Consumer medicine information

Aclin Tablets

Sulindac

BRAND INFORMATION

Brand name

Aclin Tablets

Active ingredient

Sulindac

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Aclin Tablets.

What is in this leaflet

This leaflet answers some common questions about Aclin.

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

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

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

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

What Aclin is used for

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

  • various types of arthritis including osteoarthritis, rheumatoid arthritis, ankylosing spondylitis and acute gouty arthritis
  • muscle and bone injuries such as sprains, strains, lower back pain and tendonitis (e.g. tennis elbow).

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

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

Aclin is available only with a doctor's prescription.

There is no evidence that Aclin is addictive.

Before you take Aclin

When you must not take it

Do not take Aclin if you are allergic to medicines containing sulindac, aspirin, any other NSAID or any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include skin rash, itching or hives, swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing, wheezing or shortness of breath.

If you are allergic to aspirin or NSAIDs and take Aclin, the above symptoms may be severe.

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

Do not take Aclin if:

  • you are vomiting blood or material that looks like coffee grounds
  • you are bleeding from the back passage, have black sticky bowel motions (stools) or bloody diarrhoea
  • you have an active peptic ulcer (i.e. stomach or duodenal ulcer) or have a history of recurring peptic ulcers
  • you have recently had heart bypass surgery.

Do not take Aclin if you are pregnant or intend to become pregnant.

Aclin may affect your developing baby if you take it during pregnancy.

Do not take Aclin if you are breastfeeding or plan to breastfeed.

The safety of Aclin in breastfeeding has not been established.

Do not take Aclin if the expiry date (Exp.) printed on the pack has passed.

Do not take Aclin if the packaging shows signs of tampering or the tablets do not look quite right.

Do not give Aclin to children.

Before you start to take it

Tell your doctor if you have allergies to:

  • any other medicines including aspirin or other NSAIDs
  • any other substances, such as foods, preservatives or dyes.

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

  • heartburn, indigestion, stomach ulcer or other stomach problems
  • vomiting blood or bleeding from the back passage
  • kidney or liver problems
  • diabetes mellitus or sugar diabetes
  • high blood pressure or heart disease e.g. severe heart failure
  • a tendency to bleed or other blood problems
  • are undergoing a surgery
  • asthma.

Your doctor may want to take special care if you have any of these conditions.

Tell your doctor if you currently have an infection.

If you take Aclin while you have an infection, the tablets may hide some of the signs of an infection. This may make you think, mistakenly, that you are better or that it is not serious.

If you have not told your doctor about any of the above, tell them before you start taking Aclin.

Taking other medicines

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

Some medicines may be affected by Aclin, or may affect how well it works. These include:

  • aspirin, salicylates or other NSAIDs
  • warfarin, a medicine used to prevent blood clots
  • tablets used to treat diabetes
  • methotrexate, a medicine used to treat arthritis and some cancers
  • DMSO (dimethyl sulfoxide), another medicine used to treat arthritis
  • cyclosporin, a medicine used to suppress the immune system.

These medicines may be affected by Aclin, 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.

If you are not sure whether you are taking any of these medicines, check with your doctor or pharmacist.

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

How to take Aclin

How much to take

The usual dose is 400 mg per day, taken as a single dose or twice a day.

Your doctor may advise you to take a different dose. This depends on your condition and whether or not you are taking any other medicines.

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

How to take Aclin

Swallow the tablets with a full glass of water.

When to take Aclin

Take Aclin during or immediately after food.

This will lessen the chance of a stomach upset.

If you take Aclin once a day, take the tablets in the evening.

If you forget to take Aclin

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 the missed dose as soon as you remember, and then go back to taking your tablets as you would normally.

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

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

If you have any questions about this, check with your doctor or pharmacist.

How long to take Aclin for

Keep taking Aclin for as long as your doctor recommends.

Depending on your condition, you may need Aclin for a few days, a few weeks or for longer periods.

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

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

If you are not sure how long to take your tablets, talk to your doctor.

If you take too much Aclin (overdose)

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

You may need urgent medical attention.

If you take too much Aclin, you may feel dizzy, light-headed and have a decreased urine output. You may also become unconscious.

While you are taking Aclin

Things you must do

Before starting any new medicine, tell your doctor or pharmacist that you are taking Aclin.

