Feldene Generic Name & Formulations
- 10mg: Maroon and blue #322
- 20mg: Maroon #323
Store at room temperature 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F).
Feldene Dosage and Administration
Prior to Treatment Evaluations
Correct volume status in dehydrated or hypovolemic patients.
Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals. Observe the response to initial therapy and then adjust the dose and frequency to the patient’s needs.
For rheumatoid arthritis and osteoarthritis treatment, the dosage is 20mg once daily. The daily dose may be divided.
Because Feldene has a long half-life, steady-state blood levels are not reached for 7-12 days. The effect of therapy should not be assessed for 2 weeks as there is a progressive increase in response over several weeks.
Feldene Boxed Warnings
Cardiovascular Thrombotic Events
Clinical trials of several COX-2 selective and nonselective NSAIDs of up to 3 years duration have shown an increased risk of serious cardiovascular thrombotic events, including myocardial infarction (MI) and stroke.
- Incidence of serious cardiovascular thrombotic events greater in patients with known cardiovascular disease or risk factors.
- Increased risk has been observed as early as the first weeks of treatment (based on observational studies).
- Higher doses have been linked to increased cardiovascular thrombotic risk.
- To minimize risk, use the lowest effective dose for the shortest time possible.
- Evidence regarding use of aspirin to mitigate risk has not been consistent; aspirin coadministered with piroxicam may increase the risk of serious GI adverse events.
NSAIDs are contraindicated in the setting of coronary artery bypass graft (CABG) surgery. Based on findings from 2 large studies evaluating a COX-2 selective NSAID, use in the first 10-14 days after CABG resulted in an increased incidence of MI and stroke.
Among patients treated with NSAIDs in the post-MI period, there was an increase in the risk of reinfarction, cardiovascular-related death, and all-cause mortality beginning in the first week of treatment, according to observational studies.
- Incidence of death in the first year in the NSAID cohort: 20 per 100 person years
- Incidence of death in the first year in the non-NSAID cohort: 12 per 100 person years
- The relative risk of death in NSAID users persisted over at least the next 4 years of follow up.
Avoid the use of piroxicam in patients with recent MI unless the benefits are expected to outweigh the risk of recurrent cardiovascular thrombotic events. Monitor for signs of cardiac ischemia if used in patients with recent MI.
- NSAIDs can lead to new onset hypertension or worsening of pre-existing hypertension.
- Impaired responses to thiazides and loop diuretics possible when taken with NSAIDs.
- Use with caution in patients with hypertension; monitor BP.
Heart Failure and Edema
- Meta-analysis of randomized controlled trials showed ~2-fold increase in hospitalizations for heart failure in patients treated with COX-2 selective and nonselective NSAIDs compared with placebo.
- NSAID use was also associated with increased risk of MI, hospitalization for heart failure and death in a Danish National Registry study of patients with heart failure.
- Fluid retention and edema have been observed in some patients treated with NSAIDs.
- Piroxicam may blunt the cardiovascular effects of diuretics, ACE inhibitors, ARBs.
- Avoid use in patients with severe heart failure unless benefits outweigh risk of worsening heart failure.
- Monitor for signs of worsening heart failure if piroxicam is used in patients with severe heart failure.
Gastrointestinal (GI) Effects
- NSAIDs can cause serious GI adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine.
- These can occur at any time, with or without warning symptoms (only 1 in 5 patients who develop a serious upper GI adverse event on NSAIDs is symptomatic).
- Incidence of upper GI ulcers, gross bleeding, or perforation with NSAIDs: ~1% of patients treated for 3-6 months and 2-4% of patients treated for 1 year.
- Prior history of ulcer disease or GI bleeding: Prescribe with caution; these patients have a >10-fold increased risk for developing GI bleed vs those without these risk factors.
- Other factors that increase risk of GI bleed in patients treated with NSAIDs: Concomitant oral corticosteroids, anticoagulants, aspirin, SSRIs; longer duration of NSAID use; smoking; alcohol; older age; and poor general health status.
- Patients with advanced liver disease and/or coagulopathy are at an increased risk for GI bleeding.
- Use the lowest effective dose for the shortest possible duration to minimize the potential for GI adverse events.
- If a serious GI adverse event occurs, discontinue NSAID therapy.
- Alternative therapies should be explored for patients considered at high risk for GI effects.
- Elevations of ALT and AST without any other signs and symptoms may occur in up to 15% of patients taking NSAIDs.
- For patients with symptoms/signs suggesting liver dysfunction, or in whom abnormal liver test has occurred: Evaluate for more severe hepatic reaction.
