Consumer medicine information

Naproxen Suspension

Naproxen

BRAND INFORMATION

Brand name

Phebra Naproxen Suspension

Active ingredient

Naproxen

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Naproxen Suspension.

What is in this leaflet

This leaflet answers some common questions about Naproxen Suspension. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you being given Naproxen Suspension against the benefits they expect it will have for you.

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

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

What Naproxen Suspension is used for

Naproxen Suspension contains the active ingredient naproxen.

Naproxen Suspension relieves pain and reduces inflammation (swelling, redness and soreness) that may occur in the following:

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

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

Naproxen Suspension belongs to a group of medicines called Non-Steroidal Anti-Inflammatory Drugs (or NSAIDs).

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

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

Use in children

Naproxen Suspension is recommended for use in children (over the age of 5) for the treatment of juvenile rheumatoid arthritis.

Naproxen Suspension is not addictive.

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

Before you are given Naproxen Suspension

When you must not be given it

Do not take Naproxen Suspension if you have an allergy to:

  • Naproxen suspension or any of the 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.

Some of the symptoms of an allergic reaction 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.

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

Do not take Naproxen Suspension if:

  • you are vomiting blood or material that looks like coffee grounds
  • you are bleeding from the rectum (back passage), have black sticky bowel motions (stools) or bloody diarrhoea
  • you have a peptic ulcer (i.e. stomach or duodenal ulcer), or have had peptic ulcers before
  • you are taking other medicines which contain naproxen or naproxen sodium (e.g. Naprogesic, Inza, Anaprox)
  • you have severe heart failure.
  • you have recently had or are about to have heart bypass surgery

Do not give Naproxen Suspension to a child under 2 years of age. The safety and effectiveness in children under 2 years of age has not been established.

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

Do not take Naproxen Suspension 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.

If you are not sure if you should start taking Naproxen Suspension, talk to your doctor.

Before you are given 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
Naproxen Suspension may impair fertility and is not recommended in women attempting to conceive.
Naproxen Suspension may increase the risk of miscarriage when used in early pregnancy.
Naproxen Suspension may affect your developing baby if you take it during pregnancy.
If it is necessary for you to take Naproxen Suspension, your doctor will discuss the risks and benefits of taking this medicine during pregnancy.
  1. You are breast-feeding or intend to breast-feed
Naproxen Suspension passes into breast milk. The effect on the baby is not known.
  1. 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
  • a tendency to bleed or other blood problems, such as anaemia
  • kidney or liver disease
  • heart failure
  • high blood pressure or heart problems
  • swelling of the ankles or feet.
  1. You currently have an infection
If you take Naproxen Suspension while you have an infection, the suspension may hide some of the signs of an infection (e.g. pain, fever). This may make you think, mistakenly, that you are better or that it is not serious.
  1. You plan to have surgery Naproxen
Suspension can prolong bleeding.

If you have not told your doctor about any of the above, tell them before you take any Naproxen Suspension.

Taking other medicines

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

Some medicines may interfere with Naproxen Suspension. These include:

  • antacids, medicines used to treat indigestion and heartburn
  • aspirin, salicylates or other NSAID medicines
  • cholestyramine, a medicine used to treat high cholesterol levels
  • 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
  • sucralfate, a medicine used to treat and prevent stomach ulcers
  • 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 sulfonamides/quinolones
  • some medicines used to treat diabetes
  • sodium bicarbonate, a medicine used to treat stomach upset or ulcers
  • 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.

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

Your doctor has more information on medicines to be careful with or avoid while being given this medicine.

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

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 Naproxen Suspension is given

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

Take Naproxen Suspension exactly as your doctor has prescribed. Your doctor will tell you how much Naproxen Suspension to take each day. If you do not understand the instructions on the bottle, ask your doctor or pharmacist for help.

Sprains, strains and period pain
The recommended dose is 500 mg, followed by 250 mg every 6 to 8 hours, as needed. Total daily dose is 1250 mg.

