FDA label 3a385119-a61a-4bc5-be3a-8403b1c4ae4e

WARNINGS Risk of GI Ulceration, Bleeding and Perforation with NSAID Therapy Serious gastrointestinal toxicity, such as bleeding, ulceration, and perforation, can occur at any time, with or without warning symptoms, in patients treated chronically with NSAID therapy. Although minor upper gastrointestinal problems, such as dyspepsia, are common, usually developing early in therapy, physicians should remain alert for ulceration and bleeding in patients treated chronically with NSAIDs even in the absence of previous GI tract symptoms. In patients observed in clinical trials of several months to two years duration, symptomatic upper GI ulcers, gross bleeding or perforation appear to occur in approximately 1% of patients treated for 3 to 6 months, and in about 2% to 4% of patients treated for one year. Physicians should inform patients about the signs and/or symptoms of serious GI toxicity and what steps to take if they occur. Studies to date have not identified any subset of patients not at risk of developing peptic ulceration and bleeding. Except for a prior history of serious GI events and other risk factors known to be associated with peptic ulcer disease, such as alcoholism, smoking, etc., no risk factors (e.g., age, sex) have been associated with increased risk. Elderly or debilitated patients seem to tolerate ulceration or bleeding less well than other individuals, and most spontaneous reports of fatal GI events are in this population. Studies to date are inconclusive concerning the relative risk of various NSAIDs in causing such reactions. High doses of any NSAID probably carry a greater risk of these reactions, although controlled clinical trials showing this do not exist in most cases. In considering the use of relatively large doses (within the recommended dosage range), sufficient benefit should be anticipated to offset the potential increased risk of GI toxicity.

ADVERSE REACTIONS Incidence Greater Than 1% The following adverse reactions were observed in clinical trials and included observations from more than 2,700 patients, 594 of whom were treated for one year and 248 for at least two years. Gastrointestinal: The most frequently reported adverse reactions associated with meclofenamate sodium involve the gastrointestinal system. In controlled studies of up to six months duration, these disturbances occurred in the following decreasing order of frequency with the approximate incidences in parentheses: diarrhea (10% to 33%), nausea with or without vomiting (11%), other gastrointestinal disorders (10%), and abdominal pain. In long-term uncontrolled studies of up to four years duration, one third of the patients had at least one episode of diarrhea some time during meclofenamate sodium therapy. In approximately 4% of the patients in controlled studies, diarrhea was severe enough to require discontinuation of meclofenamate sodium. The occurrence of diarrhea is dose related, generally subsides with dose reduction, and clears with termination of therapy. The incidence of diarrhea in patients with osteoarthritis is generally lower than that reported in patients with rheumatoid arthritis. Other reactions less frequently reported were pyrosis 1 , flatulence 1 , anorexia, constipation, stomatitis, and peptic ulcer. The majority of the patients with peptic ulcer had either a history of ulcer disease or were receiving concomitant anti-inflammatory drugs, including corticosteroids which are known to produce peptic ulceration. Cardiovascular: edema Dermatologic: rash 1 , urticaria, pruritus Central Nervous System: headache 1 , dizziness 1 Special Senses: tinnitus Incidence Less Than 1%—Probably Causally Related The following adverse reactions were reported less frequently than 1% during controlled clinical trials and through voluntary reports since marketing. The probability of a causal relationship exists between the drug and these adverse reactions. Gastrointestinal: bleeding and/or perforation with or without obvious ulcer formation, colitis, cholestatic jaundice Renal: renal failure Hematologic: neutropenia, thrombocytopenic purpura, leukopenia, agranulocytosis, hemolytic anemia, eosinophilia, decrease in hemoglobin and/or hematocrit Dermatologic: erythema multiforme, Stevens-Johnson Syndrome, exfoliative dermatitis Hepatic: alteration of liver function tests Allergic: lupus and serum sickness-like symptoms Incidence Less Than 1%—Causal Relationship Unknown Other reactions have been reported but under conditions where a causal relationship could not be established. However, in these rarely reported events, that possibility cannot be excluded. Therefore, these observations are listed to alert physicians. Cardiovascular: palpitations Central Nervous System: malaise, fatigue, paresthesia, insomnia, depression Special Senses: blurred vision, taste disturbances, decreased visual acuity, temporary loss of vision, reversible loss of color vision, retinal changes including macular fibrosis, macular and perimacular edema, conjunctivitis, iritis Renal: nocturia Gastrointestinal: paralytic ileus Dermatologic: erythema nodosum, hair loss