Nonsteroidal anti-inflammatory drugs may cause sodium, potassium and fluid retention, and may interfere with the natriuretic action of diuretic agents. These properties should be kept in mind when treating patients with compromised cardiac function or hypertension since they may be responsible for a worsening of those conditions.
Cardiac Glycosides (Digoxin and Digitoxin): NSAIDs may exacerbate cardiac failure, reduce glomerular filtration rate (GFR) and increase plasma glycoside levels. Concomitant administration of digoxin or digitoxin had no effect on the plasma levels of piroxicam of either drug.
Bleeding has been reported rarely when Feldene Flash has been administered to patients on coumarin-type anticoagulants. Patients should be monitored closely if Feldene Flash and oral anticoagulants are administered together.
Feldene Flash, like other NSAIDs, decreases platelet aggregation and prolongs bleeding time. This effect should be kept in mind when bleeding times are determined.
As with other NSAIDs, the use of Feldene Flash in conjunction with acetylsalicylic acid or the concomitant use of 2 NSAIDs is not recommended because data are inadequate to demonstrate that these combination produces greater improvement than that achieved with the drug alone and the potential for adverse reactions is increased.
Studies in man have shown that the concomitant administration of Feldene Flash and acetylsalicylic acid resulted in a reduction of plasma levels of piroxicam to about 80% of the normal values. Concomitant administration of antacids had no effect on piroxicam plasma levels. Neither did concurrent therapy with Feldene Flash and digoxin, or Feldene Flash and digitoxin affect the plasma levels of either drug.
Antihypertensives including Diuretics, Angiotensin-Converting Enzyme (ACE) Inhibitors and Angiotensin II/Antagonists (AIIA): NSAIDs can reduce the efficacy of diuretics and other anti-hypertensive drugs.
In patients with impaired renal function (eg, dehydrated patients or elderiy patients with the renal function compromised), the co-administration of an ACE inhibitor or an AIIA with a cyclooxygenase inhibitor can increase the deterioration of the renal function, including the possibility of acute renal failure, which is usually reversible. The occurrence of these interactions should be considered in patients taking piroxicam with a diuretic, an ACE inhibitor or an AIIA.
Therefore, the concomitant administration of these drugs should be done with caution, especially in elderly patients. Patients should be adequately hydrated and the need to monitor the renal function should be assessed in the beginning of the concomitant treatment and periodically thereafter.
Cholestyramine: Cholestyramine has been shown to enhance the oral clearance and decrease the half-life of piroxicam. To minimize this interaction, it is prudent to administer piroxicam at least 2 hrs before or 6 hrs after cholestyramine.
Corticosteroids: Increased risk of gastrointestinal ulceration or bleeding.
Cyclosporine: Increased risk of nephrotoxicity.
Methotrexate: Decreased elimination of methotrexate.
Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.
Feldene Flash is highly protein bound and therefore might be expected to displace other protein bound drugs. The physician should closely monitor patients for change in dosage requirements when administering Feldene Flash to patients on highly protein bound drugs. NSAIDs, including Feldene Flash, have been reported to increase steady-state plasma lithium levels. It is recommended that these levels be monitored when initiating, adjusting and discontinuing Feldene Flash.
Results of 2 separate studies indicate a slight increase in absorption of piroxicam following cimetidine administration but no significant changes in elimination parameters occur. Cimetidine increases the area under the curve (AUC0-120 hrs) and Cmax of piroxicam by approximately 13-15%. Elimination rate constants and half-life show no significant differences. The small but significant increase in absorption is unlikely to be clinically significant.