Migraine Headache
The recommended dose is 750 mg taken at the first sign of a migraine. An additional dose of 250 mg to 500 mg can be taken at least an hour after the initial dose, if required. The total daily dose should not exceed 1250 mg.

Arthritis
The recommended dose is 375 mg to 1000 mg a day in two divided doses.

Juvenile Rheumatoid Arthritis
The recommended dose for children 5 years and above is 10 mg/kg given in 2 equal divided doses (i.e. 5 mg/kg twice a day).

How to take it

Shake Naproxen Suspension gently before use.

Use a measuring cup or syringe to measure out the exact dose your doctor has prescribed.

Take Naproxen Suspension with a glass of water or milk.

When to take it

Take the suspension 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 Naproxen Suspension for longer than your doctor says. Depending on your condition, you may need to use Naproxen Suspension, only once, for a few days, a few weeks or for longer periods.

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

If you are using Naproxen Suspension for arthritis, it will not cure your condition, but it should help to control the pain, swelling and stiffness.

If you have arthritis, Naproxen Suspension should be taken every day for as long as your doctor prescribes.

Ask your doctor if you are not sure how long to take Naproxen Suspension 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 take a double dose to make up for the dose 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 the Emergency Department at your nearest hospital, if you think that you or anyone else may have taken too much Naproxen Suspension. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

If you take too much Naproxen Suspension, 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 Naproxen Suspension

Things you must do

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

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

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 Naproxen Suspension.

If you are going to have any laboratory tests, tell your doctor that you are taking Naproxen Suspension. Naproxen Suspension can affect the results of some of these tests.

If you get an infection while using Naproxen Suspension, tell your doctor. Naproxen Suspension 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 and change your treatment unnecessarily.

Tell your doctor if you feel the suspension is not helping your condition.

Things you must not do

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

Do not use Naproxen Suspension 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 Naproxen Suspension affects you.

Naproxen Suspension contains sorbitol. Products containing sorbitol may have a laxative effect or cause diarrhoea. 50 mL of Naproxen Suspension contains 4.5g of sorbitol.

Naproxen Suspension contains 7.87 mg of elemental sodium per mL of suspension.

Naproxen Suspension may cause dizziness or light-headedness in some people. Make sure you know how you react to Naproxen Suspension 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 Naproxen Suspension.

Naproxen Suspension helps most people with pain due to 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), heartburn, indigestion, cramps
  • constipation, diarrhoea, pain in the stomach
  • loss of appetite
  • dizziness, light-headedness
  • drowsiness, sleepiness
  • headache
  • buzzing or ringing in the ears
  • feeling thirsty
  • aching muscles, muscle tenderness or weakness, not caused by exercise.

These are the more common side effects of Naproxen Suspension.

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

  • bleeding or bruising more easily than normal, reddish or purplish blotches under the skin
  • eye problems such as blurred vision
  • severe or persistent headache
  • fast or irregular heartbeats, also called palpitations
  • difficulty hearing, deafness
  • signs of frequent or worrying infections such as fever, severe chills, sore throat or mouth ulcers
  • yellowing of the skin or eyes, also called jaundice
  • unusual weight gain, swelling of ankles or legs.

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

Tell your doctor immediately, or go to the Emergency Department at your nearest hospital if you experience any of the following:

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

These are very serious side effects. You may need urgent medical attention or hospitalisation. These side effects are very 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 this list of possible side effects. You may not experience any of them.

After taking Naproxen Suspension

Storage

Keep your suspension in a cool dry place where the temperature stays below 25°C. Do not store Naproxen Suspension, 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 Naproxen Suspension 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 Naproxen Suspension, or the suspension has passed its expiry date, ask your pharmacist what to do with any that is left over.

Product description

Availability

Naproxen Oral Suspension is available as 125 mg/5 mL strength, which is equivalent to 25 mg/mL strength, in a bottle containing 474 mL.

What it looks like

Naproxen Suspension is a light orange suspension, with a pineapple-orange flavour. Particles readily re-suspend when shaken.

