Asacol

Package leaflet: Information for the user

ASACOL 400 mg gastro-resistant tablets, 800 mg gastro-resistant tablets

mesalazine
Please read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may be harmful to people other than you, even if their symptoms are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any side effects not listed in this leaflet. See section 4.

Contents of this leaflet:

1. What ASACOL is and what it is used for
2. What you need to know before taking ASACOL
3. How to take ASACOL
4. Possible side effects
5. How to store ASACOL
6. Contents of the pack and other information

1. What ASACOL is and what it is used for

ASACOL contains the active substance mesalazine, which belongs to a class of medicines called intestinal anti-inflammatory agents.
This medicine is used in adults and children over 6 years of age for the treatment of ulcerative colitis, Crohn's disease (chronic inflammatory bowel diseases), and inflammatory bowel disease unclassified (IBDU).
The medicine is indicated both for the treatment of active disease phases and for the prevention of relapses. In severe active phases, concomitant treatment with a corticosteroid medicine is recommended.
Consult your doctor if you do not feel better or if you feel worse after the prescribed treatment period.

2. What you need to know before using ASACOL

Do not use ASACOL

• If you are allergic to mesalazine, to other related medicines (such as salicylates), or to any of the other ingredients of this medicine (listed in section 6), particularly to metabisulphites.
• If you have severe kidney problems (severe impairment of kidney function, severe nephropathy), or injury to the inner lining (mucosa) of the stomach or intestine (gastric or duodenal ulcer, active peptic ulcer).
• If you have severe impairment of liver function.
• If you have a tendency to develop bleeding (haemorrhagic diathesis).
• In children under 2 years of age. In children under 6 years of age, your doctor will evaluate the need for treatment with the tablets (see section “Children”).
• During the last weeks of pregnancy and while breastfeeding (see section “Pregnancy and breastfeeding”).

Warnings and precautions
Talk to your doctor or pharmacist before using ASACOL.
If you experience severe or recurrent headache, visual disturbances, ringing or buzzing in the ears, contact your doctor immediately.
Avoid using the tablets in children under 6 years of age.
Before starting treatment with ASACOL, you should undergo the necessary clinical investigations to confirm the diagnosis and determine the appropriate treatment.
Before starting and during treatment with ASACOL, blood tests and urine tests should be performed at your doctor’s discretion. Your doctor will decide how often these tests should be repeated.
Before starting treatment with ASACOL, inform your doctor if you have ever had allergic reactions to medicines called sulfasalazine.
After stopping treatment or during inadequate maintenance therapy, your symptoms may return.
Pay particular attention and inform your doctor if any of the following apply to you:

• If you have reduced kidney or liver function.
• If you have known kidney dysfunction, your doctor will carefully evaluate the need for treatment with mesalazine. Your doctor will assess kidney function in all patients before starting therapy and periodically during treatment, especially if you have kidney disease.
• If you have heart conditions affecting the myocardium or pericardium (myocarditis or pericarditis).
• If you have lung problems (particularly if you suffer from asthma).
• If you are taking one or more of the following medicines: oral hypoglycaemics (medicines to lower blood sugar levels), diuretics (medicines to increase urine production), coumarins (medicines to reduce blood clotting), and corticosteroids (medicines to treat inflammation).
• If you have digestive problems (such as slow digestion) or if you have a condition called “pyloric stenosis” (narrowing of the pylorus, the valve connecting the end of the stomach to the duodenum, causing obstruction).
• If you have previously developed a severe skin rash, skin peeling, blisters, and/or mouth ulcers after taking mesalazine. Be especially cautious with mesalazine: serious skin reactions, 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. Stop using mesalazine and consult a doctor immediately if you notice any of the symptoms related to these serious skin reactions described in section 4. Discontinue treatment (see also section “Possible side effects”) and inform your doctor:
• If, following treatment with ASACOL, you develop bleeding, bruising, red spots on the skin due to leakage from superficial blood vessels (purpura), decreased haemoglobin levels in the blood (anaemia), fever, or sore throat.
• In case of suspected acute intolerance syndrome, which may present with symptoms such as cramps, acute abdominal pain and bloody diarrhoea, sometimes accompanied by fever, headache, and erythema. Prolonged use of ASACOL may lead to sensitization phenomena.

The use of mesalazine may cause kidney stone formation. Symptoms may include pain in the sides of the abdomen and blood in the urine. It is recommended to drink an adequate amount of fluids during treatment with mesalazine.
Mesalazine may cause a red-brown discoloration of urine after contact with sodium hypochlorite contained in bleach present in toilet water. This is due to a harmless chemical reaction between mesalazine and bleach.
Children
ASACOL is contraindicated in children under 2 years of age (see section “Do not use ASACOL”).
ASACOL is not recommended for use in children under 6 years of age unless carefully evaluated by a doctor.
Other medicines and ASACOL
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Avoid concomitant administration of lactulose or other preparations that lower colon pH, as they may interfere with the release of mesalazine.
Use this medicine with caution together with:

• Sulfonylureas (used in the treatment of diabetes), as the hypoglycaemic effect (reduction of blood sugar levels) may be enhanced.
• Medicines to reduce blood clotting (anticoagulants belonging to the coumarin family, such as warfarin).
• Methotrexate (a medicine used in patients with psoriasis, Crohn’s disease, rheumatoid arthritis, and in the treatment of certain cancers).
• Probenecid (a medicine used to reduce blood uric acid levels).
• Sulfinpyrazone (a medicine used for prevention following a heart attack).
• Spironolactone (a potassium-sparing diuretic).
• Furosemide (a diuretic medicine that increases urine production, used in cases of fluid retention).
• Rifampicin (an antibiotic).
• Non-steroidal anti-inflammatory drugs (NSAIDs).
• Azathioprine (an anti-inflammatory and immunosuppressive medicine).
• 6-mercaptopurine and thioguanine (medicines used in the treatment of blood cancers).

The use of ASACOL together with corticosteroids may enhance the undesirable effects of corticosteroids on the stomach.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before using this medicine.
If pregnancy is confirmed or suspected, take this medicine only if clearly needed and under strict medical supervision.
Do not use ASACOL during the last weeks of pregnancy and while breastfeeding (see section “Do not use ASACOL”).
ASACOL should be used during breastfeeding only if clearly necessary and under strict medical supervision. If the newborn develops diarrhoea, breastfeeding should be discontinued.
Driving and using machines
ASACOL does not affect, or has a negligible effect on, the ability to drive or use machinery.
ASACOL contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially 'sodium-free'.

3. How to use ASACOL

Use this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
Your doctor will adjust the dosage according to the extent and severity of your condition.
When starting treatment for the first time, it is advisable to gradually increase the dose over several days before reaching the maximum dosage.

400 mg tablet: The recommended dose is 1–2 gastro-resistant tablets three times daily. The dosage may be increased up to 10 tablets per day in patients with severe disease, according to the physician's judgment.

800 mg tablet: The recommended dose is 1 gastro-resistant tablet three times daily. The dosage may be increased up to 5 tablets of 800 mg per day in patients with severe disease, according to the physician's judgment.

Use in children and adolescents
ASACOL is contraindicated in children under 2 years of age. ASACOL is not recommended for use in children under 6 years of age. After careful evaluation, the doctor may decide to administer reduced doses.

Children over 6 years of age:

• Active phase of the disease: The doctor will determine the appropriate dose on a case-by-case basis. The recommended average dose is 30–50 mg/kg/day given in divided doses. Maximum dose: 75 mg/kg/day in divided doses. The total daily dose must not exceed 4 g per day (maximum dose in adults).
• Maintenance treatment: The doctor will determine the appropriate dose on a case-by-case basis. The recommended average dose is 15–30 mg/kg/day given in divided doses. The total daily dose must not exceed 2 g per day (recommended dose in adults).

Take the tablets whole, without dividing or chewing them, preferably with a glass of water and away from meals. The duration of treatment for active phases is typically 4–6 weeks and may vary, at the physician’s discretion, depending on the patient's condition and disease progression. For long-term treatment to prevent relapses, the daily dosage and duration of therapy must be determined by the doctor according to the patient's condition and disease course.

If you take more ASACOL than you should
In case of accidental overdose, contact your doctor immediately or go to the nearest hospital.

If you forget to take ASACOL
Do not take a double dose to make up for the missed dose; instead, resume your regular dosing schedule as directed.

If you stop taking ASACOL
After stopping treatment, symptoms may recur (see section “Warnings and precautions”). If you have any questions about using this medicine, consult your doctor or pharmacist.

4. POSSIBLE ADVERSE REACTIONS

Like all medicines, this one may cause adverse reactions, although not everyone experiences them.
Serious adverse reactions:
Stop treatment with mesalazine and contact your doctor immediately if you notice any of the
following symptoms:
flat, red, target-shaped or circular patches on the trunk, often with central blisters,
skin peeling, mouth, throat, nose, genital or eye ulcers, widespread rash,
fever and swollen lymph nodes. These severe skin rashes may be preceded by fever and flu-like symptoms.
Contact your doctor immediately if you experience severe or recurrent headache, vision disturbances, ringing or buzzing in the ears. These could be symptoms of increased pressure inside the skull (idiopathic intracranial hypertension).
If you notice any of the following adverse reactions, stop treatment and contact your doctor immediately:

• Allergic reactions (skin rash, itching).
• Episodes of acute intestinal intolerance with abdominal pain.
• Presence of blood in liquid stools (bloody diarrhoea).
• Cramps.
• Headache.
• Fever.
• Skin rash.

The following adverse reactions may occur during treatment with ASACOL:
Common (may affect up to 1 in 10 people):

• Headache.
• Skin rash.
• Nausea.
• Diarrhoea.
• Abdominal distension.
• High blood pressure (hypertension).
• Generalised weakness (asthenia).
• Fever (pyrexia).

Uncommon (may affect up to 1 in 100 people):

• Itching.
• Upper abdominal pain.
• Presence of blood in liquid stools (bloody diarrhoea).
• Cramps and abdominal pain.
• Drowsiness.
• Tremor.
• Increased heart rate (tachycardia).
• Low blood pressure (hypotension).
• Fatigue.
• Facial swelling.

