Consumer medicine information

Asacol

Mesalazine

BRAND INFORMATION

Brand name

Asacol

Active ingredient

Mesalazine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Asacol.

SUMMARY CMI

ASACOL®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I taking ASACOL?

ASACOL contains the active ingredient mesalazine. ASACOL is used to treat and prevent further episodes of ulcerative colitis.

For more information, see Section 1. Why am I taking ASACOL? in the full CMI.

2. What should I know before I take ASACOL?

Do not take if you have ever had an allergic reaction to mesalazine, aspirin or any other salicylates, or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I take ASACOL? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with ASACOL and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I take ASACOL?

  • Your doctor will tell you what dose to take each day. Follow the instructions given to you by your doctor or pharmacist.
  • Swallow the tablets whole with a glass of water. Do not chew, crush or break the tablets.

More instructions can be found in Section 4. How do I take ASACOL? in the full CMI.

5. What should I know while taking ASACOL?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using ASACOL.
  • Keep all of your appointments with your doctor and have all blood tests recommended
  • Drink plenty of water to reduce the chance of getting kidney stones.
Things you should not do
  • Do not stop taking your medicine or lower the dosage without checking with your doctor. If you stop taking it suddenly, your condition may worsen.
  • Do not take ASACOL to treat any other complaints unless your doctor tells you to
  • Do not give your medicine to anyone else, even if they have the same condition as you.
Driving or using machines
  • This medicine is not expected to affect your ability to drive a car or operate machinery.
Looking after your medicine
  • Store below 25°C.

For more information, see Section 5. What should I know while taking ASACOL? in the full CMI.

6. Are there any side effects?

Less serious common side effects may include: indigestion and mild skin rash.

Serious side effects may include: severe skin rash (blisters, peeling or bruising) with fever or flu-like symptoms; sudden allergic reaction (rash, itching, hives, problems breathing, swollen face, lips, tongue, throat), severe stomach, abdominal, back or chest pain; yellow skin or eyes; pain or burning during urination; strong or recurrent headache, disturbed vision, ringing or buzzing in the ears.

For the full list of side effects and more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

ASACOL®

Active ingredient: mesalazine

Consumer Medicine Information (CMI)

This leaflet provides important information about using ASACOL. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using ASACOL.

Where to find information in this leaflet:

1. Why am I taking ASACOL?
2. What should I know before I take ASACOL?
3. What if I am taking other medicines?
4. How do I take ASACOL?
5. What should I know while taking ASACOL?
6. Are there any side effects?
7. Product details

1. Why am I taking ASACOL?

ASACOL contains the active ingredient mesalazine.

ASACOL is an anti-inflammatory medicine used to treat and prevent further episodes of ulcerative colitis.

Ulcerative colitis is a disease of the large bowel (colon) or back passage (rectum), in which the lining of the bowel becomes inflamed (red and swollen).

ASACOL acts locally at the site of inflammation (colon, rectum and terminal ileum) to reduce this inflammation.

2. What should I know before I take ASACOL?

Warnings

Do not take ASACOL if:

  • you are allergic to mesalazine, aspirin or any other salicylates, or any of the ingredients listed at the end of this leaflet. Always check the ingredients to make sure you can take this medicine.
  • you have severe liver or kidney problems.

Check with your doctor if:

  • you have any other medical conditions:
    - asthma or lung problems
    - liver or kidney problems
    - stomach or intestine ulcer
  • you have suffered any of the following:
    - a reaction after using the similar medicine sulfasalazine
    - heart problems such as inflammation of the heart muscle (myocarditis) or sac around heart (pericarditis) after using mesalazine
    - a severe skin rash or skin peeling, blistering and/or mouth sores after using mesalazine.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

Your doctor will discuss with you the risks and benefits involved.

Children and adolescents

Do not give this medicine to children and adolescents below the age of 18 years. The safety and effectiveness of ASACOL in this age group have not been established.

3. What if I am taking other medicines?

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

Some medicines may interfere with ASACOL and affect how it works. These include:

  • medicines affecting the immune system or anticancer drugs (e.g. azathioprine, 6-mercaptopurine, thioguanine)
  • medicines that prevent the formation of blood clots called anticoagulants (e.g. warfarin)
  • non-steroidal anti-inflammatory drugs (e.g. medicines containing aspirin, ibuprofen or diclofenac).

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect ASACOL.

4. How do I take ASACOL?

How much to take

  • The usual dose to treat a current episode of ulcerative colitis is 2.4 g to 4.8 g taken once daily or in divided doses. The dosage may be adjusted by your doctor.
  • The usual dose to prevent an episode of ulcerative colitis is 1.6 g to 2.4 g taken once daily or in divided doses.
  • Swallow the tablets whole with a full glass of water.
  • Do not chew, crush or break the tablets before swallowing them.
  • Follow the instructions you are given and take ASACOL for as long as your doctor tells you to. This medicine helps to control your condition but does not cure it. It is important to keep taking your medicine even if you feel well.

When to take ASACOL

The tablets can be taken with or without food.

If you forget to take ASACOL

ASACOL should be taken regularly at the same time each day. If you miss your dose at the usual time, take it as soon as you remember.

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

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

If you take too much ASACOL

If you think that you have taken too much ASACOL, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while taking ASACOL?

