Consumer medicine information

Salofalk Granules Modified Release Granules

Mesalazine

BRAND INFORMATION

Brand name

Salofalk Granules

Active ingredient

Mesalazine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Salofalk Granules Modified Release Granules.

SUMMARY CMI

SALOFALK® GRANULES modified release granules

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 using SALOFALK granules?

SALOFALK granules contain the active ingredient mesalazine (5-aminosalicylic acid). SALOFALK granules are used to treat, and prevent relapses of mild to moderate attacks of ulcerative colitis (inflammation of the large bowel).

For more information, see Section 1. Why am I using SALOFALK granules? in the full CMI.

2. What should I know before I use SALOFALK granules?

Do not use if you have ever had an allergic reaction to SALOFALK granules 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 use SALOFALK granules? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with SALOFALK granules 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 use SALOFALK granules?

Adults and elderly:

  • Acute ulcerative colitis: take 1.5 g to 3 g SALOFALK granules a day or in 2-3 divided doses.
  • Long term treatment of ulcerative colitis: take 1.5 g SALOFALK granules once a day or in 2-3 divided doses.

Children over 6 years:

  • Acute ulcerative colitis: the usual dose for a child is 30-50 mg SALOFALK granules/kg (body weight)/day in one single or 2-3 divided doses.
  • Long term treatment of ulcerative colitis: the usual dose for a child is 15-30 mg SALOFALK granules/kg (body weight)/day in one single or 2 divided doses.

More instructions can be found in Section 4. How do I use SALOFALK granules? in the full CMI.

5. What should I know while using SALOFALK granules?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using SALOFALK granules.
  • Remind them if any new medicines are about to be started.
Things you should not do
  • Do not use SALOFALK granules to treat any complaint other than that directed by your doctor. It may not be safe to use SALOFALK granules for another complaint.
  • Do not give SALOFALK granules to someone else even if their symptoms are the same. It may not be safe for another person to use SALOFALK granules.
Driving or using machines
  • This medicine is not expected to affect your ability to drive a car or operate machinery.
  • However, you should still be careful before you drive or use any machines or tools until you know how SALOFALK granules affects you. SALOFALK granules may cause dizziness in some people.
Looking after your medicine
  • Keep SALOFALK granules in their original package until it is time to use them. If you take them out of their packaging, they may not keep well.
  • Keep SALOFALK granules in a cool dry place, protected from light, where the temperature stays below 25°C.
  • Keep it where children cannot reach it.
  • A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

For more information, see Section 5. What should I know while using SALOFALK granules? in the full CMI.

6. Are there any side effects?

All medicines can have side effects. If they do occur, they are usually mild and temporary. The most common side effects using SALOFALK granules are: headache, mild stomach pains, excessive gas in the stomach or bowel, increased number of bowel motions, diarrhoea, nausea and vomiting, rash or itchy skin.

For 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

SALOFALK® GRANULES modified release granules

Active ingredient: mesalazine

Consumer Medicine Information (CMI)

This leaflet provides important information about using SALOFALK granules. 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 SALOFALK granules.

Where to find information in this leaflet:

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

1. Why am I using SALOFALK granules?

SALOFALK granules contain the active ingredient mesalazine (5-aminosalicylic acid). Mesalazine is an anti-inflammatory agent used to treat inflammatory bowel disease.

SALOFALK granules are used to treat, and prevent relapse of mild to moderate attacks of ulcerative colitis (inflammation of the large bowel).

Ask your doctor if you have any questions about why SALOFALK granules have been prescribed for you.

Your doctor may have prescribed SALOFALK granules for another reason.

Do not give SALOFALK granules to a child below 6 years of age. The safety and effectiveness of SALOFALK granules in this group have not been established.

2. What should I know before I use SALOFALK granules?

Warnings

Do not use SALOFALK granules if:

  • you are allergic to mesalazine, to salicylates such as acetylsalicylic acid (e.g. Aspirin®) or any of the ingredients listed at the end of this leaflet. Signs of allergic reactions may include itchy skin rash, shortness of breath and swelling of the face or tongue.
  • you suffer from a severe kidney or liver problem.
  • the expiry date (EXP) printed on the pack has passed.
    If you use this medicine after the expiry date has passed, it may not work as well.
  • the product is torn or shows signs of tampering.
  • Always check the ingredients to make sure you can use this medicine. If unsure, speak to your doctor or pharmacist.

Check with your doctor if you:

  • have any allergies.
  • have or have had any other medical conditions, especially lung or breathing problems such as asthma.
  • have kidney problems. Kidney stones may develop with use of mesalazine, the active ingredient in SALOFALK granules. Symptoms may include pain in the side of abdomen and blood in urine. Take care to drink sufficient amounts of liquid during treatment with SALOFALK granules.
  • have liver problems.
  • have phenylketonuria.
  • have ever developed a severe skin rash or skin peeling, blistering and/or mouth sores after using mesalazine.

