Consumer medicine information

Feldene; Feldene-D

Piroxicam

BRAND INFORMATION

Brand name

Feldene, Feldene-D

Active ingredient

Piroxicam

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Feldene; Feldene-D.

What is in this leaflet

This leaflet answers some common questions about FELDENE. It does not contain all the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking FELDENE against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Read this leaflet carefully before starting FELDENE and keep it with your medicine. You may need to read it again.

What FELDENE is used for

FELDENE treats the symptoms of

  • rheumatoid arthritis
  • osteoarthritis
  • ankylosing spondylitis, a chronic inflammatory rheumatic disorder that primarily affects, but is not limited to, the spine.

Although FELDENE can relieve the symptoms of pain and inflammation, it will not cure your condition.

FELDENE belongs to a group of medicines called Non-Steroidal Anti-inflammatory Drugs (NSAIDs). These medicines work by relieving pain and inflammation (heat, throbbing, swelling, redness).

Your doctor may have prescribed FELDENE for another reason.

Ask your doctor if you have any questions about why FELDENE has been prescribed for you.

This medicine is available only with a doctor's prescription.

Before you take FELDENE

When you must not take it

Do not take FELDENE if you have an allergy to:

  • piroxicam (the active ingredient in FELDENE) or any of the capsule or tablet ingredients listed at the end of this leaflet (see Product Description)
  • other medicines containing piroxicam e.g. PIRIFEL, FELDENE Gel. Other brands are available.
  • any medicine that is a COX-2 inhibitor
  • aspirin
  • any other medicine that is also an NSAID.

Many medicines used to treat headache, period pain and other aches and pains contain aspirin or NSAID medicines.

If you are not sure if you are taking one of these medicines, ask your pharmacist.

Symptoms of an allergic reaction to these medicines may include:

  • asthma, wheezing or shortness of breath
  • nasal polyps (growths inside the nose)
  • swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing
  • hives, itching or skin rash
  • fainting.

If you are allergic to aspirin, NSAID or COX-2 inhibitor medicines and take FELDENE, these symptoms may be severe.

Do not take FELDENE if:

  • you are pregnant, or intend on becoming pregnant, unless your doctor says otherwise.
    Like most NSAID medicines, FELDENE is not recommended for use during pregnancy. It may affect your developing baby if you take it while you are pregnant, especially during the last three months of pregnancy.
    NSAIDs have been associated with reversible infertility in some women. The use of NSAIDs in early pregnancy can increase the risk of spontaneous abortion.
    Your doctor will discuss the risks and benefits of taking FELDENE during pregnancy.
    Pregnant woman taking FELDENE should be closely monitored by their doctor if:
    - you have a peptic ulcer (i.e. stomach or duodenal ulcer), a recent history of one, or have had peptic ulcers before
    - you are vomiting blood, or material that looks like coffee grounds, or if this has happened to you recently
    - you are bleeding from the rectum (back passage), have black sticky bowel motions (stools), or bloody diarrhoea, or if this has happened to you recently
    - you have, or have had, inflammation of the lining of the stomach or bowel
    - Some examples of these conditions include Crohn's disease and ulcerative colitis.
  • if you have severe liver disease
  • if you have severe kidney disease.

If you are not sure whether you should be taking FELDENE, contact your doctor.

Do not take FELDENE if the packaging is torn or shows signs of tampering.

Do not take FELDENE if the expiry date (EXP) printed on the pack has passed.

Do not give FELDENE to children of 12 years and under. The safety and effectiveness of FELDENE in this age group have not been established.

Before you start to take it

You must tell your doctor if:

  1. you have any allergies to:
  • any other medicines including aspirin or other NSAID medicines
  • any other substances, such as foods, preservatives or dyes.
  1. you are breast-feeding or plan to breast-feed
  • Like most NSAID medicines, the active ingredient in FELDENE passes into breast milk and may affect your baby. Your doctor will discuss the benefits and risks of taking FELDENE while breast-feeding.
  1. you have or have had any medical conditions, especially the following:
  • heartburn, indigestion, stomach ulcers or other stomach problems
  • bowel or intestinal problems
  • asthma
  • kidney disease
  • liver disease
  • heart failure
  • heart disease, Use of FELDENE may increase your risk of developing a heart condition such as heart attack even if you don't have a history of heart disease.
  • high blood pressure
  • swelling of the ankles or feet (oedema)
  • a tendency to bleed.
  1. you currently have an infection
  • If you take FELDENE while you have an infection, it may hide some of the signs of an infection (e.g. pain, fever, swelling or redness). This may make you think, mistakenly, that you are better or that it is not serious.

If you have not told your doctor or pharmacist about any of the above, tell them before you start to take FELDENE.

Taking other medicines

Tell your doctor if you are taking any other medicines, including medicines you buy without a prescription from a pharmacy, supermarket or health food shop.

