ARGONAL 400 mg Enteric-Coated Tablet

Зміст інструкції

1. ARGONAL “ 400 mg gastro-resistant tablets”
   1. What ARGONAL is and what it is used for
   2. What you need to know before using ARGONAL
   3. How to use ARGONAL
   4. Possible side effects
   5. How to store ARGONAL
   6. Package Contents and Other Information
2. ARGONAL 2 g/50 ml rectal suspension, 4 g/100 ml rectal suspension
   1. What is ARGONAL and what is it used for
   2. What you need to know before using ARGONAL
   3. How to use ARGONAL
   4. Possible side effects
   5. How to store ARGONAL
   6. Contents of the pack and other information
3. ARGONAL “ 500 mg suppositories”
   1. What ARGONAL is and what it is used for
   2. What you need to know before using ARGONAL
   3. How to use ARGONAL
   4. Possible side effects
   5. How to store ARGONAL
   6. Contents of the pack and other information

ARGONAL “ 400 mg gastro-resistant tablets”

ARGONAL “800 mg gastro-resistant tablets”
Mesalazine
Generic medicine
Read this leaflet carefully before using this medicine as 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, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What ARGONAL is and what it is used for

ARGONAL contains the active ingredient 5-aminosalicylic acid (mesalazine), a substance with a local anti-inflammatory effect on the areas of the intestinal mucosa affected by lesions.
This medicine is used in adults and children over 6 years of age for the treatment of ulcerative colitis
and Crohn's disease (long-lasting inflammatory bowel diseases) and unclassifiable chronic inflammatory
bowel disease (IBD).
The medicine is indicated both in the treatment of active phases of the disease and in the prevention of relapses.
In the active phase of severe degree, association with corticosteroid treatment is advisable.
Oral pharmaceutical forms, such as tablets, allow for adequate treatment of inflammatory bowel
diseases in various locations.
Contact 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 ARGONAL

INFORM YOUR DOCTOR BEFORE USING mesalazine:

• if you have ever developed a severe skin rash or skin exfoliation, blisters and/or mouth ulcers after using mesalazine

Do not use ARGONAL:

• If you are allergic to the active ingredient mesalazine or to any of the other ingredients of this medicine (listed in section 6);
• If you are allergic to other chemically related drugs, in particular salicylates;
• If you suffer from kidney disease (severe nephropathies);
• If you have a severe impairment of liver or kidney function
• If you suffer from active gastric ulcers or duodenal ulcers;
• If you suffer from a particular predisposition to bleeding (haemorrhagic diathesis);
• If you are pregnant, especially during the last weeks of pregnancy and during breastfeeding (see section “Pregnancy and Breastfeeding”).

Do not give ARGONAL tablets to children under the age of 2 years. In children under the age of 6 years, the doctor will assess the need for treatment with tablets (see section “Children”).

Warnings and precautions:
Consult your doctor or pharmacist before using ARGONAL.
Before starting and during treatment with ARGONAL, your doctor may want to subject you to blood tests, tests to evaluate liver enzyme levels (ALT – AST) and serum creatinine, and urine tests, which you will have to perform 14 days after starting treatment and subsequently at intervals of 4 weeks for 2 or 3 times.
Mesalazine may cause a red-brown discoloration of the urine after contact with sodium hypochlorite contained in bleach present in the toilet water. This is caused by a harmless chemical reaction that occurs between mesalazine and bleach.
Pay particular attention and inform your doctor if any of the following applies to you:

• if you have particularly slow digestion or suffer from a disease that causes narrowing of the last part of the stomach (pyloric stenosis); the active ingredient contained in the tablets may be released into the stomach, causing gastric irritation and a loss of product efficacy.
• If you suffer from or have suffered from kidney or liver diseases. If you have known renal dysfunction, treatment with ARGONAL should be avoided. The doctor will assess renal function for all patients before starting therapy, and periodically during treatment, especially in the presence of kidney diseases.
• If you suffer from lung diseases, in particular asthma; in this case you must be carefully monitored during treatment with ARGONAL.
• If you are being treated with oral hypoglycemic drugs (used to lower blood sugar levels), diuretics, coumarins (drugs used to make the blood more fluid and prevent the formation of clots), corticosteroids. If, following treatment with ARGONAL, you experience bleeding, bruising, red spots on the skin due to the rupture of capillaries under the surface of the skin (purpura), decreased hemoglobin levels in the blood (anemia), fever or sore throat, as rare cases of serious blood diseases (blood dyscrasias) have been reported following treatment with mesalazine. If such a disease is suspected, treatment with ARGONAL should be discontinued.
• If you have heart disease affecting the myocardium and pericardium (myocarditis or pericarditis).
• 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 your doctor immediately if you notice any of the symptoms related to these serious skin reactions described in paragraph 4. In case of severe or recurrent headache, visual disturbances, ringing or whistling in the ears, contact your doctor immediately.