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

If you become pregnant while taking Aclin, tell your doctor.

If you plan to have surgery, including dental surgery, tell your doctor or dentist that you are taking Aclin.

If you get an infection while taking Aclin, tell your doctor.

Aclin may hide some of the signs of an infection and may make you think, mistakenly, that you are better or that it is less serious than it might be. Signs of an infection include fever, pain, swelling or redness.

Visit your doctor regularly so they can check on your progress.

Things you must not do

Do not use Aclin to treat any other conditions unless your doctor tells you to.

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

Things to be careful of

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

Aclin may cause dizziness, lightheadedness or blurred vision in some people. If any of these occur, do not drive, operate machinery or do anything else that could be dangerous. If you drink alcohol, dizziness or light-headedness may be worse.

Things that would be helpful for your arthritis

Some self help measures suggested below may help your condition. Talk to your doctor, physiotherapist, or pharmacist about these measures and for more information.

  • Weight - your doctor may suggest losing some weight to reduce the stress on your joints.
  • Exercise - may be recommended by your doctor or physiotherapist to help keep or improve movement and strengthen muscles. Ask a physiotherapist for an exercise plan suited to your condition. As a general rule if any exercise hurts then do not do it.
  • Rest - is important and is usually balanced with exercise and activity. Rest is needed when joints are hot, swollen or painful.
  • Heat - hot showers or baths may help to ease the pain and relax the muscles that can become tense with arthritis. Your physiotherapist or doctor can prescribe other forms of heat treatment.
  • Physical aids - are available to help with daily household tasks. For example, there are gadgets and aids to help turn on taps, remove screw tops, pick up objects and handles can be fitted in bathrooms. Ask your pharmacist or doctor to give you more information.

Side effects

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

Aclin helps most people with arthritis, but it may have unwanted side effects in some 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.

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

Do not be alarmed by this list of possible side effects.

You may not experience any of them.

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

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

  • stomach upset including nausea (feeling sick), vomiting, heartburn, indigestion, cramps
  • loss of appetite
  • constipation, diarrhoea, pain in the stomach, wind
  • dizziness
  • headache
  • buzzing or ringing in the ears
  • nervousness
  • swelling of the hands, feet, ankles.

These are the more common side effects of Aclin. They are usually mild and often respond to a reduction in dosage.

Some of the stomach upsets, such as nausea and heartburn, may be reduced by taking the tablets with food.

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

  • severe pain or tenderness in the stomach
  • eye problems such as blurred vision
  • severe dizziness, spinning sensation
  • change in mood, for example, depression
  • tingling or numbness of the hands or feet
  • fast or irregular heartbeats, also called palpitations
  • difficulty hearing
  • signs of frequent or worrying infections such as fever, severe chills, sore throat or mouth ulcers
  • bleeding or bruising more easily than normal
  • signs of anaemia, such as tiredness, being short of breath, and looking pale
  • yellowing of the skin and eyes, also called jaundice
  • a change in the colour of urine, blood in the urine
  • a change in the amount or frequency of urine passed, burning feeling when passing urine
  • symptoms of sunburn (such as redness, itching, swelling, blistering) which may occur more quickly than normal.

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

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

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

These are serious side effects that need urgent medical attention or hospitalisation. These side effects are rare.

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

After taking Aclin

Storage

Keep Aclin 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.

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

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

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

Do not store Aclin or any other medicine in the bathroom or near a sink.

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

Heat and dampness can destroy some medicines.

Disposal

If your doctor tells you to stop taking Aclin, or your tablets have passed its expiry date, ask your pharmacist what to do with any that are left over.

 

Product description

What it looks like

  • Aclin - orange-yellow tablet marked "SD/100" on one side and a Greek alpha symbol on the reverse.
  • Aclin 200 - orange-yellow tablet marked "SD/200" on one side and a Greek alpha symbol on the reverse.

Each bottle contains 50 tablets.

Ingredients

The active ingredient in Aclin is sulindac. Each Aclin tablet contains 100 mg of sulindac. Each Aclin 200 contains 200 mg of sulindac.

The tablets also contain:

  • lactose
  • microcrystalline cellulose
  • povidone
  • sodium starch glycollate
  • quinoline yellow CI 47005
  • purified talc
  • magnesium stearate.

The tablets are gluten free.

