Consumer medicine information

Mobilis & Mobilis D

Piroxicam

BRAND INFORMATION

Brand name

Mobilis

Active ingredient

Piroxicam

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Mobilis & Mobilis D.

What is in this leaflet

This leaflet answers some common questions about MOBILIS and MOBILIS D (hereafter referred to MOBILIS). 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 MOBILIS against the benefits they expect it will have for you.

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

Keep this leaflet with the medicine. You may need to read it again.

What MOBILIS is used for

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

MOBILIS belongs to a group of medicines called non-steroidal anti-inflammatory drugs (NSAIDs). These medicines work by relieving pain and inflammation (heat, throbbing, swelling and redness).

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

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

Before you take MOBILIS

When you must not take it

Do not take MOBILIS if you have an allergy to:

  • any medicine containing piroxicam
  • any of the ingredients listed at the end of this leaflet
  • any other medicine that is also an NSAID, including aspirin

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

Some of the symptoms of an allergic reaction may include:

  • asthma, shortness of breath, wheezing or difficulty breathing
  • nasal polyps (growths inside the nose)
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin

If you are allergic to NSAID medicines and take MOBILIS, these symptoms may be severe.

Do not take this medicine if:

  • you are pregnant or plan to become pregnant
    Like most NSAID medicines, MOBILIS 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 this medicine during pregnancy.
  • you have a peptic ulcer (i.e. a 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
  • you have severe liver disease
  • you have severe kidney disease

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

Do not take this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Before you start to take it

Tell your doctor if you have any allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

  • heartburn, indigestion, stomach ulcers or other stomach problems
  • bowel or intestinal problems
  • asthma
  • kidney or liver disease
  • heart failure
  • high blood pressure or heart problems
  • swelling of the ankles or feet (oedema)
  • a tendency to bleed

Tell your doctor if you are breast-feeding or plan to breast-feed. Your doctor can discuss with you the risks and benefits involved.

Like most NSAID medicines, the active ingredient in MOBILIS passes into breast milk and may affect your baby.

Tell your doctor if you currently have an infection. If you take MOBILIS 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 about any of the above, tell them before you start taking MOBILIS.

Taking other medicines

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

Some medicines and MOBILIS 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 that are used to stop blood clots
  • digoxin or digitoxin, medicines used to treat heart failure
  • medicines used to treat diabetes
  • certain antibiotics called sulfonamides
  • 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 supress 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
  • colestyramine, a medicine used to reduce cholesterol
  • alcohol

These medicines may be affected by MOBILIS or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

How to take MOBILIS

Follow all directions given to you by your doctor or 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 a different dose.

How to take it

Capsules
Swallow the capsule whole with a glass of water.

Dispersible Tablets
The dispersible tablet should be dissolved in a glass of water and drunk straight away.

When to take it

Take your medicine immediately after food to avoid the chance of an upset stomach.

Try to take your medicine at the same time each day. Taking it at the same time each day will have the best effect. It will also help you remember when to take it.

How long to take it for

Continue taking your medicine for as long as your doctor tells you.

This medicine helps to relieve pain and inflammation but does not cure it. It is important to keep taking your medicine even if you feel well.

If you forget to take it

If it is less than 3 hours before your next dose , skip the dose you missed and take your next dose when you are meant to.

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

Do not take a double dose to make up for the dose that you missed.

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

If you have trouble remembering to take your medicine, ask your pharmacist for some hints.

If you take too much (overdose)

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

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

While you are taking MOBILIS

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking MOBILIS.

Tell any other doctors, dentists and pharmacists who treat you that you are taking this medicine.

If you are going to have surgery, tell the surgeon that you are taking this medicine. MOBILIS can slow down blood clotting.

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

If you get an infection while taking this medicine, tell your doctor immediately. MOBILIS 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 take MOBILIS to treat any other complaints unless your doctor tells you to.

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

Do not stop taking your medicine or lower the dosage without checking with your doctor.

Things to be careful of

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

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

If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.

Be careful of ingesting alcohol whilst taking MOBILIS. As with other NSAID medicines, ingesting alcohol may increase your risk of developing stomach problems.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking MOBILIS.

This medicine helps most people but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

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

Do not be alarmed by the following lists of side effects. You may not experience any of them.

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

Tell your doctor or pharmacist 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, stomach pain, 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

The above list includes the more common side effects of your medicine. They are usually mild and short-lived.