Immediately stop treatment with ARGONAL in the event of suspected acute intolerance syndrome
which can manifest with symptoms such as, abdominal cramps, acute abdominal pain and bloody diarrhea,
fever, headache and erythema.
The use of mesalazine can 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 a sufficient amount of fluids during treat-
ment with mesalazine.
Prolonged use of the product can lead to sensitization phenomena.
After discontinuation of treatment or in case of inadequate treatment, relapses
of the disease may occur; in this case inform your doctor.
For the treatment of active phases of intestinal disease, your doctor may advise you on additional
therapy.

Children
ARGONAL is contraindicated in children under the age of 2 years (see section “Do not use ARGONAL”).
ARGONAL gastro-resistant tablets are not recommended for use in children under the age of 6 years,
unless after careful evaluation by the doctor.

Other medicines and ARGONAL
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other
medicines, including those available without a prescription.
Mesalazine can affect the action of other medicines and these, in turn, can affect the action
of mesalazine.
Therefore, it is important to inform your doctor if you are taking:

• lactulose (used as a laxative in the treatment of constipation) or other preparations that, by lowering the pH of the colon, can hinder the release of mesalazine
• sulfonylureas (medicines used to lower blood sugar levels) their effect may be increased if taken concurrently with mesalazine
• coumarins (medicines used to make the blood more fluid and prevent the formation of clots), such as warfarin, their effect may decrease if taken concurrently with mesalazine
• methotrexate (medicine used in people affected by psoriasis, Crohn's disease, rheumatoid arthritis and in the treatment of some forms of cancer)
• probenecid (medicine used to decrease the concentration of uric acid in the blood)
• sulfinpyrazone (used in prevention following a heart attack)
• spironolactone (potassium-sparing diuretic)
• furosemide (diuretic medicine, which increases urine production, used in case of fluid retention)
• rifampicin (antibiotic)
• corticosteroids, concomitant use may increase gastrointestinal side effects
• non-steroidal anti-inflammatory drugs (NSAIDs)
• azathioprine or 6-mercaptopurine (drug with anti-inflammatory and immunosuppressive action), as it may increase the risk of blood dyscrasias
• azathioprine or 6-mercaptopurine or thioguanine, as an increase in the myelosuppressive effects of these drugs may occur.

ARGONAL with food and drink
Take ARGONAL tablets away from meals (see section 3).

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant or are planning to become pregnant, or if you are breastfeeding
ask your doctor or pharmacist for advice before using this medicine. If pregnancy is confirmed or
suspected, take the medicine only if absolutely necessary and under strict medical supervision.
Do not take ARGONAL during the last weeks of pregnancy

Breastfeeding
Mesalazine and its metabolite are excreted in breast milk.
ARGONAL should be used during breastfeeding only if absolutely necessary or under strict medical
supervision. If the infant develops diarrhea, breastfeeding should be discontinued.

Driving and operating machinery
ARGONAL does not impair the ability to drive vehicles or operate machinery.

ARGONAL gastro-resistant tablets contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially ‘sodium-free’.

3. How to use ARGONAL

Use this medicine following exactly the instructions of your doctor. If you have any doubts, consult your doctor
or pharmacist.
The doctor will adjust the dosage based on the extent and severity of the disease.
In case of first-time treatment, it is advisable to gradually increase the dosage for a few days before
reaching the maximum dosage.

Adults:1-2 tablets of ARGONAL 400 mg or 1 tablet of ARGONAL 800 mg, 3 times a day.
The dosage may be increased up to 10 tablets of ARGONAL 400 mg or 5 tablets of ARGONAL
800 per day, in severe forms, or according to the doctor's judgment.

Use in children and adolescents
ARGONAL is contraindicated in children under the age of 2 years. ARGONAL is not recommended for use
in children under the age of 6 years. The doctor, after careful evaluation, may decide to administer
reduced doses.
Children over 6 years:

• Active disease phase: to be defined individually, initially with 30-50 mg/Kg per day in divided doses. The maximum dose is 75 mg/Kg per day in divided doses. The total dose should not exceed 4 g per day (maximum adult dose).
• Maintenance treatment: to be defined individually, starting with 15-30 mg/kg per day in divided doses. The total dose should not exceed 2 g per day (recommended adult dose).

