Carefully consider the potential benefits and risks of INDOCID and other treatment options before deciding to use INDOCID. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals.
As advancing years appear to increase the possibility of side effects, INDOCID should be used with greater care in the elderly.
Safe conditions for use in children under two years of age have not been established. Children should be monitored closely and periodic evaluations of liver function should be performed at appropriate intervals. Cases of hepatotoxicity including fatalities have been reported. In rare cases, Indomethacin has been associated with serious liver injury.
Cardiovascular Effects: Cardiovascular Thrombotic Events: Observational studies have shown that non-selective NSAIDs may be associated with an increased risk of serious cardiovascular thrombotic events, including myocardial infarction, stroke, and heart failure, which may increase with duration of use and patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk. There is a lack of data from randomized, placebo controlled studies. However, to minimize the potential risk for an adverse cardiovascular event, especially in patients with CV risk factors, the lowest effective dose should be used for the shortest possible duration.
There is no evidence to suggest that concurrent use of aspirin mitigates the increased risk of serious CV events associated with NSAID use. However, the concurrent use of NSAIDs and aspirin does increase the risk of serious GI events.
Hypertension: NSAIDs can lead to onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of CV events. Patients taking antihypertensives along with NSAIDs may have impaired anti-hypertensive response and hence NSAIDs, should be administered with caution in patients with hypertension. Furthermore, when given to patients with hypertension, blood pressure should be monitored closely during the initiation of NSAID treatment and at regular intervals thereafter.
Congestive Heart Failure, Fluid Retention and Oedema: Congestive heart failure, fluid retention and peripheral oedema have been observed in some patients taking INDOCID. Therefore, as with other non-steroidal anti-inflammatory drugs, INDOCID should be used with caution in patients with cardiac dysfunction, hypertension, or other conditions predisposing to fluid retention.
Serious Gastrointestinal Effects: All NSAIDs can cause gastrointestinal discomfort and serious, potentially fatal gastrointestinal effects such as ulcers, bleeding and perforation, which may increase with dose or duration of use, but can occur at any time without warning. Upper GI ulcers, gross bleeding or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3-6 months and in about 2-4% of patients treated for one year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short time therapy is not without risk.
Caution is advised in patients with risk factors for gastrointestinal events who may be at greater risk of developing serious gastrointestinal events, e.g. the elderly, those with a history of serious GI events, smoking and alcoholism. When gastrointestinal bleeding or ulcerations occur in patients receiving NSAIDs, the drug should be withdrawn immediately. Doctors should warn patients about the signs and symptoms of serious gastrointestinal toxicity.
The concurrent use of aspirin and NSAIDs also increases the risk of serious gastrointestinal adverse events.
Because of the occurrence and at times severity of gastrointestinal reactions the risks of continuing therapy with INDOCID in the face of such symptoms must be weighed against the possible benefits to the individual patient.
Gastrointestinal bleeding without obvious ulcer formation and perforation of pre-existing sigmoid lesions (diverticulum, carcinoma, etc.) have occurred. Increased abdominal pain in ulcerative colitis patients or the development of ulcerative and regional ileitis have been reported to occur rarely.
Renal Effects: Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
Advanced Renal Disease: No information is available from controlled clinical studies regarding the use of INDOCID in patients with advanced renal disease. Therefore, treatment with INDOCID is not recommended in these patients with advanced renal disease. If therapy must be initiated, close monitoring of the patient's renal function is advisable
Platelet Aggregation: INDOCID, like other non-steroidal anti-inflammatory agents, can inhibit platelet aggregation. This effect is of shorter duration than that seen with acetylsalicylic acid and usually disappears within 24 hours after discontinuation of INDOCID. INDOCID has been shown to prolong bleeding time (but within the normal range) in normal subjects. Because this effect may be exaggerated in patients with underlying haemostatic defects, INDOCID should be used with caution in persons with coagulation defects.
Anticoagulants: Concurrent use of NSAIDs and warfarin has been associated with severe, sometimes fatal, haemorrhage, especially in the elderly. The exact mechanism is unknown, but may involve enhanced bleeding from NSAID-induced gastrointestinal ulceration, or an additive effect of anticoagulation by warfarin and inhibition of platelet function by NSAIDs. INDOCID should be used in combination with warfarin only if absolutely necessary, and patients taking this combination should be closely monitored. In post marketing experience, bleeding has been reported in patients on concomitant treatment with anticoagulants and INDOCID. Caution should be exercised when INDOCID and anticoagulants are administered concomitantly. Adjustment of dosage for oral anticoagulants may be required.
Effects on Ability to Drive and Use Machines: Undesirable effects such as dizziness, drowsiness, fatigue and visual disturbances are possible after taking NSAIDs. If affected, patients should not drive or operate machinery.