If you have not told your doctor about any of the above, tell them before you start to use SALOFALK granules.

Serious skin reactions including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) have been reported in association with mesalazine the active ingredient in SALOFALK granules. Stop using mesalazine and seek medical attention immediately if you notice any of the symptoms related to these serious skin reactions described in Side effects section below.

SALOFALK granules contain aspartame which is a source of phenylalanine. It may be harmful if you have phenylketonuria (PKU), a rare genetic disorder in which phenylalanine builds up because the body cannot remove it properly.

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

People who take medicines containing mesalazine, such as SALOFALK granules, may notice red-brown discolouration in the toilet bowl. This is due to mesalazine in urine of these people coming in contact with sodium hypochlorite bleach used to clean the toilet. This is the result of a chemical reaction between mesalazine and bleach and is harmless.

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 the risks and benefits of using SALOFALK granules if you are pregnant or breastfeeding.

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.

SALOFALK granules may interfere with the action of the following types of medicines:

  • anticoagulants which are medicines used to stop blood clots, e.g. warfarin.

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

  • glucocorticoids which are medicines used to treat inflammation or swelling, e.g. prednisolone
  • sulphonylureas which are medicines used to lower blood sugar
  • methotrexate which is a medicine used to treat some types of cancer and arthritis.
  • probenecid/sulphinpyrazone which are medicines used to treat gout
  • spironolactone/frusemide which are medicines which lower blood pressure or increase volume of urine
  • rifampicin which is a medicine used to treat tuberculosis
  • azathioprine which is a medicine used to suppress the immune system
  • mercaptopurine or thioguanine which are medicines used to treat leukaemia.
  • lactulose or similar preparations which are medicines which can change the acidity of the content of the bowels.

You may need to use different amounts of the above medicines, or you may need to take different medicines when you are using SALOFALK granules. Your doctor or pharmacist will advise you.

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

4. How do I use SALOFALK granules?

How much to use

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

They may differ from the information contained in this leaflet.

Adults and elderly:

  • For acute ulcerative colitis, take 1.5 g to 3 g SALOFALK granules once a day or in 2-3 divided doses.
  • For long term treatment of ulcerative colitis, take 1.5 g SALOFALK granules once a day or in 2-3 divided doses.

Children over 6 years old:

The dose of SALOFALK granules for your child depends on disease, severity and body weight. Your doctor will tell you how much your child should take.

  • For acute ulcerative colitis, the usual dose for a child is 30-50 mg SALOFALK granules/kg (body weight)/day in one single or 2-3 divided doses.
  • For long term treatment of ulcerative colitis, the usual dose for a child is 15-30 mg SALOFALK granules/kg (body weight)/day in one single or 2 divided doses.

When to use SALOFALK granules

  • Take SALOFALK granules the same time each day. This will help you remember when to take it.

How to use SALOFALK granules

  1. Tear open the sachet along the end with the triangular mark.

  1. Pour contents of sachet onto tongue.

  1. Swallow the modified release granule whole without chewing or crushing.
  2. Drink a glass or two of water to wash down the medicine.

How long to use SALOFALK granules

This medicine helps control your condition but does not cure it. Therefore, you must use it for as long as you doctor tells you to.

If you forget to use SALOFALK granules

SALOFALK granules should be used regularly at the same time each day. If you miss your dose at the usual time, leave out that dose completely. Take your next dose at the normal time it is due.

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 trouble remembering when to use SALOFALK granules, ask your pharmacist for some hints.

If you use too much SALOFALK granules

If you think that you have used too much SALOFALK granules, you may need urgent medical attention.

You should immediately:

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

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

Possible symptoms of overdose may include feeling sick, vomiting and diarrhoea.

5. What should I know while using SALOFALK granules?

Things you should do

Make sure that all of your doctors and pharmacists who are treating you know you are using SALOFALK granules. Remind them if any new medicines are about to be started.

Tell your doctor immediately if you become pregnant while using SALOFALK granules, or if you intend to breastfeed.

Things you should not do

  • Do not use SALOFALK granules to treat any complaint other than that directed by your doctor. It may not be safe to use SALOFALK granules for another complaint.
  • Do not give SALOFALK granules to someone else even if their symptoms are the same. It may not be safe for another person to use SALOFALK granules.

Do not stop taking your SALOFALK granules or change the dosage without checking with your doctor.

Driving or using machines

This medicine is not expected to affect your ability to drive a car or operate machinery. However, you should still be careful before you drive or use any machines or tools until you know how SALOFALK granules affects you.

SALOFALK granules may cause dizziness in some people.

