Consumer medicine information

ANAPROX

Naproxen sodium

BRAND INFORMATION

Brand name

Anaprox Tablets

Active ingredient

Naproxen sodium

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using ANAPROX.

What is in this leaflet

This leaflet answers some common questions about ANAPROX tablets.

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. You doctor has weighed the risks of you taking ANAPROX tablets 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 ANAPROX is used for

ANAPROX belongs to a family of medicines called Non-Steroidal Anti-Inflammatory Drugs (NSAIDs).

ANAPROX relieves pain and reduces inflammation (swelling, redness and soreness) that may occur

  • in different types of arthritis including rheumatoid arthritis, osteoarthritis and ankylosing spondylitis
  • in muscle and bone injuries such as sprains, strains, lower back pain (lumbago), rheumatism and tendonitis, such as tennis elbow
  • from swelling and pain after setting broken or dislocated bones
  • in menstrual cramps (period pain)
  • due to migraine headache
  • following surgery
  • due to dental pain

Your doctor may have prescribed ANAPROX for another purpose.

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

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

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

ANAPROX is not addictive.

Before you take ANAPROX

When you must not take it

Do not take ANAPROX if you have an allergy to:

  • ANAPROX or any ingredients listed at the end of this leaflet
  • aspirin or any other NSAID medicine

Many medicines used to treat headache, period pain and other aches and pains contain aspirin or NSAID medicines. If you are not sure if you are taking any of these medicines, ask your pharmacist.

Symptoms of an allergic reaction to these medicines may include:

  • asthma, wheezing or shortness of breath
  • swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing
  • hives, itching or skin rash
  • fainting
  • sudden blocked or running nose

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

Do not take ANAPROX if:

  1. you are vomiting blood or material that looks like coffee grounds
  2. you are bleeding from the rectum (back passage), have black sticky bowel motions (stools) or bloody diarrhoea
  3. you currently have a peptic ulcer (i.e. stomach or duodenal ulcer) or have had one previously
  4. you have severe liver disease
  5. you have recently had or are about to have heart bypass surgery
  6. you are taking other medications which contain naproxen or naproxen sodium (e.g. Naprogesic®, Naprosyn®, Crysanal® or Inza®)
  7. you have severe heart failure

Do not give ANAPROX to a child under the age of 2 years.

The safety and effectiveness of ANAPROX in children under 2 years of age has not been established.

Do not take ANAPROX if the package is torn or shows signs of tampering.

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

If you take this medicine after the expiry date has passed, it may not work as well.

Before you start to take it

Tell your doctor if:

  1. you have any allergies to:
  • any other medicines including aspirin or other NSAID medicines
  • any other substances, such as foods, preservatives or dyes
  1. you are pregnant or intend to become pregnant
    ANAPROX may impair fertility and is not recommended in women attempting to conceive. ANAPROX may affect your developing baby if you take it during pregnancy. If it is necessary for you to take ANAPROX, your doctor will discuss the risks and benefits of taking it during pregnancy.
  2. you are breast-feeding or intend to breast-feed
    ANAPROX passes into breast milk. The effect on the baby is not known.
  3. you have or have had any medical conditions, especially the following:
  • heartburn, indigestion, stomach ulcers or other stomach problems
  • vomiting blood or bleeding from the back passage
  • bowel or intestinal problems such as ulcerative colitis
  • kidney or liver disease
  • heart failure
  • high blood pressure or heart problems
  • swelling of the ankles or feet
  • a tendency to bleed or other blood problems, such as anaemia
  1. you currently have an infection
    If you take ANAPROX while you have an infection, the tablets may hide some of the signs of an infection (eg pain, fever). This may make you think, mistakenly, that you are better or that it is not serious.
  2. you plan to have surgery
    ANAPROX can prolong bleeding.
  3. you are on a strict salt (or sodium) restricted diet
    ANAPROX contains a small amount of sodium.

If you are not sure if you should be taking ANAPROX, talk to your doctor.

Taking other medicines

Tell your doctor 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 may interfere with ANAPROX. These include:

  • antacids, medicines used to treat indigestion and heartburn
  • aspirin, salicylates or other NSAID medicines
  • diuretics, also called fluid or water tablets
  • lithium, a medicine used to treat some types of depression
  • probenecid, a medicine used to treat gout
  • phenytoin a medicine used to treat epilepsy
  • methotrexate, a medicine used to treat arthritis and some cancers
  • warfarin, a medicine used to prevent blood clots
  • heparin, a medicine used to prevent blood clots
  • medicines used to treat high blood pressure including ACE inhibitors, angiotensin receptor antagonists and beta-blockers
  • certain antibiotics called sulphonamides
  • some medicines used to treat diabetes
  • steroids, medicines used to treat inflammation
  • serotonin reuptake inhibitors, also known as SSRIs, medicines used to treat some types of depression
  • zidovudine, a medicine used to treat HIV infection
  • sodium bicarbonate, a medicine used to treat stomach upset or ulcers

These medicines may be affected by ANAPROX, or may affect how well it works. You may need to take different amounts of your medicine, or you may need to take different medicines. Your doctor will advise you.