Some medicines and FELDENE may interfere with each other. These include:

  • aspirin (including low doses used to prevent your blood from clotting in certain heart conditions), salicylates or other NSAIDs
  • warfarin or similar medicines including Eliquis, Xarelto or Pradaxa that are used to stop blood clots
  • digoxin or digitoxin, medicines used to treat heart failure
  • tablets used to treat diabetes
  • certain antibiotics called sulphonamides
  • phenytoin, a medicine used to treat epilepsy
  • lithium, a medicine used to treat some types of depression
  • selective serotonin reuptake inhibitors, medicines used to treat depression
  • corticosteroids, medicines used to suppress the immune system or reduce inflammation
  • methotrexate, a medicine used to treat arthritis and some cancers
  • diuretics, also called fluid or water tablets
  • medicines used to treat high blood pressure
  • cholestyramine, a medicine used to reduce cholesterol.
  • alcohol

These medicines may be affected by FELDENE or may affect how well it works.

Your doctor or pharmacist has more information on medicines to be careful of or avoid while taking FELDENE.

How to take FELDENE

Follow all directions given to you by your doctor and pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions on the pack, ask your doctor or pharmacist for help.

How much to take

  • the usual dose is between 10 mg and 20 mg, taken as a single dose each day.

However, depending on your condition and how you react to the medicine, your doctor may ask you to take some other dose.

How to take it

Swallow the capsules whole with water.

If you are taking the dispersible tablets (FELDENE-D), allow the tablet to dissolve in a glass of water and then drink it straight away.

Try to take your FELDENE at the same time each day, either morning or evening.

It is best to take FELDENE immediately after food to avoid the chance of an upset stomach.

How long to take it

Keep taking FELDENE every day until your doctor tells you to stop. You may need to take FELDENE for a long time.

If you need to take FELDENE for a long time, see your doctor for regular check-ups so that he/she can monitor your condition and treatment.

If you forget to take it

If it is almost time for your next dose (e.g. within 2 or 3 hours), skip the dose you missed and take the next dose when you are meant to.

Otherwise, take it as soon as you remember, then go back to taking it as you would normally.

Do not try to make up for missed doses by taking more than one dose at a time.

If you are not sure what to do, check with your doctor or pharmacist.

If you take too much (Overdose)

Immediately telephone your doctor or Poisons Information Centre (telephone 13 11 26) for advice or go to Accident and Emergency at your nearest hospital if you think that you or anyone else may have taken too much FELDENE. Do this even if there are no signs of discomfort or poisoning.

If you take too much FELDENE, you may feel sick or have stomach pain, vomiting, headache, dizziness, drowsiness and confusion.

While you are taking it

Things you must do

If you become pregnant while taking FELDENE, tell your doctor immediately.

If you are about to start any new medicines, tell your doctor and pharmacist that you are taking FELDENE.

Tell all doctors, dentists and pharmacists who are treating you that you are taking FELDENE.

If you are going to have surgery, including dental surgery, tell your doctor or dentist that you are taking FELDENE. FELDENE can slow down blood clotting.

If you get an infection while taking FELDENE, tell your doctor. FELDENE may hide some of the signs of an infection (e.g. pain, fever, redness, swelling). You may think, mistakenly, that you are better or that the infection is not serious.

Things you must not do

Do not give FELDENE to anyone else, even if they have the same condition as you.

Do not take FELDENE to treat any other complaints unless your doctor tells you to.

Things to be careful of

Be careful driving or operating machinery until you know how FELDENE affects you.

As with other NSAID medicines, FELDENE may cause dizziness, drowsiness or blurred vision in some people.

If this happens, do not drive or do things that could be dangerous if you are not alert.

Be careful of drinking alcohol whilst taking FELDENE. As with other NSAID medicines alcohol may increase your risk of developing stomach problems.

Side effects

Check with your doctor as soon as possible if you have any problems while taking FELDENE, even if you do not think the problems are connected with the medicine or are not listed in this leaflet.

Like other medicines, FELDENE can cause some side effects. If they occur, most are likely to be minor and temporary. However, some may be serious and need medical attention.

If you are over 65 years of age, you may have an increased chance of getting side effects.

Report any side effects promptly to your doctor.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following and they worry you:

  • stomach upset including nausea (feeling sick), vomiting, heartburn, indigestion, cramps
  • loss of appetite
  • constipation, diarrhoea, pain in the stomach, wind
  • dizziness, light-headedness
  • drowsiness, sleepiness
  • headache
  • buzzing or ringing in the ears
  • sore mouth or tongue
  • hair loss or thinning
  • loose nails
  • change in mood, for example depression.

These side effects are usually mild.

Tell your doctor immediately if you notice any of the following:

  • severe pain or tenderness in the stomach
  • visual disturbances such as blurred vision
  • severe dizziness, spinning sensation
  • fast or irregular heartbeat, also called palpitations
  • difficulty hearing, deafness
  • signs of frequent or worrying infections such as fever, severe chills, sore throat or mouth ulcers
  • bleeding or bruising more easily than normal, reddish or purple blotches under the skin
  • signs of anaemia such as tiredness, being short of breath and looking pale
  • yellowing of the skin and eyes, also called jaundice
  • unusual weight gain, swelling of ankles or legs
  • symptoms of sunburn (such as redness, itching, swelling, blistering) which may occur more quickly than normal.