Looking after your medicine

  • Keep SALOFALK granules in their original product pack until it is time to use them. If you take them out of their packaging they may not keep well.
  • Keep SALOFALK granules in a cool dry place, protected from light, where the temperature stays below 25°C.

Follow the instructions in the carton on how to take care of your medicine properly.

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. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

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
  • headache
  • mild stomach pain
  • excessive gas in the stomach or bowel
  • increased number of bowel motions
  • diarrhoea
  • dyspepsia
  • nausea (feeling sick)
  • rash or itchy skin
  • dizziness
  • common cold
  • fever, muscle aches and pains, painful joints and chest pain (sometimes spreading to the neck and shoulders, and sometimes fever)
  • mild skin rash, itching or hives
  • numbness, tingling or weakness of the arms and legs
  • pain in the upper belly (may be due to inflammation of the pancreas)
  • worsening of ulcerative colitis.
Speak to your doctor if you have any of these mild effects and they worry you.

Serious side effects

Serious side effectsWhat to do
  • general allergic reaction such as skin rash, fever, joint pain and/or breathing difficulties or a general inflammation of your large bowel (causing severe diarrhoea and abdominal pain)
  • marked reduction of general health, especially if accompanied by fever and/or sore throat or mouth. Very rarely this can be due to a low white blood cell count (agranulocytosis), which may increase the risk of developing a serious infection. Other blood cells may also be affected (e.g. platelets or red cells causing aplastic anemia or thrombocytopenia) and cause symptoms which may include unexplained bleeding, purple spots or patches under your skin, anemia (feeling tired, weak and looking pale, especially on lips and nails). A blood test can confirm whether your symptoms are due to this medicine. These reactions are very rare.
  • Serious skin rashes with 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. These can be preceded by fever and flu-like symptoms. These reactions occur in an unknown number of patients (frequency not known).
  • Shortness of breath, chest pain or irregular heartbeat, or swollen limbs which may be indicative of cardiac hypersensitivity reactions. These reactions are rare.
  • Problems with your kidney function (can occur very rarely), e.g. a change in the color or amount of urine produced and swollen limbs or a sudden flank pain (caused by a kidney stone) (occur in an unknown number of patients (frequency not known)). As a precaution, your doctor may have your blood, liver and kidney tested regularly during treatment with this medicine.
Other rare events, which have been reported with mesalazine include:
  • changes in liver function tests
  • liver disease with nausea, vomiting, loss of appetite, feeling generally unwell, fever, itching, yellowing of the skin and eyes, and dark colored urine
  • allergic, inflammatory or other lung conditions
  • shortness of breath, difficulty breathing, cough, wheezing, chest pain that worsens when breathing, lung shadow on x-ray due to allergic and/or inflammatory lung conditions.
  • increased sensitivity of the skin to sun and ultraviolet light (photosensitivity)
  • reversible decrease in semen production (oligospermia)
  • hair loss and the development of baldness (alopecia)
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.

As a precaution, your doctor may have your blood, liver and kidney tested regularly during treatment with SALOFALK granules.

Tell your doctor or pharmacist if you notice anything which is unusual, including anything else that may be making you feel unwell.

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

Do not be alarmed by this list of possible side effects. You may not experience any of them.

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/using any of your medicines.

7. Product details

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

What SALOFALK granules contain

Active ingredient
(main ingredient)		500 mg, 1 g, 1.5 g or 3 g mesalazine
Other ingredients
(inactive ingredients)
  • microcrystalline cellulose
  • hypromellose
  • colloidal anhydrous silica
  • methacrylic acid copolymer (500 mg, 1 g, 1.5 g only)
  • magnesium stearate
  • simethicone
  • sorbic acid (1.5 g, 3 g only)
  • methylcellulose (1.5 g, 3 g only)
  • triethyl citrate
  • purified talc
  • carmellose sodium
  • aspartame
  • citric acid
  • vanilla custard flavour 75016-31 (PI 2187)
  • povidone
  • titanium dioxide.

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

What SALOFALK granules look like

SALOFALK granules are greyish-white cylindrical to round in shape. This medicine is available in 4 different strengths, 500 mg, 1 g, 1,5 g and 3 g.

SALOFALK GRANULES 500 mg modified release granules are available in packs of 100 sachets.

SALOFALK GRANULES 1 g modified release granules are available in packs of 100 sachets.

SALOFALK GRANULES 1.5 g modified release granules are available in packs of 60 sachets.

SALOFALK GRANULES 3 g modified release granules are available in packs of 30 sachets.

Australian Registration Numbers:
500 mg: AUST R 80648
1 g: AUST R 80649
1.5 g: AUST R 143611
3 g: AUST R 214810.