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

Ask your doctor or pharmacist if you are not sure about this list of medicines.

Use in Children

There is no specific information available to recommend the use of ANAPROX in children under 5 years.

Use in People Over 65 Years

Older people may be at more risk of developing stomach ulcers and hence your doctor may prescribe a lower dose.

How to take ANAPROX

Follow all directions given to you by your doctor and pharmacist carefully.

They may differ from the information contained in this leaflet.

How much to take

Take ANAPROX exactly as your doctor has prescribed.

Your doctor will tell you how many ANAPROX tablets to take each day.

The dose your doctor recommends depends on both the type and severity of pain and/or inflammation you have.

Sprains, strains and period pain
The recommended dose is 550 mg (one tablet) given initially, then 275 mg (half-a-tablet) every 6 to 8 hours as needed. The total dose in one day should not be more than 1375 mg (two and a half tablets).

Migraine Headache
The recommended dose is 825 mg (one and a half tablets) taken at the first sign of a migraine. An additional dose of 275 mg (half a tablet) to 550 mg (one tablet) can be taken at least one hour after the initial dose, if required. The total dose in one day should not be more than 1375 mg (two and a half tablets).

Different types of arthritis
The recommended dose is 550 mg (one tablet) to 1100 mg (two tablets) a day (divided in two doses).

Your doctor may recommend lower doses than these, it is always best to use the lowest effective dose for your condition.

How to take it

Swallow ANAPROX tablets whole with a glass of water or milk.

When to take it

Take the tablets during or immediately after food with a full glass of water or milk.

This may help reduce the possibility of an upset stomach.

How long to take it

Do not take ANAPROX for longer than your doctor says.

Depending on your condition, you may need to use ANAPROX, only once, for a few days, a few weeks or for longer periods.

For sprains and strains, ANAPROX is usually only needed for a few days.

As with other NSAID medicines, if you are using ANAPROX for arthritis, it will not cure your condition, but it should help to control pain, swelling and stiffness. If you have arthritis, ANAPROX should be taken every day for as long as your doctor prescribes.

For menstrual cramps (period pain), ANAPROX is usually taken during each period as soon as the cramps begin and continued for a few days until the pain goes away.

Ask your doctor if you are not sure how long to take ANAPROX for.

If you forget to take it

If it is almost time for 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 continue taking it as you would normally.

Do not double a dose to make up for one you have missed.

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

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

If you take too much (overdose)

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

If you take too much ANAPROX you may experience drowsiness, pain or tenderness in the stomach, stomach upset including nausea (feeling sick), vomiting, heartburn, indigestion or cramps.

While you are taking ANAPROX

Things you must do

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

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

Ask your doctor or pharmacist before you start taking any new medicines.

If you are going to have surgery, tell your doctor you are taking ANAPROX.

If you are going to have any laboratory tests, tell your doctor that you are taking ANAPROX.

ANAPROX can affect the results of some of these tests.

If you get an infection while using ANAPROX, tell your doctor.

ANAPROX may hide some of the signs of an infection and may make you think, mistakenly, that you are better or that it is not serious. Signs of an infection may include fever, pain, swelling and redness.

Tell your doctor if for any reason, you have not taken your medicine exactly as prescribed.

Otherwise, your doctor may think that it was not effective or change your treatment unnecessarily.

Tell your doctor if you feel the tablets are not helping your condition.

Things you must not do

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

Do not use ANAPROX to treat other complaints unless your doctor tells you to.

Things to be careful of

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

As with other NSAID medicines, ANAPROX may cause dizziness or light-headedness in some people. Make sure you know how you react to ANAPROX before you drive a car, operate machinery, or do anything else that could be dangerous if you are dizzy or light-headed. If this occurs do not drive. If you drink alcohol, dizziness or light-headedness may be worse.

Side Effects

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

ANAPROX helps most people with pain and inflammation 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 treatment if you get some of the side effects.

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

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

  • stomach upset including nausea (feeling sick) and heartburn
  • constipation or pain in the stomach
  • loss of appetite
  • dizziness, light-headedness
  • headache, drowsiness
  • buzzing or ringing in the ears
  • itching or mild skin rashes
  • fluid retention or shortness of breath

These are more common side effects of ANAPROX. Mostly these are mild.

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

  • bleeding or bruising more easily than normal, reddish-purplish or blue-black blotches under the skin
  • eye problems such as blurred vision
  • severe or persistent headache
  • fast or irregular heartbeats, also called palpitations
  • difficulty hearing, deafness
  • unusual weight gain, swelling of ankles or legs
  • yellowing of the skin or eyes

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

Tell your doctor immediately or go to Accident and Emergency at your nearest hospital if you notice any of the following:

  • vomiting blood or material that look like coffee grounds
  • bleeding from back passage (rectum), black sticky bowel motions (stools) or bloody diarrhoea
  • severe pain or tenderness in any part of the stomach
  • difficulty breathing, wheezing or shortness of breath
  • swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing
  • sudden or severe itching, skin rash, hives
  • fainting, seizures or fits
  • pain or tightness in chest
  • severe dizziness, spinning sensation

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

This is not a complete list of all possible side effects. Others may occur in some people and there may be some side effects not yet known.