Manufacturer

Aclin is made in Australia by:
Alphapharm Pty Limited
(ABN 93 002 359 739)
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
Phone: (02) 9298 3999

Australian registration numbers:
Aclin - Aust R 17587
Aclin 200 - Aust R 10232

This leaflet was prepared on
11 November 2011.

BRAND INFORMATION

Brand name

Aclin Tablets

Active ingredient

Sulindac

Schedule

S4

 

Name of the medicine

Sulindac.

Excipients.

Lactose monohydrate, microcrystalline cellulose, povidone, sodium starch glycollate, quinoline yellow CI47005, purified talc, magnesium stearate.

Description

Chemical name: (Z)-5-fluoro-2- methyl-1-[[p-(methyl- sulfinyl)phenyl] methylene]-1H- indene-3-acetic acid. Molecular formula: C20H17FO3S. MW: 356.42. CAS: 38194-50-2. Sulindac is a nonsteroidal, antirheumatic agent with anti-inflammatory, analgesic and antipyretic properties. It is an arylalkanoic acid derivative but is not a propionic acid. Nor is it a salicylate, pyrazolone or corticosteroid.
Sulindac is a nonsteroidal anti-inflammatory indene type compound. Sulindac is a yellow crystalline compound. It is a weak organic acid (pKa (25°C) 4.7). It is soluble in water as the sodium salt or in buffers of pH 6 or higher but is practically insoluble in water below pH 4.5 and sparingly soluble in alcohol.
Each Aclin and Aclin 200 tablet contains sulindac 100 mg and 200 mg as the active ingredient, respectively. The tablets also contain the following inactive ingredients: lactose monohydrate, microcrystalline cellulose, povidone, sodium starch glycollate, quinoline yellow CI47005, purified talc, magnesium stearate.

Pharmacology

Pharmacodynamics.

Aclin usually provides prompt symptomatic relief of inflammation, pain and tenderness and promotes early restoration of joint mobility. The drug has a prolonged duration of activity which permits a once or twice a day dosage schedule, and may be used for long-term treatment. Sulindac has been shown to be an effective, well tolerated compound.
Prostaglandin synthetase inhibition has been hypothesised to be the basis of the mechanism of action of nonsteroidal anti-inflammatory agents (NSAIDs). Following absorption, sulindac undergoes two major biotransformations, reversible reduction to the sulfide metabolite and irreversible oxidation to the inactive sulfone metabolite. The sulfide metabolite is a potent inhibitor of prostaglandin synthesis and available evidence indicates that the biological activity of sulindac resides with the sulfide metabolite. Thus, the sulfoxide form (sulindac) is a prodrug.

Pharmacokinetics.

Absorption.

Sulindac is approximately 90% absorbed in man after oral administration. The peak plasma concentrations of the biologically active sulfide metabolite are achieved in about two hours when sulindac is administered in the fasting state, and in about three to four hours when sulindac is administered with food. The mean half-life of sulindac is 7.8 hours while the mean half-life of the sulfide metabolite is 16.4 hours. Sustained plasma levels of the sulfide metabolite are consistent with a prolonged anti-inflammatory action which is the rationale for a twice per day dosage schedule. Sulindac and its metabolites are extensively (90 to 98%) bound to protein in plasma.

Distribution.

Multiple dose pharmacokinetic studies comparing sulindac 400 mg once a day with 200 mg twice a day found that at steady state the maximum and minimum serum concentrations of the sulfide were not significantly different between the two dosage regimens. Moreover, when sulindac was administered once daily in the evening, plasma levels of active drug in the early morning hours were significantly higher than when administered twice a day.

Metabolism.

Sulindac and the sulfone metabolite undergo extensive enterohepatic circulation relative to the sulfide metabolite. The enterohepatic circulation together with the reversible metabolism are probably major contributors to sustained plasma levels of the active drug.

Excretion.

The primary route of excretion in man is via the urine as both sulindac and its sulfone metabolite (free as well as glucuronides), with the sulfone metabolite accounting for the major portion. Less than 1% of the administered dose of sulindac appears in the urine as the sulfide metabolite. Approximately 25% is found in the faeces, primarily as the sulfone and sulfide metabolites. Sulindac, sulfone and the active sulfide metabolite are excreted in the bile and subject to extensive enterohepatic recycling in animals. Further biotransformation of sulindac may take place in the gastrointestinal tract. Similar enterohepatic circulation, together with reversible metabolism, are probably major contributors to sustained plasma levels of the active drug in man.
The bioavailability of sulindac, as assessed by urinary excretion, was not changed by concomitant administration of an antacid containing magnesium and aluminium hydroxides.