Who distributes SALOFALK granules

Dr Falk Pharma Australia Pty Ltd,
815 Pacific Highway,
Chatswood, NSW 2067,
Australia

SALOFALK® is a registered trademark of Dr. Falk Pharma GmbH, Germany.

This leaflet was prepared in June 2023.

Published by MIMS October 2023

BRAND INFORMATION

Brand name

Salofalk Granules

Active ingredient

Mesalazine

Schedule

S4

 

1 Name of Medicine

Salofalk Granules mesalazine modified release granules mesalazine.

2 Qualitative and Quantitative Composition

Salofalk Granules modified release granules contain either 500 mg, 1 g, 1.5 g or 3 g mesalazine as the active ingredient.

Excipients of known effects.

Aspartame.
Sucrose.
See Section 4.4 Special Warnings and Precautions for Use.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Salofalk Granules modified release granules are presented as greyish white cylindrical or round granules. They have a functional coating on the particles, which ensures gastro-resistance to allow a reliable distribution and pH-dependent release of the active ingredient, mesalazine, at the intended site of action starting in the ileocaecal region. The granules also contain a matrix system inside the particle core, which releases mesalazine independently of pH.

4 Clinical Particulars

4.1 Therapeutic Indications

Salofalk Granules are indicated in the treatment of acute ulcerative colitis of mild to moderate severity, and for the maintenance of remission and/or the long-term treatment of ulcerative colitis.

4.2 Dose and Method of Administration

For adults and the elderly.

Unless otherwise prescribed, the recommended dose for acute ulcerative colitis is 1.5 g to 3 g/day. For maintenance of remission and/or long-term treatment of ulcerative colitis, the recommended dose is 1.5 g/day.

For children older than 6 years of age.

The recommended dose for acute ulcerative colitis, depending on disease severity, is 30-50 mg mesalazine/kg (bodyweight)/day. For maintenance of remission and/or long-term treatment of ulcerative colitis, the recommended dose is 15-30 mg mesalazine/kg (bodyweight)/day.
Doses may be given in one to three divided doses.
It is generally recommended that half the adult dose may be given to patients up to a bodyweight of 40 kg; and the normal adult dose to those above 40 kg.
Salofalk Granules should not be used in children below 6 years of age, as there is very limited experience with this age group.
Salofalk Granules should be swallowed without chewing or crushing with sufficient fluid. If granules are taken together with meals the gastric passage might be delayed for 1-2 hours, but does not influence the release profile or plasma concentrations of mesalazine.
Salofalk Granules should be taken on a regular basis and consistently, in the treatment of an acute inflammatory episode, in order to achieve the desired therapeutic effect. In general, an acute episode of ulcerative colitis usually subsides by 8 weeks.

4.3 Contraindications

Salofalk Granules and tablets are contraindicated in patients with the following:
hypersensitivity to salicylic acid, salicylic acid derivatives, e.g. mesalazine/5-ASA or to any of the other ingredients;
severe impairment of hepatic and renal function.

4.4 Special Warnings and Precautions for Use

Salofalk Granules should be taken under medical supervision.

Phenylketonuria.

In the case of phenylketonuria, it should be noted that Salofalk Granules contain aspartame as a sweetening agent, equivalent to the following quantities of phenylalanine. See Table 1.
Salofalk granules contain sucrose. Patients with rare hereditary problems of fructose intolerance, glucose galactose malabsorption or sucrase-isomaltase insufficiency should not take these medicines.

Use in pulmonary function impairment.

Mesalazine should be used/given with caution in patients with pulmonary function impairment, particularly asthma and in patients with known hypersensitivity to sulfasalazine containing preparations. Treatment in the latter patients should be instituted with careful medical supervision. Treatment should be discontinued immediately if symptoms of acute intolerance, e.g. cramps, acute abdominal pain, fever, severe headache and skin rash, occur.

Use in hepatic impairment.

Caution is recommended in patients with impaired hepatic function. Salofalk Granules are contraindicated in patients with severe hepatic impairment (see Section 4.3 Contraindications).
As mesalazine might cause hepatic impairment due to hypersensitivity reactions, blood parameters, like blood counts and liver function and cholestasis parameters (e.g. ALT, AST, alkaline phosphatase, γGT) may be monitored like the renal parameters.

Blood dyscrasia.

Serious blood dyscrasias have been reported very rarely with mesalazine. Haematological investigations should be performed if patients suffer from unexplained haemorrhages, bruises, purpura, anaemia, fever or pharyngolaryngeal pain. Salofalk Granules should be discontinued in case of suspected or confirmed blood dyscrasia.

Epigastric pain.