Ingredients

Active ingredient:

  • naproxen 25 mg/mL

Inactive ingredients:

  • sucrose
  • sorbitol 90 mg/mL
  • sodium chloride (equiv. to 7.87 mg of elemental sodium per mL)
  • magnesium aluminium silicate
  • fumaric acid
  • methyl hydroxybenzoate
  • imitation orange flavour
  • imitation pineapple flavour
  • the colour, Sunset Yellow FCF [110]
  • purified water.

This medicine does not contain lactose, gluten, tartrazine or alcohol.

Supplier

Naproxen Suspension is supplied in Australia by:

Phebra Pty Ltd
19 Orion Road, Lane CoveWest,
NSW 2066, Australia.

Naproxen Suspension 125 mg/5 mL 474 mL bottle.

AUST R 196596

Phebra product code- SOL048

Date of most recent amendment: 06 April 2020

Phebra and the Phi symbol are trademarks of Phebra Pty Ltd, 19 Orion Road, Lane Cove West, NSW 2066, Australia.

Published by MIMS August 2020

BRAND INFORMATION

Brand name

Phebra Naproxen Suspension

Active ingredient

Naproxen

Schedule

S4

 

1 Name of Medicine

Naproxen.

2 Qualitative and Quantitative Composition

Naproxen is a propionic acid derivative related to the arylacetic acid class of drugs. It is unrelated to salicylates and the corticosteroid hormones. It is an odourless, white to off white crystalline substance. It is lipid soluble, practically insoluble in water at low pH and freely soluble in water at high pH.
Naproxen Suspension is a suspension containing 25 mg/mL of naproxen. The suspension also contains sucrose, sorbitol, sodium chloride and methyl hydroxybenzoate. For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Naproxen Suspension is available as an orange aqueous suspension.

4 Clinical Particulars

4.1 Therapeutic Indications

Naproxen Suspension is indicated for the treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis; for the symptomatic treatment of primary dysmenorrhoea; for the relief of acute and/or chronic pain states in which there is an inflammatory component and as an analgesic in acute migraine attack.

4.2 Dose and Method of Administration

After assessing the risk/benefit ratio in each individual patient, the lowest effective dose for the shortest possible duration should be used.
Patients on long-term treatment should be reviewed regularly with regards to efficacy, risk factors and ongoing need for treatment.

Chronic conditions.

Osteoarthritis/ rheumatoid arthritis/ ankylosing spondylitis/ chronic pain states in which there is an inflammatory component.

The starting dose of naproxen should not be less than 500 mg daily and may be varied stepwise within the range 375 to 1000 mg daily maintaining twice daily administration for long-term maintenance, depending on the needs of the patient.

Acute conditions.

Acute pain states in which there is an inflammatory component.

The recommended dose of naproxen is 500 mg initially followed by 250 mg every six to eight hours as required. The total daily dose should not exceed 1250 mg.

Dysmenorrhoea.

In the symptomatic treatment of primary dysmenorrhoea, the recommended dose is 500 mg initially at the first sign of dysmenorrhoea or menstrual bleeding (whichever occurs first), followed by 250 mg every six to eight hours as required. The total daily dose should not exceed 1250 mg.

Migraine.

For the treatment of acute migraine headache, the recommended dose of naproxen is 750 mg at the first symptom of an impending headache. An additional dose of 250 to 500 mg can be given throughout the day if necessary, at least an hour after initial dose. The total daily dose should not exceed 1250 mg.

Children.

Juvenile rheumatoid arthritis.

The recommended daily dose for children 5 years and above is 10 mg/kg in two equal divided doses (i.e. 5 mg/kg twice a day).

4.3 Contraindications

Naproxen Suspension 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 NSAID 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;
under 2 years of age since safety in this age group has not been established;
with severe heart failure;
treatment of perioperative pain in setting of coronary bypass surgery (CABG).

