Generic Name: Piroxicam
Class: Other Nonsteroidal Anti-inflammatory Agents
VA Class: MS120
Chemical Name: 4-Hydroxy-2-methyl-N2-pyridinyl-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide
Molecular Formula: C15H13N3O4S
CAS Number: 36322-90-4
AUDIENCE: Health Professional, Consumer
ISSUE: FDA is strengthening an existing label warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) increase the chance of a heart attack or stroke. Based on FDAs comprehensive review of new safety information, FDA is requiring updates to the drug labels of all prescription NSAIDs. As is the case with current prescription NSAID labels, the Drug Facts labels of over-the-counter (OTC) non-aspirin NSAIDs already contain information on heart attack and stroke risk. FDA will also request updates to the OTC non-aspirin NSAID Drug Facts labels. See the FDA Drug Safety Communication (Table 1) at: for a list of non-aspirin nonsteroidal anti-inflammatory drug products.
Prescription NSAID labels will be revised to reflect the following information:
The risk of heart attack or stroke can occur as early as the first weeks of using an NSAID. The risk may increase with longer use of the NSAID.
The risk appears greater at higher doses.
It was previously thought that all NSAIDs may have a similar risk. Newer information makes it less clear that the risk for heart attack or stroke is similar for all NSAIDs; however, this newer information is not sufficient for us to determine that the risk of any particular NSAID is definitely higher or lower than that of any other particular NSAID.
NSAIDs can increase the risk of heart attack or stroke in patients with or without heart disease or risk factors for heart disease. A large number of studies support this finding, with varying estimates of how much the risk is increased, depending on the drugs and the doses studied.
In general, patients with heart disease or risk factors for it have a greater likelihood of heart attack or stroke following NSAID use than patients without these risk factors because they have a higher risk at baseline.
Patients treated with NSAIDs following a first heart attack were more likely to die in the first year after the heart attack compared to patients who were not treated with NSAIDs after their first heart attack.
There is an increased risk of heart failure with NSAID use.
BACKGROUND: The risk of heart attack and stroke with NSAIDs, either of which can lead to death, was first described in 2005 in the Boxed Warning and Warnings and Precautions sections of the prescription drug labels. Since then, FDA reviewed a variety of new safety information on prescription and OTC NSAIDs, including observational studies, a large combined analysis of clinical trials, and other scientific publications. These studies were also discussed at a joint meeting of the Arthritis Advisory Committee and Drug Safety and Risk Management Advisory Committee held on February 10-11, 2014.
RECOMMENDATION: Patients and health care professionals should remain alert for heart-related side effects the entire time that NSAIDs are being taken. Patients taking NSAIDs should seek medical attention immediately if they experience symptoms such as chest pain, shortness of breath or trouble breathing, weakness in one part or side of their body, or slurred speech.
For more information visit the FDA website at: and .
- Cardiovascular Risk
Possible increased risk of serious (sometimes fatal) cardiovascular thrombotic events (e.g., MI, stroke).1 Risk may increase with duration of use.1 Individuals with cardiovascular disease or risk factors for cardiovascular disease may be at increased risk.1 (See Cardiovascular Effects under Cautions.)
Contraindicated for the treatment of pain in the setting of CABG surgery.1
- GI Risk
Increased risk of serious (sometimes fatal) GI events (e.g., bleeding, ulceration, perforation of the stomach or intestine).1 Serious GI events can occur at any time and may not be preceded by warning signs and symptoms.1 Geriatric individuals are at greater risk for serious GI events.1 (See GI Effects under Cautions.)
Uses for Feldene
Consider potential benefits and risks of piroxicam therapy as well as alternative therapies before initiating therapy with the drug.1 Use lowest possible effective dosage and shortest duration of therapy consistent with patient's treatment goals.1
Symptomatic treatment of rheumatoid arthritis and osteoarthritis.1
Feldene Dosage and Administration
Consider potential benefits and risks of piroxicam therapy as well as alternative therapies before initiating therapy with the drug.1
To minimize the potential risk of adverse cardiovascular and/or GI events, use lowest effective dosage and shortest duration of therapy consistent with patient's treatment goals.1 Adjust dosage based on individual requirements and response; attempt to titrate to lowest effective dosage.1
Osteoarthritis or Rheumatoid ArthritisOral
Dosage reduction may be required.1
Cautions for Feldene
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Known hypersensitivity to piroxicam or any ingredient in the formulation. 1
History of asthma, urticaria, or other sensitivity reaction precipitated by aspirin or other NSAIAs.1
Treatment of perioperative pain in the setting of CABG surgery.1
Selective COX-2 inhibitors have been associated with increased risk of cardiovascular events (e.g., MI, stroke) in certain situations.112 Several prototypical NSAIAs also have been associated with increased risk of cardiovascular events.115 116 117 Current evidence (based on limited data from observational studies) suggests that use of piroxicam is not associated with increased cardiovascular risk.115
Use NSAIAs with caution and careful monitoring (e.g., monitor for development of cardiovascular events), and at the lowest effective dose for the shortest duration necessary.1
Short-term use to relieve acute pain, especially at low dosages, does not appear to be associated with increased risk of serious cardiovascular events (except immediately following CABG surgery).112
No consistent evidence that concomitant use of low-dose aspirin mitigates the increased risk of serious adverse cardiovascular events associated with NSAIAs.1 (See Specific Drugs under Interactions.)