Tell your doctor if you notice anything else that is making you feel unwell, even if it is not on this list.

Ask your doctor or pharmacist if you don't understand anything in this list.

Do not be alarmed by these lists of possible side effects. You may not experience any of them.

After taking ANAPROX

Storage

Keep your tablets in the blister pack until it is time to take them.

If you take the tablets out of the blister pack they may not keep well.

Keep your tablets protected from light.

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

Do not store it, or any other medicine, in a bathroom or near a sink.

Do not leave it in the car or on window sills.

Heat and dampness can destroy some medicines.

Keep ANAPROX where young 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 ANAPROX, or the tablets have passed their expiry date, ask your pharmacist what to do with any tablets that are left over.

Product Description

What ANAPROX looks like

ANAPROX 550 is a dark blue capsule-shaped tablet with 'NPS 550' on one side.

ANAPROX comes in packs of 50.

Ingredients

Active ingredient:
naproxen sodium

  • each ANAPROX 550 tablet contains 550mg of naproxen sodium

Inactive ingredients:

  • cellulose
  • magnesium stearate [470]
  • povidone
  • talc
  • Opadry YS-1-4216 (contains [171] and [132])

ANAPROX tablets are lactose and gluten free.

Manufacturer

Sponsor

Atnahs Pharma Australia Pty Ltd
Level 10
10 Shelley Street,
SYDNEY, NSW, 2000, Australia

Supplier

ANAPROX is supplied in Australia by:

Clinect Pty Ltd
120 - 132 Atlantic Drive
Keysborough VIC 3173
Australia

Customer enquiries: 1 800 899 005

Please check with your pharmacist for the latest Consumer Medicines Information.

Australian Registration Number:
AUST R 66544.

This leaflet was prepared in November 2016.

BRAND INFORMATION

Brand name

Anaprox Tablets

Active ingredient

Naproxen sodium

Schedule

S4

 

Name of the medicine

Naproxen sodium.

Excipients.

Microcrystalline cellulose, magnesium stearate, purified water, povidone, talc and the proprietary ingredient Opadry YS-1-4216.

Description

Chemical name: (+)-6-methoxy-α-methyl-2-naphthaleneacetic acid, sodium salt. Molecular formula: C14H13NaO3. MW: 252.2. CAS: 26159-34-2. Naproxen sodium is a propionic acid derivative related to the arylacetic acid class of drugs. It is unrelated to salicylates and the corticosteroid hormones. Naproxen sodium is an odourless, white to off white crystalline substance. It is soluble in water.
Anaprox (naproxen sodium) is a nonsteroidal anti-inflammatory drug (NSAID) with analgesic, anti-inflammatory and antipyretic properties.
Anaprox is available as a tablet containing 550 mg of naproxen sodium. Each tablet also contains the ingredients microcrystalline cellulose, magnesium stearate, purified water, povidone, talc and the proprietary ingredient Opadry YS-1-4216.

Pharmacology

Pharmacodynamics.

Anaprox dissociates into the naproxen anion and sodium in vivo at physiological pH.
Naproxen has been shown to have anti-inflammatory properties when tested in human clinical studies. In addition, it has analgesic and antipyretic actions. It exhibits its anti-inflammatory effects even in adrenalectomised animals, indicating that its action is not mediated through the pituitary axis. It inhibits prostaglandin synthetase, as do other NSAIDs, however, the exact mechanism of its anti-inflammatory action is not known.

Pharmacokinetics.

Absorption.

In humans, naproxen sodium is completely absorbed from the gastrointestinal tract after oral administration. Concomitant administration of food can delay the absorption of naproxen sodium, but does not affect its extent.
After oral administration of Anaprox, because of rapid and complete absorption, clinically significant plasma levels and pain relief are obtained in patients within 30 minutes of administration. Peak plasma levels are attained in 1-2 hours, depending on food intake.

Distribution.

Naproxen has a relatively small volume of distribution (0.09 ± 0.03 L/kg), which corresponds to about 10% of the bodyweight in humans. At therapeutic levels naproxen is greater than 99% albumin bound.
The plasma concentration of naproxen increases proportionally with doses up to 500 mg twice daily. Larger doses result in a less than proportional increase due to accelerated renal clearance of disproportionately increased amounts of nonprotein bound drug. However, whether this effect increases or decreases the toxicity of naproxen has not been established.
Steady-state plasma levels of naproxen are reached after 4-5 doses.
Naproxen enters synovial fluid and crosses the placenta. It has been found in the milk of lactating mothers at a concentration approximately 1% of that found in plasma.

Metabolism.

Naproxen is metabolised in the liver to 6-O-desmethylnaproxen (approximately 28% of an IV dose).