Indications

Aclin is indicated in osteoarthritis; rheumatoid arthritis; ankylosing spondylitis; acute gouty arthritis; the relief of acute and/or chronic pain states in which there is an inflammatory component.

Contraindications

Patients who are hypersensitive to any component of this product.
Patients in whom acute asthmatic attacks, urticaria, or rhinitis are precipitated by aspirin or other NSAIDs.
As with other anti-inflammatory agents, indomethacin may mask the signs and symptoms of peptic ulcer. Because indomethacin itself may cause peptic ulceration or irritation of the gastrointestinal tract, it should not be given to patients with active peptic ulcer, or with a recurrent history of gastrointestinal ulceration.
Treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.
Use in pregnancy (see Precautions, Use in pregnancy).
Use in lactation (see Precautions, Use in lactation).
Patients with severe heart failure.
Patients with severe hepatic impairment.

Precautions

Aclin should not be used in patients in whom acute asthmatic attacks, rhinitis or urticaria have been precipitated by aspirin or other nonsteroidal anti-inflammatory agents.

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 cardiovascular disease, history of atherosclerotic cardiovascular disease or cardiovascular risk factors may also be at greater risk.
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.
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).
There is no consistent evidence that the concurrent use of aspirin mitigates the possible increased risk of serious cardiovascular thrombotic events associated with NSAID use.

Hypertension.

NSAIDs may lead to the onset of new hypertension or worsening of pre-existing hypertension and patients taking antihypertensives with NSAIDs may have an impaired antihypertensive 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 events.

All NSAIDs can cause gastrointestinal discomfort and serious, potentially fatal gastrointestinal effects such as ulcers, bleeding and perforation which may increase with dose or duration of use, but can occur at any time without warning. Upper GI 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 GI 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. the elderly, those with a history of serious gastrointestinal events, smoking and alcoholism. When gastrointestinal bleeding or ulcerations occur in patients receiving NSAIDs, the drug should be withdrawn immediately. Doctors should warn patients about the signs and symptoms of serious gastrointestinal toxicity.
The concurrent use of aspirin and NSAIDs also increase the risk of serious gastrointestinal adverse events.
The drug should not be administered to patients with active gastrointestinal bleeding.
Aclin should be used with caution in patients with a history of gastrointestinal haemorrhage or ulcers. In patients with an active peptic ulcer, an appropriate therapeutic regimen should be instituted and the physician must weigh the benefits of Aclin against possible hazards (see Adverse Effects) and carefully monitor the patient's progress. (In a drug interaction study, an antacid (magnesium and aluminium hydroxides, in suspension, 30 mL) was administered with sulindac with no significant difference in absorption).

Severe skin reactions.

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

Hypersensitivity syndrome.

A potentially life threatening, apparent hypersensitivity syndrome has been reported. In cases where this syndrome is suspected, therapy should be discontinued immediately and not reinstituted. This syndrome may include constitutional symptoms (fever, chills, diaphoresis, flushing), cutaneous findings (rash or other dermatologic reactions, see Adverse Effects), conjunctivitis, involvement of major organs (changes in liver function tests, hepatic failure, jaundice, pancreatitis, pneumonitis with or without pleural effusion, leucopenia, leucocytosis, eosinophilia, disseminated intravascular coagulation, anaemia, renal impairment, including renal failure), and other less specific findings (adenitis, arthralgia, arthritis, myalgia, fatigue, malaise, hypotension, chest pain and tachycardia).

Platelet aggregation.

Sulindac is a moderate to weak inhibitor of platelet function and, therefore, patients who may be adversely affected by this (e.g. those undergoing surgery) should be observed closely.

Oral anticoagulants.

Concurrent use of non-steroidal anti-inflammatory drugs (NSAIDs) and warfarin has been associated with severe, sometimes fatal, haemorrhage, especially in the elderly. The exact mechanism 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. Aclin should be used in combination with warfarin only if absolutely necessary and patients taking this combination should be closely monitored. Adjustment of dosage for oral anticoagulants may be required.