These are rare but serious side effects. You may need urgent medical attention.

If any of the following happen, STOP taking FELDENE and tell your doctor immediately or go to Accident and Emergency at your nearest hospital.

  • vomiting blood or material that looks like coffee grounds
  • bleeding from your back passage (rectum), black sticky motions (stools) or bloody diarrhoea
  • swelling of the face, lips or tongue which may make swallowing or breathing difficult
  • asthma, wheezing, shortness of breath
  • sudden or severe itching, skin rash, hives
  • fainting
  • pain or tightness in the chest.

These are very serious side effects. You may need urgent medical attention or hospitalisation. These side effects are rare.

Other side effects not listed above may also occur in some patients.

Tell your doctor if you notice anything else that is making you feel unwell.

After taking FELDENE

Storage

Keep your capsules or tablets in their pack until it is time to take them. If you take them out of their packaging, they will not keep well.

Keep them in a cool, dry place where the temperature stays below 30 °C. Do not store them, or any other medicine in the bathroom or near a sink.

Do not leave them in the car or on window sills. Heat and dampness can destroy some medicines.

Keep your capsules or tablets where young children cannot reach them. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking FELDENE, or the capsules or tablets have passed their expiry date, ask your pharmacist what to do with any left over.

Product description

What it looks like

FELDENE capsules are available as:

  • FELDENE 10 mg - blue/maroon, marked FEL10 on one side and Pfizer on the other.
A box contains 50 capsules.
  • FELDENE 20 mg - maroon, marked FEL20 on one side and Pfizer on the other.
A box contains 25 capsules.

FELDENE-D dispersible tablets are available as:

  • FELDENE-D 20 mg - white, scored, capsule-shaped, marked FEL/20 on one side and plain on the other.
A box contains 25 tablets.

Ingredients

FELDENE capsules contain either 10 mg or 20 mg piroxicam as the active ingredient.

FELDENE capsules also contain:

  • lactose monohydrate
  • maize starch
  • magnesium stearate
  • sodium lauryl sulfate
  • gelatin
  • erythrosine
  • titanium dioxide
  • brilliant blue FCF (133) (10 mg only)
  • indigo carmine (120) (20 mg only).

FELDENE-D dispersible tablets contain 20 mg piroxicam as the active ingredient.

FELDENE-D dispersible tablets also contain:

  • lactose monohydrate
  • cellulose
  • hydroxypropyl cellulose
  • sodium stearylfumarate.

FELDENE does not contain gluten or sugar.

Manufacturer

FELDENE is supplied in Australia by:

Pfizer Australia Pty Ltd
Sydney NSW
Toll Free Number: 1800 675 229
www.pfizer.com.au

Australian Registration Number:

FELDENE 10 mg capsules - AUST R 47656

FELDENE 20 mg capsules - AUST R 47654

FELDENE-D 20 mg - AUST R 37312.

This leaflet was prepared in April 2020

® Registered Trademark

© Pfizer Australia Pty Ltd 2015.

Published by MIMS May 2020

BRAND INFORMATION

Brand name

Feldene, Feldene-D

Active ingredient

Piroxicam

Schedule

S4

 

1 Name of Medicine

Piroxicam.

6.7 Physicochemical Properties

Feldene and Feldene-D contain the active ingredient piroxicam. Piroxicam is a nonsteroidal anti-inflammatory drug (NSAID) of the chemical class N-heterocyclic carboxamides of 1,2-benzothiazine-1, 1-dioxide.
Piroxicam is an amphoteric compound. It exhibits a weakly acidic 4-hydroxy proton (pKa 5.1) and a weakly basic pyridyl nitrogen (pKa 1.5) as determined by ultraviolet absorption spectrophotometry in methanol-water (2.5/97.5, v/v) solvent medium. It occurs as a white to off white crystalline solid, poorly soluble in water, dilute acid and most organic solvents. It is slightly soluble in alcohols and in aqueous alkaline solution. It is a hygroscopic solid, which melts in the range 196 to 200°C.

Chemical structure.


Chemical name: 4-Hydroxy-2-methyl -N-(pyridin-2-yl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide.
Molecular formula: C15H13N3O4S.
Molecular weight: 331.4.

CAS number.

36322-90-4.

2 Qualitative and Quantitative Composition

Feldene (piroxicam) 10 mg and 20 mg capsules.
Feldene-D (piroxicam) 20 mg tablets.

Excipient(s) with known effect.

