The use of piroxicam with concomitant NSAIDs including COX-2 inhibitors should be avoided.
Cardiovascular Effects: NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction and stroke, which can be fatal. All NSAIDs, both COX-2 selective and nonselective, may have a similar risk. This risk may increase with duration of use. Patients with known cardiovascular disease or risk factors for cardiovascular disease may be at greater risk. To minimize the potential risk for an adverse cardiovascular event in patients treated with piroxicam, the lowest effective dose should be used for the shortest duration possible. Physicians and patients should remain alert for the development of such events, even in the absence of previous cardiovascular symptoms. Patients should be informed about the signs and/or symptoms of serious cardiovascular toxicity, and the steps to take if they occur (see Warnings).
There is no consistent evidence that concurrent use of acetylsalicylic acid mitigates the increased risk of serious cardiovascular thrombotic events associated with NSAID use. The concurrent use of acetylsalicylic acid and an NSAID does increase the risk of serious gastrointestinal events (see following texts on Gastrointestinal Effects under Precautions).
Two large, controlled, clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke (see Warnings).
Fluid Retention and Edema: As with other drugs known to inhibit prostaglandin synthesis, fluid retention and edema have been observed in some patients taking NSAIDs, including piroxicam. Therefore, piroxicam should be used with caution in patients with compromised cardiac function and other conditions predisposing to or worsened by, fluid retention. Patients with preexisting congestive heart failure or hypertension should be closely monitored.
Hypertension: NSAIDS, including piroxicam can lead to onset of new hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of cardiovascular events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including piroxicam, should be used with caution in patients with hypertension. Blood pressure should be monitored closely during the initiation of NSAID treatment with Feldene Flash and throughout the course of therapy.
Gastrointestinal (GI) Effects: Risk of GI Ulceration, Bleeding, and Perforation: NSAIDs, including piroxicam, can cause serious GI adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine or large intestine, which can be fatal.
These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only 1 in 5 patients, who develop a serious upper GI adverse event on NSAID therapy, is symptomatic. 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 1 year. These trends 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-term therapy is not without risk.
Nonsteroidal anti-inflammatory drugs should be prescribed with extreme caution in patients with a prior history of ulcer disease or GI bleeding. Patients with a prior history of ulcer disease and/or GI bleeding, and who use NSAIDs, have a greater than 10-fold higher risk for developing a GI bleed compared to patients with neither of these risk factors. Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age and poor general health status. Most spontaneous reports of fatal GI events are in the elderly or debilitated patients and therefore, special care should be taken in treating this population.
To minimize the potential risk for an adverse GI event, in patients treated with NSAIDs, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy, and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of the NSAID until a serious GI adverse event is ruled out. For high-risk patients, alternate therapies that do not involve NSAIDs should be considered.
Feldene Flash should be withdrawn if peptic ulceration or GI bleeding occur.
Renal Effects: In rare cases, NSAIDS may cause interstitial nephritis, glomerulitis, papillary necrosis and nephrotic syndrome. NSAIDS inhibit the synthesis of renal prostaglandin which plays a supportive role in the maintenance of renal perfusion in patients whose renal blood flow and blood volume are decreased. In these patients, administration of an NSAID may precipitate overt renal decompensation which is typically followed by recovery to pretreatment state upon discontinuation of NSAID therapy. Patients at greatest risk of such a reaction are those with congestive heart failure, liver cirrhosis, nephrotic syndrome and overt renal disease. Such patients should be carefully monitored while receiving NSAID therapy.
Caution should be used when initiating treatment with piroxicam in patients with severe dehydration. Caution is also recommended in patients with kidney disease (see Contraindications).
Because of extensive renal excretion of piroxicam and its biotransformation products lower doses of piroxicam should be considered in patients with impaired renal function, and they should be carefully monitored (see Pharmacokinetics under Actions and Contraindications).
Skin Reactions: Serious skin reactions, some of them fatal, including exfoliative dermatitis, Steven-Johnsons syndrome and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs, including piroxicam. Patients appear to be at highest risk for these events early in the course of therapy, the onset of the event occurring in the majority of cases within the 1st month of treatment. Piroxicam should be discontinued at the 1st appearance of skin rash, mucosal lesions or any other sign of hypersensitivity.
Ophthalmologic Effects: Because of reports of adverse eye findings with NSAIDs, it is recommended that patients who develop visual complaints during treatment with Feldene Flash have an ophthalmic evaluation.
General: For patients with phenylketonuria, because of its aspartame content, Feldene Flash contains phenylalanine 0.07 mg and 0.14 mg per 10-mg dose and 20-mg dose, respectively.
Effects on the Ability to Drive or Operate Machinery: Not applicable.
Use in pregnancy & lactation: Although no teratogenic effects were seen in animal testing, the use of Feldene Flash during pregnancy is not recommended. Feldene Flash inhibits prostaglandin synthesis and release through a reversible inhibition of the cyclooxygenase enzyme. This effect, as with other nonsteroidal anti-inflammatory agents has been associated with an increased incidence of dystocia and delayed parturition in pregnant animals when drug administration was continued into late pregnancy. NSAIDs are also known to induce premature closure of the ductus arteriosus in infants.
The presence of piroxicam in breast milk has been determined during initial and long-term dosing conditions (52 days). Piroxicam appeared in breast milk at about 1-3% of the maternal plasma concentration. No accumulation of piroxicam occurred in milk relative to that in plasma during treatment. Feldene Flash is not recommended for use in nursing mothers as the clinical safety has not been established.