Consumer medicine information

Moxicam Capsules

Meloxicam

BRAND INFORMATION

Brand name

Moxicam Capsules

Active ingredient

Meloxicam

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Moxicam Capsules.

What is in this leaflet

This leaflet answers some common questions about Moxicam.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have benefits and risks. Your doctor has weighed the risks of you taking Moxicam against the benefits expected for you.

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

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

What Moxicam is used for

Moxicam is used to treat the symptoms of osteoarthritis and rheumatoid arthritis. Both of these diseases mainly affect the joints causing pain and swelling.

Although Moxicam can relieve symptoms such as pain and inflammation, it will not cure your condition.

Moxicam belongs to a family of medicines called Non-Steroidal Anti-inflammatory Drugs (NSAIDs). These medicines work by relieving pain and inflammation.

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

It is available only with a doctor's prescription.

Before you take Moxicam

When you must not take it

Do not take Moxicam if you have an allergy to:

  • any medicine containing meloxicam (the active ingredient)
  • any of the other ingredients listed at the end of this leaflet. This includes rare inherited conditions of galactose intolerance.
  • aspirin or any other NSAID medicine.

Some of the symptoms of an allergic reaction may include:

  • rash, itching or hives on the skin
  • swelling of the face, lips, tongue or other parts of the body
  • shortness of breath, wheezing or troubled breathing.

Do not take Moxicam if:

  • you are about to undergo coronary artery bypass graft surgery
  • you have a disease of the heart with shortness of breath, and swelling of the feet or lips due to fluid build-up
  • you experience bleeding from the stomach, gut or any other bleeding
  • you have had a stroke resulting from a bleed in the brain or have a bleeding disorder
  • have a galactose intolerance
  • you currently have a peptic (stomach) ulcer
  • you have or have had inflammation of the lining of the stomach or intestines (e.g. Crohn's Disease or Ulcerative Colitis)
  • you have severe liver or kidney problems
  • you are currently taking other medicines known as: sulfinpyrazone (used to treat gout), fluconazole (used to treat fungal infections) or certain sulfur antibiotics (eg. sulfaphenazole or sulfamethoxazole).

Do not take this medicine if you are pregnant, or think you may be pregnant. It may affect your developing baby if you take it during pregnancy.

Do not breast-feed if you are taking this medicine. The active ingredient in Moxicam passes into breast milk and there is a possibility that your baby may be affected.

Do not give this medicine to children and adolescents under 18 years of age. Safety and effectiveness in children younger than 18 years 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 Moxicam, talk to your doctor.

Before you start to take it

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

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

  • high blood pressure or fluid retention
  • diabetes
  • high cholesterol
  • heartburn, indigestion, ulcers or other stomach problems
  • kidney or liver problems
  • asthma or any other breathing problems.

Tell your doctor if you are pregnant, planning to become pregnant. Like most NSAID medicines, meloxicam is not recommended for use during pregnancy. If there is a need to consider meloxicam during your pregnancy, your doctor will discuss with you the benefits and risks of using it.

Tell your doctor if you are using an IUD (intrauterine device) for birth control. NSAID medicines, like meloxicam may decrease the effectiveness of IUDs.

Tell your doctor if you currently have an infection. Moxicam may hide some of the signs of an infection. 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 taking Moxicam.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you buy without a prescription from your pharmacy, supermarket or health food shop. Some medicines and Moxicam may interfere with each other. These include:

  • aspirin, salicylates or other NSAID medicines
  • medicines used to thin your blood (e.g., warfarin, heparin and ticlopidine
  • medicines used to treat high blood pressure and other heart problems (e.g. ACE inhibitors, angiotensin receptor antagonists and diuretics, also called fluid or water tablets)

When taken together these medicines can cause kidney problems.

  • lithium, a medicine used to treat some types of depression
  • antidepressants called selective serotonin reuptake inhibitors (SSRIs)
  • methotrexate, a medicine used to treat rheumatoid arthritis and some types of cancer
  • ciclosporin, a medicine used to treat rheumatoid arthritis and certain problems with the immune system.
  • terfenadine and astemizole, medicines used to prevent or relieve the symptoms of allergy, such as hay fever or insect stings
  • medicines to treat diabetes
  • colestyramine, a medicine used to treat high cholesterol levels in the blood
  • corticosteroids (drugs usually used to treat inflammatory conditions, such as skin rash and asthma)
  • some medicines used to treat infections (e.g. erythromycin, sulfur antibiotics, ketoconazole, itraconazole)
  • some medicines used to treat irregular heart beats (e.g. amiodarone and quinidine)
  • pemetrexed, a medicine used in the treatment of certain lung cancers.

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

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

How to take Moxicam

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 container label, ask your doctor or pharmacist.

How much to take

For the treatment of osteoarthritis
The usual dose of Moxicam is 7.5 mg, taken as a single dose each day.

Depending on the severity of your condition and your response to treatment, your doctor may increase this dose to 15mg taken as a single dose each day.

For the treatment of rheumatoid arthritis
The usual dose of Moxicam is 15 mg taken as a single dose each day.

Depending on your response, your doctor may reduce this dose to 7.5mg taken as a single dose each day.

The maximum recommended daily dose of Moxicam is 15 mg.

For patients with kidney problems undergoing dialysis, the maximum recommended daily dose is 7.5 mg.

Ask your doctor for more information if you have been advised to take a different dose.

How to take it

Swallow the tablets with a full glass of water.

When to take it

Take your medicine at about the same time each day, either morning or evening. Taking it at the same time each day will have the best effect. It will also help you remember when to take it.

Take Moxicam during or immediately after food. This will reduce the chance of a stomach upset.

How long to take it for

Continue taking your medicine for as long as your doctor tells you. This medicine will not cure your condition but it does not cure it. It is important to keep taking your medicine even if you feel well.