Feldene 10 mg and 20 mg capsules contain lactose monohydrate.
Feldene-D dispersible 20 mg tablets contain lactose monohydrate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Feldene 10 mg capsules are blue and maroon in colour, marked FEL10 on one side and Pfizer on the other.
Feldene 20 mg capsules are maroon in colour, marked FEL20 on one side and Pfizer on the other.
Feldene-D 20 mg dispersible tablets are white, scored, capsule-shaped and marked FEL/20 on one side and plain on the other.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Piroxicam is a NSAID which also possesses analgesic and antipyretic properties. While its mode of action is not fully understood, independent studies in vitro as well as in vivo have shown that piroxicam interacts at several steps in the immune and inflammation responses through the following mechanisms:
Inhibition of prostanoid synthesis, including prostaglandins, through a reversible inhibition of the cyclooxygenase enzyme.
Inhibition of neutrophil aggregation in blood vessels.
Inhibition of lysosomal enzyme release from stimulated leucocytes.
Inhibition of polymorphonuclear cell and monocyte migration to the area of inflammation.
Inhibition of superoxide anion generation by the neutrophil.
Reduction of both systemic and synovial fluid rheumatoid factor production in patients with seropositive rheumatoid arthritis.
Piroxicam has been shown to inhibit chemotaxis of polymorphonuclear leucocytes and the migration of leucocytes in canine synovitis test. The drug also inhibits collagen induced platelet aggregation. It is established that piroxicam does not act by pituitary adrenal axis stimulation. Studies in vitro have not revealed any negative effect on cartilage metabolism.
Subacute and chronic toxicity studies have been carried out in rats, mice, dogs, and monkeys. The pathology most often seen was that characteristically associated with the animal toxicology of NSAIDs: renal papillary necrosis and gastrointestinal lesions.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Piroxicam is well absorbed following oral administration. The extent and rate of absorption are not influenced by administration in the fasting state. The plasma half-life is approximately 36 - 45 hours in man and stable plasma concentrations are maintained throughout the day on once daily dosage. After repeated administration, plasma concentrations increase for five to seven days, by which time a steady state is reached which is not exceeded following further constant daily drug administration.

Distribution.

Piroxicam is highly protein bound (99%) and therefore might be expected to displace other protein bound drugs (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions, Protein bound agents).

Metabolism and excretion.

Piroxicam is extensively metabolised and less than 5% of the daily dose is excreted unchanged in urine and faeces. One important metabolic pathway is hydroxylation of the pyridyl ring of the piroxicam side chain, followed by conjugation with glucuronic acid and urinary elimination. Approximately 5% of the dose is metabolised to and excreted as saccharin.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

4 Clinical Particulars

4.1 Therapeutic Indications

Piroxicam is indicated for symptomatic treatment of rheumatoid arthritis, osteoarthritis and ankylosing spondylitis.

4.3 Contraindications

Piroxicam should not be administered to patients with active peptic ulcerations, active gastrointestinal ulceration, bleeding or perforation, active inflammatory disease of the gastrointestinal tract or with a history of these conditions.
Piroxicam should not be used in those patients who have previously shown a hypersensitivity to the drug or in whom a hypersensitive reaction(s) (e.g. asthma, nasal polyps, angioedema or urticaria) has been precipitated by aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs), since cross sensitivity exists.
Piroxicam should not be administered to patients with a history of previous severe allergic drug reaction of any type, especially cutaneous reactions such as erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, or those who have exhibited a previous skin reaction (regardless of severity) to piroxicam.
Piroxicam is contraindicated in the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.
Piroxicam is contraindicated in patients with severe renal failure.
Piroxicam is contraindicated in patients with severe hepatic impairment.
Piroxicam is contraindicated in patients with severe heart failure.
Piroxicam should not be administered concomitantly with other NSAIDs, including cyclooxygenase-2 (COX-2) selective NSAIDs and aspirin at analgesic doses.

4.4 Special Warnings and Precautions for Use

Undesirable effects may be minimised by using the minimum effective dose for the shortest duration necessary to control symptoms. 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. Evidence from observational studies suggests that piroxicam may be associated with a high risk of serious gastrointestinal toxicity, relative to other NSAIDs. Piroxicam should only be commenced after careful weighing of the risks and benefits in each individual patient.

Cardiovascular effects.

Cardiovascular thrombotic events.

NSAIDs may cause an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction and stroke, which can be fatal. This risk may increase with dose or duration of use. The relative increase of this risk appears to be similar in those with or without known CV disease or CV risk factors. However, patients with CV disease, history of atherosclerotic CV disease or CV risk factors may be at greater risk in terms of absolute incidence, due to their increased rate at baseline. To minimise the potential risk for an adverse CV event in patients treated with piroxicam, especially those with CV risk factors, 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 CV symptoms. Patients should be informed about the signs and/or symptoms of serious CV toxicity and the steps to take if they occur (see Section 4.3 Contraindications).
There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV events associated with NSAID use.

Hypertension.

NSAIDs, including piroxicam, may lead to the onset of new hypertension or worsening of pre-existing hypertension. Patients taking anti-hypertensives with NSAIDs may have an impaired anti-hypertensive response. For example, the anti-hypertensive effect of thiazide diuretics and beta-blocking agents is antagonised by NSAIDs. NSAIDs, including piroxicam, should be used with caution in patients with hypertension. Blood pressure should be monitored closely during initiation of NSAID treatment and throughout the course of therapy.

Heart failure.