- Discontinue piroxicam if abnormal liver tests persist or worsen, if clinical signs/symptoms of liver disease develop, or if systemic manifestations (eg, eosinophilia, rash) occur.
- Long-term NSAID use has been associated with renal papillary necrosis and other renal injury.
- Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion; in these patients administration of NSAIDs may cause a dose-dependent reduction in prostaglandin formation and, secondarily in renal blood flow, which may result in overt renal decompensation.
- Patients with impaired renal function, heart failure, liver dysfunction, on diuretics, ACE inhibitors, or ARBs, those who are volume-depleted and the elderly are at greatest risk of this reaction; monitor renal function.
- Discontinuing NSAID therapy usually leads to recovery.
- Piroxicam is not recommended in patients with advanced renal disease; if treatment must be initiated, close monitoring of renal function is advised.
- Increases in serum potassium concentration have been reported with NSAIDs.
- Piroxicam should not be given to patients with the aspirin triad.
- This symptom complex typically occurs in asthmatic patients who experience rhinosinusitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs.
- Use with caution in patients with preexisting asthma.
- NSAIDs can cause serious skin adverse events including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis.
- Discontinue treatment at the first appearance of skin rash or any other sign of hypersensitivity.
- DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) has been reported in patients taking NSAIDs.
- Symptoms of DRESS: Fever, rash, lymphadenopathy, and/or facial swelling; may resemble acute viral infection.
- Other clinical manifestations of DRESS: Hepatitis, nephritis, hematological abnormalities, myocarditis, myositis.
- Discontinue treatment if signs/symptoms of DRESS develop.
- Anemia is sometimes seen in patients receiving NSAIDs.
- Check hemoglobin/hematocrit if patients exhibit signs/symptoms of anemia.
Masking of Inflammation and Fever
- Piroxicam reduces inflammation, and may reduce fever, thereby diminishing the utility of diagnostic signs in detecting infections.
- Consider periodic CBC, chemistry profile for patients on long-term NSAID therapy.
- Adverse eye reactions have been reported with NSAIDs.
- For patients who develop eye complaints, ophthalmologic studies are recommended.
NSAIDs should be avoided in pregnant women at about 30 weeks gestation and later as they increase the risk of premature closure of the fetal ductus arteriosus.
Use of NSAIDs at about 20 weeks gestation or later may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. These adverse events are seen, on average, after days or weeks of treatment. Rarely, oligohydramnios has been reported 48 hours after NSAID initiation. Oligohydramnios is often reversible with treatment discontinuation.
If NSAID treatment is necessary between 20 and 30 weeks gestation, limit treatment to the lowest effective dose for the shortest possible duration.
If piroxicam treatment extends beyond 48 hours, consider ultrasound monitoring of amniotic fluid. Discontinue if oligohydramnios occurs.
Nursing Mother Considerations
Limited data suggest piroxicam is excreted in human milk at ~1 to 3% of the maternal concentration. No accumulation of piroxicam occurred in milk relative to that in maternal plasma during treatment. Consider the mother’s clinical need vs the potential for adverse effects on the breastfed infant.
Safety and effectiveness in pediatric patients have not been established.
Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and it may be useful to monitor renal function.
Elderly patients are at greater risk for NSAID-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions; use the lowest effective dose.
Renal Impairment Considerations
Monitor patients with significantly impaired renal function closely.
Not recommended in patients with advanced renal disease; if needed, close monitoring of the patient’s renal function is advisable.
Hepatic Impairment Considerations
Patients with hepatic disease may require reduced doses of piroxicam as hepatic metabolism accounts for a substantial portion of piroxicam elimination.
Other Considerations for Specific Populations
NSAIDs may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. Consider withdrawing piroxicam in women who have difficulties conceiving or who are undergoing investigation of infertility.
Poor metabolizers of CYP2C9 substrates: Consider dose reduction as these patients may have abnormally high plasma levels due to reduced metabolic clearance.
Piroxicam is well absorbed following oral administration. Drug plasma concentrations generally peak within 3 to 5 hours after administration.
99% protein bound.
Plasma half-life is ~50 hours. Prolonged half-life results in the maintenance of stable plasma concentrations throughout the day on once daily doses and significant accumulation upon multiple dosing. Most patients approximate steady state plasma levels within 7 to 12 days.
Renal, fecal excretion.
Drugs That Interfere With Hemostasis
- Piroxicam and anticoagulants (eg, warfarin) have a synergistic effect on bleeding.
- Concomitant use of drugs that interfere with serotonin reuptake and NSAIDs may potentiate bleeding risk (based on case-control and epidemiological studies).
