Cardiovascular Thrombotic Events • Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use (See and ). WARNINGS PRECAUTIONS • Indomethacin Extended-release Capsules are contraindicated in the setting of coronary artery bypass graft (CABG) surgery (See and ). CONTRAINDICATIONS WARNINGS Gastrointestinal Risk • NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events. (See ). WARNINGS
ADVERSE 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. In controlled clinical trials, the incidence of adverse reactions to Indomethacin Extended-release Capsules USP 75 mg and equal 24-hour doses of indomethacin capsules were similar. Incidence great than 1% Incidence less than 1% GASTROINTESTINAL nausea* with or without vomiting dyspepsia* (including indigestion, heartburn and epigastric pain) diarrhea abdominal distress or pain constipation 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 pre-existing sigmoid lesions (diverticulum, carcinoma, etc.) development of ulcerative colitis and regional ileitisulcerative stomatitis toxic hepatitis and jaundice (some fatal cases have been reported) CENTRAL NERVOUS SYSTEM headache (11.7%) dizziness* vertigo somnolence depression and fatigue including malaise and listlessness) anxiety (includes nervousness) muscle weakness involuntary muscle movemets insomnia muzziness psychic disturbances including psychotic episodes mental confussion drowsiness light-headedness syncope paresthesia aggravation of epilepsy and parkinsonism depersonalization coma peripheral neuropathy convulsions dysarthria SPECIAL SENSES tinnitus ocular-corneal deposits and retinal disturbances, including those of macula, have been reported in some patients on prolonged therapy with indomethacin blurred vision diplopia hearing disturbances, deafness CARDIOVASCULAR none hypertension hypotension tachycardia chest pain congestive heart failure arrhythmia; palpitations METABOLIC none edema weight gain fluid retention flushing or sweating hyperglycemia glycosuria hyperkalemia INTEGUMENTARY none pruritus rash; urticaria petechiae or ecchymosis exfoliative dermatitis erythema nodosum loss of hair Stevens-Johnson syndrome erythema multiforme toxic epidermal necrolysis HEMATOLOGIC none leukopenia bone marrow depression anemia secondary to obvious or occult gastrointestinal bleeding aplastic anemia hemolytic anemia agranulocytosis thrombocytopenic purpura disseminated intravascular coagulation HYPERSENSITIVITY none acute anaphylaxis acute respiratory distress rapid fall in blood pressure resembling a shock -like state angioedema dyspnea asthma purpura angiitis pulmonary edema fever GENITOURINARY none hematuria vaginal bleeding proteinuria nephrotic syndrome interstitial nephritis BUN elevation renal insufficiency including renal failure MISCELLANEOUS none 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.) 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: 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 nonsteroidal anti-inflammatory agents, including indomethacin, sometimes with fatal outcome (See also ). PRECAUTIONS,General : Thrombophlebitis. Cardiovascular : Although there have been several reports of leukemia, the supporting information is weak. Hematologic : Urinary frequency. Genitourinary
adverse reactions table
<table width="631"> <tbody> <tr styleCode="First Last"> <td align="left" styleCode="BotruleToprule" valign="top">Incidence great than 1%</td> <td align="left" styleCode="BotruleToprule" valign="top">Incidence less than 1%</td> </tr> </tbody> </table>
adverse reactions table
<table width="631"> <tbody> <tr styleCode="First Last"> <td valign="top"> <paragraph>nausea* with or without vomiting</paragraph> <paragraph>dyspepsia* (including indigestion, heartburn and epigastric pain)</paragraph> <paragraph>diarrhea</paragraph> <paragraph>abdominal distress or pain constipation </paragraph> </td> <td align="left" valign="top"> <paragraph>anorexia</paragraph> <paragraph>bloating (includes distention)</paragraph> <paragraph>flatulence</paragraph> <paragraph>peptic ulcer</paragraph> <paragraph>gastroenteritis</paragraph> <paragraph>rectal bleeding</paragraph> <paragraph>proctitis</paragraph> <paragraph>single or multiple ulcerations, including perforation and hemorrhage of the esophagus, stomach,duodenum or small and large intestines</paragraph> <paragraph>Intestinal ulceration associated with stenosis and obstruction</paragraph> </td> <td align="left" valign="top"> <paragraph>gastrointestinal bleeding without obvious ulcer formation and perforation of pre-existing sigmoid lesions (diverticulum, carcinoma, etc.) development of ulcerative colitis and regional ileitisulcerative stomatitis</paragraph> <paragraph>toxic hepatitis and jaundice (some fatal cases have been reported)</paragraph> </td> </tr> </tbody> </table>