Fluid retention and oedema, (mainly ankle oedema), has been reported in 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 pre-existing congestive heart failure or hypertension should be closely monitored.

Risk of GI ulceration, bleeding and perforation with NSAID therapy.

NSAIDs, including piroxicam, can cause serious, potentially fatal gastrointestinal (GI) toxicity, including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine.
GI toxicity can occur at any time, with or without warning symptoms, in patients treated chronically with NSAID therapy. The frequency of such events may increase with dose or duration of use. Although minor upper GI problems, such as dyspepsia, are common, usually developing early in therapy, physicians should remain alert for ulceration and bleeding in patients treated chronically with NSAIDs even in the absence of previous GI tract symptoms. Administration of doses of greater than 20 mg per day carries an increased risk of GI side effects. Evidence from observational studies suggests that piroxicam may be associated with a high risk of serious GI toxicity, relative to other NSAIDs (see Section 4.3 Contraindications).
Patients most at risk of developing these types of GI complications with NSAIDs are the elderly; patients with CV disease; patients using concomitant corticosteroids, antiplatelet drugs (such as aspirin), selective serotonin reuptake inhibitors (SSRIs), patients ingesting alcohol or patients with a history of GI disease (such as ulceration, GI bleeding or inflammatory conditions); and patients with a history of smoking or alcoholism. Piroxicam should either not be prescribed, or be prescribed with caution in these patients (see Section 4.3 Contraindications).
Age over 70 years is associated with high risk of complications. The administration to patients older than 80 years should be avoided. In patients observed in clinical trials of several months to two years duration, symptomatic upper GI ulcers, gross bleeding or perforation appear to occur in approximately 1% of patients treated for 3-6 months, and in about 2-4% of patients treated for one year. Patients taking concomitant oral corticosteroids, selective serotonin reuptake inhibitors (SSRIs) or anti-platelet agents such as low dose aspirin are at increased risk of serious GI complications.
Patients and physicians should remain alert 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 GI complication is suspected during treatment, piroxicam should be discontinued immediately and additional clinical evaluation and treatment should be considered.

Asthma.

Piroxicam should be used with caution in patients with asthma because bronchial smooth muscle spasm may be aggravated by prostaglandin inhibition.

Haemorrhagic tendencies.

Piroxicam, like other NSAIDs, decreases platelet aggregation and prolongs bleeding time. This effect should be kept in mind when bleeding times are determined and in patients undergoing surgery and in patients with haemorrhagic disorders. Dosage requirements of coumarin anticoagulants and other drugs that are highly protein bound should be closely and very regularly monitored when these are administered concomitantly with piroxicam. Such drugs include warfarin, hydantoins, sulphonamides and sulfonylureas. Bleeding has been reported rarely when piroxicam as well as other NSAIDs have been administered to patients on coumarin type anticoagulants (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Concomitant use of angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor antagonists and anti-inflammatory drugs and thiazide diuretics.

The use of an ACE inhibiting drug (ACE inhibitor or angiotensin receptor antagonist), and an anti-inflammatory drug (NSAID or COX-2 inhibitor) and a thiazide diuretic at the same time, increases the risk of renal impairment. This includes use in fixed-combination products containing more than one class of drug. Concomitant use of all three classes of these medications should be accompanied by increased monitoring of serum creatinine, particularly at the institution of the treatment. The concomitant use of drugs from these three classes should be used with caution particularly in elderly patients or those with pre-existing renal impairment.

Use with oral anticoagulants.

The concomitant use of NSAIDs, including piroxicam, with oral anticoagulants increases the risk of GI and non-GI bleeding and should be given with caution. Oral anticoagulants include warfarin/ coumarin-type anticoagulants and novel oral anticoagulants (e.g. apixaban, dabigatran, rivaroxaban). Anticoagulation/ INR should be monitored in patients taking a warfarin/ coumarin type anticoagulant (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Masking of signs of infection.

As with other NSAIDs, the anti-inflammatory, antipyretic and analgesic effects of piroxicam may mask the signs of infection (pain, fever, etc.).

Ophthalmological monitoring.

Adverse ophthalmological effects have been observed with NSAIDs; accordingly, patients who develop visual disturbances during treatment with piroxicam should have an ophthalmological examination.

Skin reactions.

NSAIDs may very rarely cause serious cutaneous adverse events such as drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), exfoliative dermatitis, toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), which can be fatal and occur without warning. These serious adverse events are idiosyncratic and are independent of dose or duration of use. Evidence from observational studies suggests that piroxicam may be associated with a higher risk of severe cutaneous adverse reactions than other non-oxicam NSAIDs. Patients appear to be at highest risk of these reactions 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. Patients should be advised of the signs and symptoms of serious skin reactions and to consult their doctor at the first appearance of a skin rash, mucosal lesion or any other sign of hypersensitivity.

Use in hepatic impairment.

