Consumer medicine information

Salofalk enema

Mesalazine

BRAND INFORMATION

Brand name

Salofalk Enemas

Active ingredient

Mesalazine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Salofalk enema.

SUMMARY CMI

SALOFALK® enemas

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 enemas?

SALOFALK enemas contain the active ingredient mesalazine (5-aminosalicylic acid). SALOFALK enemas 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 enemas? in the full CMI.

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

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

3. What if I am taking other medicines?

Some medicines may interfere with SALOFALK enemas 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 enemas?

  • The usual dose is one enema a day at bedtime, although the doctor or pharmacist will tell you exactly how much to use and where to check this information.
  • This medicine may only be used rectally, so it has to be inserted through the anus. Do NOT take it by mouth.

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

5. What should I know while using SALOFALK enemas?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using SALOFALK enemas.
  • Remind them if any new medicines are about to be started.
Things you should not do
  • Do not use SALOFALK enemas to treat any complaint other than that directed by your doctor. It may not be safe to use SALOFALK enemas for another complaint.
  • Do not give SALOFALK enemas to someone else even if their symptoms are the same. It may not be safe for another person to use SALOFALK enemas.
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 enema affects you. SALOFALK enemas may cause dizziness in some people.
Looking after your medicine
  • Keep SALOFALK enemas 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 enemas in a cool dry place, protected from light, where the temperature stays below 30°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 enemas? 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 enemas 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® enemas

Active ingredient: mesalazine

Consumer Medicine Information (CMI)

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

Where to find information in this leaflet:

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

1. Why am I using SALOFALK enemas?

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

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

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

Your doctor may have prescribed SALOFALK enemas for another reason.

Do not give SALOFALK enemas to a child below 12 years of age. The safety and effectiveness of SALOFALK enemas in this group have not been established.

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

Warnings

Do not use SALOFALK enemas 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 pack 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. SALOFALK enemas contain sulfite which may cause an allergic reaction.
  • have kidney problems. Kidney stones may develop with use of mesalazine, the active ingredient of SALODALK enemas. 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 enemas.
  • have liver problems.
  • 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 enemas.

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 treatment. Stop using SALOFALK enemas 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 enemas contain potassium metabisulphite and sodium benzoate.

This medicine contains potassium metabisulphite. It may therefore cause allergic reactions like allergic shock and bronchial constriction (bronchospasm) particularly if you suffer from asthma or have a history of allergies.

SALOFALK enemas also contain sodium benzoate which may provoke hypersensitivity reactions like irritation of the skin, eyes and mucous membranes.

People who take medicines containing mesalazine, such as SALOFALK enemas, may notice red-brown discolouration in the toilet bowl. This is due to mesalazine in the 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 enemas 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 enemas 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.

You may need to use different amounts of the above medicines, or you may need to take different medicines when you are using SALOFALK enemas. 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 enemas.

4. How do I use SALOFALK enemas?

How much to use

  • The usual dose is one enema a day at bedtime, although the doctor or pharmacist will tell you exactly how much to use and where to find this information.
  • Follow the instructions provided and use SALOFALK enemas until your doctor tells you to stop.

When to use SALOFALK enemas

  • SALOFALK enemas should be used at bedtime.

How to use SALOFALK enemas

  1. If possible, go to the toilet and empty your bowels before using the enema.
  2. Wash your hands thoroughly with soap and water.
  3. Using a pair of scissors carefully cut along the dotted line of the pack containing the enema bottle. Take care not to cut or damage the bottle.
  4. Shake the enema bottle for 30 seconds.
  5. Remove the protective cap from the applicator. Place your thumb on the base of the bottle, with your index and second finger, placed at the top of the bottle and below the applicator for support as shown in the figure below.

  1. Lie down on your left side with the left leg outstretched and the right leg bent (see figure below).

  1. Gently guide the applicator deep into your rectum. Lubricant has been applied to applicator for your comfort.
  2. To administer the enema into your rectum, slowly push your thumb inwards against the base of the bottle. The concertina design of the bottle will help you to administer the enema.
  3. Remove the applicator from the rectum when the bottle is empty.
  4. Remain lying down for at least 30 minutes to allow the enema to spread throughout the lower part of the large intestine.

  1. Wash your hands thoroughly and try not to empty your bowels again until the next morning.

You may experience a little discomfort and a feeling of urgency to empty your bowels immediately after enema administration. This is normal and expected due to the inflammation present within the bowel. Try to resist this urge to empty your bowels for as long as possible. This feeling will subside as treatment continues and the inflammation decreases.

How long to use SALOFALK enemas

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 enemas

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

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

If you have trouble remembering when to use SALOFALK enemas, ask your pharmacist for some hints.

If you use too much SALOFALK enemas

If you think that you have used too much SALOFALK enemas, 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 & 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 enemas?

Things you should do

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

Tell your doctor immediately if you become pregnant or wish to breastfeed while using SALOFALK enemas.

Things you should not do

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

Driving or using machines

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

SALOFALK enemas may cause dizziness in some people.