4.4 Special Warnings and Precautions for Use

Cardiovascular thrombotic events.

Observational studies have indicated that nonselective 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 known 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 Section 4.2 Dose and Method of Administration). Healthcare professionals and patients should remain alert for such cardiovascular symptoms. Patients should be informed about signs and/or symptoms of serious cardiovascular 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 NSAIDs 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. 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 abdominal 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 to 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 Section 4.5 Interactions with Other Medicines and Other Forms of Interactions). The concurrent use of aspirin and NSAIDs also increases the risk of serious gastrointestinal adverse events.
Patients with risk factors should commence treatment on the lowest dose available.

Haematological.

Naproxen decreases platelet aggregation and prolongs bleeding time. This effect should be kept in mind when bleeding times are being determined. (See Section 4.4 Special Warnings and Precautions for Use, Effects on laboratory tests.)
Patients who have coagulation disorders or are receiving drug therapy that interferes with haemostasis should be carefully observed if Naproxen Suspension 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 Naproxen Suspension concurrently. Therefore, the benefits of prescribing Naproxen Suspension 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 Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

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 any other sign 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.

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 Naproxen Suspension, although a cause-and-effect relationship cannot be established; accordingly, patients who develop visual disturbances during treatment with Naproxen Suspension should have an ophthalmological examination.

Sodium.

Each mL of Naproxen Suspension liquid contains 8 mg of sodium. This should be considered in patients whose overall intake of sodium must be restricted.

Fluid retention and oedema.

Peripheral oedema has been observed in some patients taking Naproxen Suspension 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 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. A patient with symptoms and/or signs suggesting hepatic dysfunction, or in whom an abnormal hepatic test has occurred, should be evaluated for evidence of the development of more severe hepatic reaction while on therapy with Naproxen Suspension.
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 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.), Naproxen Suspension 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.

Use in renal impairment.

There have been reported cases of impaired renal function, renal failure, acute interstitial nephritis, haematuria, proteinuria, renal papillary necrosis, and occasionally nephritic syndrome associated with Naproxen Suspension.
Naproxen Suspension 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, Naproxen Suspension 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 Naproxen Suspension 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 and the elderly. Discontinuation of Naproxen Suspension is usually followed by recovery to the pretreatment state; however, serious adverse events may persist. Naproxen Suspension should be used with great caution in such patients and the monitoring of serum creatinine and/or creatinine clearance is advised. 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.

Use in the elderly.

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

Paediatric use.

The recommended dosage form of naproxen in children (5 years and over) is Naproxen Suspension 25 mg/mL.
Naproxen Suspension is not recommended in children under 5 years of age as the safety and efficacy in this population has not been established.

Effect on laboratory tests.

Naproxen decreases platelet aggregation and prolongs bleeding time. This effect should be considered when bleeding times are determined.
Naproxen Suspension may result in artefactual interference 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 therapy should be temporarily discontinued for at least 72 hours before testing adrenal function.

4.5 Interactions with Other Medicines and Other Forms of 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 cumulative risks of inducing serious NSAID-related adverse events.

Protein binding.

Naproxen is highly bound to plasma albumin; thus naproxen has a theoretical potential for interaction with other albumin bound drugs, for example, warfarin or bishydroxycoumarin 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 Section 4.4 Special Warnings and Precautions for Use, Haematological).

Warfarin.

The concurrent use of NSAIDs and warfarin has been associated with severe and 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. Naproxen Suspension 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 is administered. Patients on full anticoagulation therapy (e.g. heparin or dicoumarol derivatives) may be at increased risk of bleeding if given naproxen 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 Naproxen Suspension 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 hrs). This is associated with a decrease in conjugated metabolites and an increase in 6-0-desmethyl naproxen.

Methotrexate.

Concomitant administration of naproxen 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 have been reported to reduce the clearance of methotrexate; and thus possibly increasing the toxicity of methotrexate.

Beta-blockers.

Naproxen and other NSAIDs can reduce the antihypertensive effect of beta-blockers.