Things you should do

  • Keep all of your doctor's appointments so that your progress can be checked. Your doctor will do tests before you start and from time to time while you are taking ASACOL to check that your liver, kidneys, blood and lungs are all right.
  • Drink plenty of water to reduce the chance of getting kidney stones. There have been a few reports of kidney stones. Drinking plenty of water may help to prevent this.
  • Remind any doctor, dentist or pharmacist you visit that you are using ASACOL.

Stop taking ASACOL and call your doctor straight away if you:

  • develop a skin rash where the skin starts to blister or peel, ulcers in mouth, throat, nose, genitals and eyes
  • develop unexplained bruising, bleeding under your skin, purple spots or patches under your skin (see Section 6. Are there any side effects?).

These are serious skin reactions which need urgent medical attention.

Other things you should know

  • ASACOL may produce red-brown urine discoloration after contact with sodium hypochlorite bleach in the toilet water. This is caused by a chemical reaction between the active ingredient mesalazine and bleach and is harmless.
  • There have been a few reports of intact tablets found in the stool in people taking ASACOL 400 mg and 800 mg tablets. What appear to be intact tablets may sometimes be the remains of the tablet coating.
    Tell your doctor if you often observe tablets or tablet shells in your stool.

Things you should not do

  • Do not stop taking your medicine or lower the dosage without checking with your doctor. If you stop taking it suddenly, your condition may worsen.
  • Do not take ASACOL to treat any other complaints unless your doctor tells you to
  • Do not give your medicine to anyone else, even if they have the same condition as you.

Driving or using machines

This medicine is not expected to affect your ability to drive a car or operate machinery.

Looking after your medicine

Store below 25°C.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Keep it where young children cannot reach it.

When to discard your medicine

  • If your doctor or pharmacist tells you to stop taking this medicine
  • If the expiry date printed on the pack has passed
  • The packaging is torn or shows signs of tampering.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
Digestive system:
  • indigestion
  • mild abdominal pain
  • diarrhoea
  • feeling or being sick (nausea or vomiting)
  • wind (flatulence)
  • worsening ulcerative colitis symptoms
General body:
  • fever
  • weight loss
Lungs:
  • lung problems or infection with fever, chills, shortness of breath, cough and phlegm
  • pain in chest which is worse when breathing in (pleurisy)
Muscles and bones:
  • muscle aches and pains
  • joint pain
Nervous system:
  • sensation of tingling, pricking and numbness
  • headache
  • dizziness
Reproductive system:
  • low sperm count in men (reversible)
Skin:
  • mild skin rash
  • increased sensitivity of the skin to sun and ultraviolet light (photosensitivity)
  • hair loss
Tests and investigations:
  • changes in liver and kidney function
  • changes in blood test results
  • increased amylase in the saliva.
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
Digestive system:
  • severe stomach or abdominal cramps or pain with nausea, vomiting, bloody diarrhoea or fever
Heart:
  • chest pain, sometimes spreading to the neck and shoulders, and sometimes with rash and joint pain
Hypersensitivity (allergic) reaction:
  • sudden signs of allergic reactions such as rash, itching or hives, shortness of breath, wheezing, coughing, or swelling of limbs, face, lips, mouth, tongue or throat which may cause difficulty swallowing or breathing
Kidney:
  • severe pain in back, side or stomach, pain or burning during urination, blood in urine, might be symptoms of kidney stones (see also “Things you should do”)
Liver:
  • liver problems with nausea, vomiting, loss of appetite, feeling generally unwell, fever, itching, yellowing of the skin and eyes, and dark coloured urine
Nervous system:
  • strong or recurrent headache, disturbed vision, or ringing or buzzing in the ears which might be symptoms of increased pressure within your skull (idiopathic intracranial hypertension)
Skin:
  • unexplained bruising (without injury), bleeding under your skin, purple spots or patches under your skin, anaemia (feeling tired, weak and looking pale, especially on lips, nails and inside of eyelids), fever (high temperature), sore throat or unusual bleeding (e.g. nose bleeds)
  • reddish non-elevated, target-like or circular patches on the trunk, often with central blisters, skin peeling, ulcers of mouth, throat, nose, genitals and eyes, widespread rash, fever and enlarged lymph nodes which may be accompanied by fever and flu-like symptoms
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

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

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

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

What ASACOL contains

Active ingredient
(main ingredient)		mesalazine
Other ingredients
(inactive ingredients)		400 mg and 800 mg tablets
  • lactose monohydrate
  • magnesium stearate
  • povidone
  • purified talc
  • sodium starch glycollate Type A
  • film coating contains:
    iron oxide red, iron oxide yellow, macrogol 6000, methacrylic acid copolymer and triethyl citrate.
1600 mg tablets
  • colloidal anhydrous silica
  • hypromellose
  • magnesium stearate
  • microcrystalline cellulose
  • sodium starch glycollate Type A
  • film coating contains:
    glyceryl monostearate, iron oxide red, iron oxide yellow, macrogol 6000, maize starch, methacrylic acid copolymer, monobasic potassium phosphate, polysorbate 80, sodium hydroxide and triethyl citrate.
Potential allergensASACOL 400 mg and 800 mg tablets contain a small amount of lactose.

Do not take this medicine if you are allergic to any of these ingredients.