Epigastric pain, also commonly associated with inflammatory bowel disease and prednisone or sulfasalazine therapy, should be investigated in order to exclude pericarditis, hepatitis and pancreatitis either as adverse drug reactions to mesalazine or secondary manifestations of inflammatory bowel disease. Cardiac hypersensitivity reactions (myocarditis, and pericarditis) induced by mesalazine have been rarely reported. Salofalk Granules should then be discontinued immediately if these reactions occur.

Use in renal impairment.

Mesalazine is not recommended in patients with impaired renal function. The blood and renal status should be determined prior to and during treatment, at the discretion of the treating physician. As a guideline, checks are recommended 14 days after commencement of treatment, then a further 2 to 3 times at 4-weekly intervals. If the findings are normal, follow-up tests should be conducted every three months or immediately if additional signs of the disorder occur. To check renal function, it is recommended that levels of serum urea (BUN) and creatinine be determined as well as performing a urine sediment test. Mesalazine-induced renal toxicity should be considered if renal function deteriorates during treatment. If this is the case, Salofalk Granules should be discontinued immediately.

Nephrolithiasis.

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

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. Salofalk Granules should be discontinued, at the first appearance of signs and symptoms of severe skin reaction, such as skin rash, mucosal lesions, or any other sign of hypersensitivity.

Urine discoloration.

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).

Use in the elderly.

Specific clinical data in only elderly patients for mesalazine are not available, but mesalazine has been used in patients up to 75 years of age in clinical trials.

Paediatric use.

Salofalk Granules should not be used in children below 6 years of age, as there is very limited experience with this age group.

Effects on laboratory tests.

Not known to interfere with laboratory tests or physical diagnostic agents.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Studies to evaluate the potential interaction between Salofalk Granules and other drugs have not been performed. In common with other salicylates, interactions may occur during concomitant administration of mesalazine and the following drugs.

Coumarin type anticoagulants.

Possible potentiation of the anticoagulant effect action (increasing the risk of gastrointestinal haemorrhage).

Glucocorticoids.

Possible increase in undesirable gastric effects.

Sulphonylureas.

Possible increase in the blood glucose lowering effects.

Methotrexate.

Possible increase in toxic potential of methotrexate.

Probenecid/sulphinpyrazone.

Possible attenuation of the uricosuric effects.

Spironolactone/frusemide.

Possible attenuation of the diuretic effects.

Rifampicin.

Possible attenuation of the tuberculostatic effects.

Lactulose or similar preparations, which lower stool pH.

Possible reduction of mesalazine release from granules due to decreased pH caused by bacterial metabolism.
There is weak evidence that mesalazine might decrease the anticoagulant effect of warfarin.
In patients who are concomitantly treated with azathioprine, 6-mercaptopurine or thioguanine, possible enhanced myelosuppressive effects of azathioprine, 6-mercaptopurine or thioguanine should be taken into account.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Fertility and reproductive performance were not impaired in rats treated orally with mesalazine prior to and during mating (both sexes) and throughout gestation and lactation (females) at doses up to 320 mg/kg/day, which is about the same as the maximal recommended clinical dose of Salofalk Granules on a body surface area basis.
(Category C)
There was no evidence of embryotoxicity or teratogenicity in rats and rabbits treated orally with mesalazine during the period of organogenesis at respective doses of up to 320 and 495 mg/kg/day representing about the same, and 3.5 times, the maximal recommended clinical dose of Salofalk Granules on a body surface area basis. Oral mesalazine does not show direct or indirect harmful effects with respect to parturition or postnatal development in animals.
Human data on use during pregnancy are limited. No adverse effect of mesalazine on pregnancy or on the health of the foetus/newborn child was shown. To date no other relevant epidemiologic data are available. In one single case after oral use of 2-4 g mesalazine per day during the 3rd and 5th months of pregnancy, renal failure in a neonate was reported. Salofalk Granules should only be used during pregnancy if the potential benefit outweighs the possible risk.
 In rats, there were no adverse effects on dams or offspring from oral administration of mesalazine during late gestation and throughout lactation at doses up to 320 mg/kg/day which is about the same as the maximal recommended clinical dose of Salofalk Granules on a body surface area basis.
There has been a report of a patient receiving mesalazine suppositories during the lactation period. Twelve hours after the initial dose, the infant developed watery diarrhoea that disappeared on discontinuation of the mesalazine therapy but reappeared on rechallenge. There have been reports of mesalazine and of its metabolite N-acetyl-5-ASA found in breast milk. There is no experience with Salofalk Granules in lactating women. Salofalk Granules should not be used during lactation unless the likely benefit of treatment outweighs the potential hazard. If the infant develops diarrhoea, the treatment should be temporarily discontinued and further medical advice sought.

4.7 Effects on Ability to Drive and Use Machines

Mesalazine is not expected to affect the ability of patients to drive or operate machinery.