Tell your doctor as soon as possible 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 eyes or skin, also called jaundice
  • unusual weight gain, swelling of the ankles or legs
  • symptoms of sunburn (such as redness, itching, swelling, blistering) which may occur more quickly than normal
  • fever, cough, sore throat, feeling generally unwell, skin rash (in some instances it can develop over 2 to 7 days), rashes can be painful and itchy, blistering or peeling of the skin, facial swelling, sore/red eyes or lips, in some instances reactions can be delayed by up to 3 or 4 weeks.

The above list includes serious side effects that may need urgent medical attention.

If any of the following happen, stop taking Mobilis 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 bowel 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.

Tell your doctor or pharmacist if you notice anything else that is making you feel unwell. Other side effects not listed above may also occur in some people.

After taking MOBILIS

Storage

Keep your medicine tablets in the pack until it is time to take them. If you take them out of the pack, they may not keep well.

Keep MOBILIS capsules in a cool dry place where the temperature stays below 30°C.

Keep MOBILIS D dispersible tablets in a cool dry place where the temperature stays below 25°C.

Do not store MOBILIS or any other medicine in the bathroom or near a sink. Do not leave it on a window sill or in the car. Heat and dampness can destroy some medicines.

Keep it where young children cannot reach them. A locked cupboard at least one-and-a-half meters above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking this medicine, or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

MOBILIS is available as capsules or dispersible tablets.

Capsules

  • MOBILIS 10 - brown and ivory capsule marked PM 10 and a Greek alpha symbol
  • MOBILIS 20 - light grey capsule marked PM 20 and a Greek alpha symbol

The capsules are available in packs of 50.

Dispersible Tablets

  • MOBILIS D-10 - white to slightly yellow flat bevel edged tablet, approximately 10 mm in diameter, blank on one side and breakline on reverse
  • MOBILIS D-20 - white to slightly yellow capsule shaped tablets, 17mm x 6mm, with a breakline on one side and blank on the reverse

The dispersible tablets are available in packs of 25.

Ingredients

MOBILIS capsules and dispersible tablets contain 10 mg or 20 mg of piroxicam as the active ingredient.

Capsules

The capsules also contain the following inactive ingredients:

  • lactose monohydrate
  • maize starch
  • sodium starch glycollate
  • sodium lauryl sulfate
  • magnesium stearate
  • iron oxide black (E172)
  • titanium dioxide (E171)
  • colloidal anhydrous silica
  • gelatin
  • shellac
  • propylene glycol
  • ammonium hydroxide
  • potassium hydroxide
  • iron oxide yellow (E172) [10 mg capsule only]
  • iron oxide red (E172) [10 mg capsule only]

The capsules are gluten free.

Dispersible Tablets

The dispersible tablets also contain the following inactive ingredients:

  • lactose monohydrate
  • microcrystalline cellulose
  • hydroxypropylcellulose
  • sodium stearylfumarate

The tablets are gluten free.

Supplier

Mobilis is supplied by:

Alphapharm Pty Ltd
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
www.mylan.com.au

This leaflet was prepared in July 2020.

Australian registration numbers:

Mobilis 10: AUST R 52201

Mobilis 20: AUST R 52202

Mobilis D-10: AUST R 53282

Mobilis D-20: AUST R 53284

Mobilis_cmi\Jul20/00

Published by MIMS September 2020

BRAND INFORMATION

Brand name

Mobilis

Active ingredient

Piroxicam

Schedule

S4

 

1 Name of Medicine

Piroxicam.

2 Qualitative and Quantitative Composition

Each capsule or dispersible tablet contains piroxicam as the active ingredient. Each Mobilis capsule or Mobilis D dispersible tablet contains 10 mg or 20 mg of the active ingredient.

Excipients with known effect.

Sugars as lactose and trace quantities of saccharin. The capsules also contain trace quantities of sulfites.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Mobilis 10.

Size 2 capsule with brown opaque cap and ivory opaque body printed in black "PM10" on the body and "α" on the cap.

Mobilis 20.

Size 2 capsule with light grey opaque cap and body printed in black "PM20" on the body and "α" on the cap.

Mobilis D-10 dispersible tablets.

White to slightly yellow flat bevel edged tablet, approximately 10 mm in diameter, blank on one side and breakline on reverse.

Mobilis D-20 dispersible tablets.