What ASACOL looks like

ASACOL 400 mg and 800 mg tablets

ASACOL 400 mg and 800 mg tablets are coated, reddish to brownish oblong tablets with a glossy to matt finish.

The dimensions of the 400 mg tablet are: thickness 7 mm, length 15 mm and width: 6 mm.

The dimensions of the 800 mg tablet are: thickness: 8 mm, length: 17 mm and width: 8 mm.

ASACOL 400 mg tablets are not currently available.

ASACOL 800 mg tablets are supplied in blister packs of 90 tablets*.

ASACOL 400 mg: AUST R 261419

ASACOL 800 mg: AUST R 261420

ASACOL 1600 mg tablets

ASACOL 1600 mg tablets are coated, dark orange oblong tablets with a glossy to matte finish.

The dimensions of the 1600 mg tablet are: thickness:
9 mm, length: 23 mm and width: 11 mm.

The 1600 mg tablets are supplied in blister packs of 60 tablets*.

ASACOL 1600 mg: AUST R 322671

*Other pack sizes are not currently available.

Who supplies ASACOL

Chiesi Australia Pty Ltd
Level 7, Suite 1, 500 Bourke Street,
Melbourne, VIC 3000.

Email: [email protected]

Website: www.chiesi.com.au

This leaflet was prepared in May 2025.

ASACOL® is a registered trademark of Tillotts Pharma AG.

Published by MIMS July 2025

BRAND INFORMATION

Brand name

Asacol

Active ingredient

Mesalazine

Schedule

S4

 

1 Name of Medicine

Mesalazine.

2 Qualitative and Quantitative Composition

Asacol enteric coated tablets contain 400 mg, 800 mg or 1600 mg mesalazine as the active ingredient.

Excipient with known effect.

Sugars as lactose (400 mg and 800 mg tablets).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Asacol 400 mg and 800 mg.

Asacol enteric coated tablets are reddish to brownish oblong tablets with a glossy to matte finish (Asacol 400 mg dimensions: 15 x 6 x 7 mm; Asacol 800 mg dimensions: 17 x 8 x 8 mm).

Asacol 1600 mg.

Asacol enteric coated tablets are film coated dark orange oblong tablets with a glossy to matte finish (Asacol 1600 mg dimensions: 23 x 11 x 9 mm).

4 Clinical Particulars

4.1 Therapeutic Indications

Asacol is indicated for the treatment of mild to moderate ulcerative colitis and maintenance of remission in adults.

4.2 Dose and Method of Administration

Dosage.

Adults.

Acute disease.

2.4 g to 4.8 g per day taken once daily or in divided doses. The dosage can be adjusted in accordance with the response to treatment.

Maintenance therapy.

1.6 g to 2.4 g per day taken once daily or in divided doses.

Elderly population.

The normal adult dose can be taken unless liver or renal function is severely impaired, see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use. No studies have been carried out in the elderly population.

Method of administration.

The tablets must be swallowed whole preferably with some liquid.
The tablets must not be chewed, crushed or broken before swallowing. The tablets can be taken with or without food. If one or more doses have been missed, the next dose should be taken as usual.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in Section 6.1 List of Excipients.
Known hypersensitivity to salicylates.
Severe liver impairment.
Severe renal impairment (GFR < 30 mL/min/1.73 m2).

4.4 Special Warnings and Precautions for Use

Identified precautions.

Blood tests (differential blood count; liver function parameters such as ALT or AST; serum creatinine) and urinary status (dip-sticks) should be determined prior to and during treatment, at the discretion of the treating physician. As a guideline, follow-up tests are recommended 14 days after commencement of treatment, then a further two to three tests at intervals of 4 weeks.
If the findings are normal, follow-up tests should be carried out every 3 months. If additional symptoms occur, these tests should be performed immediately.

Blood dyscrasia.

Serious blood dyscrasias have been very rarely reported. Asacol therapy should be stopped immediately if there is a suspicion or evidence of blood dyscrasia (signs of unexplained bleeding, bruising, purpura, anaemia, persistent fever or sore throat), and the patient should be advised to seek immediate medical advice.

Cardiac hypersensitivity reactions.

Mesalazine-induced cardiac hypersensitivity reactions (myocarditis and pericarditis) have rarely been reported with Asacol. In case of a suspected mesalazine-induced cardiac hypersensitivity, Asacol must not be reintroduced. Caution should be taken in patients with previous myocarditis or pericarditis of allergic background regardless of its origin.

Idiopathic intracranial hypertension.

Idiopathic intracranial hypertension (pseudotumor cerebri) has been reported in patients receiving mesalazine. Patients should be warned for signs and symptoms of idiopathic intracranial hypertension, including severe or recurrent headache, visual disturbances or tinnitus. If idiopathic intracranial hypertension occurs, discontinuation of mesalazine should be considered.

Pulmonary disease.

Patients with pulmonary disease, in particular asthma, should be carefully monitored during treatment with Asacol.

Adverse drug reactions to sulfasalazine.

Patients with a history of adverse drug reactions to sulfasalazine therapy should be kept under close medical supervision. Treatment must be stopped immediately if acute symptoms of intolerance occur such as abdominal cramps, acute abdominal pain, fever, severe headache and rash.

Gastric and duodenal ulcers.

Caution is recommended when treating patients with existing gastric or duodenal ulcer.

Nephrolithiasis.

