meclofenamate sodium

INDICATIONS AND USAGE Carefully consider the potential benefits and risks of meclofenamate sodium capsules and other treatment options before deciding to use meclofenamate sodium capsules. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS ). Meclofenamate sodium capsules are indicated: • For reduction of fever in adults • For relief of mild to moderate pain in adults • For relief of signs and symptoms of juvenile arthritis. • For relief of the signs and symptoms of rheumatoid arthritis • For relief of the signs and symptoms of osteoarthritis. • For treatment of primary dysmenorrhea. • For acute or long-term use in the relief of signs and symptoms of the following: 1. Ankylosing spondylitis 2. Acute painful shoulder (Acute subacromial bursitis/supraspinatus tendinitis) 3. Acute gouty arthritis Meclofenamate sodium capsules are also indicated for the treatment of idiopathic heavy menstrual blood loss (see CLINICAL PHARMACOLOGY and PRECAUTIONS ). As with all nonsteroidal anti-inflammatory drugs, selection of meclofenamate sodium capsules require a careful assessment of the benefit/risk ratio (see WARNINGS , PRECAUTIONS and ADVERSE REACTIONS ). Meclofenamate sodium capsules are not recommended in children because adequate studies to demonstrate safety and efficacy have not been carried out.

DOSAGE AND ADMINISTRATION Carefully consider the potential benefits and risks of meclofenamate sodium capsules and other treatment options before deciding to use meclofenamate sodium capsules. 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 meclofenamate sodium capsules, the dose and frequency should be adjusted to suit an individual patient's needs. Usual Dosage For Mild to Moderate Pain The recommended dose is 50 mg every 4 to 6 hours. Doses of 100 mg may be needed in some patients for optimal pain relief (see CLINICAL PHARMACOLOGY ). However, the daily dose should not exceed 400 mg (see ADVERSE REACTIONS ). For excessive menstrual blood loss and primary dysmenorrheal The recommended dose of meclofenamate sodium is 100 mg 3 times a day, for up to 6 days, starting at the onset of menstrual flow. For rheumatoid arthritis and osteoarthritis (including acute exacerbations of chronic disease) The dosage is 200 mg to 400 mg per day, administered in three or four equal doses. Therapy should be initiated at the lower dosage, then increased as necessary to improve clinical response. The dosage should be individually adjusted for each patient, depending on the severity of the symptoms and the clinical response. The daily dosage should not exceed 400 mg per day. The smallest dosage of meclofenamate sodium that yields clinical control should be employed. Although improvement may be seen in some patients in a few days, 2 to 3 weeks of treatment may be required to obtain the optimum therapeutic benefit. After a satisfactory response has been achieved, the dosage should be adjusted as required. A lower dosage may suffice for long-term administration. If gastrointestinal complaints occur (see WARNINGS and PRECAUTIONS ), meclofenamate sodium may be administered with meals or with milk (see CLINICAL PHARMACOLOGY for a description of food effects). If intolerance occurs, the dosage may need to be reduced. Therapy should be terminated if any severe adverse reactions occur.

CONTRAINDICATIONS Meclofenamate sodium capsules are contraindicated in patients with known hypersensitivity to meclofenamate sodium. Meclofenamate sodium capsules 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-like reactions to NSAIDs have been reported in such patients (see WARNINGS: Anaphylactoid Reactions and PRECAUTIONS: Preexisting Asthma ). Meclofenamate sodium capsules are contraindicated in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS ).

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 2 years. Gastrointestinal The most frequently reported adverse reactions associated with meclofenamate sodium involve the gastrointestinal system. In controlled studies of up to 6 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 4 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 * , flatulence * , 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 * , urticaria, pruritus Central Nervous System: headache * , dizziness * Special Senses: tinnitus * Incidence between 3% and 9%. Those reactions occurring in 1% to 3% of patients are not marked with an asterisk. 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, toxic epidermal necrolysis (TEN), and fixed drug eruption (FDE) 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

Drug Interactions 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. Aspirin When meclofenamate sodium in administered with aspirin, its protein binding is reduced, although the clearance of free meclofenamate sodium is not altered. The clinical significance of this interaction is not known; however, as with other NSAIDs, concomitant administration of meclofenamate sodium capsules and aspirin is not generally recommended because of the potential of increased adverse effects. Furosemide Clinical studies, as well as post-marketing observations, have shown that meclofenamate sodium 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 PRECAUTIONS: 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. 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. 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.

DESCRIPTION Meclofenamate sodium is N-(2,6-dichloro-m-tolyl) anthranilic acid, sodium salt, monohydrate. It is an anti-inflammatory drug for oral administration. Meclofenamate sodium capsules, USP contain 50 mg or 100 mg meclofenamic acid as the sodium salt and the following inactive ingredients: colloidal silicon dioxide, D&C Yellow No. 10, FD&C Blue No. 1, FD&C Red No. 3, gelatin, magnesium stearate, microcrystalline cellulose, pregelatinized starch (corn), sodium lauryl sulfate and titanium dioxide. In addition, the imprinting ink contains black iron oxide, D&C Yellow No. 10 Aluminum Lake, FD&C Blue No. 1 Aluminum Lake, FD&C Blue No. 2 Aluminum Lake, FD&C Red No. 40 Aluminum Lake, propylene glycol and shellac glaze. The structural formula of meclofenamate sodium is: Molecular Formula: C 14 H 10 Cl 2 NNaO 2 •H 2 O It is a white to creamy white, odorless to almost odorless, crystalline powder with melting point 287° to 291°C, molecular weight 336.15, and it is freely soluble in water. Each meclofenamate sodium capsule contains 7 mg of sodium. Meclofenamate Sodium Structural Formula

OVERDOSAGE The following is based on the little information available concerning overdosage with meclofenamate sodium and related compounds. After a massive overdose, CNS stimulation may be manifested by irrational behavior, marked agitation and generalized seizures. Following this phase, renal toxicity (falling urine output, rising creatinine, abnormal urinary cellular elements) may be noted with possible oliguria or anuria and azotemia. A 24 year-old male was anuric for approximately one week after ingesting an overdose of 6 to 7 grams of meclofenamate sodium. Spontaneous diuresis and recovery subsequently occurred. Management consists of emptying the stomach by emesis or lavage and instilling an ample dose of activated charcoal into the stomach. There is some evidence that charcoal will actively absorb meclofenamate sodium, but dialysis or hemoperfusion may be less effective because of plasma protein binding. The seizures should be controlled by an appropriate anticonvulsant regimen. Attention should be directed throughout, by careful monitoring, to the preservation of vital functions and fluid-electrolyte balance. Dialysis may be required to correct serious azotemia or electrolyte imbalance.

HOW SUPPLIED Meclofenamate Sodium Capsules, USP are available containing either 50 mg or 100 mg of meclofenamic acid as the sodium salt. The 50 mg capsules are hard-shell gelatin capsules with a coral opaque cap and a coral opaque body filled with an off-white powder blend. The capsules are axially printed with MYLAN over 2150 in black ink on both the cap and body. They are available as follows: NDC 0378-2150-01 bottles of 100 capsules The 100 mg capsules are hard-shell gelatin capsules with a coral opaque cap and a white opaque body filled with an off-white powder blend. The capsules are axially printed with MYLAN over 3000 in black ink on both the cap and body. They are available as follows: NDC 0378-3000-01 bottles of 100 capsules Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Protect from light and moisture. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure. PHARMACIST: Dispense a Medication Guide with each prescription.