You may need to take Moxicam for a long time. Keep in touch with your doctor during this time.

If you forget to take it

If it is almost time for your next dose (e.g. within 2-3 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 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 you or anyone else may have taken too much Moxicam. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

Symptoms of an overdose with Moxicam may include:

  • nausea and/or vomiting
  • headache
  • drowsiness
  • blurred vision
  • dizziness
  • fits or seizures
  • low blood pressure
  • difficulty in breathing
  • impaired consciousness
  • kidney failure.

While you are taking Moxicam

Things you must do

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

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

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

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

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

Things you must not do

Do not use Moxicam 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 Moxicam affects you. As with other NSAID medicines, Moxicam 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.

Side effects

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

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the 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, vomiting, heartburn, indigestion, belching, cramps or pain
  • constipation, diarrhoea or wind
  • headache
  • 'flu'-like symptoms, including runny or blocked nose, coughing, sore mouth or throat, discomfort when swallowing
  • dizziness or light-headedness
  • skin rashes, which may be caused by exposure to sunlight, can blister and may take on the appearance of a severe burn, or itching
  • increase in blood pressure
  • tinnitus, buzzing, ringing or other persistent noise in the ears.

The above list includes the more common side effects of your medicine. These side effects are usually mild.

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

  • blurred vision
  • any change in the amount or colour of your urine (red or brown) or any pain or difficulty experienced when urinating
  • severe pain or tenderness in the stomach
  • severe dizziness
  • collapse or fainting, shortness of breath or tiredness, chest pain, swollen or sore leg veins
  • yellowing of the skin and eyes, known as jaundice
  • flaking of the skin
  • swelling of your ankles, legs or other parts of your body
  • signs of anaemia, such as tiredness, being short of breath and looking pale
  • irritation of your mucous membranes (e.g. lips, mouth, eyes or genitals).

The above list includes serious side effects that may require medical attention. Serious side effects are rare.

If any of the following happen, stop taking Moxicam and either tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

  • vomiting of 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 or shortness of breath
  • sudden or severe itching, skin rash or hives
  • weakness in one part or side of your body, slurred speech or visual disturbances

The above list includes 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 that is making you feel unwell.

Other side effects not listed above may occur in some people.

After taking Moxicam

Storage

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

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

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

Keep it where children cannot reach it. 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 Moxicam, or your tablets have passed their expiry date, ask your pharmacist what to do with any that are left over.

Product description

What it looks like

Moxicam tablets are available in two strengths: -

  • Moxicam 7.5mg - Light green / light green, size ‘2’ hard gelatin capsules filled with light yellow coloured granules.
  • Moxicam 15mg - Light green/light yellow, size ‘2’ hard gelatin capsules filled with light yellow coloured granules.

Ingredients

The active ingredient in Moxicam is meloxicam.

Each Moxicam 7.5 tablet contains 7.5 mg of meloxicam.

Each Moxicam 15 tablet contains 15 mg of meloxicam.

The tablets also contain the following inactive ingredients:

  • lactose monohydrate
  • maize starch
  • sodium citrate
  • magnesium stearate
  • Brilliant Blue FCF
  • Sunset Yellow FCF
  • gelatin
  • titanium dioxide
  • quinolone yellow (15 mg strength only)

Supplier

Moxicam is supplied by:

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

Australian registration numbers:

Moxicam 7.5 - AUST R 232584

Moxicam 15 - AUST R 232585

This leaflet was prepared on
January 2022

Published by MIMS March 2022

BRAND INFORMATION

Brand name

Moxicam Capsules

Active ingredient

Meloxicam

Schedule

S4

 

1 Name of Medicine

Meloxicam.

2 Qualitative and Quantitative Composition

Moxicam capsules are intended for oral administration. Each capsule contains either 7.5 mg or 15 mg meloxicam as the active ingredient.

Excipients of known effect.

Sugars as lactose.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Moxicam 7.5 mg capsules.

Light green/Light green, size '2' hard gelatin capsules filled with light yellow coloured granules.

Moxicam 15 mg capsules.

Light green/Light yellow, size '2' hard gelatin capsules filled with light yellow coloured granules.

4 Clinical Particulars

4.1 Therapeutic Indications

Meloxicam is indicated for the symptomatic treatment of osteoarthritis and rheumatoid arthritis.

4.2 Dose and Method of Administration

Meloxicam should be used at the lowest dose and for the shortest duration consistent with effective treatment.
The maximum recommended daily dose of meloxicam is 15 mg. A dose of 15 mg/day should not be exceeded. As a dose for children has not been established, use should be restricted to adults (see Section 4.4 Special Warnings and Precautions for Use, Paediatric use).
The dose of meloxicam in patients with end-stage renal failure on haemodialysis should not exceed 7.5 mg/day (see Section 5.2 Pharmacokinetic Properties, Renal impairment). No dose reduction is required in patients with mild or moderate renal impairment (i.e. in patients with a creatinine clearance of greater than 25 mL/min) nor in patients with mild to moderate hepatic impairment. In non-dialysed patients with severe renal impairment meloxicam is contraindicated (see Section 4.3 Contraindications).
In patients with an increased risk of adverse reactions, e.g. a history of gastrointestinal disease or risk factors for cardiovascular disease, the treatment should be started at a dose of 7.5 mg/day and increased to 15 mg/day only if clinically justified.

Osteoarthritis.

The recommended dose of meloxicam is 7.5 mg once daily, to be swallowed with fluid, in conjunction with food. Depending on the adequacy of response, the severity of the arthritic condition and the patient's concomitant diseases, the dose may be increased to 15 mg/day. Patients should generally be maintained on the lowest dose consistent with achieving a satisfactory therapeutic response.

Rheumatoid arthritis.