Cases of nephrolithiasis have been reported with the use of mesalazine, including stones with mesalazine content. Ensure adequate fluid intake during treatment.

Discolouration of urine after contact with sodium hypochlorite.

Mesalazine may produce red-brown urine discoloration after contact with sodium hypochlorite bleach (e.g. in toilets cleaned with sodium hypochlorite contained in certain bleaches).

Severe cutaneous adverse reactions.

Severe cutaneous adverse reactions (SCARs), including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in association with mesalazine treatment.
Mesalazine should be discontinued, at the first appearance of signs and symptoms of severe skin reactions, such as skin rash, mucosal lesions, or any other sign of hypersensitivity.

Asacol 400 mg and 800 mg.

Tablets in stool.

A limited number of reports of intact 400 mg and 800 mg tablets in the stool have been received. What appear to be intact tablets may in some cases represent largely empty shells of the coated tablets. If intact tablets are observed in the stool repeatedly, the patient should consult his/her physician.

Tablets contain lactose.

Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take Asacol 400 mg and 800 mg.

Use in hepatic impairment.

There have been reports of increased liver enzyme levels in patients taking preparations containing mesalazine. Caution is recommended if Asacol is administered to patients with liver impairment.

Use in renal impairment.

It is recommended that the renal function is monitored prior to and repeatedly whilst on mesalazine therapy. Caution should be exercised when initiating treatment in patients with raised serum creatinine or proteinuria.
Mesalazine-induced renal toxicity should be suspected if the renal function deteriorates during treatment and the treatment should be stopped immediately.
Short monitoring intervals for monitoring of renal function early after the start of Asacol therapy will discover rare acute renal reactions. In the absence of an acute renal reaction, monitoring intervals can be extended to every 3 months and then annually after 5 years.

Use in the elderly.

Mesalazine should be administered with caution in the elderly.
Asacol should only be used in elderly patients with normal or non-severe hepatic and renal impairment (see Section 4.4 Special Warnings and Precautions for Use, Use in hepatic impairment, Use in renal impairment).

Paediatric use.

Asacol 400 mg and 800 mg.

As there is only limited documentation for an effect in children (age 6-18 years), administration in this age group is not recommended.

Asacol 1600 mg.

The safety and efficacy of Asacol in children and adolescents aged younger than 18 years of age has not been established.

Effects on laboratory tests.

Several reports of possible interference with measurements, by liquid chromatography, of urinary normetanephrine causing false-positive test result have been observed in patients exposed to sulfasalazine or its metabolite, mesalazine.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No interaction studies have been performed.
There is weak evidence that mesalazine might decrease the anticoagulant effect of warfarin.
Caution is recommended for the concomitant use of mesalazine with known nephrotoxic agents, including non-steroidal anti-inflammatory drugs (NSAIDs) and azathioprine as these may increase the risk of renal adverse reactions.
A possible increase in the myelosuppressive effects of azathioprine, 6-mercaptopurine or thioguanine in patients who are concomitantly treated with any of these preparations, should be taken into account. Life-threatening infection can occur. Patients should be closely observed for signs of infection and myelosuppression. Haematological parameters, especially the leucocyte, thrombocyte and lymphocyte cell counts should be monitored regularly (weekly), especially at initiation of such combination therapy (see Section 4.4 Special Warnings and Precautions for Use). If white blood cells are stable after 1 month, testing every 4 weeks for the following 12 weeks followed by 3 monthly monitoring intervals appears to be justified.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No effects on fertility or reproductive performance were observed in male or female rats at oral doses of mesalazine of up to 480 mg/kg/day (similar to the maximal recommended human dose of Asacol on a body surface area basis).
(Category C)
Mesalazine is known to cross the placental barrier, but available data are insufficient to assess the risk of adverse effects on either pregnancy or the health of the foetus/neonate. Nonsteroidal anti-inflammatory drugs inhibit prostaglandin synthesis and, when given during the latter part of pregnancy, may cause closure of the foetal ductus arteriosus, foetal renal impairment, inhibition of platelet aggregation, and delay labour and birth. Continuous treatment with nonsteroidal anti-inflammatory drugs during the last trimester of pregnancy should only be given on sound indications. During the last few days before expected birth, agents with an inhibitory effect on prostaglandin synthesis should be avoided.
There are no adequate data on the use of Asacol in pregnant women. However, data on a limited number (n = 627) of exposed pregnancies indicate no adverse effect of mesalazine on pregnancy or on the health of the foetus/newborn child. To date no other relevant epidemiological data are available.
In one single case after long-term use of a high dose of mesalazine (2-4 g, orally) during pregnancy, renal failure in a neonate was reported.
Oral administration of mesalazine to rats and rabbits during the period of organogenesis at doses up to 480 mg/kg/day (about one to two times the maximum recommended clinical dose of Asacol on a body surface area basis) did not cause embryofetal toxicity or teratogenicity in the presence of maternotoxicity.
Asacol should only be used during pregnancy if the potential benefit outweighs the possible risk.
 N-acetyl-5-aminosalicylic acid and to a lesser degree mesalazine are excreted in breast milk. The clinical significance of this has not been determined. Only limited experience during lactation in women is available to date. Hypersensitivity reactions such as diarrhoea in the infant cannot be excluded. Therefore, Asacol should only be used during breast-feeding, if the potential benefit outweighs the possible risk. If the infant develops diarrhoea, breast-feeding should be discontinued.
In rats, oral administration of mesalazine from late gestation to weaning at doses of 480 mg/kg/day (similar to the maximal recommended clinical dose of Asacol on a body surface area basis) was associated with toxicity to dams and offspring. A dose of 120 mg/kg/day was devoid of toxicity in either generation.

