MINT-INDOMETHACIN

2 CONTRAINDICATIONS Indomethacin capsules are contraindicated in: • the peri-operative setting of coronary artery bypass graft surgery (CABG). Although indomethacin has NOT been studied in this patient population, a selective COX-2 inhibitor NSAID studied in such a setting has led to an increased incidence of cardiovascular/thromboembolic events, deep surgical infections and sternal wound complications.

• during the third trimester of pregnancy, because of risk of premature closure of the ductus arteriosus, and prolonged parturition • women who are breastfeeding, because of the potential for serious adverse reactions in nursing infants • severe uncontrolled heart failure • known hypersensitivity to Indomethacin capsules or to any of the components/excipients.

For a complete listing, see

1 Adverse Drug Reaction Overview The most common adverse reactions encountered with NSAIDs are gastrointestinal, of which peptic ulcer, with or without bleeding, is the most severe. Fatalities have occurred on occasion, particularly in the elderly.

2 Clinical Trial Adverse Drug Reactions The adverse reactions for indomethacin capsules listed in the following table have been arranged into two groups: (1) incidence greater than 1%; and (2) incidence less than 1%. The incidence for group (1) was obtained from 33 double-blind controlled clinical trials reported in the literature (1,092 patients).

The incidence for group (2) was based on reports in clinical trials, in the literature, and on voluntary reports since marketing. The probability of a causal relationship exists between indomethacin and these adverse reactions, some of which have been reported only rarely.

5 Post-Market Adverse Reactions Additional reports of serious adverse events temporally associated with indomethacin during worldwide post-marketing experience are included below. Because these events are reported Incidence >1% Incidence <1 % Chest pain SPECIAL SENSES Tinnitus Ocular -corneal deposits and retinal disturbances including those of the macula, have been reported in some patients on prolong therapy with indomethacin.

Blurred vision, diplopia Hearing disturbances, deafness HEMATOLOGIC None Leukopenia Bone marrow depression Anemia secondary to obvious or occult gastrointestinal bleeding Aplastic anemia Hemolytic anemia Agranulocytosis Thrombocytopenic purpura Disseminated intravascular coagulation GENITOURINARY None Hematuria Vaginal bleeding Proteinuria Nephrotic syndrome Interstitial nephritis BUN elevation Renal insufficiency, including renal failure HYPERSENSITIVITY None Acute anaphylaxis Acute respiratory distress Rapid fall in blood pressure resembling a shock-like state Angioedema Dyspnea Asthma Purpura Angiitis Pulmonary edema METABOLIC None Edema Weight gain Fluid retention Flushing or sweating Hyperglycemia Glycosuria Hyperkalemia MISCELLANEOUS None Epistaxis Breast changes including enlargement and tenderness.

1 Special Populations 02/2023 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. RECENT MAJOR LABEL CHANGES............................................................................................

2 TABLE OF CONTENTS .............................................................................................................. 2 PART I: HEALTH PROFESSIONAL INFORMATION .....................................................................

4 1 INDICATIONS .............................................................................................................. 1 Pediatrics ..........................................................................................................

2 Geriatrics........................................................................................................... 5 2 CONTRAINDICATIONS .................................................................................................

5 3 SERIOUS WARNINGS AND PRECAUTIONS BOX ............................................................ 6 4 DOSAGE AND ADMINISTRATION................................................................................. 1 Dosing Considerations .......................................................................................

2 Recommended Dose and Dosage Adjustment..................................................... 4 Administration................................................................................................... 5 Missed Dose ......................................................................................................

8 5 OVERDOSAGE ............................................................................................................. 8 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ................................. 9 7 WARNINGS AND PRECAUTIONS ..................................................................................

and 7 WARNINGS AND PRECAUTIONS). Use of MINT-INDOMETHACIN should be limited to the lowest effective dose for the shortest possible duration of treatment in order to minimize the potential risk for cardiovascular or gastrointestinal adverse events (See 2 CONTRAINDICATIONS and 7 WARNINGS AND PRECAUTIONS) MINT-INDOMETHACIN, as a NSAID, does NOT treat clinical disease or prevent its progression.

MINT-INDOMETHACIN, as a NSAID, only relieves symptoms and decreases inflammation for as long as the patient continues to take it. 1 Pediatrics Pediatrics (<18 years of age): Safety and efficacy have not been established in the pediatric population.

In a few cases of severe juvenile rheumatoid arthritis, where MINT-INDOMETHACIN was given along with other drugs, severe reactions, including fatalities, were reported. See 2 CONTRAINDICATIONS. 2 Geriatrics Geriatrics (>65 years of age): Evidence from clinical studies and post-market experience suggests that use in the geriatric population is associated with differences in safety.

4 WARNINGS AND PRECAUTIONS, Geriatrics and