4.8 Adverse Effects (Undesirable Effects)

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at http://www.tga.gov.au/reporting-problems.
The most frequent adverse reactions seen in clinical trials of Salofalk Granules are headache (3%), abdominal pain (4%), exacerbation of ulcerative colitis (2%), abnormal hepatic function (2%) and upper respiratory tract infection (1%).
In two clinical trials involving 550 patients with mild to moderate acute ulcerative colitis, tolerability was good. Table 2 shows the adverse events that occurred in at least 5% of patients in the clinical trials.
The following adverse events presented by body system have been reported in international postmarketing surveillance of all Salofalk Granules preparations including Salofalk Granules. In many cases, the relationship to Salofalk Granules treatment has not been established.
The common (≥ 1% to < 10%) adverse events were as follows.

Body as a whole - general disorders.

Headache.

Gastrointestinal system disorders.

Abdominal pain, diarrhoea, nausea and vomiting, dyspepsia, flatulence, exacerbation of ulcerative colitis.

Skin and appendages disorder.

Rash including pruritus, urticaria.
The following additional adverse events were uncommon and reported by < 1% of patients.

Body as a whole - general disorders.

Fever, allergic reaction.

Central and peripheral nervous systems disorders.

Dizziness, paraesthesia, peripheral neuropathy.

Collagen disorders.

Lupus erythematosus syndrome (as observed for preparations with a similar chemical structure).

Gastrointestinal system disorders.

Acute pancreatitis, pancolitis, neonate diarrhoea.

Liver and biliary system disorders.

Hepatitis, increased liver enzyme values (transaminase activity), intrahepatic cholestasis, increased bilirubin, changes in pancreatic enzymes (lipase and amylase increased), eosinophil count increased.

Musculoskeletal system disorders.

Arthralgia, myalgia, myositis.

Myo-, endo-, pericardial and valve disorders.

Pericarditis, myocarditis, pericardial effusion.

Platelet, bleeding and clotting disorders.

Thrombocytopenia.

Red blood cell disorders.

Aplastic anaemia, haemolytic anaemia.

Reproductive system disorders.

Oligospermia (reversible).

Respiratory, thoracic and mediastinal disorders.

Allergic and fibrotic lung reactions, dyspnoea, cough, bronchospasm, pleural effusion, alveolitis, pulmonary eosinophilia, lung infiltration, pneumonitis.

Skin and appendages disorders.

Alopecia, allergic exanthema, increased sweating.

Urinary system disorders.

Acute or chronic interstitial nephritis, renal insufficiency, renal failure, nephrotoxicity.

White cell and RES disorders.

Agranulocytosis, leukopenia, neutropenia, pancytopenia.
The following additional adverse events were rare and reported by < 0.1% of patients.

Skin and appendages disorders.

Photosensitivity.
(More severe reactions are reported in patients with pre-existing skin conditions such as atopic dermatitis and atopic eczema).
The following additional adverse events were very rare and reported by < 0.01% of patients.

Liver and biliary system disorders.

Cholestatic hepatitis.
The frequency of the following adverse events is not known:

Urinary system disorders.

Nephrolithiasis (see Section 4.4 Special Warnings and Precautions for Use for further information).

Skin and subcutaneous tissue disorders SOC.

Drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN).
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).

4.9 Overdose

There are rare data on overdosage (e.g. intended suicide with high oral doses of mesalazine), which do not indicate renal or hepatic toxicity.
Possible symptoms may include nausea, vomiting and diarrhoea, and symptoms similar to salicylate overdose.
There is no specific antidote. General supportive and symptomatic measures are recommended.
For information on the management of overdosage, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Mesalazine has been identified as the active component of sulfasalazine in inflammatory bowel disease and is thought to have a topical action. The mechanism of action by which mesalazine protects the mucosa in chronic inflammatory bowel disease is not yet fully known.
Mesalazine seems to act in multiple ways against several inflammatory mediators and principles. The results of in vitro investigations indicate that inhibition of lipoxygenase may play a role. Effects on prostaglandin concentrations in the intestinal mucosa have also been demonstrated, as has an influence on leukotriene production. Mesalazine may also function as a radical scavenger of reactive oxygen compounds.

Clinical trials.