It is generally recommended to administer to children up to 40 kg of body weight half the adult dose,
and to children weighing more than 40 kg the normal adult dose.
Take the tablets whole, without breaking or chewing them, preferably with a glass of water and lon-
g after meals.
In case of first-time treatment, it is advisable to reach the full dosage after a few days of treatment,
gradually increasing the dosage.
For active phases, the duration of treatment is on average 4-6 weeks and may vary, at the doctor's discretion,
depending on the clinical evolution. In long-term treatments to prevent relapses, the daily dosage and
duration of treatment must be established by the doctor according to the patient's condition and
the evolution of the disease.

If you use more ARGONAL than you should
If you take an excessive dose of ARGONAL, inform your doctor immediately or go to the nearest
hospital.
Data relating to cases of overdose are rare and do not indicate renal or hepatic toxicity.
There is no known specific antidote to be used in case of overdose.

If you forget to take ARGONAL
Do not take a double dose to make up for a missed dose. Simply take the next dose.

If you stop taking ARGONAL
Do not stop taking the medicine unless after consulting your doctor.
After stopping treatment, a recurrence of symptoms may occur (see section “Warnings
and precautions”).
If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

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

Stop taking mesalazine and contact your doctor immediately if you experience any of the following symptoms:

• Allergic reactions (skin rashes, itching)
• Episodes of acute intestinal intolerance with abdominal pain
• Presence of blood in liquid stools (diarrhea with blood)
• Abdominal cramps
• Headache
• Fever
• Skin rash
• Reddish, non-raised, target-shaped or circular patches on the trunk, 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 rashes may be preceded by fever and flu-like symptoms. Immediately inform your doctor if you experience severe or recurrent headache, vision disturbances, ringing or whistling in the ears. These could be symptoms of increased pressure inside the skull (idiopathic intracranial hypertension) [Frequency not known (the frequency cannot be estimated based on available data)].

While using ARGONAL, the following side effects may occur:
Common(may affect up to 1 in 10 people):

• Headache
• Increased blood pressure (hypertension)
• Skin rashes
• Nausea
• Diarrhea
• Tense abdomen
• Weakness (asthenia)
• Fever (pyrexia)

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

• Itching
• Pain in the upper abdomen
• Presence of blood in liquid stools (bloody diarrhea)
• Cramps and abdominal pain
• Drowsiness
• Tremor
• Increased heart rate (tachycardia)
• Decreased blood pressure (hypotension)
• Fatigue
• Swelling (edema) of the face

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

• Dizziness
• Presence of gas in the intestine (flatulence)
• Vomiting
• Increased sensitivity of the skin to sunlight and ultraviolet light (photosensitivity)

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), decreased number of granulocytes (a particular type of white blood cells) (agranulocytosis), reduction of blood cells (pancytopenia)
• Hypersensitivity reactions such as blisters and bubbles (allergic exanthema), drug fever, reactions similar to systemic lupus erythematosus, an autoimmune disease that affects the body's defense system (lupoid syndrome), inflammation of the colon (pancolitis)
• Damage to the peripheral nervous system manifesting as numbness or weakness of arms and legs (peripheral neuropathy)
• Inflammation of the liver (hepatitis)
• Inflammation of the liver caused by blockage of bile excretion (cholestatic hepatitis)
• Changes in some liver parameters (increased transaminase and cholestasis parameters)
• Inflammation of the pancreas (pancreatitis and acute pancreatitis)
• Formation of stones within the biliary system (cholelithiasis)
• Inflammation of the kidneys (acute and chronic interstitial nephritis), pathology at the renal and urinary level (nephrotic syndrome) and reduced kidney function (renal insufficiency)
• Inflammation of the lower respiratory tract (eosinophilic pneumonia), inflammation at the interstitial lung tissue level (interstitial pneumonia)
• Allergic and fibrotic reactions of the lungs such as difficulty breathing (dyspnea), cough, narrowing of the bronchi (bronchospasm), inflammation of the lung alveoli (alveolitis), inflammation of the lungs (in- filtration, pneumonia, eosinophilic and interstitial pneumonia)
• Hair loss (alopecia)
• Muscle pain (myalgia) and joint pain (arthralgia)
• Reduced number of sperm in the ejaculate (oligospermia), reversible
• High fever (hyperpyrexia).