4.7 Effects on Ability to Drive and Use Machines

Asacol has no or negligible influence on the ability to drive and use machines.

4.8 Adverse Effects (Undesirable Effects)

Summary of the safety profile.

Organ specific adverse drug reactions affecting the heart, lungs, liver, kidneys, pancreas, skin and subcutaneous tissue have been reported.
Treatment must be stopped immediately if acute symptoms of intolerance occur such as abdominal cramps, acute abdominal pain, fever, severe headache and rash.
Severe cutaneous adverse reactions (SCARs), including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in association with mesalazine treatment (see Section 4.4 Special Warnings and Precautions for Use).

Tabulated summary of adverse reactions.

Undesirable effects reported from clinical studies and other sources are listed in Table 1.
The following definitions apply to the incidence of undesirable effects: common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data).

Description of selected adverse reactions.

An unknown number of the above-mentioned adverse effects are probably associated to the underlying inflammatory bowel disease rather than Asacol/mesalazine medication. This holds true especially for gastrointestinal adverse effects, arthralgia and alopecia.
To avoid blood dyscrasia resulting from developing bone marrow depression patients should be monitored with care (see Section 4.4 Special Warnings and Precautions for Use).
Under co-administration of mesalazine with immunosuppressive drugs such as azathioprine or 6-mercaptopurine or thioguanine, life-threatening infection can occur (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Photosensitivity.

More severe reactions are reported in patients with pre-existing skin conditions such as atopic dermatitis and atopic eczema.

Paediatric population.

There is no safety experience with the use of Asacol tablets in the paediatric population. It is expected that the target organs of possible adverse reactions in the paediatric population are the same as for adults (heart, lungs, liver, kidneys, pancreas, skin and subcutaneous tissue).

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

There is little data on overdose (e.g. intended suicide with high oral doses of mesalazine), which do not indicate renal or hepatic toxicity. There is no specific antidote and treatment is symptomatic and supportive.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Intestinal anti-inflammatory agents, ATC code: A07EC02.

Mechanism of action.

Asacol contains mesalazine, also known as 5-aminosalicylic acid, which has a topical anti-inflammatory effect on the colonic mucosal cells through a mechanism that has not yet been fully clarified.
Mesalazine has been shown to inhibit LTB4-stimulated migration of intestinal macrophages by restricting migration of macrophages to inflamed areas. The production of pro-inflammatory leukotrienes (LTB4 and 5-HETE) in macrophages of the intestinal wall is thereby inhibited. Mesalazine has been shown to activate PPAR-γ receptors which counteract nuclear activation of intestinal inflammatory responses.
Under trial conditions mesalazine inhibited the cyclooxygenase and thus, the release of thromboxane B2 and prostaglandin E2, but the clinical meaning of this effect is still unclear.
Mesalazine inhibits the formation of platelet activating factor (PAF). Mesalazine is also an antioxidant; it has been shown to decrease formation of reactive oxygen products and to capture free radicals.

Clinical trials.

Induction of remission in mild-moderate ulcerative colitis.

Asacol 400 mg.

A phase 3, multicentre, randomised, double-blind, double-dummy, placebo controlled study conducted in 53 centres across Japan between 2005 and 2007, compared the efficacy and safety of two doses of Asacol 400 mg tablets (2.4 g/day and 3.6 g/day, given in 3 equally divided doses) versus Pentasa 250 mg tablets (2.25 g/day, given in 3 equally divided doses) and placebo, for the induction of remission in patients with mild to moderate active UC. Two hundred and twenty nine (229) patients aged 16 to 64 years were enrolled with initial UC Disease Activity Index (UC-DAI) of 3 to 8.
The primary efficacy endpoint was the reduction of the UC-DAI score from baseline to week 8 or at discontinuation. Secondary endpoints of remission rate and efficacy rates were assessed. See Table 2.
Reductions in UC-DAI score verified the superiority of the 3.6 g/day Asacol group to the Pentasa group, and non-inferiority of the 2.4 g/day Asacol group compared to the Pentasa group. The three active groups were also compared to placebo, but only the 3.6 g/day Asacol group demonstrated a statistically significant difference; group difference 2.7 (95% CI: 1.4, 3.9).
The remission rates were 30.3% in the 2.4 g/day Asacol group, 45.3% in the 3.6 g/day Asacol group, 28.6% in the 2.25 g/day Pentasa group, and 9.4% in the placebo group. The efficacy rates were 45.5% in the 2.4 g/day Asacol group, 64.1% in the 3.6 g/day Asacol group, 49.2% in the 2.25 g/day Pentasa group, and 28.1% in the placebo group.

Asacol 800 mg.