White to slightly yellow capsule shaped tablets, 17 mm x 6 mm, with a breakline on one side and blank on the reverse.

4 Clinical Particulars

4.1 Therapeutic Indications

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

4.2 Dose and Method of Administration

Pregnancy.

For patients in their third trimester of pregnancy or are breastfeeding, see Section 4.3 Contraindications; Section 4.6 Fertility, Pregnancy and Lactation.

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.
Mobilis D dispersible tablets should be used whole.
Do not split Mobilis D dispersible tablets into halves or use individual halves.
Mobilis D dispersible tablets should be dispersed in a minimum of 50 mL of water and then swallowed.

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 medicine 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 patients in their third trimester of pregnancy or are breastfeeding (see Section 4.6 Fertility, Pregnancy and Lactation).
Piroxicam is contraindicated in the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery.
Piroxicam is contraindicated in patients with severe heart failure.
Piroxicam is contraindicated in patients with severe renal failure.
Piroxicam is contraindicated in patients with severe hepatic impairment.
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. Caution is advised when prescribing NSAIDs to 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 antiplatelet drugs (such as aspirin), corticosteroids and 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 to 6 months, and in about 2 to 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, sulfonamides 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 (see 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.
Cases of fixed drug eruption (FDE) have been reported with piroxicam. Piroxicam should not be reintroduced in patients with history of piroxicam-related FDE. Potential cross reactivity might occur with other oxicams (see Section 4.8 Adverse Effects (Undesirable Effects)).

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome.

DRESS syndrome has been reported in patients taking NSAIDs. Some of these events have been fatal or life-threatening. DRESS syndrome typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. Other clinical manifestations may include hepatitis, nephritis, haematological abnormalities, myocarditis, or myositis. Sometimes symptoms of DRESS syndrome may resemble an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its presentation, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, discontinue the NSAID and evaluate the patient immediately.

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 times the 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 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, Use in renal impairment. Also see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions, Anti-hypertensives.

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.

Excipients.

Mobilis capsules and Mobilis D tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

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 coumarin anticoagulants and other drugs that are highly protein bound when these are administered concomitantly with piroxicam. Such drugs include coumarin anticoagulants (e.g. warfarin), hydantoins, sulfonamides and sulfonylureas.

Methotrexate.

When methotrexate is administered concurrently with NSAIDs, including piroxicam, the NSAID may decrease elimination of methotrexate resulting in increased plasma levels and increased haematological toxicity of methotrexate. Extreme care should also 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 anti-platelet 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 (AUC0-120 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.

Colestyramine.

Colestyramine 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 colestyramine.

Furosemide.

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

Anti-hypertensives.

NSAIDs can reduce the efficacy of diuretics and other anti-hypertensive 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, Cardiovascular effects, Hypertension).
In patients with impaired renal function (e.g. dehydrated patients or elderly patients with compromised renal function), the co-administration of an ACE inhibitor or an AIIA and/or a diuretic with a cyclo-oxygenase 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 administering 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, particularly in the elderly. Monitor renal function at the start of treatment with NSAIDs.

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)
Piroxicam is contraindicated in the third trimester of pregnancy.
Piroxicam should not be used during the first two trimesters of pregnancy unless the expected benefits to the mother outweigh the risks to the fetus. If there is a compelling need for NSAID treatment during the first or second trimester, limit use to the lowest effective dose and the shortest duration possible.
Data from epidemiological studies suggest an increased risk of miscarriage and congenital malformation associated with NSAID use in early pregnancy.
In animals, administration of prostaglandin synthesis inhibitors has been shown to result in increased pre- and post-implantation loss.

Oligohydramnios and neonatal renal impairment.

Use of NSAIDs in the second or third trimester may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. Oligohydramnios is generally seen after days to weeks of treatment, although it has been reported as soon as 48 hours after NSAID initiation. Oligohydramnios is usually, but not always, reversible with treatment discontinuation. Complications of prolonged oligohydramnios may, for example, include limb contractures and delayed lung maturation. In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required. Consider ultrasound monitoring of amniotic fluid if treatment extends beyond 48 hours. Discontinue treatment with NSAIDs if oligohydramnios occurs.
NSAIDs given during the third trimester of pregnancy may cause premature closure of the fetal ductus arteriosus, fetal renal impairment, inhibition of platelet aggregation, may delay labour, and delay birth. It is not known if piroxicam or its metabolites cross the placenta. However, because of the effects of drugs in this class (i.e. inhibitors of prostaglandins) on the fetal CV system, the use of piroxicam is contraindicated during the third trimester of pregnancy.
 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. Therefore, piroxicam is contraindicated for nursing mothers.

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. However, patients should be warned about the possible onset of dizziness during treatment with piroxicam.

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 to 40 mg daily.

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.

Skin and subcutaneous tissue disorders.

Skin rash (2.4%), pruritus (1.1%), onycholysis, alopecia. Photo-allergic 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%) include 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 non-thrombocytopenic 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.

In post-marketing experience, the following adverse effects have occurred from NSAID use that cannot be excluded as a class-effect:

Central nervous system.

Aseptic meningitis.

Dermatological.

Dermatitis exfoliative and erythema multiforme.

Renal.

Nephrotic syndrome, glomerulonephritis, interstitial nephritis; renal failure.

Body as a whole.

Fluid retention.

Gynaecological.

Decreased female fertility.

Pregnancy, puerperium and perinatal conditions.

Oligohydramnios, ductus arteriosus premature closure, prolonged labour, prolonged pregnancy, neonatal renal impairment.

Skin and subcutaneous tissue disorders.

Dermatitis exfoliating. Erythema multiforme, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome, fixed drug eruption.

Hepatobiliary.

Jaundice.

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.

4.9 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.

Treatment of overdosage.

In the event of acute overdosage with piroxicam, supportive and symptomatic therapy is indicated. There are no specific antidotes. Emesis and/or gastric lavage and/or activated charcoal may be considered dependent upon amount ingested and time since ingestion. 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).

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. Piroxicam 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, i.e. 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 to 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.

6 Pharmaceutical Particulars

6.1 List of Excipients

Mobilis 10 mg and 20 mg capsules contain the following inactive ingredients: lactose monohydrate, magnesium stearate, maize starch, sodium lauryl sulfate, sodium starch glycollate, and TekPrint SW-9008 Black Ink (ID 2328) or TekPrint SW-9009 Black Ink (ID 2343).
The 10 mg capsules also contain Empty Hard Gelatin Capsules Size 2 C/S FE A Ivory OP/FE N Brown OP B/C G2HCSRA0360 (ID 139609).
The 20 mg capsules also contain Empty Hard Gelatin Capsules Size 2 C/S Lt Grey OP/Lt Grey OP B/C G2HCSRA0320 (ID 139608).
Mobilis D 10 mg and 20 mg dispersible tablets contain the following inactive ingredients: hyprolose, lactose monohydrate, microcrystalline cellulose and sodium stearylfumarate.

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

Mobilis 10 mg and 20 mg capsules should be stored below 30°C.
Mobilis D dispersible tablets should be stored below 25°C.
Mobilis D dispersible tablets should be used whole. Do not split Mobilis D dispersible tablets into halves or use individual halves.

6.5 Nature and Contents of Container

Container type.

Mobilis capsules: HPDE bottle with PP child resistant closure.
Mobilis D dispersible tablets: PVC/PVDC/Al blister pack.

Pack sizes.

Mobilis 10 mg capsules: 5 (sample), 10, 14 and 50.
Mobilis 20 mg capsules: 5, 7 and 25.
Mobilis D-10 mg dispersible tablets: 10 and 50.
Mobilis D-20 mg dispersible tablets: 5 and 25.
Some strengths, pack sizes and/or pack types may not be marketed.

Australian register of therapeutic goods (ARTG).

AUST R 52201 - Mobilis 10 piroxicam 10 mg capsule bottle.
AUST R 52202 - Mobilis 20 piroxicam 20 mg capsule bottle.
AUST R 53282 - Mobilis D-10 piroxicam 10 mg dispersible tablet blister pack.
AUST R 53284 - Mobilis D-20 piroxicam 20 mg dispersible tablet blister pack.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Chemical structure.

Piroxicam is a nonsteroidal anti-inflammatory drug (NSAID) of the chemical class N-heterocyclic carboxamides of 1,2-benzothiazine-1,1-dioxide.
Chemical name: 4-hydroxy-2-methyl-N-(pyridin-2-yl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide.
Molecular formula: C15H13N3O4S.
Molecular weight: 331.35.
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.

CAS number.

36322-90-4.

7 Medicine Schedule (Poisons Standard)

S4 (Prescription Only Medicine).

Summary Table of Changes