The criteria used to evaluate the efficacy of the substance in the therapy of ulcerative colitis are frequency of bowel movements, rectal haemorrhage, abdominal pain, general well being, temperature, extraintestinal manifestations, ESR, and haemoglobin. These criteria have been summarised in the clinical activity index (CAI) to evaluate the efficacy of treatment for ulcerative colitis.
The safety and efficacy of Salofalk Granules (1.5 g to 3 g mesalazine/day) was compared against mesalazine tablets (Salofalk 500 mg tablets, 1.5 g to 3.0 g mesalazine/day) in a double blind randomised multicentre study in 233 patients with mild to moderately active ulcerative colitis over a period of 8 weeks. The primary efficacy criterion, complete response rate (per protocol analysis, PP), was very similar in the granules (68%) and the tablets (70%) groups. The efficacy analysis (PP) showed that more patients treated with mesalazine tablets (47%) had to increase the dose from 1.5 g mesalazine/day to 3.0 g mesalazine/day compared to patients treated with granules (38%). Similar results were obtained by the ITT (intention to treat) analysis: 39% of the granules group, 45% of the tablets group, i.e. more patients came into remission (49%) with the 1.5 g mesalazine/day from granules than from tablets (43%). Granules, therefore, in total were as efficacious and as well tolerated as the tablets at the same dose. Subgroup analyses showed that the response rates to granules were higher in patients with high baseline disease activity (CAI > 8) and with 1 or more extraintestinal manifestations than the tablets (see Table 3).
In another study the efficacy and safety of Salofalk Granules of different dosages (1.5 g, 3.0 g, 4.5 g/day) were compared in 321 patients with mild to moderately active ulcerative colitis in a double blind manner for a treatment period of 8 weeks. Complete response (CAI ≤ 4) was obtained by 50% in the 1.5 g dose group, by 66% in the 3.0 g group (in comparison to 1.5 g: p = 0.014) and by 55% in the 4.5 g group (in comparison to 1.5 g: not significant, p = 0.318). The 3.0 g/day dose appears to be the optimal dose.
In a double blind, randomised comparative study, the efficacy and tolerability of once daily (o.d.) 3.0 g Salofalk Granules was compared with three time daily (t.i.d.) 1.0 g Salofalk Granules in 380 patients with active ulcerative colitis over a period of eight weeks. The data show that for Salofalk Granules, a daily dose of 3 g mesalazine given o.d. is therapeutically equivalent to the conventional t.i.d. dosage regimen for the induction of remission (CAI ≤ 4) in patients with mild to moderate ulcerative colitis. The clinical remission rate in the PP analysis set (primary analysis) was 84.4% in the o.d. group and 81.3% in the t.i.d. group. The resulting p-value for the noninferiority test (predefined margin: -15%) was 0.0007 with a 95% CI of (-11.4%, 17.6%). With the achieved lower boundary of the derived 95% CI of 3.1%, an even narrower margin for the noninferiority was kept. Remission rates in ITT analysis set were very similar, 80.8% in the o.d. group and 77.4% in the t.i.d. group. ITT test result (p = 0.0007) and 95% CI (-11.4%, 18.1%) agreed with the PP analysis. Once daily dosing of Salofalk Granules was as safe and well tolerated as three times daily dosing of Salofalk Granules.
Results of the various studies show that oral delayed release Salofalk Granules are well tolerated in patients with ulcerative colitis.

5.2 Pharmacokinetic Properties

General considerations.

The efficacy of mesalazine (5-ASA) appears to be determined not by the systemic but the local availability of the substance at the target site.
There is no pharmacokinetic data in the elderly using Salofalk Granules.

Absorption.

The systemic absorption of mesalazine decreases in the intestinal tract from proximal to distal segments. Because of low systemic absorption rates from oral delayed release preparations or rectal applications forms of mesalazine, the main elimination route is via faeces.

Distribution.

The plasma protein binding of mesalazine and acetylated mesalazine is 43% and 78%, respectively.

Metabolism.

Metabolism of mesalazine occurs mainly in the intestinal mucosa and to a lesser extent in the liver. The main metabolite is N-acetyl-5-aminosalicylic acid, similar to mesalazine this is predominantly eliminated by the renal and faecal routes. It appears to have no therapeutic activity or specific toxic effects. The acetylation step appears irreversible. As metabolism occurs mainly in the intestinal mucosa it has not been possible to differentiate between a rapid and slow acetylation form as in the case of sulfasalazine/sulfapyridine.

Excretion.

Systemically absorbed mesalazine and N-acetyl-5-ASA are eliminated mainly via kidneys.
Less than 1% mesalazine and about 24% N-acetyl-5-ASA based on the administered mesalazine dose are excreted in the urine. Biliary excretion is a minor route of elimination.

Salofalk Granules.