Elimination.

Approximately 95% of the naproxen is excreted in the urine, primarily as naproxen (10%), 6-O-desmethylnaproxen (5%) or their conjugates. The rate of excretion of metabolites and conjugates has been found to coincide closely with the rate of naproxen clearance from the plasma. Small amounts, 5% or less, are excreted in the faeces.
The elimination half-life of naproxen is approximately 14 hours.

Pharmacokinetics in special populations.

Children.

The pharmacokinetic profile of naproxen in children aged 5-16 years is similar to that in adults.

Renal impairment.

Given that naproxen and its metabolites are primarily excreted by the kidney, the potential exists for accumulation in the presence of renal insufficiency. Elimination of naproxen is decreased in patients with severe renal impairment (creatinine clearance < 20 mL/min), in whom there is higher clearance of naproxen than estimated from the degree of renal impairment alone (see Precautions, Renal impairment).

Indications

Anaprox is indicated as an analgesic in acute migraine attacks, for the treatment of gout, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and for the relief of acute and/or chronic pain states in which there is an inflammatory component.

Contraindications

Anaprox is contraindicated in patients: who are hypersensitive to naproxen or naproxen sodium, or in whom acetylsalicylic acid (aspirin) or other nonsteroidal anti-inflammatory/ analgesic agents induce allergic manifestations, e.g. asthma, nasal polyps, rhinitis and urticaria. Severe anaphylactic-like reactions to naproxen have been reported in such patients;
with either active or a history of peptic or gastrointestinal ulceration, chronic dyspepsia or active gastrointestinal bleeding or perforation, related to previous NSAIDs therapy;
with active or history of recurrent peptic ulcer/ haemorrhage (two or more distinct episodes of proven ulceration or bleeding) unrelated to previous NSAIDs therapy;
less than 2 years of age since safety in this age group has not been established;
with severe heart failure;
undergoing treatment of perioperative pain in setting of coronary artery surgery (CABG);
with severe hepatic impairment.

Precautions

Cardiovascular thrombotic events.

Observational studies have indicated that non-selective NSAIDs may be associated with an increased risk of serious cardiovascular events, including myocardial infarction and stroke, which may increase with dose or duration of use. Patients with cardiovascular disease, history of atherosclerotic cardiovascular disease or cardiovascular risk factors may also be at greater risk. To minimise the potential risk of an adverse cardiovascular event in patients taking an NSAID, especially in those with cardiovascular risk factors, the lowest effective dose should be used for the shortest possible duration (see Dosage and Administration).
Physicians and patients should remain alert for such CV events even in the absence of previous CV symptoms. Patients should be informed about signs and/or symptoms of serious CV toxicity and the steps to take if they occur.
There is no consistent evidence to suggest that concurrent use of aspirin mitigates the possible increased risk of serious cardiovascular thrombotic events associated with NSAID use.
Clinical trial and epidemiological data suggest that use of coxibs and some NSAIDs (particularly at high doses and long-term treatment) may be associated with a small increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke).

Hypertension.

NSAIDs may lead to onset of new hypertension or worsening of pre-existing hypertension and patients taking anti-hypertensives with NSAIDs may have an impaired anti-hypertensive response. Caution is advised when prescribing NSAIDs to patients with hypertension. Blood pressure should be monitored closely during initiation of NSAID treatment and at regular intervals thereafter.

Heart failure.

Fluid retention and oedema have been observed in some patients taking NSAIDs, therefore, caution is advised in patients with fluid retention or heart failure.

Gastrointestinal.

All NSAIDs can cause gastrointestinal discomfort and, rarely, serious, potentially fatal, gastrointestinal effects such as ulcers, irritation, bleeding and perforation, which may increase with dose or duration of use, but can occur at any time without warning symptoms. Upper gastrointestinal ulcers, gross bleeding or perforation caused by NSAIDs 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 with longer duration of use, increasing the likelihood of developing a serious gastrointestinal event at some time during the course of therapy. However, even short-term therapy is not without risk.
Caution is advised in patients with risk factors for gastrointestinal events who may be at greater risk of developing serious gastrointestinal events, e.g. elderly, debilitated patients, those with a history of serious gastrointestinal events, smoking and alcoholism.
NSAIDs should be given with care to patients with a history of inflammatory bowel disease (ulcerative colitis, Crohn's disease) as their condition may be exacerbated. Patients with a history of gastrointestinal toxicity, particularly when elderly, should report any unusual symptoms (especially gastrointestinal bleeding) particularly in the initial stages of treatment. When gastrointestinal bleeding or ulceration occurs in patients receiving NSAIDs, treatment should be withdrawn immediately. Physicians should warn patients about the signs and symptoms of serious gastrointestinal toxicity.
Studies to date have not identified any subset of patients not at risk of developing peptic ulcer and bleeding. However, the elderly have an increased frequency of adverse effects from NSAIDs, especially gastrointestinal bleeding and perforation which may be fatal. Debilitated patients do not seem to tolerate ulceration or bleeding as well as others. Most of the fatal gastrointestinal events associated with NSAIDs occurred with the elderly and/or debilitated patients.
In patients with active peptic ulcer or inflammatory disease of the gastrointestinal tract and active rheumatoid arthritis, an attempt might be made to treat the arthritis with a non-ulcerogenic drug.
Caution is advised in patients receiving concomitant medications which could increase the risk of ulceration or bleeding (see Interactions with Other Medicines). The concurrent use of aspirin and NSAIDs also increases the risk of serious gastrointestinal adverse effects.
Patients with risk factors should commence treatment on the lowest dose available.