Rare (may affect up to 1 in 1,000 people):

• Increased sensitivity of the skin to sunlight and ultraviolet light (photosensitivity).
• Dizziness.
• Vomiting.
• Gas emission from the intestine (flatulence).

Very rare (may affect up to 1 in 10,000 people):

• Inflammatory diseases affecting the heart and the membrane surrounding it (pericarditis, myocarditis).
• Decrease in the number of white blood cells in the blood (leucopenia, neutropenia), decrease in the number of platelets in the blood (thrombocytopenia), a form of anaemia characterised by insufficient production in the bone marrow of all types of blood cells (aplastic anaemia), severe decrease in the number of blood cells called granulocytes (agranulocytosis), reduction in the number of all blood cells (pancytopenia).
• Inflammation of the pancreas (pancreatitis, including acute).
• Inflammation of the liver (hepatitis, cholestatic hepatitis).
• Temporary abnormalities in liver function tests.
• Gallstones (cholelithiasis).
• Kidney inflammation (acute and chronic interstitial nephritis), kidney and urinary tract disorders (nephrotic syndrome), and reduced kidney function (renal failure).
• Allergic and fibrotic pulmonary reactions (including breathing difficulties, cough, bronchospasm, alveolitis).
• Inflammation of the lower respiratory tract (eosinophilic pneumonia), lung infiltration, inflammation of the interstitial lung tissue (interstitial pneumonia), and pneumonia.
• High fever (hyperpyrexia).
• Allergic reactions such as allergic rash (skin eruption with red spots and/or pustules, blisters, bullae), drug fever, skin manifestations similar to those of systemic lupus erythematosus (lupus-like syndrome), inflammation of the colon (pancolitis).
• Decreased number of hairs in a localized or diffuse area (alopecia).
• Decreased number of spermatozoa in the semen (oligospermia).
• Nerve damage or disorder causing numbness and tingling sensations (peripheral neuropathy).
• Muscle pain (myalgia) and joint pain (arthralgia).

Not known (frequency cannot be estimated from the available data):

• Swelling of the skin, mucosa and submucosal tissues (angioedema).
• Kidney stones and associated kidney pain (see also section 2).

Reporting of adverse reactions
If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist. You may also report adverse reactions directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. HOW TO STORE ASACOL

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after "Exp.". The expiry date refers to the last day of that month.
Do not store above 30°C.
Do not use this medicine if you notice any visible signs of deterioration.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. PACKAGING CONTENTS AND OTHER INFORMATION

What ASACOL 400 mg gastro-resistant tablets contain

• The active substance is mesalazine (5-aminosalicylic acid, 5-ASA). Each tablet contains 400 mg of mesalazine.
• The other components are: Mannitol, Povidone K30, Povidone K90, Sodium starch glycolate type A, Magnesium stearate, Talc, Anhydrous colloidal silica, Methacrylic acid copolymer type B, Triethyl citrate, Iron oxide red (E 172), Iron oxide yellow (E 172), Macrogol 6000.

What ASACOL 800 mg gastro-resistant tablets contain

• The active substance is mesalazine (5-aminosalicylic acid, 5-ASA). Each tablet contains 800 mg of mesalazine.
• The other components are: Mannitol, Povidone K30, Povidone K90, Sodium starch glycolate type A, Magnesium stearate, Talc, Anhydrous colloidal silica, Methacrylic acid copolymer type B, Triethyl citrate, Iron oxide red (E 172), Iron oxide yellow (E 172), Macrogol 6000.

Description of the appearance of ASACOL and contents of the pack

ASACOL is presented as gastro-resistant tablets in blisters, packed in a cardboard box together with the package leaflet.

ASACOL is available in the following pack sizes:

• 30 gastro-resistant tablets of 400 mg, in blister packs
• 60 gastro-resistant tablets of 400 mg, in blister packs
• 24 gastro-resistant tablets of 800 mg, in blister packs
• 60 gastro-resistant tablets of 800 mg, in blister packs
• 96 gastro-resistant tablets of 800 mg, in blister packs

Not all pack sizes may be marketed.
Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
GIULIANI S.p.A., via Palagi, n 2-20129, Milan.
Manufacturer
COSMO SpA, via C. Colombo n. 1, 20045 Lainate (MI).

Package leaflet: information for the user

ASACOL 400 mg

Modified-release hard capsules
mesalazine
Please read this leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What ASACOL is and what it is used for
2. What you need to know before taking ASACOL
3. How to take ASACOL
4. Possible side effects
5. How to store ASACOL
6. Contents of the pack and other information

1. What ASACOL is and what it is used for

ASACOL contains the active substance mesalazine, which belongs to the group of intestinal anti-inflammatory medicines.
This medicine is used in adults and children over 2 years of age for the treatment of ulcerative colitis and Crohn's disease (chronic inflammatory bowel diseases), as well as for inflammatory bowel disease unclassified (IBDU).
The medicine is indicated both for the treatment of active phases of the disease and for the prevention of relapses. In severe active phases, concomitant treatment with a corticosteroid medicine is recommended.
If you do not feel better or if you feel worse after the prescribed treatment period, consult your doctor.

2. What you should know before using ASACOL

Do not use ASACOL

• If you are allergic to mesalazine, to related medicines (such as salicylates), or to any of the other ingredients of this medicine (listed in section 6), particularly to metabisulphites.
• If you have severe kidney problems (severe impairment of kidney function, severe nephropathy), or injury to the inner lining (mucosa) of the stomach or intestine (gastric or duodenal ulcer, active peptic ulcer).
• If you have severe impairment of liver function.
• If you have a tendency to develop bleeding (haemorrhagic diathesis).
• In children under 2 years of age (see section “Children”).
• During the last weeks of pregnancy and while breastfeeding (see section “Pregnancy and breastfeeding”).

Warnings and precautions
Talk to your doctor or pharmacist before taking ASACOL.
If you experience severe or recurrent headache, visual disturbances, or ringing or buzzing in the ears, contact your doctor immediately.
Before starting treatment with ASACOL, you should undergo the necessary clinical investigations to establish diagnosis and therapeutic indications.
Before starting and during treatment with ASACOL, blood tests and urine tests should be performed at your doctor’s discretion. Your doctor will decide how often you need to repeat these tests.
Before starting treatment with ASACOL, inform your doctor if you have ever had allergic reactions to medicines called sulfasalazine.
After stopping treatment or during inadequate maintenance therapy, symptoms of the disease may reappear.
Pay special attention and inform your doctor if any of the following apply to you:

• If you have reduced kidney or liver function.
• If you have known kidney dysfunction, your doctor will carefully evaluate the need for mesalazine treatment. Your doctor will assess kidney function in all patients before starting therapy, and periodically during treatment, especially if kidney disease is present.
• If you have heart conditions affecting the myocardium or pericardium (myocarditis or pericarditis).
• If you have lung problems (particularly if you suffer from asthma).
• If you are being treated with one or more of the following medicines: oral hypoglycaemics (medicines to lower blood sugar levels), diuretics (medicines to increase urine production), coumarins (medicines to reduce blood clotting), and corticosteroids (medicines to treat inflammation).
• If you have digestive problems (such as slow digestion) or if you have a condition called “pyloric stenosis” (narrowing of the pylorus, the valve connecting the end of the stomach to the duodenum, causing obstruction).
• If you have previously developed a severe skin rash, skin peeling, blisters, and/or mouth ulcers after taking mesalazine.

Exercise particular caution with mesalazine:
Serious skin reactions, 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. Stop taking mesalazine and consult a doctor immediately if you notice any of the symptoms related to these serious skin reactions described in section 4.
Stop treatment (see also section “Possible side effects”) and inform your doctor:

• If, after treatment with ASACOL, you develop bleeding, bruising, red spots on the skin due to leakage from superficial blood vessels (purpura), decreased haemoglobin levels in the blood (anaemia), fever, or sore throat.
• In case of suspected acute intolerance syndrome, which may present with symptoms such as cramps, acute abdominal pain and bloody diarrhoea, sometimes accompanied by fever, headache, and erythema.

Prolonged use of ASACOL may lead to sensitization phenomena.
Use of mesalazine may cause kidney stone formation. Symptoms may include pain in the sides of the abdomen and blood in the urine. It is recommended to drink sufficient fluids during treatment with mesalazine.
Mesalazine may cause a red-brown discoloration of urine after contact with sodium hypochlorite contained in bleach present in toilet water. This is due to a harmless chemical reaction between mesalazine and bleach.

Children
ASACOL is contraindicated in children under 2 years of age (see section “Do not use ASACOL”).

Other medicines and ASACOL
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Avoid concomitant administration of lactulose or other preparations that lower colonic pH, as they may interfere with the release of mesalazine.
Use this medicine with caution together with:

• Sulfonylureas (used in the treatment of diabetes), as the hypoglycaemic effect (reduction of blood sugar levels) may be enhanced.
• Medicines to reduce blood clotting (anticoagulants belonging to the coumarin family, such as warfarin).
• Methotrexate (a medicine used in patients with psoriasis, Crohn’s disease, rheumatoid arthritis, and in the treatment of certain tumours).
• Probenecid (a medicine used to reduce uric acid concentration in the blood).
• Sulfinpyrazone (a medicine used for prevention following myocardial infarction).
• Spironolactone (a potassium-sparing diuretic).
• Furosemide (a diuretic medicine that increases urine production, used in cases of fluid retention).
• Rifampicin (an antibiotic).
• Non-steroidal anti-inflammatory drugs (NSAIDs).
• Azathioprine (an anti-inflammatory and immunosuppressive medicine).
• 6-mercaptopurine and thioguanine (medicines used in the treatment of blood cancers).

