Pfizer Healthcare Ireland

Feldene 10 mg capsules, hard

Feldene 20 mg capsules, hard

Capsules containing 10mg or 20mg piroxicam (anhydrous).

Excipients: Each capsule contains 243.24 mg lactose monohydrate.

For a full list of excipients, see section 6.1.

Capsules, hard.

10mg capsules: Red cap and blue body, coded 'PFIZER' and 'FEL10'.

20mg capsules: White opaque cap and body, coded 'PFIZER' and 'FEL20'.

Feldene is indicated for symptomatic relief of osteoarthritis, rheumatoid arthritis or ankylosing spondylitis.

Due to its safety profile (see sections 4.2, 4.3 and 4.4), Feldene is not a first line option should an NSAID be indicated. The decision to prescribe Feldene should be based on an assessment of the individual patient's overall risks (see sections 4.3 and 4.4).

Treatment should only be initiated by specialist clinicians.

The prescription of Feldene should be initiated by physicians with experience in the diagnostic evaluation and treatment of patients with inflammatory or degenerative rheumatic diseases.

The maximum recommended daily dose is 20 mg.

Children

Dosage recommendations and indications for use in children have not been established.

Elderly

Elderly, frail or debilitated patients may tolerate side-effects less well and such patients should be carefully supervised. As with other NSAID's, caution should be used in the treatment of elderly patients who are more likely to be suffering from impaired renal, hepatic or cardiac function.

Undesirable effects may be minimised by using the minimum effective dose for the shortest duration necessary to control symptoms. The benefit and tolerability of treatment should be reviewed within 14 days. If continued treatment is considered necessary, this should be accompanied by frequent review.

Given that piroxicam has been shown to be associated with an increased risk of gastrointestinal complications, the possible need for combination therapy with gastro-protective agents (e.g. misoprostol or proton pump inhibitors) should be carefully considered, in particular for elderly patients.

• History of gastro-intestinal ulceration, bleeding or perforation.

• Patient history of gastrointestinal disorders that predispose to bleeding disorders such as ulcerative colitis, Crohn's disease, gastrointestinal cancers or diverticulitis.

• Patients with active peptic ulcer, inflammatory gastrointestinal disorder or gastrointestinal bleeding.

• Concomitant use with other NSAIDs, including COX-2 selective NSAIDs and acetyl-salicylic acid at analgesic doses.

• Concomitant use with anticoagulants.

• History of previous serious allergic drug reaction of any type, especially cutaneous reactions such as erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.

• Hypersensitivity to the active substance, previous skin reaction (regardless of severity) to piroxicam, other NSAIDs and other medications.

• Peanut or soya allergy (10mg capsules)

• Allergy to peanut or soya (20mg capsules)

• Patients in whom aspirin and other non-steroidal anti-inflammatory drugs induce the symptoms of asthma, rhinitis, angioedema or urticaria.

• Moderate or severe heart failure.

Undesirable effects may be reduced by using the minimum effective dose for the shortest duration necessary to control symptoms. Patients treated with NSAIDs long term should undergo regular medical supervision to monitor for adverse events.

The clinical benefit and tolerability should be re-evaluated periodically and treatment should be immediately discontinued at the first appearance of cutaneous reactions or relevant gastrointestinal events.

Gastrointestinal (GI) Effects, Risk of GI Ulceration, Bleeding, and Perforation

NSAIDs, including piroxicam, can cause serious gastrointestinal events including 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.

NSAID exposures of both short and long duration have an increased risk of serious GI event. Evidence from observational studies suggests that piroxicam may be associated with a high risk of serious gastrointestinal toxicity, relative to other NSAIDs.

Patients with significant risk factors for serious GI events should be treated with piroxicam only after careful consideration (see sections 4.3 and below).

The possible need for combination therapy with gastro-protective agents (e.g. misoprostol or proton pump inhibitors) should be carefully considered (see section 4.2).