Use in renal impairment.

There have been reports of impaired renal function, renal failure, acute interstitial nephritis, haematuria, proteinuria, renal papillary necrosis and occasionally nephritic syndrome associated with Anaprox.
Anaprox should not be given to patients with creatinine clearance less than 30 mL/minute because accumulation of naproxen metabolites has been seen in such patients.
As with other NSAIDs, Anaprox should be used with caution in patients with impaired renal function or a history of kidney disease because naproxen is an inhibitor of prostaglandin synthesis. Caution should be observed in patients with conditions leading to a reduction in blood volume and/or renal blood flow as prostaglandins have a supportive role in the maintenance of renal perfusion. In these patients, administration of Anaprox or other NSAIDs may cause a dose-dependent reduction in renal prostaglandin formation and may precipitate overt renal decompensation or failure. Patients at greatest risk are those with impaired renal function, hypovolaemia, heart failure, liver dysfunction, salt depletion, those taking diuretics, angiotensin converting enzyme inhibitors or angiotensin receptor blockers and the elderly. Discontinuation of Anaprox is usually followed by recovery to the pre-treatment state; however, serious adverse events may persist. Anaprox should be used with great caution in such patients and the monitoring of serum creatinine and/or creatinine clearance is advised and patients should be adequately hydrated. A reduction of daily dosage should be considered to avoid the possibility of excessive accumulation of naproxen metabolites in these patients.
Haemodialysis does not decrease the plasma concentration of naproxen because of the high degree of its protein binding.

Haematological.

Naproxen decreases platelet aggregation and prolongs bleeding time. This effect should be kept in mind when bleeding times are being determined (see Interactions with Other Medicines, Effects on laboratory tests).
Patients who have coagulation disorders or are receiving drug therapy that interferes with haemostasis should be carefully observed if Anaprox is administered. Patients at high risk of bleeding and those on anticoagulation therapy (e.g. heparin or dicoumarol derivatives) may be at increased risk of bleeding if given Anaprox concurrently. Therefore, benefits of prescribing Anaprox should be weighed against these risks.
Patients with initial haemoglobin values of 10 g or less and who are to receive long-term therapy should have haemoglobin values determined frequently.
Patients on other drugs such as hydantoins, sulfonamides, sulfonylureas or methotrexate should be observed for increased effect or toxicity (see Interactions with Other Medicines).

Severe skin reactions.

NSAIDs may very rarely cause serious cutaneous adverse events such as exfoliative dermatitis, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which can be fatal and occur without warning. These serious adverse events are idiosyncratic and are independent of dose or duration of use. Patients should be advised of the signs and symptoms of serious skin reactions and to consult their physician at the first appearance of a skin rash or other signs of hypersensitivity.

Anaphylactic reactions.

Hypersensitivity reactions may occur in susceptible individuals. Anaphylactic (anaphylactoid) reactions may occur both in patients with and without a history of hypersensitivity or exposure to aspirin or other NSAIDs or naproxen-containing products. They may also occur in individuals with a history of angioedema, bronchospastic reactivity (e.g. asthma), rhinitis and nasal polyps. Anaphylactoid reactions, like anaphylaxis, may have a fatal outcome.
Bronchospasm may be precipitated in patients suffering from, or with a history of, asthma or allergic disease or aspirin sensitivity.

Use in hepatic impairment.

As with other NSAIDs, elevations of one or more liver function tests may occur in up to 15% of patients. These abnormalities may progress, may remain essentially unchanged or may resolve with continued therapy. The ALT test is probably the most sensitive indicator of liver dysfunction. Meaningful elevations (three times the upper limit of normal) of ALT or AST occurred in controlled clinical trials in less than 1% of patients. Physicians and patients should remain alert for hepatotoxicity. Patients should be informed about the signs and/or symptoms of hepatotoxicity. A patient with symptoms and/or signs suggesting hepatic dysfunction (e.g. nausea, fatigue, lethargy, pruritus, jaundice, abdominal tenderness in the right upper quadrant and flu-like symptoms), or in whom an abnormal hepatic test has occurred, should be evaluated for evidence of the development of more severe hepatic reactions while on therapy with Anaprox.
Hepatic abnormalities may be the result of hypersensitivity or direct toxicity.
Severe hepatic reactions, including jaundice and cases of fatal hepatitis, have been reported with naproxen sodium as with other NSAIDs. Cross reactivity has been reported. Although such reactions are rare, if abnormal hepatic tests persist or worsen, if clinical signs and symptoms consistent with hepatic disease develop or if systemic manifestations occur (e.g. eosinophilia, rash, etc.), Anaprox should be discontinued.
Chronic alcoholic hepatic disease and potentially other forms of cirrhosis reduce the total plasma concentration of naproxen; however, the plasma concentration of unbound naproxen is increased. The implication of this finding for naproxen dosing is unknown.
In patients with impaired hepatic function, the lowest effective dose is recommended.