Oral hypoglycaemic agents.

Data available from limited animal studies have shown no evidence of interaction of sulindac with oral hypoglycaemic agents. However, Aclin should be used with caution in patients receiving such agents.

Renal effects.

As the drug is mainly excreted in urine, it should be used with caution in patients with impaired renal function. In severe renal failure the dosage may need to be reduced.
As with other nonsteroidal anti-inflammatory drugs, long-term administration of sulindac to animals has resulted in renal papillary necrosis and other abnormal renal pathology. In humans, there have been reports of acute interstitial nephritis with haematuria, proteinuria and occasionally nephrotic syndrome.
A second form of renal toxicity has been observed in patients with prerenal and renal conditions leading to a reduction in renal blood flow or blood volume, where the renal prostaglandins have a supportive role in the maintenance of renal perfusion. In these patients, administration of an NSAID may cause a dose dependent reduction in prostaglandin formation and precipitate overt renal decompensation. Aclin may affect renal function less than other NSAIDs in patients with chronic glomerular renal disease (see Pharmacology). Until these observations are better understood and clarified, however, and because renal adverse experiences have been reported with sulindac (see Adverse Effects), caution should be exercised when administering this drug to patients with those conditions associated with increased risk of the effects of nonsteroidal anti-inflammatory drugs on renal function, such as those with renal or hepatic dysfunction, diabetes mellitus, complications associated with advanced age, extracellular volume depletion from any cause, congestive heart failure, sepsis or concomitant use of any nephrotoxic drug. An NSAID should be given with caution and renal function should be monitored in any patient who may have reduced renal reserve. Discontinuation of NSAID therapy is typically followed by recovery to the pretreatment state.
As Aclin is eliminated primarily by the kidneys, those patients with significantly impaired renal functions should be closely monitored and a lower daily dosage anticipated to avoid excessive drug accumulation.
Sulindac metabolites have been reported rarely as the major or a minor component in renal stones in association with other calculus components. Aclin should be used with caution in patients with a history of renal lithiasis, and they should be kept well hydrated while receiving Aclin.

Infections.

Nonsteroidal anti-inflammatory drugs, including Aclin, may mask the usual signs and symptoms of infection. Therefore, the physician must be continually on the alert for this and should use the drug with extra care in the presence of existing infection.

Corticosteroids.

As is the case during therapy with other anti-inflammatory/ analgesic/ antipyretic drugs, if corticosteroids are reduced or discontinued during therapy with Aclin, the dose of the corticosteroid should be reduced slowly and the patient observed closely for adverse effects, particularly adrenal insufficiency and exacerbation of rheumatoid arthritis.

Hepatic effects.

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. Significant (3 times the upper limit of normal) elevations of ALT (SGPT) or AST (SGOT) occurred in controlled clinical trials in less than 1% of patients receiving this therapy.
Physicians and patients should remain alert for hepatotoxicity. It is recommended that, in those patients with a history of liver dysfunction, periodic liver function tests be carried out. A patient should be informed about the symptoms and/or signs suggesting liver dysfunction (e.g. nausea, fatigue, lethargy, pruritus, jaundice, abdominal tenderness in the right upper quadrant and 'flu-like' symptoms). If symptoms/ signs or abnormal liver tests were to occur, patient should be evaluated for evidence of the development of more severe hepatic reactions while on therapy.
In patients with poor liver function, delayed, elevated and prolonged circulating levels of the sulfide and sulfone metabolites may occur. Such patients should be monitored closely and a reduction of daily dosage may be required.
Cases of hepatitis, jaundice, or both, with or without fever, may occur within the first three months of therapy. In some patients, the findings are consistent with those of cholestatic hepatitis.
Fever and other evidence of hypersensitivity, including abnormalities in one or more liver function tests and skin reactions, have occurred during therapy with sulindac. Fatalities have occurred in some of these patients.
Determinations of liver function should be considered whenever a patient on therapy with Aclin develops unexplained fever, rash or other dermatological reactions or constitutional symptoms. If unexplained fever or other evidence of hypersensitivity occurs, therapy with Aclin should be discontinued. Administration of Aclin should not be reinstituted in such patients.
The elevated temperature and abnormalities in liver function tests observed with sulindac characteristically have reverted to normal after discontinuation of therapy.