Serious GI Complications

Identification of at-risk subjects

The risk for developing serious GI complications increases with age. Age over 70 years is associated with high risk of complications. The administration to patients older than 80 years should be avoided.

Patients taking concomitant oral corticosteroids, selective serotonin reuptake inhibitors (SSRIs) or anti-platelet agents such as low-dose acetylsalicylic acid are at increased risk of serious GI complications (see below and section 4.5). As with other NSAIDs, the use of piroxicam in combination with protective agents (e.g. misoprostol or proton pump inhibitors) must be considered for these at-risk patients.

Patients and physicians should remain alerted for signs and symptoms of GI ulceration and/or bleeding during piroxicam treatment. Patients should be asked to report any new or unusual abdominal symptom during treatment. If a gastrointestinal complication is suspected during treatment, piroxicam should be discontinued immediately and additional clinical evaluation and treatment should be considered.

Appropriate monitoring and advice are required for patients with a history of hypertension and/or mild to moderate congestive heart failure as fluid retention and oedema have been reported in association with NSAID therapy.

Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with piroxicam after careful consideration. Similar consideration should be made before initiating longer-term treatment of patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).

Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high dose and in long term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). There are insufficient data to exclude such a risk for piroxicam.

In rare cases, non-steroidal anti-inflammatory drugs may cause interstitial nephritis, glomerulonephritis, papillary necrosis and the nephrotic syndrome. Such agents 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 a non-steroidal anti-inflammatory drug may precipitate overt renal decompensation, which is typically followed by recovery to pretreatment state upon discontinuation of non-steroidal anti-inflammatory 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 whilst receiving non-steroidal anti-inflammatory therapy.

Because of reports of adverse eye findings with non-steroidal anti-inflammatory drugs, it is recommended that patients who develop visual complaints during treatment with Feldene have ophthalmic evaluation.

As NSAIDs can interfere with platelet function, they should be used with caution in patients with intracranial haemorrhage and bleeding diathesis (see section 4.5).

Skin reactions

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs (see section 4.8). Epidemiological evidence suggests that piroxicam may be associated with a higher level of risk of serious skin reactions than non-oxicam NSAIDs. Patients appear to be at highest risk of these events early in the course of therapy, the onset of the reaction occurring in the majority of cases within the first month of treatment. Piroxicam should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Use in patients with impaired hepatic function: See above

Use in patients with renal impairment: See above

Children: See section 4.2 Posology and method of administration

Use in the elderly: The elderly have an increased frequency of adverse reactions to NSAIDs especially GI bleeding and perforation which may be fatal (see section 4.2).

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

The use of piroxicam may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of piroxicam should be considered.

Care should be taken in patients treated with any of the following drugs as interactions have been reported:

Aspirin and other NSAIDs: As with other NSAIDs, the use of piroxicam together with acetyl-salicylic acid or concomitant use with other NSAIDs, including other piroxicam formulations, must be avoided, since data are inadequate to show that such combinations produce greater improvement than that achieved with piroxicam alone; moreover, the potential for adverse reactions is enhanced (see section 4.4). Human studies have shown that concomitant use of piroxicam and acetyl-salicylic acid reduces the plasma piroxicam concentration to about 80% of the usual value.

Anticoagulants: NSAIDs, including piroxicam, may enhance the effects of anticoagulants, such as warfarin. Therefore, the use of piroxicam with concomitant anticoagulants such as warfarin should be avoided (see section 4.3).

Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see section 4.4).

Anti-hypertensives: reduced anti-hypertensive effect.

Diuretics: reduced diuretic effect. Diuretics can increase the risk of nephrotoxicity of NSAIDs.

Cardiac glycosides: NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma cardiac glycoside levels.

Lithium: decreased elimination of lithium.

Methotrexate: decreased elimination of methotrexate.

Ciclosporin: increased risk of nephrotoxicity with NSAIDs.

Corticosteroids: increased risk of gastrointestinal ulceration or bleeding (see section 4.4).