Infection.

The antipyretic, anti-inflammatory and analgesic effects of naproxen may mask the usual signs or symptoms of infection.

Ocular events.

Adverse ophthalmological effects have been observed with NSAIDs. In rare cases, adverse ocular disorders including papillitis, retrobulbar optic neuritis and papilloedema have been reported in users of NSAIDs including Anaprox, although a cause-and-effect relationship cannot be established; accordingly, patients who develop visual disturbances during treatment with Anaprox should have an ophthalmological examination.

Sodium.

A 550 mg tablet of Anaprox contains approximately 50 mg of sodium. This should be considered in patients whose overall intake of sodium must be markedly restricted.

Fluid retention and oedema.

Peripheral oedema has been observed in some patients taking Anaprox or other NSAIDs. Although sodium retention has not been reported in metabolic studies, it is possible that patients with compromised cardiac function may be at greater risk when taking naproxen. For this reason, naproxen should be used with caution in patients with fluid retention, hypertension or heart failure.

Use in pregnancy.

(Category C)
NSAIDs inhibit prostaglandin synthesis and, when given during the latter part of pregnancy, may cause closure of the foetal ductus arteriosus, prolong labour and delay birth. During the last few days before expected birth, agents with an inhibitory effect on prostaglandin synthesis should be avoided. Continuous treatment with NSAIDs during the last month of pregnancy should only be given when clearly indicated.
Anaprox should only be administered during pregnancy if the benefit justifies the potential risk.
The use of Anaprox, as with any drug known to inhibit cyclooxygenase/ prostaglandin synthesis, may impair fertility and is not recommended in women attempting to conceive. In women who have difficulty conceiving or are undergoing investigation of infertility, withdrawal of naproxen should be considered.
Data from epidemiological studies suggest an increased risk of miscarriage after the use of a prostaglandin synthesis inhibitor in early pregnancy.

Use in lactation.

Naproxen has been found in the milk of lactating mothers at a concentration approximately 1% of that found in plasma. As the effect of naproxen in the newborn is not known, the use of Anaprox in lactating mothers is not recommended.

Paediatric use.

Anaprox is not recommended in children under 5 years of age as the safety and efficacy in this population has not been established.

Use in elderly.

The lowest effective dose is recommended in elderly patients.
Studies indicate that although the total plasma concentration of naproxen is unchanged, the unbound plasma fraction of naproxen is increased in the elderly.

Effects on ability to drive and operate machinery.

Some patients may experience drowsiness, dizziness, vertigo, insomnia or depression with the use of Anaprox. If patients experience these or similar undesirable effects, they should exercise caution in carrying out activities that require alertness.

Interactions

Concomitant administration of sucralfate or cholestyramine can delay the absorption of naproxen, but does not affect its extent. Antacids have a variable effect on absorption.

Other NSAIDs.

Combination of naproxen containing products and other NSAIDs, including cyclooxygenase-2 (COX-2) selective inhibitors, is not recommended because of the risk of inducing serious NSAID related adverse events.

Protein binding.

Naproxen sodium is highly bound to plasma albumin; thus naproxen sodium has a theoretical potential for interaction with other albumin bound drugs, for example warfarin or bishydroxycoumarin, which may be displaced and induce excessively prolonged prothrombin times. Similarly, patients receiving hydantoins, sulfonamides or sulfonylureas should be observed for increased effect or toxicity (see Precautions, Haematological).

Warfarin.

The concurrent use of NSAIDs and warfarin has been associated with severe, sometimes fatal haemorrhage. The exact mechanism of the interaction between NSAIDs and warfarin 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. Anaprox should be used in combination with warfarin only if absolutely necessary, and patients taking this combination of drugs should be closely monitored.

Anticoagulants/ antiplatelet agents.

Patients who have coagulation disorders or are receiving drug therapy that interferes with haemostasis should be carefully observed if naproxen sodium is administered. Patients on full anticoagulation therapy (e.g. heparin or dicoumarol derivatives) may be at increased risk of bleeding if given naproxen sodium concurrently. Thus, the benefits should be weighed against these risks.
There is an increased risk of gastrointestinal bleeding when antiplatelet agents are combined with NSAIDs.

Selective serotonin reuptake inhibitors (SSRIs).

There is an increased risk of gastrointestinal bleeding when SSRIs are combined with NSAIDs.

Steroids.

If steroid dosage is reduced or eliminated during Anaprox therapy, the steroid dosage should be reduced slowly and the patients must be observed closely for any evidence of adverse effects, including adrenal insufficiency and exacerbation of symptoms of underlying disease.

