Central Nervous System: Central nervous system adverse effects are headache, dizziness, light-headedness, depression, vertigo and fatigue (including malaise and listlessness). Reactions reported infrequently include mental confusion, anxiety, syncope, drowsiness, convulsions, coma, peripheral neuropathy, muscle weakness, involuntary muscle movements, insomnia, psychic disturbances such as depersonalisation, psychotic episodes and rarely, paraesthesias, dysarthria, aggravation of epilepsy and parkinsonism. These are often transient and disappear frequently with continued treatment or with a reduction of dosage. However, the severity of these may, on occasion, require stopping therapy.
Gastrointestinal: Gastrointestinal reactions which occur most frequently are nausea, anorexia, vomiting, epigastric distress, abdominal pain, constipation, and diarrhoea. Others which may develop are ulceration - single or multiple - of oesophagus, stomach, duodenum or small or large intestine, including perforation and haemorrhage with a few fatalities having been reported; gastrointestinal tract bleeding without obvious ulcer formation; and increased abdominal pain when used in patients with pre-existing ulcerative colitis. Rarely, intestinal strictures (diaphragms) and intestinal ulceration followed by stenosis and obstruction has been reported. Reactions which occur infrequently are stomatitis; gastritis, flatulence; bleeding from the sigmoid colon - occult or from a diverticulum; and perforation of pre-existing sigmoid lesions (diverticula, carcinoma). Other gastrointestinal side effects which may or may not be caused by indomethacin include ulcerative colitis and regional ileitis.
Studies in man with radioactive chromate tagged red blood cells indicate that the highest recommended oral dosage of indomethacin (50 mg, 4 times a day) produces less faecal blood loss than average doses of acetylsalicylic acid (600 mg, 4 times a day).
Hepatic: Hepatic reactions reported on rare occasions are jaundice and hepatitis and some fatal cases have been reported.
Cardiovascular-Renal: Cardiovascular-renal reactions which may occur infrequently include oedema, elevation of blood pressure, tachycardia, chest pain, arrhythmia, palpitations, hypotension, congestive heart failure, BUN elevation, and haematuria.
Hypersensitivity: Hypersensitivity reactions reported infrequently are pruritus, urticaria, angiitis, erythema nodosum, skin rashes, exfoliative dermatitis, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, loss of hair, acute respiratory distress, a rapid fall in blood pressure resembling a shock-life state, acute anaphylaxis, angioneurotic oedema, sudden dyspnoea, asthma and pulmonary oedema.
Haematological: Haematological reactions which may develop infrequently in conjunction with indomethacin therapy are leucopenia, petechiae or ecchymosis, purpura, aplastic and haemolytic anaemia and thrombocytopenia and disseminated intravascular coagulation. Rarely, agranulocytosis and bone marrow depression have been reported, but a definite relationship to indomethacin has not been established. Some patients may manifest anaemia secondary to obvious or occult gastrointestinal bleeding. Therefore, appropriate blood determinations are recommended.
Eye: Blurred vision, diplopia and orbital and periorbital pain may occur infrequently. Corneal deposits and retinal disturbances, including those of the macula, have been reported in some patients with rheumatoid arthritis on prolonged therapy with INDOCID. Similar eye changes have been observed in some patients with this disease who have not received INDOCID.
Ear: Tinnitus, hearing disturbances, and deafness rarely, have been reported to occur.
Genitourinary: Reported rarely: Proteinuria, nephrotic syndrome, interstitial nephritis and renal insufficiency, including renal failure.
Miscellaneous: Miscellaneous adverse reactions reported rarely include vaginal bleeding, hyperglycaemia and glycosuria, hyperkalaemia, flushing and sweating, epistaxis, ulcerative stomatitis and breast changes, including enlargement and tenderness, or gynaecomastia.
Adverse effect-causal relationship unknown: The following additional adverse effects have been reported; however a causal relationship to therapy with INDOCID has not been established: Cardiovascular: Thrombophlebitis.
Haematologic: Although there have been several reports of leukaemia, the supporting information is weak.
Genitourinary: Urinary frequency.
Miscellaneous: Rare occurrences of fulminant necrotizing fasciitis, particular in association with Group A β-haemolytic streptococcus, has been described in persons treated with non-steroidal anti-inflammatory agents, sometimes with fatal outcome (see also Precautions).