Hypertension and worsening of preexisting hypertension reported; either event may contribute to the increased incidence of cardiovascular events.1 Use with caution in patients with hypertension; monitor BP.1 Impaired response to certain diuretics may occur.1 (See Specific Drugs under Interactions.)
Serious GI toxicity (e.g., bleeding, ulceration, perforation) can occur with or without warning symptoms; increased risk in those with a history of GI bleeding or ulceration, geriatric patients, smokers, those with alcohol dependence, and those in poor general health.1 94 102 109
For patients at high risk for complications from NSAIA-induced GI ulceration (e.g., bleeding, perforation), consider concomitant use of misoprostol;16 47 68 94 102 alternatively, consider concomitant use of a proton-pump inhibitor (e.g., omeprazole)16 68 94 or use of an NSAIA that is a selective inhibitor of COX-2 (e.g., celecoxib).16
Direct renal injury, including renal papillary necrosis, reported in patients receiving long-term NSAIA therapy.1
Potential for overt renal decompensation.1 31 48 49 50 65 Increased risk of renal toxicity in patients with renal or hepatic impairment or heart failure, in geriatric patients, in patients with volume depletion, and in those receiving a diuretic, ACE inhibitor, or angiotensin II receptor antagonist.1 31 48 65 114 (See Renal Impairment under Cautions.)
Anaphylactoid reactions reported. 1
Immediate medical intervention and discontinuance for anaphylaxis.1
Avoid in patients with aspirin triad (aspirin sensitivity, asthma, nasal polyps); caution in patients with asthma.1
Serious skin reactions (e.g., exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) reported; can occur without warning.1 Discontinue at first appearance of rash or any other sign of hypersensitivity (e.g., blisters, fever, pruritus).1
Severe reactions including jaundice, fatal fulminant hepatitis, liver necrosis, and hepatic failure (sometimes fatal) reported rarely with NSAIAs. 1
Elevations of serum ALT or AST reported.1
Monitor for symptoms and/or signs suggesting liver dysfunction; monitor abnormal liver function test results.1 Discontinue if signs or symptoms of liver disease or systemic manifestations (e.g., eosinophilia, rash) occur or if liver function test abnormalities persist or worsen.1
May inhibit platelet aggregation and prolong bleeding time. 1
Visual disturbances reported; ophthalmic evaluation recommended if visual changes occur. 1
Not a substitute for corticosteroid therapy; not effective in the management of adrenal insufficiency.1
May mask certain signs of infection.1
Obtain CBC and chemistry profile periodically during long-term use.1
Distributed into milk in humans; use not recommended.1
Safety and efficacy not established.1
Caution advised.1 Geriatric adults appear to tolerate NSAIA-induced adverse effects less well than younger individuals.96 Fatal adverse GI effects reported more frequently in geriatric patients than younger adults.96
Consider lowest effective dosage for the shortest possible duration.1
Monitor closely.1 (See Hepatic Impairment under Dosage and Administration.)
Use not recommended in patients with advanced renal disease; close monitoring of renal function advised if used.1
Common Adverse Effects
Dyspepsia, nausea, diarrhea, constipation, rash, dizziness, headache, edema, tinnitus.1
Interactions for Feldene
Pharmacokinetic interaction possible with other highly protein-bound drugs; monitor patient; dosage adjustment may be needed.1
Reduced BP response to ACE inhibitor1
Angiotensin II receptor antagonists
Reduced BP response to angiotensin II receptor antagonist118
Antacids (magnesium- or aluminum-containing)
Possible bleeding complications1
Diuretics (furosemide, thiazides)
Monitor for diuretic efficacy and renal failure1
Use with caution1
NSAIAs including aspirin: Increased risk of GI ulceration and other complications 1
Aspirin: No consistent evidence that use of low-dose aspirin mitigates the increased risk of serious cardiovascular events associated with NSAIAs112
Decreased plasma piroxicam concentrations with concomitant use of 20 mg piroxicam and 3.9 g aspirin daily 1
Concomitant use not recommended1
Thrombolytic agents (streptokinase)
Possible bleeding complications26
Use with caution26
Distributed into synovial fluid.3
Plasma Protein Binding
Advice to Patients
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Importance of reading the medication guide for NSAIAs that is provided to the patient each time the drug is dispensed.1
Risk of serious cardiovascular events with long-term use.1
Risk of GI bleeding and ulceration.1
Risk of hepatotoxicity.1
Importance of notifying clinician if signs and symptoms of a cardiovascular event (chest pain, dyspnea, weakness, slurred speech) occur.1
Importance of notifying clinician if signs and symptoms of GI ulceration or bleeding, unexplained weight gain, or edema develops.1
Importance of discontinuing piroxicam and contacting clinician if rash or other signs of hypersensitivity (blisters, fever, pruritus) develop.1 Importance of seeking immediate medical attention if an anaphylactic reaction occurs.1
Importance of discontinuing therapy and contacting clinician immediately if signs and symptoms of hepatotoxicity (nausea, fatigue, lethargy, pruritus, jaundice, upper right quadrant tenderness, flu-like symptoms) occur.1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant diseases.1
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
AHFS DI Essentials. © Copyright, 2016, American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814. Review Date: September 06, 2016.
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