- Concomitant anticoagulants (eg, warfarin), antiplatelets (eg, aspirin), SSRIs, SNRIs: Monitor for signs of bleeding.
- Concomitant use of aspirin (analgesic doses) does not produce a greater therapeutic effect and may result in greater GI adverse reactions than NSAIDs alone.
- Concomitant aspirin lowers piroxicam concentrations (clinical significance unknown).
- Because of the increased risk for bleeding, concomitant aspirin is not recommended.
- Piroxicam is not a substitute for low dose aspirin for cardiovascular protection.
ACE Inhibitors, ARBs, and Beta-Blockers
- NSAIDs may diminish the antihypertensive effect of these agents; monitor blood pressure.
- Deterioration of renal function possible when NSAIDs coadministered with ACE inhibitors or ARBs in patients who are elderly, volume-depleted, or have renal impairment; monitor for signs of worsening renal function.
- Patients should be adequately hydrated.
- Assess renal function at the start of concomitant treatment and periodically thereafter.
- NSAIDs reduce the natriuretic effect of loop diuretics (eg, furosemide) and thiazide diuretics in some patients resulting from renal prostaglandin synthesis inhibition.
- If concomitant use is needed, observe for worsening renal function and evaluate antihypertensive effects.
- Piroxicam increases serum concentration and prolongs the half-life of digoxin.
- Monitor serum digoxin levels.
- NSAIDs may elevate lithium levels (by 15%) and reduce lithium clearance (by 20%) due to inhibition of renal prostaglandin synthesis.
- Monitor patients for lithium toxicity.
- Increased risk of methotrexate toxicity (eg, neutropenia, thrombocytopenia, renal dysfunction) with concomitant piroxicam.
- Monitor patients for methotrexate toxicity.
- Concomitant use may increase cyclosporine-associated nephrotoxicity.
- Monitor for signs of worsening renal function.
NSAIDs and Salicylates
- GI toxicity may be increased with concomitant use of piroxicam and NSAIDs or salicylates.
- Concomitant use is not recommended as there is little or no increase in efficacy.
- Concomitant use may increase risk of pemetrexed-associated myelosuppression, renal and GI toxicity.
- CrCl 45-79mL/min: monitor for toxicity when piroxicam is used with pemetrexed.
- Avoid NSAIDs with short elimination half-lives (eg, diclofenac, indomethacin) for a period of 2 days before, the day of, and 2 days following administration of pemetrexed.
- Patients taking NSAIDs with longer half-lives (eg, meloxicam, nabumetone) should interrupt dosing for at least 5 days before, the day of, and 2 days after pemetrexed administration.
Highly Protein Bound Drugs
- Piroxicam is a highly protein bound drug and therefore may be expected to displace other protein bound drugs.
- Monitor when piroxicam is administered with other highly protein bound drugs.
- Concomitant use may increase the risk of GI ulceration and bleeding.
- Monitor for signs of bleeding.
Feldene Adverse Reactions
Feldene Clinical Trials
The effectiveness of Feldene has been established for both acute exacerbations and long term management of rheumatoid arthritis and osteoarthritis in controlled clinical trials.
The therapeutic effects of Feldene are seen early in the treatment of both RA and osteoarthritis with a progressive increase in response over 8-12 weeks. Efficacy was measured by pain relief and, when present, a reduction in inflammation.
Doses of Feldene 20mg/day were observed to have a therapeutic effect comparable to therapeutic doses of aspirin, with a lower incidence of minor GI effects and tinnitus.
Feldene has been administered concomitantly with fixed doses of gold and corticosteroids. The existence of a “steroid sparing” effect has not been adequately studied to date.
Feldene Patient Counseling
Be alert to the symptoms of cardiovascular thrombotic events, as the use of NSAIDs may increase the risk of these events.
Be alert to the signs/symptoms of GI tract ulcerations and bleeding (eg, epigastric pain, dyspepsia, melena, and hematemesis)’ follow-up is important if GI effects occur. Risk of GI toxicity is increased with concomitant use of other NSAIDs,including OTC medications that contain NSAIDs.
Be alert to the symptoms of CHF (eg, shortness of breath, unexplained weight gain, or edema).
Be alert to the signs/symptoms of serious skin manifestations; use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.
Hepatotoxicity is possible; discontinue therapy if symptoms such as nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms occur.
Seek immediate emergency help if anaphylactic/anaphylactoid reaction (eg,difficulty breathing, swelling of the face or throat) occurs.
Pregnant patients: Avoid piroxicam starting at 30 weeks gestation.
Women of reproductive age: NSAIDs have been associated with a reversible delay in ovulation.