As with other NSAIDs, borderline elevations of liver function tests may occur in up to 15% of patients. A patient with symptoms or signs suggesting impaired hepatic function or in whom an abnormal liver function test has been reported should be evaluated for evidence of development of some severe hepatic dysfunction. These abnormalities may progress, remain essentially unchanged or be transient with continued therapy. The ALT (SGPT) is probably the most sensitive indicator of liver dysfunction. Meaningful (3 x upper limit of normal) elevations of ALT or AST (SGOT) occurred in controlled trials in less than 1% of patients.
Physician and patients should remain alert for the hepatotoxicity. Patients should be informed about the signs and/or symptoms of hepatotoxicity (e.g. nausea, fatigue, lethargy, pruritus, jaundice, abdominal tenderness in the right upper quadrant and 'flu-like' symptoms) and the steps to take should these signs and/or symptoms occur. Severe hepatic reactions, including jaundice and cases of fatal hepatitis, have been reported with piroxicam. Although such reactions are rare, if abnormal liver tests persist or worsen, if clinical signs consistent with liver disease develop or if systemic manifestations occur (e.g. eosinophilia, rash etc.), piroxicam should be discontinued.

Use in renal impairment.

As with other NSAIDs, long-term administration of piroxicam to animals has resulted in renal papillary necrosis and other pathology. In rare cases, NSAIDs may cause interstitial nephritis, glomerulitis, haematuria, proteinuria, papillary necrosis and, occasionally, 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 the pretreatment state on discontinuation of the NSAID. Patients at greatest risk of this complication include those with impaired liver or renal function (e.g. liver cirrhosis, nephrotic syndrome, overt renal disease), with heart failure, taking diuretics or the elderly. Such patients should be carefully monitored while receiving NSAID therapy.
Blood urea nitrogen elevation has been observed in some patients. These elevations are not progressive over the course of treatment with piroxicam, a plateau being reached which returns to or towards baseline levels if treatment is stopped. The rise in blood urea nitrogen as a rule is not associated with elevations in serum creatinine.
As with other NSAIDs, it is recommended that piroxicam be given under close supervision in patients with a history of impaired renal function, and periodic renal function tests carried out.
Caution should be used when initiating treatment with piroxicam in patients with severe dehydration. Caution is also recommended in patients with kidney disease (see Section 4.3 Contraindications).
Lower doses should be considered in patients with impaired renal function and they should be carefully monitored.

Use in the elderly.

See Section 4.4 Special Warnings and Precautions for Use, Risk of GI ulceration, bleeding and perforation with NSAID therapy, Concomitant use of angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor antagonists and anti-inflammatory drugs and thiazide diuretics and Use in renal impairment. Also see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions, Antihypertensives.

Paediatric use.

The use of piroxicam in children under the age of 12 years is not recommended as safety and efficacy in this age group are not established.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Anticoagulants.

The concurrent use of NSAIDs and coumarin anticoagulants (including warfarin) has been associated with severe, sometimes fatal, haemorrhage. Patients should be monitored closely if piroxicam is administered concurrently with oral anticoagulants, including warfarin/ coumarin type anticoagulants and novel oral anticoagulants (e.g. apixaban, dabigatran, rivaroxaban) (see Section 4.4 Special Warnings and Precautions for Use, Use with oral anticoagulants).
Piroxicam, like other NSAIDs, decreases platelet aggregation and prolongs bleeding time. This effect should be kept in mind when bleeding times are determined.
The exact mechanism of the interaction between warfarin and NSAIDs is unknown, but may involve enhanced bleeding from NSAID induced gastrointestinal ulceration, or an additive effect of anticoagulation by warfarin and inhibition of platelet function by NSAIDs.
Warfarin should be used in combination with piroxicam only if necessary (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions, Protein bound agents).

Protein bound agents.

Piroxicam is highly protein bound and therefore might be expected to displace other protein bound drugs. The physician should closely monitor dosage requirements of drugs that are highly protein bound when these are administered concomitantly with piroxicam. Such drugs include coumarin anticoagulants (e.g. warfarin), hydantoins, sulphonamides and sulphonylureas.

Methotrexate.

When methotrexate is administered concurrently with NSAIDs, including piroxicam, the NSAID may decrease elimination of methotrexate resulting in increased plasma levels of methotrexate. Extreme care should be exercised in giving methotrexate especially high doses, to patients on piroxicam therapy, because lethal interactions have been reported between NSAIDs and methotrexate.

Aspirin.

As with other NSAIDs, the use of piroxicam in conjunction with aspirin or the concomitant use of two NSAIDs is not recommended because data are inadequate to demonstrate that the combination produces greater benefit than with the drug alone and the potential for adverse reactions is increased (see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use).
Plasma levels of piroxicam are depressed to approximately 80% of their normal values when piroxicam is administered in conjunction with aspirin (3900 mg/day), but concomitant administration of antacids has no effect on piroxicam plasma levels.
Piroxicam interferes with the antiplatelet effect of low dose aspirin, and thus may interfere with aspirin's prophylactic treatment of CV disease.

Lithium.

NSAIDs including piroxicam have been shown to decrease the renal clearance and increase steady-state plasma concentrations of lithium. Plasma lithium concentrations should be monitored when initiating, adjusting or discontinuing concurrent piroxicam therapy.