The recommended dose of meloxicam is 15 mg once daily, to be swallowed with fluid, in conjunction with food. Depending on the adequacy of response and the severity of the condition, the dose may be reduced to 7.5 mg/day. Patients should generally be maintained on the lowest dose consistent with achieving a satisfactory therapeutic response.

Pregnancy.

See Section 4.3 Contraindications; Section 4.6 Fertility, Pregnancy and Lactation.

4.3 Contraindications

Peri-operative treatment of pain in patients undergoing coronary artery bypass graft surgery (CABG).
Known hypersensitivity to meloxicam or any excipients in this medicine. There is a potential for cross sensitivity to aspirin and other NSAIDs.
Signs/symptoms of asthma, nasal polyps, angioedema or urticaria, following the administration of aspirin or other NSAIDs.
Active gastrointestinal ulceration/ perforation.
Active inflammatory bowel disease (Crohn's disease or ulcerative colitis).
Patients with severe hepatic impairment.
Non-dialysed severe renal insufficiency.
Severe uncontrolled heart failure.
Children and adolescents under 18 years of age.
Pregnancy.
Breastfeeding.
Concomitant administration of drugs known to inhibit CYP 2C9 (e.g. sulfaphenazole, sulfinpyrazone, sulfamethoxazole and fluconazole).
The use of meloxicam is contraindicated in patients with rare hereditary galactose intolerance, due to the lactose content in this medicine.
As with all NSAIDs, meloxicam is contraindicated in patients with recent cerebrovascular bleeding or established systemic bleeding disorders.

4.4 Special Warnings and Precautions for Use

Gastrointestinal effects.

As with other NSAIDs gastrointestinal (GI) bleeding, ulceration or perforation, potentially fatal, can occur at any time during treatment, with or without warning symptoms or a previous history of serious GI events. The consequences of such events are generally more serious in the elderly. Minor upper GI problems, such as dyspepsia, are common and may occur at any time during NSAID therapy. Therefore, physicians and patients should remain alert for ulceration and bleeding, even in the absence of previous GI tract symptoms. Patients should be informed about the signs and/or symptoms of serious GI toxicity and the steps to take if they occur. The utility of periodic laboratory monitoring has not been demonstrated, nor has it been adequately assessed. Only one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic. It has been demonstrated that upper GI ulcers, gross bleeding or perforation, caused by NSAIDs, appear to occur in approximately 1% of patients treated for 3-6 months and in about 2-4% of patients treated for one year. These trends continue, increasing the likelihood of developing a serious adverse GI event at some time during the course of therapy. However, even short term therapy is not without risk.
Studies have shown that patients with a prior history of ulcer disease and/or gastrointestinal bleeding and who use NSAIDs have a greater than 10-fold higher risk of developing a gastrointestinal bleed than patients with neither of these factors.
Caution is advised in patients most at risk of developing a gastrointestinal complication with NSAIDs: the elderly, patients using any other NSAID or aspirin concomitantly or patients with a prior history of or recent gastrointestinal disease such as ulceration and gastrointestinal bleeding.
NSAIDs should be prescribed with caution in patients with a prior history of or recent ulcer disease or gastrointestinal bleeding.
For high risk patients, alternate therapies that do not involve NSAIDs should be considered.
In clinical trials, meloxicam has been shown to cause fewer GI adverse events (including dyspepsia, abdominal pain, nausea, vomiting etc.) than other NSAIDs with which it has been compared (see Table 1).
Caution should be exercised when treating patients with a history of upper gastrointestinal disease and in patients receiving treatment with anticoagulants. Patients with GI symptoms should be monitored. Meloxicam therapy should cease if peptic ulceration or GI ulceration or bleeding occurs.
Co-administration of meloxicam with drugs known to inhibit CYP 3A4 should be undertaken with caution. A combination of meloxicam and substances known to inhibit both CYP 3A4 and CYP 2C9 should be avoided because of the increased risk of toxicity.

Cardiovascular effects.

Long term therapy with some COX-2 selective NSAIDs of the coxib class has been shown to increase the risk of serious cardiovascular thrombotic events. Meloxicam is a COX-2 selective NSAID. Meloxicam has not been demonstrated to increase the risk of cardiovascular adverse events compared to non-selective NSAIDs in clinical trials. However, long-term placebo-controlled data to adequately assess any cardiovascular risk are not available for meloxicam.
All NSAIDs, both COX-2 selective and non-selective, may cause an increased risk of serious cardiovascular thrombotic events. This may increase with duration of use. Patients with cardiovascular disease, history of atherosclerotic cardiovascular disease or risk factor for cardiovascular disease may be at great risk. To minimise the potential risk of an adverse cardiovascular event in patients taking meloxicam especially in those with cardiovascular risk factors the lowest effective dose should be used for the shortest possible duration.
Physicians and patients should remain alert for such cardiovascular events even in the absence of previous cardiovascular symptoms. Patients should be informed about signs and/or symptoms of serious cardiovascular toxicity and the steps to take if they occur.

Skin reactions.

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported rarely in association with the use of meloxicam. 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. Meloxicam should be discontinued at the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity.

Combination use of ACE inhibitors or angiotensin receptor antagonists, anti-inflammatory drugs and thiazide diuretics.

The use of an ACE inhibiting drug (ACE-inhibitor or angiotensin receptor antagonist), 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. Combined use of these medications should be accompanied by increased monitoring of serum creatinine, particularly at the institution of the combination. The combination of drugs from these three classes should be used with caution particularly in elderly patients or those with pre-existing renal impairment.

Fluid retention and oedema.

Induction of sodium, potassium and water retention and interference with the natriuretic effects of diuretics may occur with NSAIDs. Cardiac failure or hypertension may be precipitated or exacerbated in susceptible patients as a result. For patients at risk, clinical monitoring is recommended.

Pre-existing asthma.

Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bronchospasm which can be fatal. Since cross-reactivity, including bronchospasm, between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, meloxicam should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with pre-existing asthma.