A multi-national, multicentre, randomised, placebo-controlled, double-blind phase 3 study was conducted by Tillotts Pharma in 26 study centres in the Ukraine, Belarus, India, and Turkey to determine the efficacy of Asacol 4.8 g/day (3 x 800 mg tablets, given twice a day) to induce remission after 6 weeks of treatment compared to placebo in patients with mild to moderate UC.
The initial primary efficacy endpoint (as per FDA Guidelines) of the proportion of patients achieving clinical and endoscopic remission at week 6 was modified prior to the unblinding of treatment allocation in order to be consistent with the European Guideline which defined clinical remission (UC-DAI; score of 0 for stool frequency and rectal bleeding and absence of urgency) at week 6 as the only primary efficacy endpoint for the analysis. Endoscopic remission (sigmoidoscopic score of ≤ 1 at week 6) was added as a new secondary endpoint.
For the ITT population clinical remission (primary endpoint) at week 6 was achieved in 42 (30.0%) of the subjects who received Asacol 800 mg tablets and 29 (20.68%) of the subjects who received placebo (p = 0.069; 95% CI of the between group difference = [-0.7%, 19.43%]). The difference between Asacol 800 mg and placebo did not meet the pre-set significance level of p < 0.05 for clinical remission, however, all pre-specified secondary endpoints were met.
For the ITT population week 6 endoscopic remission was achieved in 64 (45.7%) of the subjects who received Asacol 800 mg tablets and 35 (24.8%) of the subjects who received placebo (p < 0.001; 95% CI: 9.7%, 31.3%). Endoscopic remission at week 10 was achieved in 73 (52.1%) of the subjects who received Asacol 800 mg tablets and 52 (36.9%) of placebo-treated subjects (p = 0.010; CI: 3.6%, 26.3%). Clinical remission at week 10 was achieved in 57 (40.7%) of the subjects who received Asacol 800 mg and 30 (21.3%) of placebo-treated subjects (p < 0.001; 95% CI: 8.6%, 29.6%).
A secondary post-hoc analysis was also conducted, in which data form India (identified as the outlier country) were excluded. This reanalysis showed a statistically significant result (p = 0.02) for the primary endpoint; clinical remission at week 6. All secondary endpoints apart from the modified UC-DAI score at week 6 were statistically significant. The results of the secondary endpoints were similar to what was observed with the ITT population, where all secondary endpoints were statistically significant.

Asacol 1600 mg.

This indication was investigated in a randomised, active-controlled, double-blind, multi-centre, non-inferiority induction trial study with 817 patients receiving 3.2 g mesalazine daily for 8 weeks.
At week 8, 22.4% of the Per-Protocol patients treated with Asacol 1600 mg tablets and 24.6% of those treated with Asacol 400 mg tablets achieved clinical and endoscopic remission. The unadjusted between group difference was 2.2% (95% confidence interval: -8.1% up to 3.8%). Once daily Asacol 1600 mg were considered to be non-inferior to twice daily Asacol 400 mg in inducing clinical and endoscopic remission.
A total of 10.3% of patients treated with Asacol 1600 mg and 9.8% of patients receiving Asacol 400 mg reported treatment related adverse events. The incidence of subjects with serious adverse events (SAEs) in both treatment groups was 2.0% versus 1.7%.
Maintenance of remission in mild-moderate ulcerative colitis.

Asacol 400 mg tablets.

A multi-centre, randomised, double-blind study was conducted to verify the non-inferiority of Asacol 400 mg (2.4 g/day, given in 3 equally divided doses) to Pentasa 250 mg tablets (2.25 g/day, given in 3 equally divided doses) for the maintenance of remission in patients with mild to moderate UC. The primary endpoint was the proportion of patients without bloody stools.
One hundred and thirty one (131) outpatients aged 16 to 64 years with quiescent UC (UC-DAI ≤ 2) 2 and a bloody stool score of 0 were included. Over a period of 48 weeks, the two groups were administered either Asacol 2.4 g/day (n = 65) or Pentasa 2.25 g/day (n = 66). A total of 34 patients withdrew from the study. The most frequent reason for withdrawal was relapse of UC based on the discontinuation criteria of a bloody stool score of 1 or more and UC-DAI of 3 or more (Asacol, 10; Pentasa, 13), and the second most common reason was the occurrence of AEs (Asacol, 1; Pentasa, 3).
The proportion of patients without bloody stools after the 48 week treatment period was 76.9% in the Asacol group and 69.2% in the Pentasa group. The difference between the two groups was 7.7% (95% CI: -7.4, 22.8), and the lower limit of CI was more than "-10.0%", the critical value for demonstration of predetermined non-inferiority. The hazard ratio for time to bloody stools was 0.690 (95% CI: 0.353, 1.350). There was no significant difference in the results of the log-rank test between the two groups (p = 0.27), but the time to bloody stools (secondary endpoint) tended to be longer in the Asacol group in comparison with the Pentasa group.
The proportion of patients without relapse was 80.0% in the Asacol group and 79.7% in the Pentasa group. The time to relapse was prolonged in the Asacol group compared to the Pentasa group, but the difference was not statistically significant (p = 0.79). The decrease in UC-DAI at the final assessment was -0.8 in the Asacol group and -0.9 in the Pentasa group, respectively, and the difference between the two groups was not significant.

Asacol 1600 mg.