Diuretics.

As with other NSAIDS, naproxen 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.

As with other NSAIDs, naproxen may increase the risk of renal impairment associated with the use of angiotensin I converting enzyme (ACE) inhibitors.

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.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

The use of Naproxen Suspension, 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.
(Category C)
Naproxen Suspension is Pregnancy Category C - Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human foetus or neonate without causing malformations. These effects may be reversible.
NSAIDs inhibit prostaglandin synthesis. Data from epidemiological studies suggest an increased risk of miscarriage after the use of a prostaglandin synthesis inhibitor in early pregnancy. When given during the latter part of pregnancy, NSAIDs 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 needed.
Naproxen Suspension should only be administered during pregnancy if the benefit justifies the potential risk.
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 infant is not known, the use of Naproxen Suspension in lactating mothers is not recommended.

4.7 Effects on Ability to Drive and Use Machines

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

4.8 Adverse Effects (Undesirable 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 events 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 reactions were reported less frequently than 1% during controlled clinical trials and in postmarketing reports. The probability of a causal relationship exists between naproxen 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.

Haematological.

Eosinophilia, granulocytopenia, leucopenia, thrombocytopenia.

Central nervous system.

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

Dermatological.

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 epidemolysis bullosa.

Special senses.

Hearing impairment.

Cardiovascular.

Vasculitis, congestive heart failure.

General.

Menstrual disorder, pyrexia (chills and fever), eosinophilic pneumonitis, anaphylactoid reactions (see Section 4.4 Special Warnings and Precautions for Use, Anaphylactic reactions).

Causal relationship unknown.

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

Haematological.

Agranulocytosis, aplastic anaemia, haemolytic anaemia.

Central and peripheral nervous system.

Cognitive dysfunction, convulsions, paraesthesia.

Dermatological.

Urticaria, photosensitivity.

Mouth and throat.

Sore throat.

General.

Angioneurotic oedema, hyperglycaemia, hypoglycaemia, hyperkalaemia.

Reproductive.

Female infertility.

Post-marketing experience.

The following adverse effects have been reported with NSAIDs and Naproxen Suspension.

Gastrointestinal.

Peptic ulcers, perforation, gastrointestinal bleeding, 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 the 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.

Reporting suspected adverse reactions.

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

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 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 four 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.
For information on the management of overdosage, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Naproxen Suspension is a non-steroidal anti-inflammatory drug (NSAID) with analgesic, anti-inflammatory and antipyretic properties.
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 effect 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.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

In humans, naproxen is completely absorbed from the gastrointestinal tract after oral administration. Concomitant administration of food can delay the absorption of naproxen, but does not affect its extent.
After administration of Naprosyn tablets, peak plasma levels are attained in two to four 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 non-protein 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 to 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 6-0-desmethyl naproxen (approximately 28% of an intravenous dose).

Excretion.

Approximately 95% of the naproxen is excreted in the urine, primarily as naproxen (10%), 6-O-desmethyl naproxen (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 Section 4.4 Special Warnings and Precautions for Use, Use in renal impairment).

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Naproxen Suspension also contains sucrose, sorbitol, sodium chloride, aluminium magnesium silicate, fumaric acid, methyl hydroxybenzoate, imitation orange flavour, imitation pineapple flavour, the colour sunset yellow FCF and water - purified.

6.2 Incompatibilities

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

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG)1. The expiry date can be found on the packaging.
1 AUST R 196596.

6.4 Special Precautions for Storage

Store below 25°C. Protect from light.

6.5 Nature and Contents of Container

Naproxen Suspension containing naproxen 25 mg in 1 mL is available as an orange aqueous suspension in bottles of 474 mL.
Phebra product code: SOL048.

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

The chemical name of naproxen is (+)-6-methoxy-α- methyl-2- naphthaleneacetic acid. Its molecular formula is C14H14O3 and molecular weight is 230.3.

Chemical structure.


CAS number.

2224531.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

Summary Table of Changes