Aminoglycosides: reduction in renal function in susceptible individuals decreased elimination of aminoglycoside and increased plasma concentrations.

Probenecid: reduction in metabolism and elimination of NSAID and metabolites.

Oral hypoglycemic agents: inhibition of metabolism of sulfonylurea drugs prolonged half-life and increased risk of hypoglycaemia.

Antacids: Concomitant administration of antacids had no effect on piroxicam plasma levels.

Digoxin, digitoxin: Concurrent therapy with Feldene and digoxin, or Feldene and digitoxin did not affect the plasma levels of either drug.

Highly protein bound drugs: Feldene 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 to patients on highly protein-bound drugs.

Cimetidine: Results of two separate studies indicate a slight but significant increase in absorption of piroxicam following cimetidine administration but no significant changes in elimination rate constants or half-life. The small increase in absorption is unlikely to be clinically significant.

Use in pregnancy: Although no teratogenic effects were seen in animal testing, the safety of Feldene during pregnancy or during lactation has not yet been established. Feldene inhibits prostaglandin synthesis and release through a reversible inhibition of the cyclo-oxygenase enzyme. This effect, as with other non-steroidal anti-inflammatory drugs, has been associated with an increased incidence of dystocia and delayed parturition in pregnant animals when drug administration was continued in late pregnancy. Non-steroidal anti-inflammatory drugs are also known to induce closure of the ductus arteriosus in infants.

Nursing mothers: A study indicates that piroxicam appears in breast milk at about 1% to 3% of the maternal plasma concentrations. No accumulation of piroxicam occurred in milk relative to that in plasma during treatment for up to 52 days. Feldene is not recommended for use in nursing mothers, as clinical safety has not been established.

None known.

Gastro-intestinal: The most commonly observed adverse events are gastrointestinal in nature. Ulcerative stomatitis, anorexia, epigastric distress, gastritis, nausea, vomiting, constipation, dyspepsia, abdominal discomfort, flatulence, diarrhoea, abdominal pain, indigestion, exacerbation of colitis and Crohn's disease (see section 4.4) have been reported following administration. Less frequently gastritis has been observed. Objective evaluations of gastric mucosal appearances and intestinal blood loss show that 20mg/day of Feldene administered either in single or divided daily doses is significantly less irritating to the gastro-intestinal tract than aspirin. Peptic ulceration, perforation and gastro-intestinal bleeding (including haematemesis and melaena) in rare cases fatal, particularly in the elderly, have been reported with Feldene (see section 4.4). Rare cases of pancreatitis have been reported. Long-term administration of doses of 30mg or higher carries an increased risk of gastro-intestinal side-effects.

Elderly patients tend to be more susceptible to gastrointestinal bleeding, and as with other agents, elderly patients should be carefully monitored.

Oedema, hypertension and cardiac failure: Oedema, hypertension and cardiac failure have been reported in association with NSAID treatment. The possibility of precipitating congestive cardiac failure in elderly patients or those with compromised cardiac function should therefore be borne in mind.

CNS: Dizziness, headache, somnolence, insomnia, depression, nervousness, hallucinations, mood alterations, dream abnormalities, mental confusion, paraesthesiae and vertigo have been reported rarely.

Dermal hypersensitivity: Rash and pruritus. Onycholysis and alopecia have rarely been reported. Photosensitivity reactions occur infrequently. As with other non-steroidal anti-inflammatory drugs, toxic epidermal necrolysis (Lyell's disease) and Stevens-Johnson syndrome may develop in rare cases. Vesiculo-bullous reactions have been reported rarely.

Hypersensitivity reactions: Hypersensitivity reactions such as anaphylaxis, bronchospasm, urticaria/angioneurotic oedema, vasculitis and serum sickness have been reported rarely.

Renal function: Reversible elevations of BUN and creatinine have been reported (see section 4.4 Special warnings and precautions for use).

