therapy for 7 days is usually adequate. **Incidence between 3% and 9%. Those reactions occurring in 1% to 3% of patients are not marked with an asterisk.

CONTRAINDICATIONS Sulindac is contraindicated in patients with known hypersensitivity to sulindac or the excipients (see DESCRIPTION ). Sulindac should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic/anaphylactoid reactions to NSAIDs have been reported in such patients (see WARNINGS – Anaphylactic/Anaphylactoid Reactions , and PRECAUTIONS – Preexisting Asthma ). Sulindac is contraindicated in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS ).

ADVERSE REACTIONS The following adverse reactions were reported in clinical trials or have been reported since the drug was marketed. The probability exists of a causal relationship between sulindac and these adverse reactions. The adverse reactions which have been observed in clinical trials encompass observations in 1,865 patients, including 232 observed for at least 48 weeks. Incidence Greater Than 1% Gastrointestinal The most frequent types of adverse reactions occurring with sulindac are gastrointestinal; these include gastrointestinal pain (10%), dyspepsia***, nausea*** with or without vomiting, diarrhea***, constipation***, flatulence, anorexia and gastrointestinal cramps. Dermatologic Rash***, pruritus. Central Nervous System Dizziness***, headache***, nervousness. *** Incidence between 3% and 9%. Those reactions occurring in 1% to 3% of patients are not marked with an asterisk. Special Senses Tinnitus. Miscellaneous Edema (see WARNINGS ). Incidence Less Than 1 in 100 Gastrointestinal Gastritis, gastroenteritis or colitis. Peptic ulcer and gastrointestinal bleeding have been reported. GI perforation and intestinal strictures (diaphragms) have been reported rarely. Liver function abnormalities; jaundice, sometimes with fever; cholestasis; hepatitis; hepatic failure. There have been rare reports of sulindac metabolites in common bile duct “sludge” and in biliary calculi in patients with symptoms of cholecystitis who underwent a cholecystectomy. Pancreatitis (see PRECAUTIONS ). Ageusia; glossitis. Dermatologic Stomatitis, sore or dry mucous membranes, alopecia, photosensitivity. Erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, fixed drug eruption (FDE), and exfoliative dermatitis have been reported. Cardiovascular Congestive heart failure, especially in patients with marginal cardiac function; palpitation; hypertension. Hematologic Thrombocytopenia; ecchymosis; purpura; leukopenia; agranulocytosis; neutropenia; bone marrow depression, including aplastic anemia; hemolytic anemia; increased prothrombin time in patients on oral anticoagulants (see PRECAUTIONS ). Genitourinary Urine discoloration; dysuria; vaginal bleeding; hematuria; proteinuria; crystalluria; renal impairment, including renal failure; interstitial nephritis; nephrotic syndrome. Renal calculi containing sulindac metabolites have been observed rarely. Metabolic Hyperkalemia. Musculoskeletal Muscle weakness. Psychiatric Depression; psychic disturbances including acute psychosis. Nervous System Vertigo; insomnia; somnolence; paresthesia; convulsions; syncope; aseptic meningitis (especially in patients with systemic lupus erythematosus (SLE) and mixed connective tissue disease, see PRECAUTIONS ). Special Senses Blurred vision; visual disturbances; decreased hearing; metallic or bitter taste. Respiratory Epistaxis. Hypersensitivity Reactions Anaphylaxis; angioneurotic edema; urticaria; bronchial spasm; dyspnea. Hypersensitivity vasculitis. A potentially fatal apparent hypersensitivity syndrome has been reported. This syndrome may include constitutional symptoms (fever, chills, diaphoresis, flushing), cutaneous findings (rash or other dermatologic reactions — see above), conjunctivitis, involvement of major organs (changes in liver functions including hepatic failure, jaundice, pancreatitis, pneumonitis with or without pleural effusion, leukopenia, leukocytosis, eosinophilia, disseminated intravascular coagulation, anemia, renal impairment, including renal failure), and other less specific findings (adenitis, arthralgia, arthritis, myalgia, fatigue, malaise, hypotension, chest pain, tachycardia). Causal Relationship Unknown A rare occurrence of fulminant necrotizing fasciitis, particularly in association with Group A β-hemolytic streptococcus, has been described in persons treated with non-steroidal anti-inflammatory agents, sometimes with fatal outcome (see also PRECAUTIONS, General ). Other reactions have been reported in clinical trial …