Not known(the frequency cannot be estimated based on available data)

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

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. You can also report side effects directly through 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 ARGONAL

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date indicated on the packaging and on the blister after 'Scad'.
The expiry date refers to the last day of that month.
Do not store at a temperature above 25°C.
Do not use the product if the packaging shows visible signs of deterioration.
Do not dispose of any medicine in the water 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 ARGONAL contains
ARGONAL “400 mg gastro-resistant tablets”
One tablet contains
Active ingredient: Mesalazine 400 mg

Excipients:Maltodextrin, povidone, sodium lauryl sulfate, sodium starch glycolate, talc, magnesium stearate,
eudragit FS30 D, sodium hydroxide, triethyl citrate, yellow iron oxide, red iron oxide,
titanium dioxide, polyethylene glycol 6000.
ARGONAL “800 mg gastro-resistant tablets”
One tablet contains
Active ingredient: Mesalazine 800 mg

Excipients:Maltodextrin, povidone, sodium lauryl sulfate, sodium starch glycolate, talc, magnesium
stearate, eudragit S100, sodium hydroxide, triethyl citrate, yellow iron oxide, red iron oxide,
titanium dioxide, polyethylene glycol 6000.

Description of the appearance of ARGONAL and package contents
ARGONAL “400 mg gastro-resistant tablets”: 50 gastro-resistant tablets in blisters
ARGONAL “800 mg gastro-resistant tablets”: 24 gastro-resistant tablets in blisters
ARGONAL “800 mg gastro-resistant tablets”: 60 gastro-resistant tablets in blisters

Marketing Authorisation Holder and Manufacturer
HOLDER
Dicofarm S.p.A. - Via del Casale della Marcigliana, 29 - 00138 Rome

EXCLUSIVE DISTRIBUTOR FOR SALES IN ITALY
Ag pharma S.r.l. - Via del Casale della Marcigliana, 29 - 00138 Rome

MANUFACTURER
Special Product’s Line S.p.A. – Via Fratta Rotonda Vado Largo, 1, 03012 Anagni (FR)

ARGONAL 2 g/50 ml rectal suspension, 4 g/100 ml rectal suspension

Mesalazine
Generic medicine

Read this leaflet carefully before you use 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, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What is ARGONAL and what is it used for

ARGONAL contains the active ingredient mesalazine, a substance with a local anti-inflammatory effect on the
sections of the intestinal mucosa affected by lesions.
This medicine is used in adults and children over 2 years of age for the treatment of ulcerative colitis
(long-lasting inflammatory bowel diseases affecting the final part of the intestine) located at the
rectal level.
The medicine is indicated both in the treatment of the active phases of the disease and in the prevention of
relapses. In the active phase of severe degree, association with corticosteroid treatment is advisable.
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 ARGONAL

INFORM YOUR DOCTOR BEFORE USING mesalazine:

• if you have ever developed a severe skin rash or skin exfoliation, blisters and/or mouth ulcers after using mesalazine

Do not use ARGONAL:

• If you are allergic to the active ingredient mesalazine or to any of the other ingredients of this medicine (listed in section 6);
• If you are allergic to other chemically related drugs, in particular salicylates;
• If you suffer from kidney disease (severe nephropathies);
• If you have a severe impairment of liver or kidney function;
• If you suffer from active gastric ulcers or duodenal ulcers;
• If you suffer from a particular predisposition to bleeding (haemorrhagic diathesis);
• In children under the age of 2 years (see section “Children”);
• If you are pregnant, especially during the last weeks of pregnancy and during breastfeeding (see section “Pregnancy and breastfeeding”).

Warnings and precautions:
Consult your doctor or pharmacist before using ARGONAL.
Before starting and during treatment with ARGONAL, your doctor may want to subject you to blood tests, tests to assess liver enzyme levels (ALT or AST) and serum creatinine, and urine tests, which you will have to perform 14 days after starting treatment and subsequently at intervals of 4 weeks for 2 or 3 times.
Mesalazine may cause a red-brown discoloration of the urine after contact with sodium hypochlorite contained in bleach present in the toilet water. This is caused by a harmless chemical reaction that occurs between mesalazine and bleach.
Pay particular attention and inform your doctor if any of the following applies to you:

• If you suffer from or have suffered from kidney or liver diseases: if you have known renal dysfunction, treatment with ARGONAL should be avoided. The doctor will evaluate renal function for all patients before starting therapy, and periodically during treatment, especially in the presence of kidney diseases.
• If you suffer from lung diseases, particularly asthma, you must be carefully monitored during treatment with ARGONAL.
• If you are being treated with oral hypoglycemic drugs (used to lower blood sugar levels), diuretics, coumarins (drugs used to make the blood more fluid and prevent the formation of clots), corticosteroids.
• If you have heart disease affecting the myocardium and pericardium (myocarditis or pericarditis).
• If, following treatment with ARGONAL, you experience bleeding, bruising, red spots on the skin due to the rupture of capillaries under the surface of the skin (purpura), decreased hemoglobin levels in the blood (anemia), fever or sore throat, because rare cases of serious blood diseases (blood dyscrasias) have been reported following treatment with mesalazine. If such a disease is suspected, treatment with ARGONAL should be discontinued.
• 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 using mesalazine and consult a doctor immediately if you notice any of the symptoms related to these severe skin reactions described in section
• 4. In case of severe or recurrent headache, visual disturbances, ringing or whistling in the ears, contact your doctor immediately.