Looking after your medicine

  • Keep SALOFALK enemas 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 enemas in a cool dry place, protected from light, where the temperature stays below 30°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
  • 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) with 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 enemas.

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 enemas contain

Active ingredient
(main ingredient)		mesalazine 2.0 g or 4 g
Other ingredients
(inactive ingredients)
  • carbomer 934P
  • disodium edetate
  • potassium acetate
  • potassium metabisulphite
  • sodium benzoate
  • xanthan gum
  • water - purified.

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

What SALOFALK enemas look like

SALOFALK enemas are a very light tan to brown suspension.

They are available as a product pack containing 7 enema bottles.

SALOFALK enemas Australian Registration Numbers:
2 g/30 mL: AUST R 80651
2 g/60 mL: AUST R 80653
4 g/60 mL: AUST R 80652

Not all strengths are available in Australia.

Who distributes SALOFALK enemas

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 Enemas

Active ingredient

Mesalazine

Schedule

S4

 

1 Name of Medicine

Salofalk Enemas mesalazine 2 g/30 mL, 2 g/60 mL or 4 g/60 mL mesalazine.

2 Qualitative and Quantitative Composition

Salofalk Enemas contain either 2 g/30 mL, 2 g/60 mL or 4 g/60 mL mesalazine as the active ingredient.

Excipients with known effect.

Sulphites and benzoates.
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 2 g/30 mL, 2 g/60 mL and 4 g/60 mL enemas are presented as a very light tan to brown, homogeneous suspension.

4 Clinical Particulars

4.1 Therapeutic Indications

Salofalk Enemas are indicated in the treatment of acute ulcerative colitis of mild to moderate severity and for the maintenance treatment of ulcerative colitis.

4.2 Dose and Method of Administration

Unless otherwise advised a dose of 2 g or 4 g mesalazine as Salofalk Enema once a day is used for the treatment of acute ulcerative colitis or for the maintenance of remission.
The content of one enema bottle (2 g/30 mL, 2 g/60 mL, or 4 g/60 mL) is instilled in the rectum once every evening prior to going to bed.
The best results are achieved if the bowels are evacuated prior to instillation of Salofalk Enema.
The action of Salofalk Enemas is enhanced if the patient lies on the left side when introducing the enema after the insertion of the applicator, which is lubricated for patient comfort. The concertina design of the bottle helps the patient to administer the enema. The dosage should be adjusted to suit the progress of the condition.
Discontinuation of treatment should be under supervision of the physician. Due to the considerable variation in the severity of the ulcerative colitis and the extent of the affected area it is not possible to recommend a uniform dose of mesalazine which will provide optimal effects. In clinical trials, rectal doses of 2-4 g mesalazine/day as enemas have been used in the therapy of both acute ulcerative colitis and maintenance of remission.

Use in children.

Salofalk Enemas should not be used in children 12 years old and under, as there is little experience with this age group.

4.3 Contraindications

Salofalk Enemas is contraindicated in patients with the following:
hypersensitivity to salicylic acid, salicylic acid derivatives, e.g. mesalazine/5-ASA, sulfites and benzoates or to any of the other ingredients;
severe impairment of hepatic and renal function.
Salofalk Enemas should be used with caution in patients with bronchial asthma. They contain sulfite which may cause hypersensitivity reactions.

4.4 Special Warnings and Precautions for Use

Salofalk Enemas should be given/used under medical supervision.

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 Enemas 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 Enemas 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 5-ASA or secondary manifestations of inflammatory bowel disease. Cardiac hypersensitivity reactions (myocarditis, and pericarditis) induced by mesalazine have been rarely reported. Salofalk Enemas 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 Enemas 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 reaction (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.

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 Enemas should not be used in children 12 years old and under, as there is little experience with this age group.

Effects on laboratory tests.

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

Excipients with known effect.

Salofalk Enemas contain potassium metabisulphite, which can induce allergic reactions, including anaphylactic symptoms and bronchial constriction (bronchospasm) in sensitive patients, particularly in those with asthma or a history of allergies.
Salofalk Enemas 2 g/30 mL contain 30 mg sodium benzoate. Salofalk Enemas 2 g/60 mL and 4 g/60 mL contain 60 mg sodium benzoate. Sodium benzoate may provoke hypersensitivity reactions in suitably predisposed patients in the form of irritation of the skin, eyes and mucous membranes.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Studies to evaluate the potential interaction between Salofalk Enemas 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.

Sulfonylureas.

Possible increase in the blood glucose lowering effects.

Methotrexate.

Possible increase in toxic potential of methotrexate.

Probenecid/sulfinpyrazone.

Possible attenuation of the uricosuric effects.

Spironolactone/frusemide.

Possible attenuation of the diuretic effects.

Rifampicin.

