Carefully consider the potential benefits and risks of indomethacin extended-release capsules and other treatment options before deciding to use indomethacin extended-release capsules.

Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).

Indomethacin extended-release capsules have been found effective in active stages of the following: 1.

Moderate to severe rheumatoid arthritis including acute flares of chronic disease.

2.

Moderate to severe ankylosing spondylitis.

3.

Moderate to severe osteoarthritis.

4.

Acute painful shoulder (bursitis and/or tendinitis).

Indomethacin extended-release capsules, USP are not recommended for the treatment of acute gouty arthritis.

Indomethacin may enable the reduction of steroid dosage in patients receiving steroids for the more severe forms of rheumatoid arthritis.

In such instances the steroid dosage should be reduced slowly and the patients followed very closely for any possible adverse effects.

The use of indomethacin in conjunction with aspirin or other salicylates is not recommended.

Controlled clinical studies have shown that the combined use of indomethacin and aspirin does not produce any greater therapeutic effect than the use of indomethacin alone.

Furthermore, in one of these clinical studies, the incidence of gastrointestinal side effects was significantly increased with combined therapy.

(See PRECAUTIONS,DRUG INTERACTIONS).

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.

In controlled clinical trials, the incidence of adverse reactions to indomethacin extended-release capsules and equal 24-hour doses of indomethacin capsules were similar.

Incidence greater than 1% GASTROINTESTINAL nausea* with or without vomiting dyspepsia* (including indigestion, heartburn and epigastric pain) diarrhea abdominal distress or pain constipation CENTRAL NERVOUS SYSTEM headache (11.7%) dizziness* vertigo somnolence depression and fatigue (including malaise and listlessness) SPECIAL SENSES tinnitus CARDIOVASCULAR none METABOLIC none INTEGUMENTARY none HEMATOLOGIC none HYPERSENSITIVITY none GENITOURINARY none MISCELLANEOUS none Incidence less than 1% GASTROINTESTINAL anorexia bloating (includes distention) flatulence peptic ulcer gastroenteritis rectal bleeding proctitis single or multiple ulcerations, including perforation and hemorrhage of the esophagus, stomach, duodenum or small and large intestines Intestinal ulceration associated with stenosis and obstruction gastrointestinal bleeding without obvious ulcer formation and perforation of preexisting sigmoid lesions (diverticulum, carcinoma, etc.) development of ulcerative colitis and regional ileitis ulcerative stomatitis toxic hepatitis and jaundice (some fatal cases have been reported) CENTRAL NERVOUS SYSTEM anxiety (includes nervousness) muscle weakness involuntary muscle movements insomnia muzziness psychic disturbances including psychotic episodes mental confusion drowsiness light-headedness syncope paresthesia aggravation of epilepsy and parkinsonism depersonalization coma peripheral neuropathy convulsions dysarthria SPECIAL SENSES ocular-corneal deposits and retinal disturbances, including those of the macula, have been reported in some patients on prolonged therapy with Indomethacin blurred vision diplopia hearing disturbances, deafness CARDIOVASCULAR congestive heart failure hypertension hypotension tachycardia chest pain arrhythmia; palpitations METABOLIC edema weight gain fluid retention flushing or sweating hyperglycemia glycosuria hyperkalemia INTEGUMENTARY pruritus rash; urticaria petechiae or ecchymosis exfoliative dermatitis erythema nodosum loss of hair Stevens-Johnson Syndrome erythema multiforme toxic epidermal necrolysis HEMATOLOGIC leukopenia bone marrow depression anemia secondary to obvious or occult gastrointestinal bleeding aplastic anemia hemolytic anemia agranulocytosis thrombocytopenic purpura disseminated intravascular coagulation HYPERSENSITIVITY acute anaphylaxis acute respiratory distress rapid fall in blood pressure resembling a shock-like state angioedema dyspnea asthma purpura angiitis pulmonary edema fever GENITOURINARY hematuria vaginal bleeding proteinuria, nephrotic syndrome, interstitial nephritis BUN elevation renal insufficiency including renal failure MISCELLANEOUS epistaxis breast changes, including enlargement and tenderness, or gynecomastia *Reactions occurring in 3% to 9% of patients treated with indomethacin.

(Those reactions occurring in less than 3% of the patients are unmarked.) Causal Relationship Unknown: Other reactions have been reported but occurred under circumstances where a causal relationship could not be established.

However, in these rarely reported events, the possibility cannot be excluded.

Therefore, these observations are being listed to serve as alerting information to physicians: A rare occurrence of fulminant necrotizing fasciitis, particularly in association with Group A β-hemolytic streptococcus, has been described in persons treated with nonsteroidal anti-inflammatory agents, including indomethacin, sometimes with fatal outcome (see also PRECAUTIONS, GENERAL).

Cardiovascular: Thrombophlebitis Hematologic: Although there have been several reports of leukemia, the supporting information is weak.

Genitourinary: Urinary frequency