Immediately stop treatment with ARGONAL in case of suspected acute intolerance syndrome which can manifest with symptoms such as abdominal cramps, acute abdominal pain and bloody diarrhea, fever, headache and erythema.
The use of mesalazine can 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 a sufficient amount of fluids during treatment with mesalazine.
Prolonged use of the product can lead to sensitization phenomena.
After discontinuation of treatment or in case of inadequate treatment, relapses of the disease may occur; in this case, inform your doctor.

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

Other medicines and ARGONAL
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including those available without a prescription.
Mesalazine can affect the action of other medicines and these, in turn, can affect the action of mesalazine. Therefore, it is important to inform your doctor if you are taking:

• sulfonamides (medicines used to lower blood sugar levels) their effect may be increased if taken in conjunction with mesalazine
• coumarins (medicines used to make the blood more fluid and prevent the formation of clots), such as warfarin, their effect may decrease if taken in conjunction with mesalazine
• methotrexate (a medicine used in people with psoriasis, Crohn's disease, rheumatoid arthritis and in the treatment of some forms of cancer)
• probenecid (used to decrease the concentration of uric acid in the blood)
• sulfinpyrazone (used in prevention following a heart attack)
• spironolactone (potassium-sparing diuretic)
• furosemide (diuretic medicine, which increases urine production, used in case of fluid retention)
• rifampicin (antibiotic)
• corticosteroids, concomitant use may increase the undesirable effects at the gastric level
• non-steroidal anti-inflammatory drugs (NSAIDs)
• azathioprine or 6-mercaptopurine (drug with anti-inflammatory and immunosuppressive action), because it may increase the risk of blood dyscrasias
• azathioprine or 6-mercaptopurine or thioguanine, because an increase in the immunosuppressive effects of these drugs may occur.

Pregnancy and breastfeeding
If you are pregnant, suspect or are planning a pregnancy, or if you are breastfeeding, ask your doctor or pharmacist for advice before using this medicine. If pregnancy is confirmed or suspected, take the medicine only if absolutely necessary and under strict medical supervision.
Do not take ARGONAL during the last weeks of pregnancy

Breastfeeding
Mesalazine and its metabolite are excreted in breast milk.
ARGONAL should be used during breastfeeding only if absolutely necessary or under strict medical supervision. If the infant develops diarrhea, breastfeeding should be discontinued.

Driving and operating machinery
ARGONAL does not impair the ability to drive vehicles or operate machinery.

ARGONAL rectal suspension contains benzoic acid
This medicine contains 50 mg of sodium benzoate per 50 ml dose and 100 mg of sodium benzoate per 100 ml dose.

3. How to use ARGONAL

Use this medicine following always exactly the doctor’s instructions. If you have doubts consult your doctor
or pharmacist
The doctor will adjust the dosage based on the extent and severity of your illness.
Adults: on average 1 enema of 2 g/50 ml, 1-2 times a day, morning and/or evening before bedtime, or 1 enema
of 4 g/100 ml 1 time a day (preferably in the evening before bedtime).

Use in children and adolescents
Children over 2 years:proportionally reduced doses at the doctor’s discretion; for example 1/2 enema of 2
g/50 ml 1-2 times a day.
Shake well before use to obtain a homogeneous suspension, then remove the cap from the rectal cannula.
For application, lie on your left side, keeping your left leg straight and bending your right leg, gently insert the
cannula into the anal opening and press the bottle with gradual and constant pressure until complete expulsion of the
contents is obtained. After introducing the preparation, turn over several times on both sides to facilitate better
distribution of the drug, remain lying down for at least 30 minutes. Better efficacy of the product is obtained by
retaining the drug for as long as possible or, better still, leaving it in place all night. For this reason, it is preferable
that at least one of the daily applications is carried out before bedtime.
The duration of treatment expected for the active phases is on average 4-6 weeks and may vary at the doctor’s
discretion, according to the patient’s conditions and the evolution of the disease. In long-term treatments,
to prevent relapses, the daily dosage and the duration of treatment must be established by the doctor
according to the patient’s conditions and the evolution of the disease.

If you use more ARGONAL than you should
If you use more ARGONAL than indicated for a single dose, immediately inform your doctor or go to the
nearest hospital.
Cases of overdose following rectal administrations are not foreseeable.