Possible attenuation of the tuberculostatic effects.
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 less than the maximal recommended clinical dose of Salofalk Enemas 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 less than, and about twice, the maximal recommended clinical dose of Salofalk Enemas 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 Enemas 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 less than the maximal recommended clinical dose of Salofalk Enemas 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. But, there is no experience with Salofalk Enemas in lactating women. Salofalk Enemas 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 common adverse events seen in the clinical studies for Salofalk Enemas are headache, hair loss, abdominal pain, diarrhoea and rash. In a randomized, double-blind placebo controlled clinical trial of Salofalk 4 g/60 mL enemas in a total of 153 patients, adverse events occurred in 25% and 40% of patients in the Salofalk Enemas and placebo enema groups respectively. Events reported in at least 2 patients in this trial are shown in Table 1.
The following adverse events presented by body system have been reported in international post marketing surveillance of all Salofalk preparations including Salofalk Enemas. In many cases, the relationship to Salofalk 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, flatulence, exacerbation of ulcerative colitis.

Skin and appendages disorder.

Rash including pruritus, urticarial.
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.

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.
(In isolated cases hypersensitivity reactions, principally in the form of respiratory problems, may be experienced by nonasthmatics due to the content of potassium bisulfite in enemas.)

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, mucosal appearance on endoscopy and severity of the disease as evaluated by a physician. These criteria are included in the Disease Activity Index (DAI) used to evaluate the efficacy of treatments for ulcerative colitis (UC). In a multicentre, randomised, double blind, placebo controlled study involving 153 patients, the efficacy of Salofalk 4 g/60 mL enemas in the therapy of ulcerative colitis was significantly better than that of placebo at 6 weeks. The study showed an endoscopic improvement of 70% vs. 37% of placebo (p = 0.001). It also showed a 63% improvement by the physician global assessment (PGA) in the mesalazine group vs. 29% in the placebo group (p < 0.001) while evaluation by the DAI showed a 55% decline (7.42 to 3.37) in the 5-ASA group vs. 22% (7.7 to 5.83) in the placebo group (p = 0.0001). All components of the DAI were significantly lower for the treatment group than the placebo group, see Table 2.
On completing the above study, all patients were randomised to receive Salofalk 4 g/60 mL or 2 g/60 mL enemas, once daily in an open label maintenance study. After 6 months of treatment, the DAI score improved by 62-75% from baseline and there was no significant difference in the degree of improvement between the groups. A dose dependent relationship with Salofalk Enemas does not seem to be evident in the maintenance of remission.

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 little pharmacokinetic data available for rectal administered mesalazine in children. There is no pharmacokinetic data in the elderly using Salofalk Enemas.

Absorption.

The systemic absorption of mesalazine decreases in the intestinal tract from the 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, which is, similar to mesalazine, 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. Biliary excretion is a minor route of elimination.

Salofalk Enemas.

4 g/60 mL enema in patients with ulcerative colitis in remission show a median Cmax value of 0.92 microgram/mL for 5-ASA at tmax of 11 hours, and for N-acetyl-5-ASA a median Cmax of 1.62 microgram/mL at a tmax of 12 hours. The median urinary recovery was 13% during the 45 hour observational period, indicating a low absorption.
The administration of high doses of mesalazine enema (2 x Salofalk 4 g/60 mL enemas daily) in patients with severely active ulcerative colitis, administered into the caecum, showed the following Cmax values in plasma for 5-ASA at tmax of 1.5 h and for N-acetyl-5-ASA at tmax of 2.8 h. See Table 3.
Total urinary recovery on day 1 was 10.5% and on day 3 (steady state) 18.6% with 22% of that being mesalazine, demonstrating a low absorption rate, similar to the oral administration of Salofalk Granules. The serum elimination half-life on day 1 was 4.2 h, also comparable with that of the Salofalk Granules (4.4 h).
In children with ulcerative colitis, Salofalk Enemas showed the following steady-state plasma concentrations. See Table 4.
Scintigraphic evaluation of (99Tc) technetium-sulfur colloid labelled Salofalk 2 g/30 mL and Salofalk 4 g/60 mL Enema showed the following distribution in patients with mild to moderate active ulcerative colitis at the beginning of therapy (time: 0 week) and at time of remission after 12 weeks of treatment (median and range). See Table 5.

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.
There is growing information that 5-ASA/mesalazine protects patients with ulcerative colitis from colorectal cancer.

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 the granules and Salofalk 4 g/60 mL enemas.

6 Pharmaceutical Particulars

6.1 List of Excipients

Salofalk Enemas contain the following excipients: carbomer 934P, disodium edetate, potassium acetate, potassium metabisulfite, purified water, sodium benzoate and xanthan gum.

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 30°C. Protect from light.

6.5 Nature and Contents of Container

Salofalk Enemas are supplied in opaque, concertina shaped LDPE squeeze bottles with a PVC applicator nozzle in cardboard cartons. The disposable unit consists of a PVC applicator tip protected by a LDPE cover and lubricated with white soft paraffin and/or liquid paraffin. The unit has a one-way valve to prevent back flow of the dispensed product.
Salofalk Enemas, 2 g/30 mL: Each carton contains 7 enemas in individual blister packs.
Salofalk Enemas, 2 g/60 mL: Each carton contains 7 enemas in individual blister packs.
Salofalk Enemas, 4 g/60 mL: Each carton contains 1 or 7 enemas in individual blister packs.
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