Ocular effects.

Adverse ophthalmological effects have been observed with nonsteroidal anti-inflammatory agents; accordingly, patients who develop visual disturbances during treatment with Aclin should have an ophthalmological examination.

Use in pregnancy.

(Category C)
Australian Pregnancy Categorisation Definition of Category C. Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details.
Aclin should not be given to pregnant women since safety for its use has not been established.
Data from epidemiological studies suggest an increased risk of miscarriage after the use of prostaglandin synthesis inhibitor in early pregnancy.
Nonsteroidal anti-inflammatory drugs have an inhibitory effect on prostaglandin synthesis and, when given during the third trimester of pregnancy, may cause closure of the foetal ductus arteriosus, tricuspid incompetence and pulmonary hypertension, nonclosure of ductus arteriosus postnatally which may be resistant to medical management, myocardial degenerative changes, platelet dysfunction with resultant bleeding, intracranial bleeding, renal dysfunction or failure, renal injury/ dysgenesis which may result in prolonged or permanent renal failure, oligohydramnios, gastrointestinal bleeding or perforation, increased risk of necrotising enterocolitis, and delayed labour and birth.

Use in lactation.

Aclin should not be given to nursing mothers since safety for its use has not been established.

Paediatric use.

Aclin should not be given to children.

Interactions

Dimethyl sulfoxide.

DMSO (dimethyl sulfoxide) should not be used with sulindac. Concomitant administration has been reported to reduce plasma levels of the active sulfide metabolite and may potentially reduce efficacy. In addition, this combination has been reported to cause peripheral neuropathy.

Methotrexate.

Caution should be used if Aclin is administered concomitantly with methotrexate. NSAIDs have been reported to decrease the tubular secretion of methotrexate and potentiate the toxicity.

Cyclosporin.

Administration of NSAIDs concomitantly with cyclosporin has been associated with an increase in cyclosporin induced toxicity, possibly due to decreased synthesis of renal prostacyclin. NSAIDs should be used with caution in patients taking cyclosporin, and renal function should be monitored carefully.

Oral hypoglycaemic.

Although sulindac and its sulfide metabolite are highly bound to protein, studies in which sulindac was given at a dose of 400 mg daily have shown no proven interaction with oral hypoglycaemic agents. However, patients should be monitored carefully until it is certain that no change in their hypoglycaemic dosage is required.

Other NSAIDs.

The concomitant use of Aclin with other NSAIDs is not recommended due to the increased possibility of gastrointestinal toxicity, with little or no increase in efficacy.

Aspirin (acetylsalicylic acid).

The concomitant administration of aspirin with sulindac in normal volunteers significantly depressed the plasma levels of the active sulfide metabolite. In a clinical study, the combination showed an increase in the incidence of gastrointestinal side effects. Since the addition of aspirin did not have a favourable effect on the therapeutic response to sulindac, the combination is not recommended.

Dextroproxyphene hydrochloride/ paracetamol.

Neither dextropropoxyphene hydrochloride nor paracetamol had any effect on the plasma levels of sulindac or its sulfide metabolite.

Diflunisal.

The concomitant administration of sulindac and diflunisal in normal volunteers resulted in lowering of the plasma levels of the active sulindac sulfide metabolite by approximately one-third.

Antacids.

A single dose crossover study compared sulindac 100 mg with sulindac 100 mg administered with an antacid (magnesium and aluminium hydroxides, in suspension, 30 mL). There was no significant difference in absorption as measured by the urinary recovery of sulindac.

Probenecid.

Probenecid given concomitantly with sulindac had only a slight effect on plasma sulfide levels, while plasma levels of sulindac and sulfone were increased. Sulindac was shown to produce a modest reduction in the uricosuric action of probenecid, which probably is not significant under most circumstances.

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

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

Adverse Effects

Sulindac is generally well tolerated. Those side effects experienced are usually mild and may often respond to a reduction in dosage.
The following adverse effects were reported in clinical trials or have been reported since the drug was marketed.

Gastrointestinal.

The most frequent types of side effects occurring with sulindac are gastrointestinal; these include gastrointestinal pain, dyspepsia, nausea with or without vomiting, diarrhoea, constipation, flatulence, anorexia and gastrointestinal cramps.

Dermatological.