If you forget to use ARGONAL
Do not use more ARGONAL for a single application to compensate for the forgotten dose.

If you stop using ARGONAL
Do not stop taking the medicine unless after consulting your doctor.
After stopping treatment, a recurrence of symptoms may occur (see paragraph
“Warnings and precautions”).
If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

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

Stop taking mesalazine and contact your doctor immediately if you experience any of the following symptoms:

• Allergic reactions (skin rashes, itching).
• Episodes of acute intestinal intolerance with abdominal pain.
• Presence of blood in watery stools (diarrhea with blood).
• Abdominal cramps.
• Headache.
• Fever.
• Skin rash.
• Reddish, non-raised patches, target-shaped or circular on the trunk, 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 rashes may be preceded by fever and flu-like symptoms. Immediately inform your doctor if you experience severe or recurrent headache, vision disturbances, ringing or whistling in the ears. These could be symptoms of increased pressure inside the skull (idiopathic intracranial hypertension) [Frequency not known (the frequency cannot be estimated based on available data)].

While using ARGONAL, the following side effects may occur:
Common(may affect up to 1 in 10 people):

• Headache
• Increased blood pressure (hypertension).
• Skin rashes
• Nausea
• Diarrhea
• Tense abdomen
• Weakness (asthenia)
• Fever (pyrexia)

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

• Itching
• Pain in the upper abdomen
• Presence of blood in watery stools (bloody diarrhea)
• Cramps and abdominal pain
• Drowsiness
• Tremor
• Increased heart rate (tachycardia)
• Decreased blood pressure (hypotension)
• Fatigue
• Swelling (edema) of the face

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

• Dizziness
• Presence of gas in the intestine (flatulence)
• Vomiting
• Increased skin sensitivity to sunlight and ultraviolet light (photosensitivity)

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), decreased number of granulocytes (a particular type of white blood cells) (agranulocytosis), reduction of blood cells (pancytopenia).
• Hypersensitivity reactions such as blisters and bubbles (allergic exanthema), drug fever, reactions similar to systemic lupus erythematosus, an autoimmune disease that affects the body's defense system (lupoid syndrome), inflammation of the colon (pancolitis).
• Damage to the peripheral nervous system manifested by numbness or weakness of arms and legs (peripheral neuropathy)
• Inflammation of the liver (hepatitis).
• Inflammation of the liver caused by blockage of bile excretion (cholestatic hepatitis).
• Changes in some liver parameters (increased transaminase levels and cholestasis).
• Inflammation of the pancreas (pancreatitis and acute pancreatitis).
• Formation of stones within the biliary system (cholelithiasis).
• Inflammation of the kidneys (acute and chronic interstitial nephritis), pathology at the renal and urinary level (nephrotic syndrome) and reduced kidney function (renal insufficiency).
• Inflammation of the lower respiratory tract (eosinophilic pneumonia), inflammation at the interstitial lung tissue level (interstitial pneumonia).
• Allergic and fibrotic reactions of the lungs such as difficulty breathing (dyspnea), cough, narrowing of the bronchi (bronchospasm), inflammation of the alveoli (alveolitis), inflammation of the lungs (in- filtration of the lungs, pneumonia, eosinophilic and interstitial pneumonia).
• Hair loss (alopecia).
• Muscle pain (myalgia) and joint pain (arthralgia).
• Reduced number of sperm in the ejaculate (oligospermia), reversible.
• High fever (hyperpyrexia).

Not known(the frequency cannot be estimated based on available data)

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

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. You can also report side effects directly through the national reporting system at the address: 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 ARGONAL

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date indicated on the packaging and on the blister after 'Scad'.
The expiry date refers to the product in intact packaging, correctly
stored.
Do not store at a temperature above 25°C.
Do not use the product if the packaging shows visible signs of deterioration.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to dispose of the
medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What ARGONAL contains
ARGONAL 2 g/50 ml rectal suspension
One single-dose container of 50 ml contains:
Active ingredient: Mesalazine g 2
ARGONAL 4 g/100 ml rectal suspension
One single-dose container of 50 ml contains:
Active ingredient: Mesalazine g 4
The other components are: tragacanth gum, xanthan gum, sodium edetate, sodium metabisulfite, sodium benzoate, sodium acetate, purified water.

Description of the appearance of ARGONAL and contents of the pack
ARGONAL 2 g/50 ml rectal suspension:
One pack contains 7 single-dose containers of 50 ml of ready-to-use rectal suspension.
ARGONAL 4 g/100 ml rectal suspension:
One pack contains 7 single-dose containers of 100 ml of ready-to-use rectal suspension.