Cimetidine.

Results of two separate studies indicate a slight increase in absorption of piroxicam following cimetidine administration but no significant changes in elimination parameters. Cimetidine increases the area under the curve (AUC 0-120 hours) and Cmax of piroxicam by approximately 13 to 15%. Elimination rate constants and half-life show no significant differences. The small but significant increase in absorption is unlikely to be clinically significant.

Cholestyramine.

Cholestyramine has been shown to enhance the oral clearance and decrease the half-life of piroxicam. To minimise this interaction, it is prudent to administer piroxicam at least 2 hours before or 6 hours after cholestyramine.

Frusemide.

As with other NSAIDs, care should be taken in the administration of piroxicam in combination with frusemide for treating cardiac failure because NSAIDs antagonise the diuretic effect of frusemide.

Antihypertensives.

NSAIDs can reduce the efficacy of diuretics and other antihypertensive drugs, including ACE inhibitors, angiotensin II antagonists (AIIAs; also known as angiotensin receptor blockers or ARBs) and beta-blockers (see Section 4.4 Special Warnings and Precautions for Use, Hypertension).
In patients with impaired renal function (e.g. dehydrated patients or elderly patients with compromised renal function), the coadministration of an ACE inhibitor or an AIIA and/or a diuretic with a cyclooxygenase inhibitor can increase the deterioration of 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 an ACE inhibitor or an AIIA and/or a diuretic. Thus, caution should be taken when administrating piroxicam with these drugs, especially in elderly patients (see Section 4.4 Special Warnings and Precautions for Use, Concomitant use of angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor antagonists and anti-inflammatory drugs and thiazide diuretics).
Patients should be adequately hydrated and the need to monitor renal function should be assessed before, and periodically during, concomitant treatment.

Cardiac glycosides (digoxin and digitoxin).

Concomitant administration of NSAIDs with cardiac glycosides (e.g. digoxin, digitoxin) may exacerbate cardiac failure, reduce glomerular filtration rate (GFR) and increase plasma glycoside levels.

Corticosteroids or selective serotonin reuptake inhibitors (SSRIs).

Concomitant administration of NSAIDs and corticosteroids or selective serotonin reuptake inhibitors (SSRIs) increases the risk of gastrointestinal ulceration or bleeding.

Ciclosporin or tacrolimus.

Concomitant administration of NSAIDs with ciclosporin or tacrolimus increases the risk of nephrotoxicity.

Poor metabolisers of CYP2C9 substrates.

Patients who are known or suspected to be poor CYP2C9 metabolisers 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.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Based on the mechanism of action, the use of NSAIDs, including piroxicam, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. In women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of NSAIDs, including piroxicam, should be considered.
(Category C)
Inhibition of prostaglandin synthesis might adversely affect pregnancy. Epidemiological studies suggest an increased risk of spontaneous abortion after use of prostaglandin synthesis inhibitors in early pregnancy. In animals, administration of prostaglandin synthesis inhibitors has been shown to result in increased pre- and post-implantation loss.
NSAIDs given during the latter part of pregnancy, may cause premature closure of the fetal ductus arteriosus, prolong labour and delay birth. Therefore, piroxicam should be avoided during the third trimester of pregnancy. Continuous treatment with NSAIDs during the last month of pregnancy should be given only on sound indications. During the last few days before expected birth, agents with an inhibitory effect on prostaglandin synthesis should be avoided.
If used during second or third trimester of pregnancy, NSAIDs may cause fetal renal dysfunction which may result in reduction of amniotic fluid volume or oligohydramnios in severe cases. Such effects may occur shortly after treatment initiation and is usually reversible. Pregnant women on piroxicam should be closely monitored for amniotic fluid volume.
Although no teratogenic effects were seen in animal testing, piroxicam should not be used in pregnant women or those likely to become pregnant unless the expected benefits outweigh the potential risk.
Studies in 6 women treated for up to 52 days have shown that piroxicam appeared in breast milk in a concentration approximately 1% to 3% of that reached in maternal plasma.
Piroxicam is not recommended for nursing mothers unless the expected benefits outweigh any potential risk, as clinical safety has not been demonstrated.

4.8 Adverse Effects (Undesirable Effects)

Results from clinical trials involving approximately 2300 patients (of whom about 400 were treated for more than one year and 170 for more than two years) indicate that about 30% of patients reported side effects at a dose of 20 mg/day. This increased with doses of 30 - 40 mg/day.

More common reactions (more than 3%).

Gastrointestinal.

These have been the most frequent side effects, occurring in about 20%. Approximately 5% discontinued therapy, with an overall incidence of peptic ulcer of about 1%. The gastrointestinal side effects included abdominal discomfort (5.7%), flatulence (5.2%), nausea (4.8%), abdominal pain (4.7%), epigastric distress (4.1%), constipation (3.8%) and diarrhoea (3.2%).

Central nervous system.

Dizziness (4.1%), headache (4.1%).

Less common reactions (less than 3%).

Auditory and vestibular.