Drug Interactions ACE-Inhibitors and Angiotensin II Antagonists Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors and angiotensin II antagonists. These interactions should be given consideration in patients taking NSAIDs concomitantly with ACE-inhibitors or angiotensin II antagonists. In some patients with compromised renal function (e.g., elderly patients or patients who are volume-depleted, including those on diuretic therapy) who are being treated with non-steroidal anti-inflammatory drugs, the co-administration of an NSAID and an ACE-inhibitor or an angiotensin II antagonist may result in further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, monitor renal function periodically in patients receiving ACEIs or AIIAs and NSAIDs in combination therapy. Acetaminophen Acetaminophen had no effect on the plasma levels of sulindac or its sulfide metabolite. Aspirin The concomitant administration of aspirin with sulindac significantly depressed the plasma levels of the active sulfide metabolite. A double-blind study compared the safety and efficacy of sulindac tablets 300 or 400 mg daily given alone or with aspirin 2.4 g/day for the treatment of osteoarthritis. The addition of aspirin did not alter the types of clinical or laboratory adverse experiences for sulindac tablets; however, the combination showed an increase in the incidence of gastrointestinal adverse experiences. Since the addition of aspirin did not have a favorable effect on the therapeutic response to sulindac tablets, the combination is not recommended. Cyclosporine Administration of non-steroidal anti-inflammatory drugs concomitantly with cyclosporine has been associated with an increase in cyclosporine-induced toxicity, possibly due to decreased synthesis of renal prostacyclin. NSAIDs should be used with caution in patients taking cyclosporine, and renal function should be carefully monitored. Diflunisal The concomitant administration of sulindac tablets and diflunisal in normal volunteers resulted in lowering of the plasma levels of the active sulindac sulfide metabolite by approximately one-third. Diuretics Clinical studies, as well as post marketing observations, have shown that sulindac tablets can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of 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. DMSO DMSO should not be used with sulindac. Concomitant administration has been reported to reduce the plasma levels of the active sulfide metabolite and potentially reduce efficacy. In addition, this combination has been reported to cause peripheral neuropathy. 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. 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. NSAIDs The concomitant use of sulindac tablets with other NSAIDs is not recommended due to the increased possibility of gastrointestinal toxicity, with little or no increase in efficacy. Oral anticoagulants Although sulindac and its sulfide metabolite are highly bound to protein, studies in which sulindac tablets were given at a dose of 400 mg daily have shown no clinic …

DESCRIPTION Sulindac is a non-steroidal, anti-inflammatory indene derivative designated chemically as (Z)-5-fluoro-2-methyl-1- [[p-(methylsulfinyl) phenyl]methylene] -1 H -indene-3-acetic acid. It is not a salicylate, pyrazolone or propionic acid derivative. Its empirical formula is C 20 H 17 FO 3 S, with a molecular weight of 356.42. Sulindac, a yellow crystalline compound, is a weak organic acid practically insoluble in water below pH 4.5, but very soluble as the sodium salt or in buffers of pH 6 or higher. Sulindac is available in 150 and 200 mg tablets for oral administration. Each tablet contains the following inactive ingredients: magnesium stearate, microcrystalline cellulose, plasdone and sodium starch glycolate. Following absorption, sulindac undergoes two major biotransformations - reversible reduction to the sulfide metabolite, and irreversible oxidation to the sulfone metabolite. Available evidence indicates that the biological activity resides with the sulfide metabolite. The structural formulas of sulindac and its metabolites are: structural-formula

MANAGEMENT OF OVERDOSAGE Cases of overdosage have been reported and rarely, deaths have occurred. The following signs and symptoms may be observed following overdosage: stupor, coma, diminished urine output and hypotension. In the event of overdosage, the stomach should be emptied by inducing vomiting or by gastric lavage, and the patient carefully observed and given symptomatic and supportive treatment. Animal studies show that absorption is decreased by the prompt administration of activated charcoal and excretion is enhanced by alkalinization of the urine.

HOW SUPPLIED Sulindac Tablets USP, 150 mg are yellow, round tablets, bisected and debossed with “Є” to the left of bisect and “10” to the right of bisect on one side, and plain on the other side. They are supplied as follows: NDC 42806-018-01 in bottles of 100. NDC 42806-018-05 in bottles of 500. NDC 42806-018-10 in bottles of 1000. Sulindac Tablets USP, 200 mg are yellow, oval-shaped tablets, bisected and debossed with “Є” to the left of bisect and “11” to the right of bisect on one side, and plain on the other side. They are supplied as follows: NDC 42806-011-01 in bottles of 100. NDC 42806-011-05 in bottles of 500. NDC 42806-011-10 in bottles of 1000. Storage Store in a well-closed container at 20° to 25° C (68 to 77° F) [See USP Controlled Room Temperature]. Dispense with Medication Guide available at: www.epic-pharma.com/medguide/Sulindac-Tablet.pdf Manufactured by: Epic Pharma, LLC Laurelton, NY 11413 Manufactured in USA Rev.07-2024-00 MF018REV07/24 OE1000