The use of ASACOL together with corticosteroids may enhance the adverse effects of corticosteroids on the stomach.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before using this medicine. If pregnancy is confirmed or suspected, take the medicine only if clearly needed and under strict medical supervision.
Do not use ASACOL during the last weeks of pregnancy and while breastfeeding (see section “Do not use ASACOL”).
ASACOL should be used during breastfeeding only if clearly needed and under strict medical supervision. If the newborn develops diarrhoea, breastfeeding should be discontinued.

Driving and using machines
ASACOL does not affect or has negligible effect on the ability to drive vehicles or use machinery.

3. How to use ASACOL

Use this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
Your doctor will adjust the dosage according to the extent and severity of your condition.
At the beginning of treatment, it is advisable to gradually increase the dose over a few days before reaching the maximum dosage.
The recommended dose in adults is 1–2 modified-release hard capsules, taken three times a day.
In patients with severe disease, the dosage may be increased up to 10 capsules, according to the physician's judgment.

Use in children and adolescents
Children over 2 years: the dose should be proportionally reduced at the physician's discretion.
Children from 6 years of age:

• Active phase of the disease: the physician will determine the appropriate dose on a case-by-case basis. The recommended average dose is 30–50 mg/kg daily, given in divided doses. Maximum dose: 75 mg/kg daily in divided doses. The total daily dose must not exceed 4 g per day (maximum dose in adults).
• Maintenance treatment: the physician will determine the appropriate dose on a case-by-case basis. The recommended average dose is 15–30 mg/kg daily in divided doses. The total daily dose must not exceed 2 g per day (recommended dose in adults).

Take the modified-release hard capsules whole, preferably with a glass of water and away from meals. If you are unable to swallow the capsules whole, open the capsule and take all microgranules after dispersing them in an aqueous solution. Caution: do not chew the microgranules.
The duration of treatment during active phases is generally 4–6 weeks and may vary, at the physician’s discretion, depending on the patient's condition and disease progression.
For long-term treatment to prevent relapses, the daily dosage and treatment duration must be determined by the physician according to the patient's condition and disease course.

If you take more ASACOL than you should
In case of accidental overdose, contact your doctor immediately or go to the nearest hospital.

If you forget to take ASACOL
Do not take a double dose to make up for the missed dose. Instead, resume your regular dosing schedule as directed.

If you stop taking ASACOL
After stopping treatment, symptoms may recur (see section “Warnings and precautions”).
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this one may cause side effects, although not everybody experiences them.
Serious side effects:
Stop treatment with mesalazine and contact your doctor immediately if you notice any of the following symptoms:
reddish, flat, target-shaped or circular skin patches on the trunk, often with central blisters, skin peeling, mouth ulcers, or ulcers in the throat, nose, genitals, and eyes, widespread rash, fever, and swollen lymph nodes. These severe skin rashes may be preceded by fever and flu-like symptoms.
Contact your doctor immediately if you experience severe or recurrent headache, vision disturbances, ringing or buzzing in the ears. These could be symptoms of increased pressure inside the skull (idiopathic intracranial hypertension).
If you notice any of the following side effects, stop treatment and contact your doctor immediately:

• Allergic reactions (skin rash, itching).
• Episodes of acute intestinal intolerance with abdominal pain.
• Presence of blood in liquid stools (haematochezia).
• Cramps.
• Headache.
• Fever.
• Skin rash.

The following side effects may occur during treatment with ASACOL:
Common (may affect up to 1 in 10 people):

• Headache.
• Skin rash.
• Nausea.
• Diarrhoea.
• Abdominal distension.
• High blood pressure (hypertension).
• General weakness (asthenia).
• Fever (pyrexia).

Uncommon (may affect up to 1 in 100 people):

• Itching.
• Upper abdominal pain.
• Presence of blood in liquid stools (haematochezia).
• Cramps and abdominal pain.
• Drowsiness.
• Tremor.
• Increased heart rate (tachycardia).
• Low blood pressure (hypotension).
• Fatigue.
• Facial swelling.

Rare (may affect up to 1 in 1,000 people):

• Increased sensitivity of the skin to sunlight and ultraviolet light (photosensitivity).
• Dizziness.
• Vomiting.
• Gas release from the intestine (flatulence).

Very rare (may affect up to 1 in 10,000 people):

• Inflammatory diseases affecting the heart and the membrane surrounding it (pericarditis, myocarditis).
• Decreased number of white blood cells in the blood (leucopenia, neutropenia), decreased number of platelets in the blood (thrombocytopenia), a form of anaemia characterised by insufficient production in the bone marrow of all types of blood cells (aplastic anaemia), severe decrease in the number of blood cells called granulocytes (agranulocytosis), reduction in all types of blood cells (pancytopenia).
• Inflammation of the pancreas (pancreatitis, including acute pancreatitis).
• Inflammation of the liver (hepatitis, cholestatic hepatitis).
• Temporary changes in liver function tests.
• Gallstones (cholelithiasis).
• Kidney inflammation (impaired kidney function, acute and chronic interstitial nephritis), kidney and urinary tract disorders (nephrotic syndrome), and reduced kidney function (renal failure).
• Allergic and fibrotic pulmonary reactions (including dyspnoea, cough, bronchospasm, alveolitis).
• Inflammation of the lower respiratory tract (eosinophilic pneumonia), lung infiltration, inflammation of the interstitial lung tissue (interstitial pneumonia), and pneumonia.
• High fever (hyperpyrexia).
• Allergic reactions such as allergic rash (skin eruption with red spots and/or pustules, blisters, bullae), drug fever, skin manifestations similar to those of systemic lupus erythematosus (lupus-like syndrome), inflammation of the colon (pancolitis).
• Decreased number of hairs and body hair in a localized or diffuse area (alopecia).
• Decreased number of spermatozoa in the semen (oligospermia).
• Nerve damage or abnormality causing numbness and tingling sensations (peripheral neuropathy).
• Muscle pain (myalgia) and joint pain (arthralgia).

Not known (frequency cannot be estimated from the available data):

• Swelling of the skin, mucosa, and submucosal tissues (angioedema).
• Kidney stones and associated kidney pain (see also section 2).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store ASACOL

Keep this medicine out of the sight and reach of children.
Store in the original packaging to protect the medicine from light.
Do not use this medicine after the expiry date stated on the pack after “Exp.”. The expiry date refers to the last day of that month.
Do not use this medicine if you notice any visible signs of deterioration.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What ASACOL 400 mg modified-release hard capsules contain

• The active substance is mesalazine (5-aminosalicylic acid, 5-ASA). Each capsule contains 400 mg of mesalazine.
• The other components are: hydroxypropylcellulose, Methacrylic acid copolymer (methacrylic acid-methyl methacrylate copolymer 1:2), Triethyl citrate, Talc, Anhydrous colloidal silica, Gelatin, Iron oxide red (E172), Iron oxide yellow (E172), Titanium dioxide.

Description of the appearance of ASACOL and pack contents
ASACOL is presented as modified-release hard capsules and is available in packs of 50
400 mg capsules in blisters.
Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
GIULIANI S.p.A., via Palagi, n 2- 20129 Milan.
Manufacturer
COSMO S.p.A., via C. Colombo, n.1- 20045 Lainate, Milan.

Package leaflet: Information for the user

ASACOL 1 g suppositories, 500 mg suppositories

mesalazine
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What ASACOL is and what it is used for
2. What you need to know before using ASACOL
3. How to use ASACOL
4. Possible side effects
5. How to store ASACOL
6. Contents of the pack and other information

1. What ASACOL is and what it is used for

ASACOL contains the active substance mesalazine, which belongs to a class of medicines called intestinal anti-inflammatory agents.
This medicine is used in adults and children over 2 years of age for the treatment of ulcerative colitis (a long-term inflammatory bowel disease affecting the lower parts of the intestine) localized at the rectal level.
The medicine is indicated both for the treatment of active phases of the disease and for the prevention of relapses. In severe active phases, concomitant use of a corticosteroid medicine is recommended.
If you do not feel better or feel worse after the prescribed treatment period, consult your doctor.

2. What you should know before using ASACOL

Do not use ASACOL

• If you are allergic to mesalazine, to other related medicines (such as salicylates), or to any of the other ingredients of this medicine (listed in section 6), particularly metabisulfites.
• If you have severe kidney problems (severe impairment of renal function, severe nephropathy), or injury to the inner lining (mucosa) of the stomach or intestine (gastric or duodenal ulcer, active peptic ulcer).
• If you have severe impairment of liver function.
• If you have a tendency to develop bleeding (hemorrhagic diathesis).
• In children under 2 years of age (see section “Children”).
• During the last weeks of pregnancy and while breastfeeding (see section “Pregnancy and breastfeeding”).

Warnings and precautions
Talk to your doctor or pharmacist before taking ASACOL.
If you experience severe or recurrent headache, visual disturbances, or ringing or buzzing in the ears, contact your doctor immediately.
Before starting treatment with ASACOL, you should undergo the necessary clinical investigations to establish diagnosis and therapeutic indications.
Before starting and during treatment with ASACOL, blood and urine tests may be performed at your doctor’s discretion. Your doctor will decide how often these tests should be repeated.
Before starting treatment with ASACOL, inform your doctor if you have ever had allergic reactions to medicines called sulfasalazine.
After stopping treatment or during inadequate maintenance therapy, symptoms of the disease may reappear.
Pay special attention and inform your doctor if any of the following apply to you:

• If you have reduced kidney or liver function.
• If you have known renal dysfunction, your doctor will carefully evaluate the need for treatment with mesalazine. Your doctor will assess renal function in all patients before starting therapy and periodically during treatment, especially if you have existing kidney disease.
• If you have heart conditions affecting the myocardium or pericardium (myocarditis or pericarditis).
• If you have lung problems (particularly if you suffer from asthma).
• If you are taking one or more of the following medicines: oral hypoglycemics (medicines to lower blood sugar levels), diuretics (medicines to increase urine production), coumarins (medicines to reduce blood clotting), or corticosteroids (medicines to treat inflammation).
• If you have previously developed a severe skin rash, skin peeling, blisters, and/or mouth ulcers after taking mesalazine. Exercise particular caution with mesalazine: severe skin reactions, 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. Stop taking mesalazine and contact a doctor immediately if you notice any of the symptoms related to these severe skin reactions described in section 4. Discontinue treatment (see also section “Possible side effects”) and inform your doctor:
• if, after treatment with ASACOL, you develop bleeding, bruising, red spots on the skin due to leakage from superficial blood vessels (purpura), decreased hemoglobin levels in the blood (anemia), fever, or sore throat.
• In case of suspected acute intolerance syndrome, which may present with symptoms such as cramps, acute abdominal pain, bloody diarrhea, sometimes fever, headache, and erythema. Prolonged use of ASACOL may lead to sensitization phenomena. Mesalazine may cause the formation of kidney stones. Symptoms may include pain in the sides of the abdomen and blood in the urine. It is recommended to drink an adequate amount of fluids during treatment with mesalazine.