Use in patients being treated with corticosteroids.

Meloxicam cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids.

Use in patients with fever and infection.

The pharmacological activity of meloxicam in reducing inflammation and possibly fever may diminish the utility of these diagnostic signs in detecting complications of presumed non-infectious, painful conditions.

Anaphylactoid reactions.

As with other NSAIDs, anaphylactoid reactions may occur in patients without known prior exposure to meloxicam. Meloxicam should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs. Emergency help should be sought in cases where an anaphylactoid reaction occurs.

Lactose.

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

Hepatic effects.

Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs, including meloxicam. These laboratory values may progress, may remain unchanged or may be transient with continuing therapy. Notable elevations of ALT or AST (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with NSAIDs. In addition, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some of them with fatal outcomes, have been reported with NSAIDs.
Physicians and patients should remain alert for hepatotoxicity. Patients should be informed about the signs and/or symptoms of hepatotoxicity. Patients with signs and/or symptoms suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with meloxicam. If clinical signs and symptoms consistent with liver disease develop or if systemic manifestations occur (e.g. eosinophilia, rash, etc), meloxicam should be discontinued.

Renal effects.

NSAIDs inhibit the synthesis of renal prostaglandins, which play a supportive role in the maintenance of renal perfusion. In patients whose renal blood flow and blood volume are decreased, administration of an NSAID may precipitate overt renal decompensation which is typically followed by recovery to pre-treatment state upon discontinuation of non-steroidal anti-inflammatory therapy.
Patients at greatest risk of such a reaction are elderly individuals, dehydrated patients, those with congestive heart failure, liver cirrhosis, nephrotic syndrome and overt renal disease, those receiving concomitant treatment with a diuretic, ACE inhibitor or angiotensin II receptor antagonist or those having undergone major surgical procedures which led to hypovolaemia. In such patients, the renal function, including volume of diuresis, should be carefully monitored at the beginning of therapy.
In rare cases, NSAIDs may cause interstitial nephritis, glomerulonephritis, renal medullary necrosis or nephrotic syndrome.

Use in renal impairment.

The dose of meloxicam in patients with end-stage renal failure on haemodialysis should not exceed 7.5 mg. No dose reduction is required in patients with mild or moderate renal impairment (i.e. in patients with a creatinine clearance of greater than 25 mL/min).
The extent to which metabolites of meloxicam may accumulate in patients with renal failure has not been studied. As some metabolites are excreted by the kidney, patients with significantly impaired renal function should be more closely monitored.

Paediatric use.

Meloxicam is not recommended for use in children and adolescents under 18 years of age (see Section 4.3 Contraindications).

Use in the elderly.

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

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

General.

In vitro drug interaction studies revealed that the metabolism of meloxicam is predominantly mediated via the CYP 2C9 isoenzyme, with a minor contribution of the CYP 3A4 isoenzyme in the liver. Co-administration of meloxicam with drugs known to inhibit CYP 2C9 is contraindicated. Co-administration of meloxicam with drugs known to inhibit CYP 3A4 (e.g. ketoconazole, itraconazole and erythromycin) or drugs known to be metabolized by CYP 3A4 (e.g. terfenadine, astemizole, cyclosporin and class III antiarrythmic drugs, such as amiodarone and quinidine) should be undertaken with caution (see Section 4.4 Special Warnings and Precautions for Use, Gastrointestinal effects).

Antacids.

No pharmacokinetic interaction was detected with concomitant administration of antacids.

Cimetidine.

Concomitant administration of 200 mg cimetidine qid did not alter the single dose pharmacokinetics of 30 mg meloxicam.

Digoxin.

Meloxicam 15 mg once daily for 7 days did not alter the plasma concentration profile of digoxin after beta-acetyldigoxin administration for 7 days at clinical doses. In vitro testing found no protein binding drug interaction between digoxin and meloxicam.

Furosemide (frusemide).

Clinical studies, as well as post-marketing observations, have shown that NSAIDs can reduce the natriuretic effect of furosemide (frusemide) and thiazide diuretics in some patients. This effect has been attributed to inhibition of renal prostaglandin synthesis. Studies with furosemide (frusemide) agents and meloxicam have not demonstrated a reduction in natriuretic effect. Furosemide (frusemide) single and multiple dose pharmacodynamics and pharmacokinetics are not affected by multiple doses of meloxicam. Nevertheless, during concomitant therapy with furosemide (frusemide) and meloxicam, patients should be observed closely for signs of declining renal function (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions, Diuretics), as well as to assure diuretic efficacy.

Cytochrome P450 inhibitors.

Co-administration of meloxicam with drugs known to inhibit CYP 2C9 is contraindicated. Co-administration of meloxicam with drugs known to inhibit CYP 3A4 should be undertaken with caution (see Section 4.4 Special Warnings and Precautions for Use).

Other prostaglandin synthetase inhibitors (PSIs) including glucocorticoids and salicylates (acetylsalicylic acid).

Co-administration of PSIs may increase the risk of gastrointestinal ulcers and bleeding, via a synergistic effect and is not recommended. The concomitant use of meloxicam with other NSAIDs is not recommended.

Oral anticoagulants, antiplatelet drugs, systemically administered heparin, thrombolytics and selective serotonin reuptake inhibitors (SSRIs).

There is an increased risk of bleeding via inhibition of platelet function, when NSAIDs are co-administered. If such co-prescribing cannot be avoided, close monitoring of their effects on coagulation is required.

Lithium.

NSAIDs have been reported to increase lithium plasma levels (via decreased renal excretion of lithium), which may reach toxic values. The concomitant use of lithium and NSAIDs is not recommended. If this combination appears necessary, lithium plasma concentrations should be monitored carefully during the initiation, adjustment and withdrawal of meloxicam treatment.

Methotrexate.

Meloxicam did not have a significant effect on the pharmacokinetics of single doses of methotrexate. In vitro, methotrexate did not displace meloxicam from human serum binding sites. However, as with other NSAIDs, meloxicam may increase the haematologic toxicity of methotrexate. In this situation, strict monitoring of blood cell count is recommended.
NSAIDs can reduce the tubular secretion of methotrexate thereby increasing the plasma concentrations of methotrexate. For this reason, for patients on high dosages of methotrexate (more than 15 mg/week), the concomitant use of NSAIDs is not recommended. The risk of an interaction between NSAIDs and methotrexate should be considered also in patients on low dosage of methotrexate, especially in patients with impaired renal function. In case combination treatment is necessary, blood cell count and renal function should be monitored. Caution should be taken in case both NSAID and methotrexate are given within 3 days, in which case the plasma level of methotrexate may increase and cause increased toxicity. Although the pharmacokinetics of methotrexate (15 mg/week) were not affected by concomitant meloxicam treatment, it should be considered that the haematological toxicity of methotrexate can be amplified by treatment with NSAIDs.

Pemetrexed.

For the concomitant use of meloxicam with pemetrexed in patients with creatinine clearance from 45 to 79 mL/min, the administration of meloxicam should be paused for 5 days before, on the day of, and 2 days following pemetrexed administration. If a combination of meloxicam with pemetrexed is necessary, patients should be closely monitored, especially for myelosuppression and gastro-intestinal adverse reactions. In patients with creatinine clearance below 45 mL/min the concomitant administration of meloxicam with pemetrexed is not recommended.

Contraception.

NSAIDs have been reported to decrease the efficacy of intrauterine devices.

Diuretics.

Treatment with NSAIDs is associated with the potential for acute renal insufficiency in patients who are dehydrated. Patients receiving meloxicam and diuretics should be adequately hydrated and be monitored for renal function prior to initiating treatment.

Ciclosporin.

Nephrotoxicity of ciclosporin may be enhanced by NSAIDs via renal prostaglandin mediated effects. During combined treatment, renal function is to be measured.

Antihypertensives (beta-blockers, ACE-inhibitors, vasodilators, diuretics).

A reduced effect of the antihypertensive drug by inhibition of vasodilating prostaglandins has been reported during treatment with NSAIDs.

Angiotensin-II receptor antagonists.

NSAIDs and angiotensin-II receptor antagonists as well as ACE inhibitors exert a synergistic effect on the decrease of glomerular filtration. In patients with pre-existing renal impairment this may lead to acute renal failure.

Cholestyramine.

Cholestyramine binds to meloxicam in the gastrointestinal tract leading to a faster elimination of meloxicam.

Oral hypoglycaemics.

Interactions via CYP 2C9 can be expected in combination with medicinal products such as oral anti-diabetics (sulfonylureas), which may lead to increased plasma levels of these drugs and meloxicam. Patients concomitantly using meloxicam with sulfonylureas should be carefully monitored for hypoglycemia.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Oral treatment with meloxicam at doses up to 5 mg/kg/day in female rats (approximately 2.7 times the human dose based on BSA) and up to 9 mg/kg/day (approximately 5 times the human dose based on BSA) in male rats did not affect mating behaviour or fertility.
Oral treatment of female rats with meloxicam at doses of 1 mg/kg/day (approximately half of the human dose based on BSA) reduced the number of embryonic implantations and increased the number of early resorptions. A no-effect dose for these effects was not established. A reduction in the number of corpora lutea was also observed at 5 mg/kg/day, with the no-effect dose being 2.5 mg/kg/day (approximately 1.5-fold greater than the human dose based on BSA).
The use of meloxicam, as with any drug known to inhibit cyclooxygenase/prostaglandin synthesis, may impair fertility and is not recommended in women attempting to conceive. Meloxicam may delay ovulation. Therefore, in women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of meloxicam should be considered.
(Category C)
Meloxicam use is contraindicated in pregnancy (see Section 4.3 Contraindications).
Inhibition of prostaglandin-synthesis may adversely affect pregnancy and/or the embryofetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastrochisis after the use of a prostaglandin synthesis inhibitor in early pregnancy.
The absolute risk for cardiovascular malformation was increased from less than 1%, up to approximately 1.5%. The risk is believed to increase with dose and duration of therapy. In preclinical studies, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss and embryofetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenesis period.
From about 20 weeks of pregnancy all prostaglandin-synthesis inhibitors may expose the fetus to: renal dysfunction, which may progress to renal failure with oligohydroamniosis (see Oligohydramnios and neonatal renal impairment).
During the third trimester of pregnancy all prostaglandin-synthesis inhibitors may expose the fetus to: cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension); the mother and the neonate, at the end of pregnancy, to: possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses; inhibition of uterine contractions resulting in delayed or prolonged labour.
Meloxicam was not teratogenic in rats up to an oral dose of 4 mg/kg/day (approximately 2.2 times the human dose at 15 mg/day for a 50 kg adult based on body-surface-area [BSA]) when given during organogenesis. Meloxicam caused an increased incidence of septal defect of the heart, a rare event, at an oral dose of 60 mg/kg/day (about 60 times the human dose based on BSA) and embryo-lethality at oral doses > 5 mg/kg/day (5 times the human dose based on BSA) when rabbits were treated throughout organogenesis.
Studies in rats with meloxicam, as with other drugs known to inhibit prostaglandin synthesis, showed an increased incidence of still births, increased length of delivery time and delayed parturition at oral doses > 1 mg/kg/day (approximately 0.6 times the human dose based on BSA) and decreased pup survival at an oral dose of 4 mg/kg/day (approximately 2.1 times the human dose based on BSA) throughout organogenesis. Similar findings were observed in rats receiving oral doses > 0.125 mg/kg/day (less than 0.1 times the human dose based on BSA) during late gestation and the lactation period.
Meloxicam crosses the placental barrier. There are no adequate, well-controlled studies in pregnant women. Meloxicam should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.

Oligohydramnios and neonatal renal impairment.

Use of NSAIDs from about 20 weeks gestation may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment.
These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. Oligohydramnios is often, but not always, reversible with treatment discontinuation.
Complications of prolonged oligohydramnios may, for example, include limb contractures and delayed lung maturation. In some post-marketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required.
 Studies of meloxicam excretion in human milk have not been conducted. However, meloxicam was excreted in the milk of lactating rats at concentrations higher than those in plasma. The safety of meloxicam in humans during lactation has not been established and therefore, the drug should not be used during lactation.

4.7 Effects on Ability to Drive and Use Machines

There are no specific studies about effects on the ability to drive vehicles and to use machinery. Patients who experience visual disturbances, drowsiness or other central nervous system disturbances should refrain from these activities.

4.8 Adverse Effects (Undesirable Effects)

A meloxicam phase II/III safety database includes 10,122 osteoarthritis patients and 1,012 rheumatoid arthritis patients treated with meloxicam 7.5 mg/day and 3,505 osteoarthritis patients and 1,351 rheumatoid arthritis patients treated with meloxicam 15 mg/day. Meloxicam at these doses was administered to 661 patients for at least six months and to 312 patients for at least one year. Approximately 10,500 of these patients were treated in ten placebo and/or active-controlled osteoarthritis trials and 2,362 of these patients were treated in ten placebo and/or active-controlled rheumatoid arthritis trials. Gastrointestinal (GI) adverse events were the most frequently reported adverse events in all treatment groups across meloxicam trials.
A 12-week, multi-centre, double-blind, randomized trial was conducted in patients with osteoarthritis of the knee or hip to compare the efficacy and safety of meloxicam with placebo and with an active control. Table 2 presents the adverse events that occurred in ≥ 1% of the meloxicam treatment groups.
Adverse events that occurred in ≥ 1% of the meloxicam treatment groups in two 12-week placebo controlled rheumatoid arthritis trials are presented in Table 3.
Higher doses of meloxicam (22.5 mg and greater) have been associated with an increased risk of serious GI events, therefore the daily dose of meloxicam should not exceed 15 mg.
The following is a list of adverse events occurring in < 1% of patients, which may be causally related to the administration of meloxicam. The information is based on clinical trials involving patients who have been treated with daily oral doses of 7.5 or 15 mg meloxicam tablets or capsules over a period of up to 18 months (mean duration of treatment 127 days).

Blood and lymphatic system disorders.

Blood count abnormal (including differential white cell count), leukopenia, thrombocytopenia, anaemia. Concomitant administration of a potentially myelotoxic drug, in particular methotrexate, appears to be a predisposing factor to the onset of a cytopenia.

Cardiac disorders.

Palpitations.

Ear and labyrinth disorders.

Tinnitus.

Gastrointestinal disorders.

Gastrointestinal perforation, occult or macroscopic gastrointestinal haemorrhage, gastroduodenal ulcer, colitis, oesophagitis, stomatitis. Gastro-intestinal haemorrhage, ulceration or perforation may potentially be fatal.

Hepatobiliary disorders.

Transitory abnormalities of liver function parameters (e.g. raised transaminases or bilirubin).

Nervous system disorders.

Somnolence.

Renal and urinary disorders.

Renal function test abnormal (increased serum creatinine and/or serum urea).

Respiratory, thoracic and mediastinal disorders.

Onset of asthma attacks in individuals allergic to aspirin or other NSAIDs.

Skin and subcutaneous tissue disorders.

Urticaria, photosensitivity reaction.

Vascular disorders.

Flushing.

Post-market adverse drug reactions.

Additional reports of adverse events which may be causally associated to the administration of meloxicam during worldwide post-marketing experience are included below.

General disorders and administration site conditions.

In rare cases, other drugs of this class are reported to cause meningitis.

Eye disorders.

Visual disturbance including blurred vision, conjunctivitis.

Gastrointestinal disorders.

Gastritis.

Hepatobiliary disorders.

Hepatitis.

Immune system disorders.

Anaphylactic reaction, anaphylactoid reaction and other immediate hypersensitivity.

Psychiatric disorders.

Confusional state, disorientation, mood altered.

Renal and urinary disorders.

Acute renal failure. The use of NSAIDs may be related to micturition disorders, including acute urinary retention.

Reproductive system and breast disorders.

Infertility female, ovulation delayed.

Skin and subcutaneous tissue disorders.

Toxic epidermal necrolysis, Stevens-Johnson syndrome, angioedema, dermatitis bullous, erythema multiforme.

Other adverse events.

Additional adverse events, reported from clinical trials or from spontaneous reports, where evidence for a causal association with meloxicam use is unclear, are the following: cardiac failure, angina, myocardial infarction, arrhythmia, vasculitis, agranulocytosis, interstitial nephritis, convulsion, liver failure.
The following serious undesirable effects have been reported in association with the use of NSAIDs and cannot be ruled out for meloxicam. These include oligohydramnios and neonatal renal impairment.

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 http://www.tga.gov.au/reporting-problems.

4.9 Overdose

In case of poisoning or overdose, advice should be sought from a Poisons Information Centre.
Patients should be managed with symptomatic and supportive care following an NSAID overdose. In cases of acute overdose, activated charcoal is recommended. Administration of activated charcoal is recommended for patients who present 1-2 hours after overdose. For substantial overdose or severely symptomatic patients, activated charcoal may be administered repeatedly.
It has been shown in a clinical trial that cholestyramine accelerates the elimination of meloxicam.
The typical signs and symptoms of NSAID overdose include nausea, vomiting, headache, drowsiness, blurred vision and dizziness. Rare cases of seizures, hypotension, apnoea, coma and renal failure have been reported with severe NSAID overdose.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) of the enolic acid class, which has shown anti-inflammatory, analgesic and antipyretic properties in animals. Meloxicam showed anti-inflammatory activity in all standard models of inflammation. A common mechanism for the above effects may exist in the ability of meloxicam to inhibit the biosynthesis of prostaglandins, known mediators of inflammation, by inhibition of cyclooxygenase (COX).
Comparison of the ulcerogenic dose and the anti-inflammatory effective dose in rat adjuvant arthritis model confirmed a greater therapeutic margin in animals over other NSAIDs (piroxicam, diclofenac, naproxen, flurbiprofen). In rats, meloxicam showed greater inhibitory effect on prostaglandin biosynthesis at the site of inflammation than in the gastric mucosa or the kidney.
Selective inhibition of the cyclooxygenase (COX-2) isoenzyme, relative to COX-1, by meloxicam has been demonstrated in vitro on various cell systems: guinea pig macrophages, bovine aortic endothelial cells (for testing of COX-1 activity), mouse macrophages (for testing for COX-2 activity) and human recombinant enzymes expressed in cos-cells and in human whole blood.

Clinical trials.

The efficacy of meloxicam in treating the symptoms of osteoarthritis and rheumatoid arthritis has been confirmed in several clinical studies.

Osteoarthritis trials.

Two clinical studies of 6 months duration were performed in patients with osteoarthritis of the hip or knee. In the first study, the efficacy of meloxicam 15 mg (n = 306) and piroxicam 20 mg (n = 149) were found to be comparable, using as efficacy endpoints improvement in overall pain, pain on movement, global efficacy, change in duration of inactivity and change in quality of life score. In the second study, the efficacy of meloxicam 7.5 mg (n = 169) was found to be comparable to that of diclofenac 100 mg SR (n = 167) using similar endpoints.
Once daily dosing of meloxicam 7.5 mg (n = 153) and 15 mg (n = 156) showed a consistently more efficacious response than placebo (n = 155) in a 12-week trial in patients with osteoarthritis of the knee or hip. Efficacy was measured by global assessment of disease activity, global assessment of pain and arthritic condition, as measured by the WOMAC (Western Ontario and McMaster University) Osteoarthritis Index. Both doses of meloxicam were also shown to be comparable to diclofenac 50 mg bd (n = 152) with regard to efficacy, with a lower incidence of GI adverse events when compared to diclofenac.
Two large-scale, randomized, active-controlled clinical studies of 4 weeks duration were conducted in patients with osteoarthritis of the hand, hip, knee or spine. In the first study (MELISSA), the effects of meloxicam 7.5 mg (n = 4,635) were compared against the effects of diclofenac 100 mg SR (n = 4,688). In the second study (SELECT), the effects of meloxicam 7.5 mg (n = 4,320) were compared against the effects of piroxicam 20 mg (n = 4,336). The results from both studies indicated that meloxicam 7.5 mg was as efficacious as diclofenac 100 mg SR and piroxicam 20 mg, in the treatment of symptomatic osteoarthritis.

Rheumatoid arthritis trials.

The use of meloxicam for the symptomatic treatment of rheumatoid arthritis was evaluated in a double-blind, controlled trial involving 894 patients treated for 12 weeks. Meloxicam (7.5 mg, 15 mg and 22.5 mg daily) was compared to placebo, with diclofenac (75 mg twice daily) compared to placebo to establish trial sensitivity. The primary endpoints were number of painful or tender joints, number of swollen joints, investigator's global assessment of disease activity, patient's global assessment of disease activity and patient's assessment of pain. For all five primary endpoints, the meloxicam 7.5 mg group was significantly better than placebo for both mean on trial and last observation. The meloxicam 15 mg group was significantly better for three of five primary endpoints, excluding painful and swollen joints. In patients who had flared at baseline tender joints, the meloxicam 15 mg group differed almost significantly from the placebo group (p < 0.05 not met due to the lower number of patients).
A second trial also investigated the use of meloxicam for the symptomatic treatment of rheumatoid arthritis. This double-blind, placebo-controlled trial used three doses of meloxicam (7.5 mg, 15 mg and 22.5 mg daily), in patients with rheumatoid arthritis over a 12-week period. A total of 898 patients were treated with meloxicam. The primary endpoint in this study was the American College of Rheumatology (20%) response criterion (ACR20) response rate, a composite measure of clinical, laboratory and functional measures of rheumatoid arthritis response. For this parameter, all three doses of meloxicam were more effective than placebo for the duration of the study. For the endpoints that comprised the ACR20 criteria, each of the meloxicam groups was superior to placebo at all visits except for C-Reactive Protein. Efficacy reached a plateau at the meloxicam 15 mg dose (Table 4). The overall incidence and severity of adverse events was similar among all three meloxicam groups. The data from both studies indicate that meloxicam is effective and safe for the treatment of patients with rheumatoid arthritis.

5.2 Pharmacokinetic Properties

Absorption.

Meloxicam is well absorbed from the gastrointestinal tract following oral administration (absolute bioavailability 89%). Once daily dosing leads to drug plasma concentrations with a relatively small peak-trough fluctuation in the range of 0.4-1.0 microgram/mL for 7.5 mg doses or 0.8-2.0 microgram/mL for 15 mg doses. However, values outside of this range have been encountered (Cmin and Cmax at steady state, respectively).
Absorption is not altered by concomitant food intake; however, food can shorten the tmax, and marginally increases the Cmax, of capsules. Maximum plasma concentrations were achieved by ~6 hours following capsule administration with concomitant food consumption; this is similar to that observed with tablet administration, irrespective of concomitant food consumption.
Drug concentrations are dose-proportional for oral 7.5 mg and 15 mg doses. Steady state conditions are achieved in three to five days. Continuous treatment for periods of up to six months results in similar drug concentrations to those seen at steady state after two weeks of oral treatment with 15 mg meloxicam per day.

