Acetaminophen: Prolonged concurrent use of acetaminophen with an NSAID may increase the risk of adverse renal effects; it is recommended that patients be under close medical supervision while receiving such combined therapy.
Alcohol or Corticosteroids, glucocorticoid or Corticotropin (chronic therapeutic use) or Potassium supplements: Concurrent use with an NSAID may increase the risk of gastrointestinal side effects, including ulceration or hemorrhage; however, concurrent use with a glucocorticoid or corticotropin in the treatment of arthritis may provide additional therapeutic benefit and permit reduction of glucocorticoid or corticotropin dosage.
Anticoagulants, coumarin-or indandione-derivative or Heparin or Thrombolytic agents: Inhibition of platelet aggregation by NSAIDs, and the possibility of NSAID-induced gastrointestinal ulceration or bleeding, may be hazardous to patients receiving anticoagulant or thrombolytic therapy; although with usual doses, diclofenac, may be less likely than other NSAIDs to significantly alter platelet aggregability.
Antidiabetic agents, oral or Insulin: NSAIDs may increase the effect of these medications because prostaglandins are involved in regulatory mechanisms of glucose metabolism and possibly because of displacement of the oral antidiabetics from serum proteins; dosage adjustments of the antidiabetic agent may be necessary.
Diclofenac has also been reported to decrease the effects of these medications, leading to hyperglycemia.
Antihypertensives or Diuretics, especially Triamterene: Increased monitoring of the response to an antihypertensive agent may be advisable when any NSAID is used concurrently because flurbiprofen, indomethacin, ibuprofen, naproxen, oxaprozin, and piroxicam have been shown to reduce or reverse the effects of antihypertensives, possibly by inhibiting renal prostaglandin synthesis and/or causing sodium and fluid retention.
Concurrent use of an NSAID and a diuretic may increase the risk of renal failure secondary to a decrease in renal blood flow caused by inhibition of renal prostaglandin synthesis.
Concurrent use of a potassium-sparing diuretic with diclofenac may increase the risk of hyperkalemia.
Aspirin or NSAIDs, two or more concurrently: Concurrent use of two or more NSAIDs, including aspirin, is not recommended; concurrent therapy may increase the risk of gastrointestinal toxicity, including ulceration or hemorrhage, without providing additional symptomatic relief. Concurrent use of aspirin with other NSAIDs may also increase the risk of bleeding at sites other than the gastrointestinal tract because of additive inhibition of platelet aggregation.
Concurrent administration of two or more NSAIDs may alter the pharmacokinetic profile of at least one of the medications, which may alter the therapeutic effect and/or increase the risk of adverse effect; specifically, aspirin decreases the bioavailability of diclofenac [by 50%].
Bone marrow depressants: leukopenic and/or thrombocytopenic effects of these medications may be increased with concurrent or recent therapy if an NSAID cause the same effects; dosage adjustment of the bone marrow depressant, if necessary, should be based on blood counts.
Cefamandole or Cefoperazone or Cefotetan or Plicamycin or Valproic acid: These medications may cause hypoprothrombinemia; in addition, plicamycin or valproic acid may inhibit platelet aggregation; concurrent use with an NSAID may increase the risk of bleeding because of additive interference with platelet function and/or the potential occurrence of NSAID-induced, gastrointestinal ulceration or hemorrhage.
Colchicine: Concurrent use with an NSAID may increase the risk of gastrointestinal ulceration or hemorrhage.
Inhibition of platelet by NSAIDs, added to colchicine's effects on blood clotting mechanisms [colchicines may cause thrombocytopenia with chronic use and clotting defects, including disseminated intravascular coagulation, with overdose], may increase the risk of bleeding at sites other than the gastrointestinal tract.
Cyclosporine or Gold compound or Nephrotoxic medications, other: Inhibition of renal prostaglandin activity by NSAIDs may increase the plasma concentration of cyclosporine and/or the risk of cyclosporine-induced nephrotoxicity; patients should be carefully monitored during concurrent use.
The risk of adverse renal effects may also be increased when an NSAID is used concurrently with other nephrotoxic medications, possibly including gold compounds [although NSAIDs and gold compounds are commonly used concurrently in the treatment of arthritis].
Digitalis glycosides: Diclofenac has been shown to increase serum digoxin concentrations, leading to an increased risk of digital toxicity, increased monitoring and dosage adjustments of the digitalis glycoside may be necessary during and following concurrent NSAID therapy.
Lithium: Diclofenac has been reported to increase the steady-concentration of lithium, possibly by decreasing its renal clearance; increased monitoring of lithium concentration is recommended during and following concurrent use.
Methotrexate: NSAIDs may decrease protein binding and/or renal elimination of methotrexate, resulting in increased and prolonged methotrexate plasma concentrations and increased risk of toxicity, especially during high dose methotrexate infusion therapy; fatalities have been reported; it is recommended that NSAID therapy be withheld for varying periods of time, depending on the elimination half-life of the individual NSAID [12 to 24 hours for agents with a short elimination half-life to up to 10 or 12 days for agents with a very long elimination half-life] prior to administration of a high-dose methotrexate infusion: also, NSAID therapy should not be resumed following the infusion until the methotrexate plasma concentration has decreased to a level, usually at least 12 hours].
Severe, sometimes fatal, methotrexate toxicity has also been reported when NSAIDs were used concurrently with low to moderate doses of methotrexate, including doses commonly used in the treatment of rheumatoid arthritis or psoriasis; caution in concurrent use is recommended, with dosage of methotrexate being adjusted as determined by monitoring the plasma methotrexate concentration and/or adequacy of the patient's renal function.
Photosensitizing medications, other: Concurrent use with photosensitising NSAIDs may cause additive photosensitising effects.
Platelet aggregation inhibitors, other: Concurrent use with an NSAID may increase the risk of bleeding because of additive inhibition of platelet aggregation, as well as the potential for NSAID induced gastrointestinal ulceration or hemorrhage.
Concurrent use of sulfinpyrazone with NSAIDs may also increase the risk of gastrointestinal ulceration or hemorrhage.
Probenecid: Probenecid may decrease excretion and increase serum concentrations of NSAIDs possibly enhancing effectiveness and/or increasing the potential for toxicity; a decrease in dosage of the NSAID may be necessary if adverse effects occur.