727 patients participated in an open label extension (OLE) of the induction study.
The daily dose of Asacol in the maintenance phase was allocated depending on the 8 or 12-week induction results.
Patients in clinical remission (202) at week 12 on either formulation had a dose reduction to 1.6 g/day with 70.3% (142/202) maintaining remission to week 38.
Patients with a clinical response (274) at week 12 on either formulation continued to receive 3.2 g/day and a further 33.9% (93/274) of them went into remission.
Initial non-responders on either formulation (243) at week 8 who responded after a further 8 weeks on 4.8 g/day plus another 8 non responders at week 12 on 3.2 g/day (total 199), remained on 4.8 g/day for another 22 weeks in the study. Of those up dosed to 4.8 g/day 26.8% (61/228) achieved a later clinical remission.
The incidence of treatment related adverse events was 13.9% (28/202), 8.8% (24/274) and 10.7% (26/243) of patients in the 1.6, 3.2 and 4.8 g/day dose groups, respectively.
The incidence of SAEs in the OLE was low and independent of daily dose, with 5.0% (10/202), 4.4% (12/274) and 1.6% (4/243) of patients in the 1.6, 3.2 and 4.8 g/day dose groups affected.

5.2 Pharmacokinetic Properties

Absorption.

Asacol 400 mg and 800 mg tablets consists of a tablet core which is coated with a copolymer providing the tablet a pH-dependent disintegration behaviour. Therefore Asacol tablets resist the acidic environment of the stomach and small intestine, whereas disintegration and drug release occurs from pH 7 onwards to ensure start of drug delivery at the target site (i.e. from the terminal ileum onwards). Asacol 1600 mg tablets contain a core of mesalazine covered by a multi-layer coating system. This system consists of a layer of methacrylic acid copolymer combined with starch particles on top of a middle alkaline buffer layer (which accelerates drug release). The coating is designed to delay release of mesalazine until intestinal fluids reach a pH of 7. The starch can be digested by colonic bacteria which also provides a second trigger for release of mesalazine from the coated tablet.
Systemic bioavailability/plasma concentrations of mesalazine are of no relevance for therapeutic efficacy, but rather a criterion for safety.

Asacol 400 mg.

After administration of a single dose of 2.4 g mesalazine (6 x Asacol 400 mg tablets) to healthy volunteers under fasting conditions, quantifiable amounts (> 2.00 nanogram/mL) of mesalazine were observed in plasma after 4.5 h (median Tlag). The geometric mean Cmax value of mesalazine was 722.11 nanogram/mL with a median Tmax of about 9.5 h, whereas that of N-acetyl mesalazine was 1437.90 nanogram/mL with a median Tmax of 12.0 h.
The same study showed that when administered with concomitant food intake, quantifiable amounts of mesalazine were observed after 9.0 h (median tlag). The geometric mean Cmax value of mesalazine was 1725.93 nanogram/mL with a median Tmax of about 22.0 h, whereas that of N-acetyl mesalazine was 2235.32 nanogram/mL with a median Tmax of 24.0 h.
Based on the recovery of unchanged mesalazine and the main metabolite N-acetyl mesalazine in collected urine after oral administration under fed conditions approximately 30% of the dose (about 90% as metabolite) was excreted renally within 60 h.
Mesalazine Cmax values increased 2.39-fold under fed conditions, and the extent of exposure (AUC0-tlast) increased 1.57-fold. Under the same conditions, N-acetyl mesalazine Cmax-values increased 1.55-fold, whereas the extent of exposure only increased by about 1.1-fold.

Asacol 800 mg.

After administration of a single dose of 2.4 g mesalazine (3 x Asacol 800 mg tablets) to healthy volunteers under fasting conditions, quantifiable amounts (> 2.00 nanogram/mL) of mesalazine were observed in plasma after 4.5 h (median Tlag). The geometric mean Cmax value of mesalazine was 387.86 nanogram/mL with a median Tmax of 14.0 h, whereas that of N-acetyl mesalazine was 971.09 nanogram/mL with an identical median Tmax (i.e. 14.0 h).
The same study showed that when administered with concomitant food intake, quantifiable amounts of mesalazine were observed after 14.5 h (median tlag). The geometric mean Cmax-value of mesalazine was 653.56 nanogram/mL with a median tmax of about 30.0 h, whereas that of N-acetyl mesalazine was 1245.46 nanogram/mL with a median tmax of 30.0 h.
Based on the recovery of unchanged mesalazine and the main metabolite N-acetyl mesalazine in collected urine after oral administration under fed conditions, approximately 23% of the dose (more than 95% as metabolite) was excreted renally within 60 h.
Mesalazine Cmax-values increased 1.69-fold, and the extent of exposure (AUC0-tlast) increased 1.23-fold. Under the same conditions, N-acetyl mesalazine Cmax-values increased 1.28-fold, whereas the extent of exposure remained practically unchanged.

Asacol 1600 mg.

A single dose of a Asacol 1600 mg in healthy volunteers in the fasted state resulted in a 1.5-fold increase of mesalazine Cmax and a 1.4-fold increase of AUC compared to fed state.

Distribution.

About 43% mesalazine and about 78% N-acetyl mesalazine are bound to plasma proteins.

Asacol 400 mg.

Approximately 75% of the administered dose remains in the gut lumen and the mucosal tissue.
The mean apparent volume of distribution per kg of body weight (Vdw) was 59.07 L/kg (geometric mean: 48.86 L/kg) after a single dose of 2.40 g of mesalazine (6 x Asacol 400 mg tablets) in healthy volunteers under fasting conditions. Based upon the absorption of 24.8% of the administered dose, this parameter is equal to 14.65 L/kg (geometric mean: 12.12 L/kg).