Mesalazine may cause a red-brown discoloration of urine after contact with sodium hypochlorite contained in bleach present in toilet water. This is due to a harmless chemical reaction between mesalazine and bleach.

Children
ASACOL is contraindicated in children under 2 years of age (see section “Do not use ASACOL”).

Other medicines and ASACOL
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Use this medicine with caution together with:

• Sulfonylureas (used in the treatment of diabetes), as the hypoglycemic effect (lowering of blood sugar levels) may be enhanced.
• Medicines to reduce blood clotting (anticoagulants belonging to the coumarin family, such as warfarin).
• Methotrexate (a medicine used in patients with psoriasis, Crohn’s disease, rheumatoid arthritis, and in the treatment of certain cancers).
• Probenecid (a medicine used to reduce blood uric acid concentration).
• Sulfinpyrazone (a medicine used for prevention after a heart attack).
• Spironolactone (a potassium-sparing diuretic).
• Furosemide (a diuretic medicine that increases urine production, used in cases of fluid retention).
• Rifampicin (an antibiotic).
• Non-steroidal anti-inflammatory drugs (NSAIDs).
• Azathioprine (an anti-inflammatory and immunosuppressive medicine).
• 6-mercaptopurine and thioguanine (medicines used in the treatment of blood cancers).

The use of ASACOL together with corticosteroids may enhance the undesirable effects of corticosteroids on the stomach.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before using this medicine. If pregnancy is confirmed or suspected, take the medicine only if clearly needed and under strict medical supervision.
Do not use ASACOL during the last weeks of pregnancy and while breastfeeding (see section “Do not use ASACOL”).
ASACOL should be used during breastfeeding only if clearly needed and under strict medical supervision. If the newborn develops diarrhea, breastfeeding should be discontinued.

Driving and using machines
ASACOL does not affect or has negligible effect on the ability to drive vehicles or use machinery.

3. How to use ASACOL

Use this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
Your doctor will adjust the dosage according to the extent and severity of your condition.
The recommended average dose for adults is 1 suppository of 1 g daily or 3 suppositories of 500 mg daily, divided into 2–3 administrations administered rectally.
Use in children and adolescents
Children over 2 years: the dose will be proportionally reduced at the doctor's discretion.
To achieve the best therapeutic effect, it is important to retain the suppository for at least 30 minutes; better still, retain it for longer periods (e.g., overnight).
The duration of treatment for active phases is on average 4–6 weeks and may vary, at the doctor's discretion, depending on the patient's condition and disease progression.
For long-term treatment to prevent relapses, the daily dosage and duration of treatment must be determined by the doctor according to the patient's condition and disease progression.
If you use more ASACOL than you should
There are no known cases of overdose following rectal administration.
If you forget to use ASACOL
Do not use a double dose to make up for the missed dose; instead, resume the normal dosing schedule as indicated.
If you stop using ASACOL
After stopping treatment, symptoms may recur (see section “Warnings and precautions”).
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this one can cause side effects, although not everybody gets them.

Serious side effects:
Stop treatment with mesalazine and contact your doctor immediately if you notice any of the following symptoms:
reddish, flat spots on the trunk, target-shaped or circular, often with central blisters, skin peeling, ulcers in the mouth, throat, nose, genitals, and eyes, widespread rash, fever, and swollen lymph nodes. These severe skin reactions may be preceded by fever and flu-like symptoms.

Contact your doctor immediately if you experience severe or recurring headache, vision disturbances, or ringing or buzzing in the ears. These could be symptoms of increased pressure inside the skull (idiopathic intracranial hypertension).

If you notice any of the following side effects, stop treatment and contact your doctor immediately:

• Allergic reactions (skin rash, itching).
• Episodes of acute intestinal intolerance with abdominal pain.
• Presence of blood in watery stools (bloody diarrhea).
• Cramps.
• Headache.
• Fever.
• Skin rash.

The following side effects may occur during treatment with ASACOL:
Common (may affect up to 1 in 10 people):

• Headache.
• Skin rash.
• Nausea.
• Diarrhea.
• Abdominal distension.
• High blood pressure (hypertension).
• Generalized weakness (asthenia).
• Fever (pyrexia).

Uncommon (may affect up to 1 in 100 people):

• Itching.
• Upper abdominal pain.
• Presence of blood in watery stools (bloody diarrhea).
• Cramps and abdominal pain.
• Drowsiness.
• Tremor.
• Increased heart rate (tachycardia).
• Low blood pressure (hypotension).
• Fatigue.
• Facial swelling.

Rare (may affect up to 1 in 1,000 people):

• Increased sensitivity of the skin to sunlight and ultraviolet light (photosensitivity).
• Dizziness.
• Vomiting.
• Gas release from the intestine (flatulence).

Very rare (may affect up to 1 in 10,000 people):

• Inflammatory diseases affecting the heart and the membrane surrounding it (pericarditis, myocarditis).
• Decreased number of white blood cells in the blood (leukopenia, neutropenia), decreased number of platelets in the blood (thrombocytopenia), a form of anemia characterized by insufficient production in the bone marrow of all types of blood cells (aplastic anemia), severe decrease in blood cells called granulocytes (agranulocytosis), reduction in the number of all blood cells (pancytopenia).
• Inflammation of the pancreas (pancreatitis, including acute).
• Inflammation of the liver (hepatitis, cholestatic hepatitis).
• Temporary abnormalities in liver function tests.
• Gallstones (cholelithiasis).
• Kidney inflammation (impaired kidney function, acute and chronic interstitial nephritis), kidney and urinary tract disorders (nephrotic syndrome), and reduced kidney function (renal failure).
• Allergic and fibrotic pulmonary reactions (including difficulty breathing, cough, bronchospasm, alveolitis).
• Inflammation of the lower respiratory tract (eosinophilic pneumonia), lung infiltration, inflammation of the interstitial lung tissue (interstitial pneumonia), and pneumonia.
• High fever (hyperpyrexia).
• Allergic reactions such as allergic exanthema (skin rash with red spots and/or pustules, blisters, bullae), drug fever, skin manifestations similar to those of systemic lupus erythematosus (lupus-like syndrome), inflammation of the colon (pancolitis).
• Decreased number of hairs and body hair in a localized or diffuse area (alopecia).
• Decreased number of spermatozoa in seminal fluid (oligospermia).
• Nerve damage causing numbness and tingling sensations (peripheral neuropathy).
• Muscle pain (myalgia) and joint pain (arthralgia).

Not known (frequency cannot be estimated from the available data):

• Swelling of the skin, mucosa, and submucosal tissues (angioedema).
• Kidney stones and associated kidney pain (see also section 2).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor or pharmacist. You may also report side effects directly via the national reporting system at: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. HOW TO STORE ASACOL

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after “Exp.”. The expiry date refers to the last day of that month.
Do not store above 30°C.
Do not use this medicine if you notice any visible signs of deterioration.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What ASACOL 1g suppositories contains

• The active substance is mesalazine (5-aminosalicylic acid, 5-ASA). Each suppository contains 1 g of mesalazine.
• The other components are: solid semisynthetic glycerides (with vegetable lecithin).

What ASACOL 500 mg suppositories contains

• The active substance is mesalazine (5-aminosalicylic acid, 5-ASA). Each suppository contains 500 mg of mesalazine.
• The other components are: solid semisynthetic glycerides (with vegetable lecithin).

Description of the appearance of ASACOL and contents of the pack
ASACOL is available as suppositories. The suppositories are contained in preformed blisters made of rigid plastic material (PVC/PE), placed in a cardboard box together with the package leaflet.
ASACOL is available in the following pack sizes:
28 suppositories of 1 g
10 suppositories of 500 mg
20 suppositories of 500 mg.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
GIULIANI S.p.A., via Palagi, n 2 - 20129 Milan, Italy.
Manufacturer
COSMO S.p.A., via C. Colombo, n.1 - 20045 Lainate, Milan, Italy.

Package leaflet: information for the user

ASACOL 2g/50 mL rectal suspension, 4g/50 mL rectal suspension, 4g/100 mL rectal suspension

mesalazine
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What ASACOL is and what it is used for
2. What you need to know before using ASACOL
3. How to use ASACOL
4. Possible side effects
5. How to store ASACOL
6. Contents of the pack and other information

1. What ASACOL is and what it is used for

ASACOL contains the active substance mesalazine, which belongs to a class of medicines known as intestinal anti-inflammatory agents.
This medicine is used to treat left-sided ulcerative colitis (a chronic inflammatory bowel disease affecting the lower part of the intestine) in adults and children over 2 years of age.
The medicine is indicated both for the treatment of active phases of the disease and for the prevention of relapses. In severe active phases, concomitant treatment with a corticosteroid medicine is recommended.
If you do not feel better or if you feel worse after the prescribed treatment period, consult your doctor.

2. What you should know before using ASACOL

Do not use ASACOL

• If you are allergic to mesalazine, to other related medicines (such as salicylates), or to any of the other ingredients of this medicine (listed in section 6), particularly metabisulphites.
• If you have severe kidney problems (severe impairment of kidney function, severe nephropathy), or injury to the inner lining (mucosa) of the stomach or intestine (gastric or duodenal ulcer, active peptic ulcer).
• If you have severe liver function impairment.
• If you have a tendency to develop bleeding (haemorrhagic diathesis).
• In children under 2 years of age (see section “Children”).
• During the last weeks of pregnancy and while breastfeeding (see section “Pregnancy and breastfeeding”).

Warnings and precautions
Talk to your doctor or pharmacist before using ASACOL.
If you experience severe or recurrent headache, visual disturbances, ringing or buzzing in the ears, contact your doctor immediately.
Before starting treatment with ASACOL, you should undergo the necessary clinical investigations to confirm the diagnosis and determine appropriate treatment indications.
Before starting and during treatment with ASACOL, blood and urine tests may be performed at your doctor’s discretion. Your doctor will decide how often these tests should be repeated.
Before starting treatment with ASACOL, inform your doctor if you have ever had allergic reactions to medicines called sulfasalazine.
After stopping treatment or during inadequate maintenance therapy, symptoms of the disease may reappear.
Pay special attention and inform your doctor if any of the following apply to you:

• If you have reduced kidney or liver function.
• If you have known kidney dysfunction, your doctor will carefully evaluate the need for mesalazine treatment. Your doctor will assess kidney function in all patients before starting therapy and periodically during treatment, especially if kidney disease is present.
• If you have heart conditions affecting the myocardium or pericardium (myocarditis or pericarditis).
• If you have lung problems (particularly if you suffer from asthma).
• If you are taking one or more of the following medicines: oral hypoglycaemics (medicines to lower blood sugar levels), diuretics (medicines to increase urine production), coumarins (medicines to reduce blood clotting), and corticosteroids (medicines used to treat inflammation).
• If you have ever developed a severe skin rash, skin peeling, blisters, and/or mouth ulcers after taking mesalazine.

Exercise particular caution with mesalazine:
Serious skin reactions, 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. Stop using mesalazine and consult a doctor immediately if you notice any of the symptoms related to these serious skin reactions described in section 4.
Stop treatment (see also section “Possible side effects”) and inform your doctor:

• If, after treatment with ASACOL, you develop bleeding, bruising, red spots on the skin due to leakage from superficial blood vessels (purpura), decreased haemoglobin levels in the blood (anaemia), fever, or sore throat.
• In case of suspected acute intolerance syndrome, which may present with symptoms such as cramps, acute abdominal pain and bloody diarrhoea, sometimes accompanied by fever, headache, and erythema. Prolonged use of ASACOL may lead to sensitisation. Mesalazine may cause kidney stone formation. Symptoms may include pain in the sides of the abdomen and blood in the urine. It is recommended to drink sufficient fluids during treatment with mesalazine.

Mesalazine may cause a red-brown discoloration of urine after contact with sodium hypochlorite contained in bleach present in toilet water. This is due to a harmless chemical reaction between mesalazine and bleach.
Children
ASACOL is contraindicated in children under 2 years of age (see section “Do not use ASACOL”).
Other medicines and ASACOL
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Use this medicine with caution together with:

• Sulphonylureas (used in the treatment of diabetes), as mesalazine may enhance their hypoglycaemic effect (lowering of blood sugar levels).
• Medicines that reduce blood clotting (anticoagulants belonging to the coumarin family, such as warfarin).
• Methotrexate (a medicine used in patients with psoriasis, Crohn’s disease, rheumatoid arthritis, and in the treatment of certain cancers).
• Probenecid (a medicine used to reduce uric acid levels in the blood).
• Sulfinpyrazone (a medicine used for prevention after a heart attack).
• Spironolactone (a potassium-sparing diuretic).
• Furosemide (a diuretic medicine that increases urine production, used in cases of fluid retention).
• Rifampicin (an antibiotic).
• Non-steroidal anti-inflammatory drugs (NSAIDs).
• Azathioprine (an anti-inflammatory and immunosuppressive medicine).
• 6-mercaptopurine and thioguanine (medicines used to treat blood cancers).
  The use of ASACOL together with corticosteroids may enhance the adverse effects of corticosteroids on the stomach.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before using this medicine.
If pregnancy is confirmed or suspected, take this medicine only if clearly needed and under strict medical supervision.
Do not use ASACOL during the last weeks of pregnancy and while breastfeeding (see section “Do not use ASACOL”).
ASACOL should be used during breastfeeding only if clearly necessary and under strict medical supervision.
If the newborn develops diarrhoea, breastfeeding should be discontinued.

Driving and using machines
ASACOL does not affect, or has a negligible effect on, the ability to drive or use machinery.

ASACOL 2g/50 mL rectal suspension contains sodium benzoate
This medicine contains 190 mg of sodium benzoate per dose, equivalent to one single-dose container.
Sodium benzoate may cause local irritation.

ASACOL 4 g/50 mL rectal suspension contains sodium benzoate
This medicine contains 190 mg of sodium benzoate per dose, equivalent to one single-dose container.
Sodium benzoate may cause local irritation.

ASACOL 4g/100 mL rectal suspension contains sodium benzoate
This medicine contains 380 mg of sodium benzoate per dose, equivalent to one single-dose container.
Sodium benzoate may cause local irritation.

ASACOL contains potassium metabisulphite
Rarely, this may cause severe hypersensitivity reactions and bronchospasm.

3. How to use ASACOL

Use this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts,
consult your doctor or pharmacist.
Your doctor will adjust the dosage according to the extent and severity of your condition.
The recommended average dose in adults is 1 dose of 2 g of mesalazine in 50 mL, 1–2 times daily, in the morning
and/or in the evening before going to bed, or 1 dose of 4 g of mesalazine in 50 mL or 1 dose of 4 g in 100 mL, once
daily, preferably in the evening before going to bed.
Use in children and adolescents
Children over 2 years: the dose will be proportionally reduced at the doctor’s discretion.
For administration, proceed as follows:

1. Shake the rectal suspension well before use to obtain a homogeneous suspension.
2. Break the cap with light pressure and insert the rectal cannula provided into the plastic container.
3. Lie on your left side, keeping your left leg straight and bending your right leg.
4. Insert the cannula into the anal opening, gently pushing it in completely.
5. Squeeze the container gradually and steadily until all the contents have been expelled.
   After administering the preparation, turn from side to side several times to facilitate better distribution of
   the medicine and remain lying down for at least 30 minutes. Optimal effectiveness is achieved by retaining
   the medicine as long as possible or, preferably, leaving it in place overnight. Therefore, it is advisable that
   at least one daily administration be performed before going to bed.
   The duration of treatment during active phases is typically 4–6 weeks and may vary, at the doctor’s discretion,
   depending on the patient’s condition and disease progression.
   For long-term treatment to prevent relapses, the daily dosage and duration of treatment must be determined
   by the doctor according to the patient’s condition and disease progression.
   If you use more ASACOL than you should
   Cases of overdose following rectal administration have not been reported.
   If you forget to use ASACOL
   Do not use a double dose to make up for the missed dose; instead, resume the normal dosing schedule as indicated.
   If you stop using ASACOL
   After stopping treatment, symptoms may reappear (see section “Warnings and precautions”).
   If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this one can cause side effects, although not everyone experiences them.
Serious side effects:
Stop treatment with mesalazine and contact your doctor immediately if you notice any of the following symptoms:
reddish, non-elevated patches, target-shaped or circular rashes on the trunk, often with central blisters, skin peeling, mouth, throat, nose, genital, or eye ulcers, widespread rash, fever, and swollen lymph nodes. These severe skin reactions may be preceded by fever and flu-like symptoms.
Contact your doctor immediately if you experience severe or recurring headache, vision disturbances, ringing or buzzing in the ears. These could be symptoms of increased pressure inside the skull (idiopathic intracranial hypertension).
If you notice any of the following side effects, stop treatment and contact your doctor immediately:

• Allergic reactions (skin rash, itching).
• Episodes of acute intestinal intolerance with abdominal pain.
• Presence of blood in liquid stools (haematochezia).
• Cramps.
• Headache.
• Fever.
• Skin rash.

The following side effects may occur during treatment with ASACOL:
Common (may affect up to 1 in 10 people):

• Headache.
• Skin rash.
• Nausea.
• Diarrhoea.
• Abdominal distension.
• High blood pressure (hypertension).
• General weakness (asthenia).
• Fever (pyrexia).

Uncommon (may affect up to 1 in 100 people):

• Itching (pruritus).
• Upper abdominal pain.
• Presence of blood in liquid stools (haematochezia).
• Cramps and abdominal pain.
• Drowsiness.
• Tremor.
• Increased heart rate (tachycardia).
• Low blood pressure (hypotension).
• Fatigue.
• Facial swelling.

Rare (may affect up to 1 in 1,000 people):

• Increased sensitivity of the skin to sunlight and ultraviolet light (photosensitivity).
• Dizziness.
• Vomiting.
• Gas from the intestine (flatulence).

Very rare (may affect up to 1 in 10,000 people):

• Inflammatory diseases affecting the heart and the membrane surrounding it (pericarditis, myocarditis).
• Decreased number of white blood cells in the blood (leucopenia, neutropenia), decreased number of platelets in the blood (thrombocytopenia), a form of anaemia characterised by insufficient production in the bone marrow of all types of blood cells (aplastic anaemia), severe decrease in granulocytes (agranulocytosis), reduction in all types of blood cells (pancytopenia).
• Inflammation of the pancreas (pancreatitis, including acute pancreatitis).
• Inflammation of the liver (hepatitis, cholestatic hepatitis).
• Temporary abnormalities in liver function tests.
• Gallstones (cholelithiasis).
• Kidney inflammation (impaired kidney function, acute and chronic interstitial nephritis), kidney and urinary tract disorders (nephrotic syndrome), and reduced kidney function (renal failure).
• Allergic and fibrotic lung reactions (including difficulty breathing, cough, bronchospasm, alveolitis).
• Inflammation of the lower respiratory tract (eosinophilic pneumonia), lung infiltration, inflammation of the interstitial lung tissue (interstitial pneumonia), and pneumonia.
• High fever (hyperpyrexia).
• Allergic reactions such as allergic rash (skin eruption with red spots and/or pustules, blisters, bullae), drug fever, skin manifestations similar to systemic lupus erythematosus (lupus-like syndrome), inflammation of the colon (pancolitis).
• Decreased number of hairs in a localized or widespread area (alopecia).
• Decreased number of spermatozoa in the semen (oligospermia).
• Nerve damage or disorder causing numbness and tingling (peripheral neuropathy).
• Muscle pain (myalgia) and joint pain (arthralgia).

Not known (frequency cannot be estimated from the available data):

• Swelling of the skin, mucous membranes, and submucosal tissues (angioedema).
• Kidney stones and associated kidney pain (see also section 2).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store ASACOL

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after "Exp.". The expiry date refers to the last day of that month.
Do not use this medicine if you notice visible signs of deterioration (for example, encrustations or loss of contents).
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package Contents and Other Information

What ASACOL 2 g/50 mL rectal suspension contains

• The active substance is mesalazine (5-aminosalicylic acid, 5-ASA). Each single-dose container of 50 mL contains 2 g of mesalazine.
• The other components are: Colloidal silicon dioxide, Povidone, Methylcellulose, Sodium benzoate, Potassium metabisulfite, Phosphoric acid, Water.

What ASACOL 4 g/50 mL rectal suspension contains

• The active substance is mesalazine (5-aminosalicylic acid, 5-ASA). Each single-dose container of 50 mL contains 4 g of mesalazine.
• The other components are: Colloidal silicon dioxide, Povidone, Methylcellulose, Sodium benzoate, Potassium metabisulfite, Phosphoric acid, Water.

What ASACOL 4 g/100 mL rectal suspension contains

• The active substance is mesalazine (5-aminosalicylic acid, 5-ASA). Each single-dose container of 100 mL contains 4 g of mesalazine.
• The other components are: Colloidal silicon dioxide, Povidone, Methylcellulose, Sodium benzoate, Potassium metabisulfite, Phosphoric acid, Water.

Description of the appearance of ASACOL and the contents of the pack
ASACOL is a rectal suspension available in the following pack sizes:

• Rectal suspension 2 g/50 mL – 7 single-dose containers of 50 mL with 7 accompanying rectal applicator nozzles.
• Rectal suspension 4 g/50 mL – 7 single-dose containers of 50 mL with 7 accompanying rectal applicator nozzles.
• Rectal suspension 4 g/100 mL – 7 single-dose containers of 100 mL with 7 accompanying rectal applicator nozzles.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
GIULIANI S.p.A., via Palagi n. 2, 20129 Milano, Italy.
Manufacturer
ZETA FARMACEUTICI S.p.A., via Galvani n. 10, 36066 Sandrigo (VI), Italy
LABORATORIO CHIMICO FARMACEUTICO A. SELLA S.r.l., via Vicenza n. 67, 36015 Schio (VI), Italy

Package leaflet: Information for the user

ASACOL 2 g

Granules for rectal suspension
mesalazine
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What ASACOL is and what it is used for
2. What you need to know before using ASACOL
3. How to use ASACOL
4. Possible side effects
5. How to store ASACOL
6. Contents of the pack and other information

1. What ASACOL is and what it is used for

ASACOL contains the active substance mesalazine, which belongs to the class of intestinal anti-inflammatory
medicinal products.
This medicine is used to treat left-sided ulcerative colitis (a chronic inflammatory bowel disease affecting the lower parts of the intestine) in adults and children over 2 years of age.
This medicine is indicated both for the treatment of active phases of the disease and for the prevention of relapses. In severe active phases, concomitant treatment with a corticosteroid medicine is recommended.
If you do not feel better or if you feel worse after the prescribed treatment period, consult your doctor.

2. What you must know before using ASACOL

Do not use ASACOL

• If you are allergic to mesalazine, to other related medicines (such as salicylates), or to any of the other ingredients of this medicine (listed in section 6), particularly metabisulphites.
• If you have severe kidney problems (severe impairment of renal function, severe nephropathy), or injury to the inner lining (mucosa) of the stomach or intestine (gastric or duodenal ulcer, active peptic ulcer).
• If you have severe impairment of liver function.
• If you have a tendency to develop bleeding (haemorrhagic diathesis).
• In children under 2 years of age (see section “Children”).
• During the last weeks of pregnancy and while breastfeeding (see section “Pregnancy and breastfeeding”).

Warnings and precautions
Talk to your doctor or pharmacist before taking ASACOL.
If you experience severe or recurrent headache, visual disturbances, or ringing or buzzing in the ears, contact your doctor immediately.
Before starting treatment with ASACOL, you should undergo the necessary clinical investigations to establish diagnosis and therapeutic indications.
Before starting and during treatment with ASACOL, blood tests and urine tests should be performed at your doctor’s discretion. Your doctor will decide how often you need to repeat these tests.
Before starting treatment with ASACOL, inform your doctor if you have ever had allergic reactions to medicines called sulfasalazine.
After stopping treatment or during inadequate maintenance therapy, symptoms of the disease may reappear.
Pay special attention and inform your doctor if any of the following apply to you:

• If you have reduced kidney or liver function.
• If you have known renal dysfunction, your doctor will carefully evaluate the need for treatment with mesalazine. Your doctor will assess renal function in all patients before starting therapy and periodically during treatment, especially in the presence of kidney disease.
• If you have heart conditions affecting the myocardium or pericardium (myocarditis or pericarditis).
• If you have lung problems (particularly if you suffer from asthma).
• If you are being treated with one or more of the following medicines: oral hypoglycaemics (medicines to lower blood sugar levels), diuretics (medicines to increase urine production), coumarins (medicines to reduce blood clotting), and corticosteroids (medicines to treat inflammation).
• If you have ever developed a severe skin rash or skin peeling, blisters, and/or mouth ulcers after taking mesalazine.

Exercise particular caution with mesalazine:
Serious skin adverse reactions have been reported in association with mesalazine treatment, including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Discontinue use of mesalazine and consult a doctor immediately if you notice any of the symptoms related to these serious skin reactions described in section 4.
Discontinue treatment (see also section “Possible side effects”) and inform your doctor:

• If, following treatment with ASACOL, you develop bleeding, bruising, red spots on the skin due to leakage from superficial blood vessels (purpura), decreased haemoglobin levels in the blood (anaemia), fever, or sore throat.
• If acute intolerance syndrome is suspected, which may present with symptoms such as cramps, acute abdominal pain and bloody diarrhoea, sometimes fever, headache, and erythema.

Prolonged use of ASACOL may lead to sensitization phenomena.
Use of mesalazine may cause kidney stone formation. Symptoms may include pain in the sides of the abdomen and blood in the urine. It is recommended to drink sufficient fluids during treatment with mesalazine.
Mesalazine may cause a red-brown discoloration of urine after contact with sodium hypochlorite contained in bleach present in toilet water. This is due to a harmless chemical reaction between mesalazine and bleach.

Children
ASACOL is contraindicated in children under 2 years of age (see section “Do not use ASACOL”).

Other medicines and ASACOL
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
Use this medicine with caution together with:

• Sulphonylureas (used in the treatment of diabetes), as the hypoglycaemic effect (lowering of blood sugar levels) may be enhanced.
• Coumarin drugs (used to slow down or inhibit blood clotting).
• Methotrexate (a medicine used in patients with psoriasis, Crohn’s disease, rheumatoid arthritis, and in the treatment of certain tumours).
• Probenecid (a medicine used to reduce uric acid concentration in the blood).
• Sulfinpyrazone (a medicine used for prevention following a heart attack).
• Spironolactone (a potassium-sparing diuretic).
• Furosemide (a diuretic medicine that increases urine production, used in cases of fluid retention).
• Rifampicin (an antibiotic).
• Non-steroidal anti-inflammatory drugs (NSAIDs).
• Azathioprine (an anti-inflammatory and immunosuppressive medicine).
• 6-mercaptopurine and thioguanine (medicines used in the treatment of blood cancers).

The use of ASACOL together with corticosteroids may enhance the undesirable effects of corticosteroids on the stomach.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before using this medicine. If pregnancy is confirmed or suspected, take the medicine only if clearly needed and under strict medical supervision.
Do not use ASACOL during the last weeks of pregnancy and while breastfeeding (see section “Do not use ASACOL”).
ASACOL should be used during breastfeeding only if clearly needed and under strict medical supervision. If the newborn develops diarrhoea, breastfeeding should be discontinued.

Driving and using machines
ASACOL does not affect or has negligible effect on the ability to drive vehicles or use machinery.

3. How to use ASACOL

Use this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
Your doctor will adjust the dosage according to the extent and severity of your condition.
The recommended average dose for adults is one 2 g dose of mesalazine in 50 mL, 1–2 times daily, in the morning and/or evening before going to bed.

Use in children and adolescents
Children over 2 years: the dose will be proportionally reduced at the doctor’s discretion.

For administration, proceed as follows:

1. Pour the granules for rectal suspension contained in a sachet into the plastic container.
2. Add water up to the mark.
3. Shake well to obtain a homogeneous suspension, then screw the rectal cannula onto the container.
4. Lie on your left side, keeping your left leg straight and bending your right leg.
5. Insert the cannula completely into the anal opening and gently push it in until fully inserted.
6. Squeeze the container, applying gradual and constant pressure, until all the contents have been expelled.

After administration, turn from side to side several times to help distribute the medicine more evenly, and remain lying down for at least 30 minutes. Optimal effectiveness is achieved by retaining the medicine as long as possible, preferably overnight.
Therefore, it is advisable that at least one daily administration is performed before going to bed.

The expected duration of treatment during active phases is generally 4–6 weeks, but may vary according to the patient's condition and disease progression, at the doctor’s discretion.
For long-term treatment to prevent relapses, the daily dosage and duration of treatment must be determined by the doctor based on the patient's condition and disease evolution.

If you use more ASACOL than you should
There are no known cases of overdose following rectal administration.

If you forget to use ASACOL
Do not use a double dose to make up for the forgotten dose; instead, resume your regular dosing schedule as indicated.

If you stop using ASACOL
After stopping treatment, symptoms may recur (see section “Warnings and precautions”).

If you have any questions about using this medicine, consult your doctor or pharmacist.

4. POSSIBLE ADVERSE EFFECTS

Like all medicines, this one may cause adverse effects, although not everyone experiences them.
Serious adverse effects:
Stop treatment with mesalazine and contact your doctor immediately if you notice any of the following symptoms:
reddish, flat, target-like or circular skin patches, often with central blisters, skin peeling, mouth, throat, nose, genital, or eye ulcers, widespread rash, fever, and swollen lymph nodes. These severe skin reactions may be preceded by fever and flu-like symptoms.
Contact your doctor immediately if you experience severe or recurrent headache, vision disturbances, ringing or buzzing in the ears. These may be symptoms of increased pressure inside the skull (idiopathic intracranial hypertension).
If you notice any of the following adverse effects, stop treatment and contact your doctor immediately:

• Allergic reactions (skin rash, itching).
• Episodes of acute intestinal intolerance with abdominal pain.
• Presence of blood in liquid stools (haematochezia).
• Cramps.
• Headache.
• Fever.
• Skin rash.

The following adverse effects may occur during treatment with ASACOL:
Common (may affect up to 1 in 10 people):

• Headache.
• Skin rash.
• Nausea.
• Diarrhoea.
• Abdominal distension.
• High blood pressure (hypertension).
• General weakness (asthenia).
• Fever (pyrexia).

Uncommon (may affect up to 1 in 100 people):

• Itching.
• Upper abdominal pain.
• Presence of blood in liquid stools (haematochezia).
• Cramps and abdominal pain.
• Drowsiness.
• Tremor.
• Increased heart rate (tachycardia).
• Low blood pressure (hypotension).
• Fatigue.
• Facial swelling.

Rare (may affect up to 1 in 1,000 people):

• Increased skin sensitivity to sunlight and ultraviolet light (photosensitivity).
• Dizziness.
• Vomiting.
• Excessive gas from the intestine (flatulence).

Very rare (may affect up to 1 in 10,000 people):

• Inflammatory diseases affecting the heart and the membrane surrounding it (pericarditis, myocarditis).
• Decreased number of white blood cells in the blood (leucopenia, neutropenia), decreased number of platelets in the blood (thrombocytopenia), a form of anaemia characterised by inadequate production in the bone marrow of all types of blood cells (aplastic anaemia), severe decrease in blood cells called granulocytes (agranulocytosis), reduction in all types of blood cells (pancytopenia).
• Inflammation of the pancreas (pancreatitis, including acute pancreatitis).
• Inflammation of the liver (hepatitis, cholestatic hepatitis).
• Temporary abnormalities in liver function tests.
• Gallstones (cholelithiasis).
• Kidney inflammation (impaired kidney function, acute and chronic interstitial nephritis), kidney and urinary tract disorders (nephrotic syndrome), and reduced kidney function (renal failure).
• Allergic and fibrotic pulmonary reactions (including breathing difficulties, cough, bronchospasm, alveolitis).
• Inflammation of the lower respiratory tract (eosinophilic pneumonia), lung infiltration, inflammation of the interstitial lung tissue (interstitial pneumonia), and pneumonia.
• High fever (hyperpyrexia).
• Allergic reactions such as allergic rash (skin eruption with red spots and/or pustules, blisters, bullae), drug fever, skin manifestations similar to those of systemic lupus erythematosus (lupus-like syndrome), inflammation of the colon (pancolitis).
• Decreased hair and body hair in localized or widespread areas (alopecia).
• Decreased number of spermatozoa in semen (oligospermia).
• Nerve damage causing numbness and tingling sensations (peripheral neuropathy).
• Muscle pain (myalgia) and joint pain (arthralgia).

Not known (frequency cannot be estimated from the available data):

• Swelling of the skin, mucosa, and submucosal tissues (angioedema).
• Kidney stones and associated kidney pain (see also section 2).

Reporting of adverse effects
If you experience any adverse effect, including those not listed in this leaflet, consult your doctor or pharmacist. You may also report adverse effects directly via the national reporting system at: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. How to store ASACOL

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack after "Exp.". The expiry date refers to the last day of that month.
Do not use this medicine if you notice any visible signs of deterioration.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What ASACOL 2 g granules for rectal suspension contains

• The active substance is mesalazine (5-aminosalicylic acid, 5-ASA). Each sachet contains 2 g of mesalazine.
• Other components: Povidone, Methylcellulose, Colloidal anhydrous silica.

Description of the appearance of ASACOL and package contents
ASACOL is a granular preparation for rectal suspension, available in a pack containing 10 sachets of 2 g mesalazine for the extemporaneous preparation of 10 enemas of 50 mL.
Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
GIULIANI S.p.A., via Palagi n 2, 20129 Milano, Italy.
Manufacturer
COSMO S.p.A., via C. Colombo n. 1, 20045 Lainate, Milano, Italy.

Package leaflet: information for the user

ASACOL 1 g rectal foam, 2 g rectal foam, 4 g rectal foam

mesalazine
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What ASACOL is and what it is used for
2. What you need to know before using ASACOL
3. How to use ASACOL
4. Possible side effects
5. How to store ASACOL
6. Contents of the pack and other information

1. What ASACOL is and what it is used for

ASACOL contains the active substance mesalazine, which belongs to the class of intestinal anti-inflammatory medicines.
This medicine is used in adults and children over 2 years of age for the treatment of ulcerative colitis (a long-lasting inflammatory bowel disease affecting the lower parts of the intestine).
The medicine is indicated both for the treatment of active phases of the disease and for the prevention of relapses. In severe active phases, concomitant use with a corticosteroid medicine is recommended.
Consult your doctor if you do not feel better or if you feel worse after the prescribed treatment period.

2. What you should know before using ASACOL

Do not use ASACOL

• If you are allergic to mesalazine, to other related medicines (such as salicylates), or to any of the other ingredients of this medicine (listed in section 6), particularly to metabisulphites.
• If you have severe kidney problems (severe impairment of kidney function, severe nephropathy), or injury to the inner lining (mucosa) of the stomach or intestine (gastric or duodenal ulcer, active peptic ulcer).
• If you have severe impairment of liver function.
• If you have a tendency to develop bleeding (haemorrhagic diathesis).
• In children under 2 years of age (see section “Children”).
• During the last weeks of pregnancy and while breastfeeding (see section “Pregnancy and breastfeeding”).

Warnings and precautions
Talk to your doctor or pharmacist before using ASACOL.
If you experience severe or recurrent headache, visual disturbances, ringing or buzzing in the ears, contact your doctor immediately.
Before starting treatment with ASACOL, you should undergo appropriate clinical investigations to confirm the diagnosis and determine the need for treatment.
Before starting and during treatment with ASACOL, blood and urine tests may be required at your doctor’s discretion. Your doctor will decide how often these tests should be repeated.
Before starting treatment with ASACOL, inform your doctor if you have ever had allergic reactions to medicines called sulfasalazine.
After stopping treatment or during inadequate maintenance therapy, symptoms of the disease may reappear.
Pay particular attention and inform your doctor if any of the following apply to you:

• If you have reduced kidney or liver function.
• If you have known kidney dysfunction, your doctor will carefully assess the need for treatment with mesalazine. Kidney function should be evaluated by your doctor in all patients before starting therapy and periodically during treatment, especially if you have kidney disease.
• If you have heart conditions affecting the myocardium or pericardium (myocarditis or pericarditis).
• If you have lung problems (especially if you suffer from asthma).
• If you are taking one or more of the following medicines: oral hypoglycaemics (medicines to lower blood sugar levels), diuretics (medicines to increase urine production), coumarins (medicines to reduce blood clotting), and corticosteroids (medicines to treat inflammation).
• If you have ever developed a severe skin rash, skin peeling, blisters, and/or mouth ulcers after taking mesalazine.

Exercise special caution with mesalazine:
Serious skin reactions have been reported in association with mesalazine treatment, including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN).
Stop using mesalazine and contact a doctor immediately if you notice any of the symptoms related to these serious skin reactions described in section 4.
Stop treatment (see also section “Possible side effects”) and inform your doctor:

• If, after treatment with ASACOL, you develop bleeding, bruising, red spots on the skin due to leakage from superficial blood vessels (purpura), decreased haemoglobin levels in the blood (anaemia), fever, or sore throat.
• If acute intolerance syndrome is suspected, which may present with symptoms such as cramps, acute abdominal pain and bloody diarrhoea, sometimes accompanied by fever, headache, and erythema.

Prolonged use of ASACOL may lead to sensitization.
Mesalazine may cause the formation of kidney stones. Symptoms may include pain in the sides of the abdomen and blood in the urine. It is recommended to drink sufficient fluids during treatment with mesalazine.
Mesalazine may cause a red-brown discoloration of urine after contact with sodium hypochlorite contained in bleach present in toilet water. This is due to a harmless chemical reaction between mesalazine and bleach.

Children
ASACOL is contraindicated in children under 2 years of age (see section “Do not use ASACOL”).

Other medicines and ASACOL
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Use this medicine with caution together with:

• Sulphonylureas (used to treat diabetes), as the hypoglycaemic effect (reduction of blood sugar levels) may be enhanced.
• Medicines to reduce blood clotting (anticoagulants belonging to the coumarin family, such as warfarin).
• Methotrexate (a medicine used in patients with psoriasis, Crohn’s disease, rheumatoid arthritis, and in the treatment of certain cancers).
• Probenecid (a medicine used to reduce blood uric acid levels).
• Sulfinpyrazone (a medicine used to prevent complications after a heart attack).
• Spironolactone (a potassium-sparing diuretic).
• Furosemide (a diuretic medicine that increases urine production, used in cases of fluid retention).
• Rifampicin (an antibiotic).
• Non-steroidal anti-inflammatory drugs (NSAIDs).
• Azathioprine (an anti-inflammatory and immunosuppressive medicine).
• 6-mercaptopurine and thioguanine (medicines used to treat blood cancers).
  The use of ASACOL together with corticosteroids may enhance the adverse effects of corticosteroids on the stomach.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before using this medicine. If pregnancy is confirmed or suspected, take the medicine only if clearly needed and under strict medical supervision. Do not use ASACOL during the last weeks of pregnancy and while breastfeeding (see section “Do not use ASACOL”). ASACOL should be used during breastfeeding only if clearly needed and under strict medical supervision. If the newborn develops diarrhoea, breastfeeding should be discontinued.