Tinnitus, vertigo, deafness.

Laboratory abnormalities.

Elevated levels of liver enzymes (LDH, alkaline phosphatase, transaminases); elevation of blood urea nitrogen (BUN) and serum creatinine; depression of levels of haemoglobin and haematocrit; depression of levels of serum proteins, platelet and white blood cell count.

Cardiovascular.

Hypertension, tachycardia, palpitations.

Dermatological.

Skin rash (2.4%), pruritus (1.1%), onycholysis, alopecia. Photoallergic reactions have been infrequently associated with therapy. As with other NSAIDs, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), toxic epidermal necrolysis (Lyell's disease) and Stevens-Johnson syndrome may develop in rare cases. Vesiculobullous reactions have been reported rarely.

Gastrointestinal.

Anorexia, vomiting, indigestion, pancreatitis, hepatitis.

Central nervous system.

Sedation, drowsiness (2.1%), others (each less than 1%) include amnesia, anxiety, depression, malaise, hallucinations, insomnia, dream abnormalities, nervousness, paraesthesia, personality change, tremors, akathisia.

Genitourinary.

Oedema (2.7%), others (less than 1%) dysuria, urinary frequency, haematuria, oliguria, menorrhagia.

Eyes, nose, throat.

Stomatitis (1.0%), blurred vision, eye irritation/ swelling, epistaxis, glossitis.

Haematological.

Decreases in haemoglobin and haematocrit, unassociated with obvious gastrointestinal bleeding, have occurred. Anaemia has been reported. Thrombocytopenic and nonthrombocytopenic purpura (Henoch-Schonlein), petechial rash, ecchymosis, leucopenia and eosinophilia have been reported. Rare cases of aplastic anaemia and haemolytic anaemia are also reported.

Miscellaneous (each less than 1.0%).

Breathlessness, chest pain, hyperglycaemia, hypoglycaemia, thirst, chills, sweating, flushing, increased appetite, weight increase or decrease. Rare anecdotal reports of positive antinuclear antibodies.

Serious or life threatening reactions.

Peptic ulceration and gastrointestinal haemorrhage may occur. The patient should be admitted to hospital to determine the underlying lesion, followed by appropriate treatment.

Post-marketing experience.

Additional adverse events reported post-marketing include:

Central nervous system.

Aseptic meningitis.

Dermatological.

Dermatitis exfoliative, erythema multiforme.

Renal.

Nephrotic syndrome, glomerulonephritis, interstitial nephritis; renal failure.

Body as a whole.

Fluid retention.

Gynaecological.

Decreased female fertility.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

Rheumatoid arthritis, osteoarthritis and ankylosing spondylitis.

After assessing the risk versus benefit for each patient, use the minimum effective dose for the shortest duration possible. The duration of treatment should preferably be limited to 14 days. If continued treatment is considered necessary, this should be accompanied by evaluation at 14 days and subsequent frequent review with regards to efficacy, risk factors and ongoing need for treatment.
The dose should be adjusted to each individual patient's response and toleration. In studies to date, the optimal response generally has been achieved at a daily dose of 20 mg, given as a single dose. The recommended starting dose is 10 mg and administration of doses higher than 20 mg daily carries an increased risk of adverse effects and is not recommended.
Feldene-D dispersible tablets should be dispersed in a minimum of 50 mL of water and then swallowed.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.9 Overdose

Insufficient human data are available to fully assess the toxicity following acute overdosage.

Signs and symptoms.

Mild symptoms of lethargy, drowsiness and gastrointestinal upset have been reported. Rarely, severe overdose may cause hypotension, coma, respiratory depression, gastrointestinal bleeding or acute renal insufficiency. Low grade fever and sinus tachycardia have been reported following NSAID overdose. Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDs and may occur following overdose.

Recommended treatment.

In the event of overdosage with piroxicam, 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. Activated charcoal is most effective when administered within 1-hour of ingestion. In patients who are not fully conscious or who have an impaired gag reflex, consideration should be given to administering activated charcoal via a nasogastric tube once the airway is protected. Haemodialysis, forced diuresis or haemoperfusion are probably ineffective in enhancing elimination, since the drug is highly protein bound. There appears to be no indication for alkalinisation of the urine.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Feldene capsules contain the following inert ingredients: lactose monohydrate, maize starch, magnesium stearate/sodium lauryl sulfate 9:1 blend, gelatine, erythrosine, titanium dioxide, brilliant blue FCF (10 mg capsule only), indigo carmine (20 mg capsule only).
Feldene-D dispersible tablets contain the following inert ingredients: lactose monohydrate, microcrystalline cellulose, hyprolose, sodium stearyl fumarate.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 30°C.

6.5 Nature and Contents of Container

Feldene 10 mg capsules are available in PVC/Al blister packs of 50 capsules.
Feldene 20 mg capsules are available in PVC/Al blister packs of 25 capsules.
Feldene-D 20 mg dispersible tablets are available in PVC/Al blister packs of 25 tablets. Not all pack sizes may be marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

Summary Table of Changes