Rash, pruritus.

Central nervous system.

Dizziness, headache, nervousness.

Special senses.

Tinnitus.

Miscellaneous.

Oedema.

Adverse effects reported less frequently.

The probability exists of a causal relationship between sulindac and these side effects.

Gastrointestinal.

Stomatitis, gastritis or gastroenteritis. Peptic ulcer, colitis, gastrointestinal bleeding and GI perforations have been reported rarely. Fatalities have occurred. Liver function test abnormalities, jaundice (sometimes with fever), cholestasis, hepatitis, hepatic failure, pancreatitis, ageusia, glossitis and intestinal strictures (diaphragms). It has been reported that a probable sulindac metabolite has been found in biliary sludge in patients with symptoms of cholecystitis who underwent a cholecystectomy.

Dermatological.

Sore or dry mucous membranes, alopecia, photosensitivity, erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, exfoliative dermatitis.

Cardiovascular.

Congestive heart failure (especially in patients with marginal cardiac function), hypertension, palpitation.

Haematological.

Thrombocytopenia, ecchymosis, purpura, agranulocytosis, leucopenia, neutropenia, bone marrow depression (including aplastic anaemia), haemolytic anaemia, increased prothrombin time in patients on oral anticoagulants.

Genitourinary.

Urine discolouration, dysuria, haematuria, proteinuria, crystalluria, renal impairment (including renal failure), interstitial nephritis, nephrotic syndrome, vaginal bleeding.

Nervous system.

Vertigo, insomnia, somnolence, paraesthesiae, convulsions, syncope, depression, psychic disturbances including acute psychosis, aseptic meningitis, sweating, asthenia.

Metabolic.

Hyperkalaemia.

Musculoskeletal.

Muscle weakness.

Special senses.

Visual disturbances including blurred vision, decreased hearing, metallic or bitter taste.

Respiratory.

Epistaxis.

Hypersensitivity reactions.

Anaphylaxis and angioneurotic oedema. Bronchial spasm, dyspnoea, hypersensitivity vasculitis, hypersensitivity syndrome (see Precautions).

Causal relationship unknown.

Other reactions have been reported in clinical trials or since the drug was marketed, but occurred under circumstances where a causal relationship could not be established. However, in these rarely reported events, that possibility cannot be excluded. Therefore, these observations are listed to serve as alerting information to physicians.

Nervous system.

Neuritis.

Miscellaneous.

Gynaecomastia. Rare occurrences of fulminant necrotising fasciitis, particularly in association with Group A β-haemolytic streptococcus, has been described in persons treated with nonsteroidal anti-inflammatory agents, sometimes with fatal outcome (see Precautions).

Cardiovascular.

Arrhythmia.

Metabolic.

Hyperglycaemia.

Special senses.

Disturbances of the retina and its vasculature.

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.
Aclin should be administered once or twice a day with fluids or food. Dosage should be adjusted to the severity of the disease. If used once daily, the drug should be taken in the evening.
The usual daily dosage of Aclin is 400 mg per day. However, the dosage may be lowered depending on the response. Doses above 400 mg per day are not recommended.
In acute gouty arthritis, therapy for seven days is usually adequate.
Patients on long-term treatment should be reviewed regularly with regards to efficacy, risk factors and ongoing need for treatment.

Overdosage

Symptoms.

Cases of overdosage have been reported and, rarely, fatalities have occurred. The following signs and symptoms may be observed following overdosage: stupor, coma, diminished urine output and hypotension. In isolated cases, patients have received up to 900 mg a day without adverse consequences being reported.

Treatment.

In the event of acute overdosage, the patient should be carefully observed and given symptomatic and supportive treatment.
Animal studies show that absorption is decreased by the prompt administration of activated charcoal, which should be given within 1 to 2 hours after ingestion.
Contact the Poisons Information Centre on 131 126 for advice on management and treatment of overdosage.

Presentation

Aclin.

100 mg tablet: orange yellow, marked "SD" breakline "100" on one side, "α" on the other.
Available in bottles of 50's.

Aclin 200.

200 mg tablet: orange yellow, marked "SD" breakline "200" on one side, "α" on the other.
Available in bottles of 50's.
Some strengths, pack sizes and/or pack types may not be marketed.

Storage

Store below 30°C.

Poison Schedule

S4.