Distribution.

Volume of distribution is low (on average, 16 L). In plasma, more than 99% is bound to plasma proteins. Meloxicam penetrates well into synovial fluid to give concentrations approximately half those in plasma.

Metabolism.

Meloxicam is eliminated almost entirely by hepatic metabolism: two thirds by cytochrome (CYP) P450 enzymes (CYP 2C9 two thirds and CYP 3A4 one third) and one third by other pathways, such as peroxidase oxidation. Meloxicam is almost completely metabolized to four pharmacologically inactive metabolites. The major metabolite, 5'-carboxymeloxicam (60% of dose), from CYP 2C9 mediated metabolism, is formed by oxidation of an intermediate metabolite 5'-hydroxymethylmeloxicam, which is also excreted to a lesser extent (9% of dose). In vitro studies suggest that CYP 2C9 plays an important role in this metabolic pathway, with a minor contribution from the CYP 3A4 isoenzyme. The patient's peroxidase activity is probably responsible for the other two metabolites which account for 16% and 4% of the administered dose respectively.

Excretion.

Meloxicam excretion is predominantly in the form of metabolites and occurs to equal extents in the faeces and urine. Only traces of the unchanged parent compound are excreted in the urine (0.2%) and faeces (1.6%). The extent of the urinary excretion was confirmed for unlabelled multiple 7.5 mg doses: 0.5%, 6% and 13% of the dose were found in urine in the form of meloxicam and the 5'-hydroxymethyl and 5'-carboxy metabolites, respectively.
There is significant biliary and/or enteral secretion of the drug. This was demonstrated when oral administration of cholestyramine following a single IV dose of meloxicam decreased the AUC of meloxicam by 50%. Meloxicam is eliminated from the body with a mean elimination half-life of 20 hours. Total plasma clearance ranges from 7-9 mL/min following multiple oral doses of meloxicam.

Special populations.

Hepatic impairment.

Following a single 15 mg dose of meloxicam, there was no marked difference in plasma concentrations in subjects with mild (Child-Pugh Class I) and moderate (Child-Pugh Class II) hepatic impairment compared to healthy volunteers. Protein binding of meloxicam was not affected by hepatic insufficiency. Patients with severe hepatic impairment (Child-Pugh Class III) have not been adequately studied.

Renal impairment.

Meloxicam pharmacokinetics have been investigated in subjects with different degrees of renal insufficiency. Total drug plasma concentrations decreased with the degree of renal impairment, while free AUC values were similar. Total clearance of meloxicam increased in these patients, probably due to the increase in free fraction, leading to an increased metabolic clearance. There is no need for dose adjustment in patients with mild to moderate renal failure (creatinine clearance greater than 25 mL/min). Patients with severe renal insufficiency have not been adequately studied. The use of meloxicam in patients with severe renal impairment is not recommended (see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use).

Haemodialysis.

Following a single dose of meloxicam, the free Cmax plasma concentrations were higher in patients with renal failure on chronic haemodialysis (1% free fraction) in comparison to healthy volunteers (0.3% free fraction). Haemodialysis did not lower the total drug concentration in plasma; therefore, additional doses are not necessary after haemodialysis. Meloxicam is not dialysable.

Elderly.

Clearance is decreased in the elderly. In clinical studies, steady state pharmacokinetics in the elderly (mean age: 67 years) did not differ significantly from those in a younger population (mean age: 50 years); however elderly females had a higher systemic exposure to meloxicam than did elderly males.

Gender.

Young females exhibited slightly lower plasma concentrations relative to young males. After single doses of 7.5 mg meloxicam, the mean elimination half life was 19.5 hours for the female group as compared to 23.4 hours for the male group. At steady state, the data were similar (17.9 hours vs. 21.4 hours). This pharmacokinetic difference due to gender is likely to be of little clinical importance. There was linearity of pharmacokinetics and no appreciable difference in the Cmax or tmax across genders.

5.3 Preclinical Safety Data

Genotoxicity.

Meloxicam did not demonstrate genotoxic potential in assays for gene mutation in vitro and chromosomal damage in vitro and in vivo.

Carcinogenicity.

Two-year dietary studies showed no evidence for carcinogenic activity at meloxicam doses up to 0.8 mg/kg/day (approximately half of the highest human dose at 15 mg/day for a 50 kg person based on body-surface-area [BSA]) in rats and up to 8 mg/kg/day (2.2 times the highest human dose based on BSA) in mice. In rats, the highest dose used was nephrotoxic, while the highest dose used in mice was sub-toxic.

6 Pharmaceutical Particulars

6.1 List of Excipients

Each capsule contains the following inactive ingredients: lactose monohydrate, maize starch, sodium citrate dihydrate, magnesium stearate, Brilliant Blue FCF, Sunset Yellow FCF, gelatin, titanium dioxide and quinolone yellow (15 mg strength only).

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 found on the public summary of Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C. Protect from light.

6.5 Nature and Contents of Container

7.5 mg capsules and 15 mg capsules.

PVC/PVDC/Al blister packs of 30 capsules.
Not all strengths and/or 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.

6.7 Physicochemical Properties

Chemical Structure.


Chemical Name: 4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide.
Molecular Formula: C14H13N3O4S2.
Molecular Weight: 351.4.
Meloxicam is a pastel yellow solid with pKa values of 1.09 and 4.18 and a melting point of about 256°C. The substance is practically insoluble in water, soluble in dimethylformamide, slightly soluble in chloroform and acetone and very slightly soluble in methanol. There are no chiral centres.

CAS number.

71125-38-7.

7 Medicine Schedule (Poisons Standard)

S4: Prescription Only Medicine.

Summary Table of Changes