Marketing Authorisation Holder and Manufacturer
HOLDER
Dicofarm S.p.A. - Via del Casale della Marcigliana, 29 - 00138 Rome

MANUFACTURER
Special Product’s Line S.p.A. – Via Fratta Rotonda Vado Largo, 1, 03012 Anagni (FR)

ARGONAL “ 500 mg suppositories”

Mesalazine
Generic medicine

Read this leaflet carefully before you start to use this medicine as 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, even if they have the same symptoms as you, as it may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What ARGONAL is and what it is used for

ARGONAL contains the active substance mesalazine, a substance with local anti-inflammatory effect
on the sections of the intestinal mucosa affected by lesions.
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 final part of the intestine) located in the
rectal area.
The medicine is indicated both in the treatment of active phases of the disease and in the prevention of recur-
rences.
In the active phase of severe degree, association with cortisone treatment is advisable.
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 ARGONAL

INFORM YOUR DOCTOR BEFORE USING mesalazina:

• if you have ever developed a severe skin rash or skin exfoliation, blisters and/or mouth ulcers after using mesalazina

Do not use ARGONAL:

• If you are allergic to the active ingredient mesalazina or to any of the other ingredients of this medicine (listed in section 6);
• If you are allergic to other chemically related drugs, in particular salicylates;
• If you suffer from kidney disease (severe nephropathies);
• If you have a severe impairment of liver or kidney function;
• If you suffer from active gastric ulcers or duodenal ulcers;
• If you suffer from a particular predisposition to bleeding (haemorrhagic diathesis);
• In children under 2 years of age (see section “Children”).
• If you are pregnant, especially during the last weeks of pregnancy and during breastfeeding (see section “Pregnancy and Breastfeeding”).

Warnings and precautions:
Consult your doctor or pharmacist before using ARGONAL.
Before starting and during treatment with ARGONAL, your doctor may want to subject you to blood tests, tests to assess liver enzyme levels (ALT or AST) and serum creatinine, urine tests, which you will have to perform 14 days after starting treatment and subsequently at intervals of 4 weeks for 2 or 3 times.
Mesalazine may cause a reddish-brown discoloration of the urine after contact with sodium hypochlorite contained in bleach present in the toilet water. This is caused by a harmless chemical reaction that occurs between mesalazine and bleach.
Pay particular attention and inform your doctor if any of the following applies to you:

• If you suffer from or have suffered from kidney or liver diseases. If you have known renal dysfunction, treatment with ARGONAL should be avoided. The doctor will evaluate renal function for all patients before starting therapy, and periodically during treatment, especially in the presence of kidney diseases.
• If you suffer from lung diseases, particularly asthma, you should be carefully monitored during treatment with ARGONAL.
• If you are being treated with oral hypoglycemic drugs (used to lower blood sugar levels), diuretics, coumarins (drugs used to make the blood more fluid and prevent the formation of clots), corticosteroids;
• If you have heart disease affecting the myocardium and pericardium (myocarditis or pericarditis).
• If, following treatment with ARGONAL, you experience bleeding, bruising, red spots on the skin due to the rupture of capillaries under the surface of the skin (purpura), decreased hemoglobin levels in the blood (anemia), fever or sore throat, as rare cases of severe blood diseases (blood dyscrasias) have been reported following treatment with mesalazine. If such a disease is suspected, treatment with ARGONAL should be discontinued.
• 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 using mesalazine and consult your doctor immediately if you notice any of the symptoms related to these severe skin reactions described in section
• 4. If you experience severe or recurrent headaches, visual disturbances, ringing or whistling in the ears, contact your doctor immediately.

Immediately discontinue treatment with ARGONAL in the event of suspected acute intolerance syndrome that can manifest with symptoms such as cramps, acute abdominal pain and bloody diarrhea, fever, headache and erythema.
The use of 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 a sufficient amount of fluids during treatment with mesalazine.
Prolonged use of the product may lead to sensitization phenomena.
After discontinuation of treatment or in case of inadequate treatment, relapses of the disease may occur; in this case, inform your doctor.

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

Other medicines and ARGONAL
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including those available without a prescription.
Mesalazine may affect the action of other medicines and these, in turn, may affect the action of mesalazine. Therefore, it is important to inform your doctor if you are taking:

• sulfonylureas (medicines used to lower blood sugar levels) their effect may be increased if taken in combination with mesalazine
• coumarins (medicines used to make the blood more fluid and prevent the formation of clots), such as warfarin, their effect may decrease if taken in combination with mesalazine
• methotrexate (medicine used in patients with psoriasis, Crohn's disease, rheumatoid arthritis and in the treatment of some forms of cancer)
• probenecid (used to decrease the concentration of uric acid in the blood)
• sulfinpyrazone (used in prevention following a heart attack)
• spironolactone (potassium-sparing diuretic)
• furosemide (diuretic medicine, which increases urine production, used in case of fluid retention)
• rifampicin (antibiotic)
• corticosteroids, concomitant use may increase the undesirable effects at the gastric level
• non-steroidal anti-inflammatory drugs (NSAIDs)
• azathioprine or 6-mercaptopurine (drug with anti-inflammatory and immunosuppressive action), as it may increase the risk of blood dyscrasias.
• azathioprine or 6-mercaptopurine or thioguanine, as an increase in the immunosuppressive effects of these drugs may occur.