Haematological: Decreases in haemoglobin and haematocrit, unassociated with obvious gastro-intestinal bleeding, have occurred. Anaemia, thrombocytopenia and non-thrombocytopenic purpura (Henoch-Schoenlein), leucopenia and eosinophilia have been reported. Cases of aplastic anaemia, haemolytic anaemia and epistaxis have rarely been reported.

Liver function: Changes in various liver function parameters have been observed. As with most other non-steroidal anti-inflammatory drugs, some patients may develop increased serum transaminase levels during treatment with Feldene. Severe hepatic reactions including jaundice and cases of fatal hepatitis have been reported with Feldene. Although such reactions are rare, if abnormal liver function tests persist or worsen, if clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g. eosinophilia, rash etc), Feldene should be discontinued.

Other: The following have been reported rarely, palpitations and dyspnoea, anecdotal cases of positive ANA, anecdotal cases of hearing abnormalities, metabolic abnormalities such as hypoglycaemia, hyperglycaemia, weight increase or decrease. Swollen eyes, blurred vision and eye irritations have been reported. Routine ophthalmoscopy and slit-lamp examination have revealed no evidence of ocular changes. Malaise and tinnitus may occur.

Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke) (see section 4.4).

In the event of overdosage with Feldene, supportive and symptomatic therapy is indicated. Studies indicate that administration of activated charcoal may result in reduced absorption and reabsorption of piroxicam, thus reducing the total amount of active drug available.

Although there are no studies to date, haemodialysis is probably not useful in enhancing elimination of piroxicam since the drug is highly protein bound.

Feldene is a non-steroidal anti-inflammatory agent useful in the treatment of inflammatory conditions. Although the mode of action for this agent is not precisely understood, Feldene inhibits prostaglandin synthesis and release through a reversible inhibition of the cyclo-oxygenase enzyme.

Feldene pharmacokinetics are similar following oral or rectal administration. Following oral administration with food, there is a slight delay in the rate, but not the extent, of absorption. The plasma half-life is approximately 50 hours in man and stable plasma concentrations are maintained throughout the day on once-daily dosage. Continuous treatment with 20mg/day for periods of one year produces similar blood levels to those seen once steady state is first achieved.

Feldene is extensively metabolised and less than 5% of the daily dose is excreted unchanged in urine and faeces. Piroxicam metabolism is predominantly mediated via cytochrome P450 CYP 2C9 in the liver. One important metabolic pathway is hydroxylation of the pyridyl ring of the piroxicam side chain, followed by conjugation with glucuronic acid and urinary elimination.

Patients who are known or suspected to be poor CYP2C9 metabolizers based on previous history/experience with other CYP2C9 substrates should be administered piroxicam with caution as they may have abnormally high plasma levels due to reduced metabolic clearance.

None stated

Capsule contents

Lactose monohydrate

Magnesium stearate

Maize starch

Sodium laurilsulfate

Capsule Shell – 10mg

Cap (red)

Gelatin

Titianium dioxide (E171)

Red iron oxide (E172)

Body (blue)

Gelatin

Titanium dioxide (E171)

Indigotin (E132)

Capsule Shell – 20mg

Gelatin

Titanium dioxide (E171).

Printing Ink

Shellac (E904)

Black iron oxide (E172)

Soya lecithin (E322)

Not applicable

3 years

Do not store above 30^ºC.

10mg Capsules: Original packs of 30 capsules contained in a white HDPE bottle with a blue round ribbed cap in an outer cardboard carton.

20mg Capsules: Original packs of 30 capsules in a white HDPE bottle with a blue round ribbed cap in an outer cardboard carton.

No special requirements.

Pfizer Limited

Ramsgate Road

Sandwich

Kent CT13 9NJ

United Kingdom

10mg Capsules PA 19/24/2

20mg Capsules PA 19/24/3

Date of first authorisation: 03 April 1979

Date of last renewal: 03 April 2009

June 2011

S1B

Ref: FE 13_0