Salofalk Granules are gastric juice resistant and release mesalazine in the terminal ileal region in a pH dependent manner due to the Eudragit-L coating. The release of mesalazine from the granules is prolonged due to the matrix granule structure. Owing to the granule size, under starved condition transit from the stomach to the small intestine is fast (0.65 + 0.40 hours). For the granules, food intake may cause a shift of 1 to 2 hours to a longer tlag value (lag time after which mesalazine concentrations are first detectable in blood plasma) and a longer tmax value, but does not cause dose dumping due to the small granule size. Food does cause a slight increase in Cmax and AUC values.
Pharmacokinetic data are summarised in Table 4 for Salofalk Granules and Salofalk tablets (granules: 3 x 500 mg mesalazine/day, tablets: 3 x 2 (250 mg) mesalazine/day, steady-state conditions, 24 healthy volunteers).
The total quantity of mesalazine and N-acetyl-5-ASA eliminated by the renal pathway over 24 hours is equivalent to about 25% to 32%, respectively of the administered dose of Salofalk Granules and Salofalk tablets. About 30% of this amount is absorbed in the ileocaecal area and about 90% in total in the ileocaecal and ascending colon regions. Therefore, about 80 to 90% mesalazine of administered dose is available in the descending colon, sigmoid and rectum where absorption of mesalazine is low.
Granule and tablet preparations radiolabelled with 153Sm (Samarium) showed the following gastrointestinal distribution (means ± S.D.) (see Table 5).
Plasma Cmax values of mesalazine and Ac-5-ASA during steady state were about 1.4-fold and 1.2-fold higher after once daily dosing (o.d.) when compared to values obtained after dosing three times daily (t.i.d.) dosing of the same daily dose. Plasma trough levels at the end of the dosing interval were only slightly (0.3 and 0.4 times, mesalazine and Ac-5-ASA, respectively) lower after o.d. dosing when compared to that after t.i.d. dosing. There is no indication of systemic drug accumulation, when given o.d.
The administration of a single oral dose of Salofalk Granules, 20 mg/kg bodyweight, in 13 children with active colonic inflammatory bowel disease (IBD) (age range: 5.9 to 15.8 years) showed that the pharmacokinetics of systemic exposure in children corresponds with those in adults. Salofalk Granules was safe and well tolerated.

5.3 Preclinical Safety Data

Genotoxicity.

There was no evidence of genotoxic potential with mesalazine in bacterial gene mutation assays, of chromosomal damage in mouse haematopoietic cells following a single oral dose, or of increases in sister chromatid exchange frequencies in Chinese hamster bone marrow following a single intraperitoneal dose.

Carcinogenicity.

There was no evidence of carcinogenicity in rats treated with mesalazine in the diet for 127 weeks at doses up to 320 mg/kg/day, associated with plasma concentrations of mesalazine and N-acetyl-5-ASA of 1 and 6-fold the respective clinical plasma concentrations associated with a 1500 mg dose of Salofalk Granules.

6 Pharmaceutical Particulars

6.1 List of Excipients

Salofalk Granules 500 mg and 1 g granules contain the following excipients: microcrystalline cellulose, hypromellose, colloidal anhydrous silica, methacrylic acid copolymer, magnesium stearate, simethicone, triethyl citrate, purified talc, carmellose sodium, aspartame, citric acid, vanilla custard flavour 75016-32 (PI 2187, contains sucrose), povidone and titanium dioxide.
Salofalk Granules 1.5 g granules contain the following excipients: microcrystalline cellulose, hypromellose, colloidal anhydrous silica, methacrylic acid copolymer, magnesium stearate, simethicone, sorbic acid, methylcellulose, triethyl citrate, purified talc, carmellose sodium, aspartame, citric acid, vanilla custard flavour 75016-32 (PI 2187, contains sucrose), povidone and titanium dioxide.
Salofalk Granules 3 g granules contain the following excipients: microcrystalline cellulose, hypromellose, colloidal anhydrous silica, methacrylic acid copolymer, magnesium stearate, simethicone, sorbic acid, methylcellulose, triethyl citrate, purified talc, carmellose sodium, aspartame, citric acid, vanilla custard flavour 75016-32 (PI 2187, contains sucrose), povidone and titanium dioxide.

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. Protect from light.

6.5 Nature and Contents of Container

Salofalk modified release granules are available in aluminium sachets of 500 mg, 1 g, 1.5 g or 3 g doses of mesalazine.
500 mg sachets are available in packs of 50, 100 or 300 sachets.
1 g sachets are available in packs of 50, 100 or 150 sachets.
1.5 g sachets are available in packs of 6, 60 or 100 sachets.
3 g sachets are available in packs of 6, 30 or 50 sachets.
Not all pack sizes are currently available in Australia.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Mesalazine is a white to greyish, voluminous powder, slightly pink in colour. It is practically insoluble in ethanol (90%), methanol (70%), water, ether, and chloroform, soluble in HCl (warmed 10% solution); soluble in NaOH (10% solution, with salt formation).
Proper name: 5-Aminosalicylic Acid, chemical name: 2-hydroxy-5-aminobenzoic acid, also referred to as 5-amino salicylic acid or 5-ASA. C7H7NO3 = 153.1.

Chemical structure.


CAS number.

89-57-6.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes