Acetylsalicylic acid: The use of INDOCID in conjunction with acetylsalicylic acid or other salicylates is not recommended. Controlled clinical studies have shown that the combined use of INDOCID and acetylsalicylic acid does not produce any greater therapeutic effect than the use of INDOCID alone. Furthermore, in one of these clinical studies, the incidence of gastrointestinal side effects was significantly increased with combined therapy. In a study in normal volunteers, it was found that chronic concurrent administration of 3.6 gm of acetylsalicylic acid per day decreases indomethacin blood levels approximately 20%.
Diflunisal: The combined use of INDOCID and diflunisal has been associated with fatal gastrointestinal hemorrhage. The coadministration of diflunisal and INDOCID results in an increase of about 30-35% in indomethacin plasma levels and a concomitant decrease in renal clearance of indomethacin and its conjugate. Therefore, INDOCID and diflunisal should not be used concomitantly.
Other NSAIDS: The concomitant use of INDOCID with other NSAIDs is not recommended due to the increased possibility of gastrointestinal toxicity, with little or no increase in efficacy.
Probenecid: When INDOCID is given to patients receiving probenecid, the plasma levels of indomethacin are likely to be increased. Therefore, a lower total daily dosage of INDOCID may produce a satisfactory therapeutic effect. When increases in the dose of INDOCID are made under these circumstances they should be made cautiously and in small increments.
Methotrexate: Caution should be used if INDOCID is administered simultaneously with methotrexate. INDOCID has been reported to decrease the tubular secretion of methotrexate and to potentiate toxicity.
Cyclosporine: Administration of non-steroidal anti-inflammatory drugs concomitantly with cyclosporine has been associated with an increase in cyclosporine-induced toxicity, possibly due to decreased synthesis of renal prostacyclin. NSAIDs should be used with caution in patients taking cyclosporine, and renal function should be monitored carefully.
Lithium: Indomethacin 50 mg given three times a day produced a clinically relevant elevation of plasma lithium and reduction in renal lithium clearance in psychiatric patients and normal subjects with steady state plasma lithium concentrations. This effect has been attributed to inhibition of prostaglandin synthesis. As a consequence, when indomethacin and lithium are given concomitantly, the patient should be observed carefully for signs of lithium toxicity. (Read circulars for lithium preparations before use of such concomitant therapy). In addition, the frequency of monitoring serum lithium concentrations should be increased at the outset of such combination drug treatment.
Diuretics: In some patients, the administration of INDOCID can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing, and thiazide diuretics. Therefore, when INDOCID and diuretics are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.
INDOCID reduces basal plasma renin activity (PRA) as well as those elevations of PRA induced by frusemide administration, or salt or volume depletion. These facts should be considered when evaluating plasma renin activity in hypertensive patients.
It has been reported that the addition of triamterene to a maintenance schedule of INDOCID resulted in reversible acute renal failure in two of four healthy volunteers. INDOCID and triamterene should not be administered together.
INDOCID and potassium-sparing diuretics each may be associated with increased serum potassium levels. The potential effects of INDOCID and potassium-sparing diuretics on potassium kinetics and renal function should be considered when these agents are administered concurrently.
Most of the previously mentioned effects concerning diuretics have been attributed, at least in part, to mechanisms involving inhibition of prostaglandin synthesis by INDOCID.
Antihypertensive medications: Co-administration of INDOCID and some antihypertensive agents has resulted in an attenuation of the latter's hypotensive effect acutely, due at least in part to indomethacin's inhibition of prostaglandin synthesis. The prescriber should, therefore, exercise caution when considering the addition of INDOCID to the regimen of a patient taking one of the following antihypertensive agents: An alpha-adrenergic blocking agent (such as prazosin), an angiotensin converting enzyme inhibitor (such as captopril or lisinopril), a beta-adrenergic blocking agent, a diuretic (see diuretic), hydralazine, or losartan (an angiotensin II receptor antagonist).
In some patients, the administration of INDOCID can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing, and thiazide diuretics. Therefore, when INDOCID and diuretics are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.
In some patients with compromised renal function (e.g., elderly patients or patients who are volume-depleted, including those on diuretic therapy) who are being treated with non-steroidal anti-inflammatory drugs, including selective cyclooxygenase-2 inhibitors, the co-administration of angiotensin II receptor antagonists or ACE inhibitors may result in further deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Therefore, the combination should be administered with caution in patients with compromised renal function.
Beta-Adrenergic Receptor Blocking Agents: A decrease in the anti-hypertensive effect of beta-adrenergic receptor blocking agents by non-steroidal anti-inflammatory drugs including indomethacin has been reported. Therefore, when using a beta-blocking agent to treat hypertension, patients should be observed carefully in order to confirm that the desired therapeutic effect has been obtained.
Digoxin: INDOCID given concomitantly with digoxin has been reported to increase the serum concentration and prolong the half-life of digoxin. Therefore, when INDOCID and digoxin are used concomitantly, serum digoxin levels should be closely monitored.
Phenylpropanolamine: Hypertensive crises have been reported due to oral phenylpropanolamine alone and rarely to phenylpropanolamine given with INDOCID. This additive effect is probably due at least in part to indomethacin's inhibition of prostaglandin synthesis. Caution should be exercised when INDOCID and phenylpropanolamine are administered concomitantly.