Asacol 800 mg.

Approximately 77% of the administered dose remains in the gut lumen and the mucosal tissue. The mean apparent volume of distribution per kg of body weight (Vdw) was 147.73 L/kg (geometric mean: 76.06 L/kg) after a single dose of 2.40 g of mesalazine (3 x Asacol 800 mg tablets) in healthy volunteers under fasting conditions. Based upon the absorption of 23.2% of the administered dose, this parameter is equal to 34.27 L/kg (geometric mean: 17.65 L/kg).

Asacol 1600 mg.

The mean apparent volume of distribution (Vdw) was 25 L/kg.

Metabolism.

Mesalazine is metabolised both by the intestinal mucosa and the liver to the inactive metabolite N-acetyl mesalazine. At least 90% of the drug recovered in the urine after oral administration is found as the main metabolite N-acetyl-mesalazine.

Excretion.

Asacol 400 mg.

The elimination of mesalazine is essentially urinary and faecal in the form of mesalazine and its N-acetyl metabolite. The geometric mean of total apparent clearance of mesalazine after administration of 2.40 g of mesalazine (6 x Asacol 400 mg tablets) in healthy volunteers under fasting conditions was about 135 L/h (geometric mean, CV% = 61.43%, inter-subject). The median elimination half-life was 20 h ranging from 5 to 77 h.
About 25% of the total dose administered was recovered in the urine within 60 h after fasted administration mainly as N-acetyl mesalazine and as the parent compound (about 1%).

Asacol 800 mg.

The elimination of mesalazine is essentially urinary and faecal in the form of mesalazine and its N-acetyl metabolite. The geometric mean of total apparent clearance of mesalazine after administration of 2.40 g of mesalazine (3 x Asacol 800 mg tablets) in healthy volunteers under fasting conditions was about 318 L/h (geometric mean, CV% = 137.67%, inter-subject). The median elimination half-life was 17 h ranging from 10 to 50 h.
About 23% of the total dose administered was recovered in the urine within 60 h after fasted administration mainly as N-acetyl mesalazine and as the parent compound (about 1%).

Asacol 1600 mg.

The elimination of mesalazine is essentially urinary and faecal in the form of mesalazine and its N-acetyl metabolite. The median elimination half-life of mesalazine was 10 h range 4 to 23 h.

Linearity/non-linearity.

In a cross-over design with 3 test periods and 3 ascending oral doses of Asacol 400 mg tablets administered 6 hourly over 4 consecutive doses (total daily dose of mesalazine: 3200, 4800, 6400 mg) it was shown that the absorption and elimination kinetics for mesalazine are dose independent for the 3 doses evaluated. For each dose, about ¾ of the dose was available for the therapeutic activity for the colon. Only about ¼ of each dose was absorbed and excreted in the urine, primarily as the metabolite. Based on urine drug excretion, plasma drug Cmax and the combined plasma AUC values, there was a linear dose response for the 3 Asacol tablet doses. The clinical performance of Asacol 400 mg tablets should be similar for the range of doses evaluated in this study.

5.3 Preclinical Safety Data

Genotoxicity.

No evidence of genotoxicity was observed with mesalazine in assays for bacterial gene mutation in vitro, mammalian cell sister chromatid exchange, chromosomal aberrations in Chinese hamster ovary cells in vitro, or chromosomal damage in vivo.

Carcinogenicity.

There was no evidence of carcinogenicity in rats or mice treated with mesalazine in the diet for two years at respective doses up to 480 and 2000 mg/kg/day. In rats, estimated respective exposures (plasma AUC) of mesalazine and its metabolite N-acetyl-5-aminosalicyclic acid were about 4- and 2.5-fold the corresponding clinical exposures at the maximum recommended dose of Asacol. In mice, the highest dose tested was about twice the maximum recommended human dose on a body surface area basis.

6 Pharmaceutical Particulars

6.1 List of Excipients

Asacol 400 mg and 800 mg.

The 400 mg and 800 mg tablet core contains: lactose monohydrate, sodium starch glycollate type A, magnesium stearate, purified talc and povidone. The film-coating contains: methacrylic acid copolymer, triethyl citrate, iron oxide yellow, iron oxide red and macrogol 6000.

Asacol 1600 mg.

The 1600 mg tablet core contains: microcrystalline cellulose, sodium starch glycollate type A, hypromellose, colloidal anhydrous silica and magnesium stearate. The film-coating contains: methacrylic acid copolymer, triethyl citrate, glycerol monostearate, maize starch, polysorbate 80, macrogol 6000, iron oxide yellow, iron oxide red, monobasic potassium phosphate and sodium hydroxide.

6.2 Incompatibilities

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

6.3 Shelf Life

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

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

Asacol 400 mg and 800 mg.

PVC/aluminium blister strips packed in cartons containing either 30, 60, 90 or 180 tablets.

Asacol 1600 mg.

PVC/aluminium blister strips packed in cartons containing either 30, 60 or 90 tablets.
Not all pack sizes may be marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.


Formula: C7H7NO3.
Molecular weight: 153.1.

CAS number.

89-57-6.

7 Medicine Schedule (Poisons Standard)

Prescription only medicine (Schedule 4).

Summary Table of Changes