Interactions : אינטראקציות

4.5 Interaction with other medicinal products and other forms of interaction

•   Other Analgesics including cyclooxygenase-2 selective inhibitors: Avoid concomitant use of two or more NSAIDs (including aspirin) as this may increase the risk of adverse effects (see section 4.4).
•   Antacids: the bioavailability of indomethacin may be reduced by concomitant antacid therapy

•   Anticoagulants: NSAIDs may enhance the effects of anti-coagulants, such as warfarin (See section 4.4).

•   Anti-diabetics: The effect of sulphonylureas may be increased by NSAIDs.

•   Antidepressants (SSRI): increased risk of bleeding (see section 4.4) 
•   Antihypertensive medications: Reduced anti-hypertensive effect. Indovis may acutely reduce the antihypertensive effect of beta-blockers due partly to indomethacin's inhibition of prostaglandin synthesis. Patients receiving dual therapy should have the antihypertensive effect of their therapy reassessed.
Therefore, caution should be exercised when considering the addition of Indovis to the regimen of a patient taking any of the following antihypertensive agents: alpha- adrenergic blocking agents, ACE inhibitors, beta-adrenergic blocking agents, angiotensin II receptor antagonists, hydralazine, or nifedipine. An increased risk of hyperkalaemia has also been reported when NSAIDs are taken with ACE inhibitors.

•   Diuretics: NSAIDS may reduce the effect of diuretics and antihypertensive medicinal products. The risk of acute renal insufficiency, which is usually reversible, may be increased in some patients with compromised renal function (e.g. dehydrated patients or elderly patients) when angiotensin II receptor antagonists are combined with NSAIDs. Therefore, the combination should be administrated with caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring of renal function after initiation of concomitant therapy, and periodically thereafter.
Indovis may reduce the diuretic and antihypertensive effect of thiazides and furosemide in some patients. Indovis may cause blocking of the furosemide- induced increase in plasma rennin activity. Diuretics can increase the risk of nephrotoxicity of NSAIDs.

•   Anti-platelet agents: increased risk of gastrointestinal bleeding. Indovis can inhibit platelet aggregation, an effect which disappears within 24 hours of discontinuation; the bleeding time may be prolonged and this effect may be exaggerated in patients with an underlying haemostatic defect (see section 4.4).

•   Antipsychotics: increased drowsiness with Indovis and haloperidol.

•   Antivirals: Increased risk of haematological toxicity when NSAIDs are given with zidovudine. There is evidence of an increased risk of haemarthroses and haematoma in HIV (+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.
Risk of Indovis toxicity with ritonavir, avoid concomitant use.

•   Cardiac glycosides: NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma glycoside levels.

•   Ciclosporin: Increased risk of nephrotoxicity. Administration NSAIDs concomitantly with ciclosporin has been associated with an increase in ciclosporin-induced toxicity, possibly due to decreased synthesis of renal prostacyclin. NSAIDs should be used with caution in patients taking ciclosporin, and renal function should be monitored carefully.

•   Corticosteroids: Increased risk of gastrointestinal ulceration or bleeding (See section 4.4). If the patient is receiving corticosteroids concomitantly, a reduction in dosage of these may be possible but should only be effected slowly under supervision.
•   Cytotoxics: Indovis may decrease the tubular secretion of methotrexate thus potentiating toxicity; simultaneous use should be undertaken with caution.

•   Desmopressin: effect potentiated by Indovis.

•   Diflunisal: avoid concomitant use. Increased plasma level of Indovis by about a third with a concomitant decrease in renal clearance. Fatal gastro-intestinal haemorrhage has occurred.

•   Lithium: Decreased elimination of lithium.
Indovis is an inhibitor of prostaglandin synthesis and therefore the following drug reaction may occur; Indovis may raise plasma lithium levels and reduce lithium clearance in subjects with steady state plasma lithium concentration. At the onset of such combined therapy, plasma lithium concentrations should be monitored more frequently.

•   Methotrexate: Decreased elimination of methotrexate.

•   Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone.

•   Muscle Relaxants: increased risk of baclofen toxicity due to reduced rate of excretion.

•   Pentoxifylline: possible increased risk of bleeding when taken with NSAIDs.

•   Probenecid: co-administration of probenecid may increase plasma levels of indomethacin. When increases in the dose of Indovis are made under these circumstances, they should be made cautiously and in small increments.

•   Quinolone antibiotics: Animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing convulsions.

•   Salicylates: the use of Indovis with aspirin or other salicylates is not recommended because there is no enhancement of therapeutic effect while the incidence of gastro- intestinal side effects is increased. Moreover, coadministration of aspirin may decrease the blood concentrations of indomethacin
.
•   Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.

•   Tiludronic acid: the bioavailability of tiludronic acid is increased by Indovis.

•   Triamterene: Indovis and triamterene should not be administered together since reversible renal failure may be induced.

•   Laboratory tests: false-negative results in the dexamethasone suppression test (DST) in patients being treated with Indovis have been reported. Thus, results of this test should be used with caution in these patients.