Driving and using machines
ASACOL does not affect or has a negligible effect on the ability to drive vehicles or operate machinery.

ASACOL 1g rectal foam contains propylene glycol
ASACOL 1g rectal foam contains methyl para-hydroxybenzoate and propyl para-hydroxybenzoate
It may cause allergic reactions (including delayed reactions) and, rarely, bronchospasm.
ASACOL 2g and ASACOL 4g rectal foam contain potassium metabisulphite
Rarely may cause severe hypersensitivity reactions and bronchospasm.
ASACOL 2g rectal foam contains sodium benzoate
This medicine contains 43.70 mg of sodium benzoate per dose, equivalent to one single-dose container.
Sodium benzoate may cause local irritation.
ASACOL 4g rectal foam contains sodium benzoate
This medicine contains 87.40 mg of sodium benzoate per dose, equivalent to one single-dose container.
Sodium benzoate may cause local irritation.

3. How to use ASACOL

Use this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
Your doctor will adjust the dosage according to the extent and severity of your condition.

Single-dose containers
The recommended average dose is: one single-dose container of 2 g, 1–2 times daily, in the morning and/or in the evening before going to bed, or one single-dose container of 4 g, once daily, in the evening before going to bed.

Multi-dose containers
The recommended average dose is two consecutive administrations of ASACOL foam of 1 g each, equivalent to 2 g of mesalazine, 1–2 times daily, in the morning and/or in the evening before going to bed, or three to four consecutive administrations, equivalent to 3–4 g of mesalazine, once daily, in the evening before going to bed.

Use in children and adolescents
Children over 2 years of age: the dose will be proportionally reduced at the physician’s discretion.

For application, proceed as follows (see figure).

Single-dose containers

1. Remove the rectal cannula from its protective case.
2. Shake the container vigorously.
3. Insert the provided rectal cannula into the designated opening in the container cap until it is securely in place.
4. Tear off the ring-shaped seal completely around the base of the container cap.
5. Lie on your left side, keeping your left leg straight and bending your right leg.
6. Hold the container upside down, with your index finger above the container cap.
7. Gently insert the cannula into the anal opening, advancing it gently until fully inserted.
8. Without removing the cannula, press the container cap 3–5 times at intervals of several seconds until the entire dose has been administered.

For multi-dose containers: without removing the cannula, press the container cap fully down and then release it completely to administer the first dose (equivalent to 1 g of mesalazine).

For multi-dose containers:
9) After several seconds, repeat the procedure to administer the second dose, and so on, according to the recommended dosing schedule, bearing in mind that each administration corresponds to 1 g of mesalazine.

After administration, roll over several times onto both sides to facilitate better distribution of the medicine and remain lying down for at least 30 minutes. Optimal effectiveness is achieved by retaining the medicine as long as possible, preferably leaving it in place overnight. Therefore, it is advisable that at least one daily administration be performed before going to bed.

The duration of treatment for active phases is generally 4–6 weeks and may vary, at the physician’s discretion, depending on the patient’s condition and disease progression.

For long-term treatment to prevent relapses, the daily dosage and duration of treatment must be determined by the physician according to the patient’s condition and disease progression.

If you use more ASACOL than you should
There are no known cases of overdose following rectal administration.

If you forget to use ASACOL
Do not use a double dose to make up for the missed dose; instead, resume the normal dosing schedule as indicated.

If you stop using ASACOL
After stopping treatment, symptoms may recur (see section “Warnings and precautions”).

If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Serious side effects:
Stop treatment with mesalazine and contact your doctor immediately if you notice any of the following symptoms:
reddish, flat spots, target-shaped or circular rashes on the trunk, often with central blisters, skin peeling, mouth ulcers, sores in the throat, nose, genitals or eyes, widespread rash, fever and swollen lymph nodes. These severe skin rashes may be preceded by fever and flu-like symptoms.

Inform your doctor immediately if you experience severe or recurrent headache, vision disturbances, ringing or buzzing in the ears. These could be symptoms of increased pressure inside the skull (idiopathic intracranial hypertension).

If you notice any of the following side effects, stop treatment and contact your doctor immediately:

• Allergic reactions (skin rash, itching).
• Episodes of acute intestinal intolerance with abdominal pain.
• Presence of blood in liquid stools (bloody diarrhoea).
• Cramps.
• Headache.
• Fever.
• Skin rash.

During treatment with ASACOL, the following side effects may occur:
Common (may affect up to 1 in 10 people):

• Headache.
• Skin rashes.
• Nausea.
• Diarrhoea.
• Abdominal distension.
• High blood pressure (hypertension).
• Generalised weakness (asthenia).
• Fever (pyrexia).

Uncommon (may affect up to 1 in 100 people):

• Itching.
• Upper abdominal pain.
• Presence of blood in liquid stools (bloody diarrhoea).
• Cramps and abdominal pain.
• Drowsiness.
• Tremor.
• Increased heart rate (tachycardia).
• Low blood pressure (hypotension).
• Fatigue.
• Facial swelling.

Rare (may affect up to 1 in 1,000 people):

• Increased sensitivity of the skin to sunlight and ultraviolet light (photosensitivity).
• Dizziness.
• Vomiting.
• Gas formation in the intestine (flatulence).

Very rare (may affect up to 1 in 10,000 people):

• Inflammatory diseases affecting the heart and the membrane surrounding it (pericarditis, myocarditis).
• Decrease in the number of white blood cells in the blood (leucopenia, neutropenia), decrease in the number of platelets in the blood (thrombocytopenia), a form of anaemia characterised by insufficient production in the bone marrow of all types of blood cells (aplastic anaemia), severe decrease in the number of blood cells called granulocytes (agranulocytosis), reduction in the number of all blood cells (pancytopenia).
• Inflammation of the pancreas (pancreatitis, including acute pancreatitis).
• Inflammation of the liver (hepatitis, cholestatic hepatitis).
• Temporary abnormalities in liver function tests.
• Gallstones (cholelithiasis).
• Kidney inflammation (impaired kidney function, acute and chronic interstitial nephritis), kidney and urinary tract disorders (nephrotic syndrome), and reduced kidney function (renal failure).
• Allergic and fibrotic lung reactions (including dyspnoea, cough, bronchospasm, alveolitis).
• Inflammation of the lower respiratory tract (eosinophilic pneumonia), lung infiltration, inflammation of the interstitial lung tissue (interstitial pneumonia) and pneumonia.
• High fever (hyperpyrexia).
• Allergic reactions such as allergic rash (skin eruption with red spots and/or pustules, blisters, bullae), drug fever, skin manifestations similar to systemic lupus erythematosus (lupus-like syndrome), inflammation of the colon (pancolitis).
• Decreased number of hairs and body hair in a localized or widespread area (alopecia).
• Decreased number of spermatozoa in semen (oligospermia).
• Nerve damage or disorder causing numbness and tingling sensations (peripheral neuropathy).
• Muscle pain (myalgia) and joint pain (arthralgia).

Not known (frequency cannot be estimated from the available data):

• Swelling of the skin, mucous membranes and submucosal tissues (angioedema).
• Kidney stones and associated kidney pain (see also section 2).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store ASACOL

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after "Exp.". The expiry date refers to the last day of that month.
Do not use this medicine if you notice visible signs of deterioration (e.g. encrustations or leakage of contents).
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What ASACOL 1 g rectal foam contains

• The active substance is: mesalazine (5-aminosalicylic acid or 5-ASA). Each multidose container delivers 14 single doses, each corresponding to 1 g of mesalazine.
• The other components are: Propylene glycol, PEGylated caprylic/capric glycerides, Polysorbate 20, Emulsifying wax, Citric acid monohydrate, Sodium hydroxide, Palmitoyl ascorbate, Ascorbic acid, Methyl p-hydroxybenzoate, Propyl p-hydroxybenzoate, Purified water, Isobutane,
  Propane, n-Butane.

What ASACOL 2 g rectal foam contains

• The active substance is mesalazine (5-aminosalicylic acid, 5-ASA). Each single-dose container contains 2 g of mesalazine.
• The other components are: Xanthan gum, Polysorbate 20, Macrogol monostearate, Edetate disodium, Potassium metabisulfite, Sodium benzoate, Purified water, Propane, Isobutane, n-Butane.

What ASACOL 4 g rectal foam contains

• The active substance is mesalazine (5-aminosalicylic acid, 5-ASA). Each single-dose container contains 4 g of mesalazine.
• The other components are: Xanthan gum, Polysorbate 20, Macrogol monostearate, Edetate disodium, Potassium metabisulfite, Sodium benzoate, Purified water, Propane, Isobutane, n-Butane.

Description of the appearance of ASACOL and package contents
ASACOL is a rectal foam available in the following pack sizes:

• 1 g rectal foam – packs containing 1 multidose container delivering 14 single doses of 1 g mesalazine, with 7 accompanying rectal applicators; or 2 multidose containers each delivering 14 single doses of 1 g mesalazine, with 14 accompanying rectal applicators.
• 2 g rectal foam – pack of 7 single-dose aluminum containers.
• 4 g rectal foam – pack of 7 single-dose aluminum containers.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
GIULIANI S.p.A., via Palagi, n. 2- 20129, Milan, Italy.
Manufacturer
Farmol Health Care S.r.l., via del Maglio 6, 23868 Valmadrera (Lecco) - Italy