Probenecid.

Probenecid significantly prolongs the half-life of naproxen (from 14 to 37 hours). This is associated with a decrease in conjugated metabolites and an increase in 6-O-desmethylnaproxen.

Methotrexate.

Concomitant administration of naproxen sodium and methotrexate should be administered with caution because naproxen has been reported, among other NSAIDs, to reduce the tubular secretion of methotrexate in animal models, and thus possibly increasing the toxicity of methotrexate.

Beta-blockers.

Naproxen sodium and other NSAIDs can reduce the antihypertensive effect of β-blockers, angiotensin converting enzyme inhibitors (ACE inhibitors), and angiotensin receptor blockers (ARBs).

Diuretics.

As with other NSAIDs, naproxen sodium may inhibit the natriuretic effect of frusemide.

Lithium.

Inhibition of renal lithium clearance leading to increases in plasma lithium concentrations has been reported.

Sodium bicarbonate.

Sodium bicarbonate may enhance the rate of naproxen absorption.

Zidovudine.

In vitro studies have shown that naproxen may interfere with the metabolism of zidovudine, resulting in higher zidovudine plasma levels. Therefore, to avoid the potential side effects associated with increased zidovudine plasma levels, dose reduction should be considered.

ACE inhibitors.

Concomitant use of NSAIDs with ACE inhibitors or angiotensin receptor blockers may increase the risk of renal dysfunction, especially in patients with pre-existing poor renal function (see Precautions).

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 (triple whammy) 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 initiation 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.

Effects on laboratory tests.

Naproxen sodium decreases platelet aggregation and prolongs bleeding time. This effect should be considered when bleeding times are determined.
Anaprox may artefactually interfere with some tests for 17-ketogenic steroid and may interfere with some urinary assays for 5-hydroxy-indoleacetic acid (5HIAA). 17-hydroxycorticosteroid measurements (Porter/ Silber test) do not appear to be altered.
Naproxen sodium therapy should be temporarily discontinued for at least 72 hours before testing adrenal function.

Adverse Effects

Adverse effects reported in controlled clinical trials in 960 patients treated for rheumatoid arthritis and osteoarthritis are listed below. In general, these effects were reported 2 to 10 times more frequently than they were in studies of 962 patients treated for mild to moderate pain.

Incidence between 3% and 9%.

Gastrointestinal.

The most frequently reported adverse effects were related to the gastrointestinal tract. These were: constipation, heartburn, abdominal pain, nausea.

Central nervous system.

Headache, dizziness, drowsiness.

Dermatologic.

Itching (pruritus), skin eruption, ecchymoses.

Special senses.

Tinnitus.

Cardiovascular.

Oedema, dyspnoea.

Incidence between 1% and less than 3%.

Gastrointestinal.

Dyspepsia, diarrhoea, stomatitis.

Central nervous system.

Lightheadedness, vertigo.

Dermatologic.

Sweating, purpura.

Special senses.

Hearing disturbances, visual disturbances.

Cardiovascular.

Palpitations.

General.

Thirst.

Incidence less than 1%.

Probable causal relationship.

The following adverse effects were reported less frequently than 1% during controlled clinical trials and in postmarketing reports. A causal relationship probably exists between naproxen sodium and these adverse effects.

Gastrointestinal.

Abnormal liver function tests, gastrointestinal bleeding, haematemesis, jaundice, melaena, peptic ulceration with bleeding and/or perforation, nonpeptic gastrointestinal ulceration, vomiting, ulcerative stomatitis, colitis, fatal hepatitis.

Renal.

Glomerular nephritis, haematuria, interstitial nephritis, renal papillary necrosis, nephrotic syndrome, renal disease, hyperkalaemia, renal failure.

Haematologic.

Eosinophilia, granulocytopenia, leucopenia, thrombocytopenia.

Central nervous system.

Depression, dream abnormalities, inability to concentrate, insomnia, malaise, myalgia, muscle weakness, aseptic meningitis.

Dermatologic.

Porphyria cutanea tarda, epidermolysis bullosa, alopecia, skin rashes, epidermal necrolysis, erythema multiforme, Stevens-Johnson syndrome (SJS), photosensitivity reactions including rare cases in which the skin resembles porphyria cutanea tarda (pseudoporphyria) or epidermolysis bullosa.

Special senses.

Hearing impairment.

Cardiovascular.

Vasculitis, congestive heart failure.

General.

Menstrual disorders, pyrexia (chills and fever), eosinophilic pneumonitis, anaphylactoid reactions (see Precautions, Anaphylactic reactions).

Causal relationship unknown.

Other reactions have been reported in circumstances in which a causal relationship could not be established. Although rarely reported, the physician should be alerted to these.

Haematologic.

Agranulocytosis, aplastic anaemia, haemolytic anaemia.

Central and peripheral nervous system.

Cognitive dysfunction, convulsions, paraesthesia.

Dermatologic.

Urticaria, photosensitivity.

Mouth and throat.

Sore throat.

General.

Angioneurotic oedema, hyperglycaemia, hypoglycaemia.

Reproductive.

Female infertility.

Postmarketing experience.

The following adverse effects have been reported with Anaprox.

Gastrointestinal.

Inflammation, peptic ulcers, ulceration, perforation and obstruction of the upper and lower gastrointestinal tract, gastrointestinal bleeding (sometimes fatal, particularly in the elderly), heartburn, nausea, oesophagitis, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, nonpeptic gastrointestinal ulceration, melaena, haematemesis, stomatitis, ulcerative stomatitis, exacerbation of ulcerative colitis and Crohn's disease, pancreatitis, gastritis.

Infection.

Aseptic meningitis.

Blood and lymphatic system disorders.

Agranulocytosis, aplastic anaemia, eosinophilia, haemolytic anaemia, leucopenia, thrombocytopenia.

Immune system disorders.

Anaphylactoid reactions.

Metabolic and nutrition disorders.

Hyperkalaemia.

Psychiatric disorders.

Depression, dream abnormalities, insomnia.

Nervous system disorders.

Dizziness, drowsiness, headache, lightheadedness, retrobulbar optic neuritis, convulsions, cognitive dysfunction, inability to concentrate.

Eye disorders.

Visual disturbances, corneal opacity, papillitis, papilloedema.

Ear and labyrinth disorders.

Hearing impairment, hearing disturbances, tinnitus, vertigo.

Cardiac disorders.

Palpitations, cardiac failure, congestive heart failure.

Vascular disorders.

Hypertension, vasculitis.

Respiratory, thoracic and mediastinal disorders.

Dyspnoea, pulmonary oedema, asthma, eosinophilic pneumonitis.

Hepatobiliary disorders.

Hepatitis, jaundice.

Skin and subcutaneous tissue disorders.

Ecchymoses, itching (pruritus), purpura, skin eruptions, sweating, alopecia, epidermal necrolysis, very rarely toxic epidermal necrolysis (TEN), erythema multiforme, bullous reactions (including SJS), erythema nodosum, fixed drug eruption, lichen planus, pustular reaction, skin rashes, systemic lupus erythematosus (SLE), urticaria, photosensitivity reactions including rare cases resembling porphyria cutanea tarda (pseudoporphyria) or epidermolysis bullosa or angioneurotic oedema.
If skin fragility, blistering or other symptoms suggestive of pseudoporphyria occur, treatment should be discontinued and patient monitored.

Musculoskeletal and connective tissue disorders.

Myalgia, muscle weakness.

Renal and urinary disorders.

Haematuria, interstitial nephritis, nephritic syndrome, renal disease, renal failure, renal papillary necrosis.

Reproductive system.

Female infertility.

General disorders.

Oedema, thirst.

Investigations.

Abnormal liver function tests, raised serum creatinine.

Dosage and Administration

After assessing the risk/ benefit ratio in each individual patient, the lowest effective dose for the shortest possible duration should be used.

Acute migraine headache.

The recommended dose is 825 mg at the first symptom of an impending headache. An additional 275 mg to 550 mg dose can be given at least an hour after the initial dose if necessary. The total daily dose should not exceed 1375 mg.

Acute pain states with an inflammatory component.

The recommended dose is 550 mg initially followed by 275 mg every six to eight hours as required. The total daily dose should not exceed 1375 mg.

Rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and chronic pain states with an inflammatory component.

The dosage range of naproxen sodium is 550 mg to 1100 mg daily in two divided doses. The starting dose should not be less than 550 mg daily. The dose may be increased gradually up to 1100 mg daily, depending on the needs of the patient.
Patients on long-term treatment should be reviewed regularly with regards to efficacy, risk factors and ongoing need for treatment.

Overdosage

Significant overdose of the medicine may be characterised by dizziness, drowsiness, epigastric pain, abdominal discomfort, indigestion, transient alterations in liver function, hypoprothrombinaemia, renal dysfunction, metabolic acidosis, apnoea, disorientation, nausea or vomiting. A few patients have experienced seizures but it is unclear if these were causally related to naproxen. It is not known what dose of naproxen sodium would be life threatening.
Gastrointestinal bleeding may occur. Hypertension, acute renal failure, respiratory depression and coma may occur after the ingestion of NSAIDs and may occur following an overdose.
Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDs and may occur following an overdose.
Patients should be managed by symptomatic and supportive care following NSAIDs overdose. There are no specific antidotes. Prevention of further absorption (e.g. activated charcoal) may be indicated in symptomatic patients seen within 4 hours of ingestion or following a large overdose. Forced diuresis, alkalinisation of urine, haemodialysis or haemoperfusion may not be useful due to high protein binding.
Contact the Poisons Information Centre for advice on management of overdosage.

Presentation

Tablets, 550 mg (dark blue, oblong, film coated, scored on both sides, marked NPS 550 on one side): 50's (PVC/ aluminium blister pack).

Storage

Store below 30°C. Protect from light.

Poison Schedule

S4.