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant or are planning to become pregnant, or if you are breastfeeding, ask your doctor or pharmacist for advice before using this medicine.
If pregnancy is confirmed or suspected, take the medicine only if absolutely necessary and under strict medical supervision.
Do not take ARGONAL during the last weeks of pregnancy (see section “Do not use ARGONAL”).

Breastfeeding
Mesalazine and its metabolite are excreted in breast milk.
ARGONAL should be used during breastfeeding only if absolutely necessary or under strict medical supervision. If the infant develops diarrhea, breastfeeding should be discontinued.

Driving and using machines
ARGONAL does not impair the ability to drive vehicles or operate machinery.

3. How to use ARGONAL

Use this medicine following the instructions of your doctor exactly. If you have any doubts, consult your doctor
or pharmacist.
The doctor will adjust the dosage based on the extent and severity of your condition.

Adults:on average 3 suppositories per day, divided into 2-3 administrations during the active phase.

Use in children and adolescents
Children over 2 years: proportionally reduced doses at the doctor's discretion.
To obtain a better therapeutic effect, it is important that the suppository is retained for at least 30 mi-
nutes, or preferably for longer periods (e.g. for the entire night)
The duration of treatment for active phases is on average 4-6 weeks and may vary, at the doctor's discretion,
according to the patient's condition and the evolution of the disease. In long-term treatments to prevent
relapses, the daily dosage and duration of treatment must be established by the doctor according to the
patient's condition or the evolution of the disease.

If you use more ARGONAL than you should
If you use more ARGONAL than indicated for a single dose, inform your doctor immediately or go to
the nearest hospital.
Cases of overdose following rectal administration are not foreseeable.

If you forget to use ARGONAL
Do not use more ARGONAL for a single application to compensate for the forgotten dose.

If you stop using ARGONAL
Do not stop taking the medicine unless after consulting your doctor.
After stopping treatment, a recurrence of symptoms may occur (see paragraph
“Warnings and precautions”).
If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

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

Stop taking mesalazine and contact your doctor immediately if you experience any of the following symptoms:

• Allergic reactions (skin rashes, itching).
• Episodes of acute intestinal intolerance with abdominal pain.
• Presence of blood in watery stools (diarrhea with blood).
• Abdominal cramps.
• Headache.
• Fever.
• Skin rash.
• Reddish, non-raised patches, target-shaped or circular on the trunk, 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 rashes may be preceded by fever and flu-like symptoms. Immediately inform your doctor if you experience severe or recurrent headache, vision disturbances, ringing or whistling in the ears. These could be symptoms of increased pressure inside the skull (idiopathic intracranial hypertension) [Frequency not known (the frequency cannot be estimated based on available data)].

While using ARGONAL, the following side effects may occur:
Common(may affect up to 1 in 10 people):

• Headache
• Increased blood pressure (hypertension).
• Skin rashes
• Nausea
• Diarrhea
• Tense abdomen
• Weakness (asthenia)
• Fever (pyrexia)

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

• Itching
• Pain in the upper abdomen
• Presence of blood in watery stools (bloody diarrhea)
• Cramps and abdominal pain
• Drowsiness
• Tremor
• Increased heart rate (tachycardia)
• Decreased blood pressure (hypotension)
• Fatigue
• Swelling (edema) of the face

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

• Dizziness
• Presence of gas in the intestine (flatulence)
• Vomiting
• Increased skin sensitivity to sunlight and ultraviolet light (photosensitivity)

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), decreased number of granulocytes (a particular type of white blood cells) (agranulocytosis), reduction of blood cells (pancytopenia).
• Hypersensitivity reactions such as blisters and bubbles (allergic exanthema), drug fever, reactions similar to systemic lupus erythematosus, an autoimmune disease that affects the body's defense system (lupoid syndrome), inflammation of the colon (pancolitis).
• Damage to the peripheral nervous system manifesting as numbness or weakness of arms and legs (peripheral neuropathy)
• Inflammation of the liver (hepatitis).
• Inflammation of the liver caused by blockage of bile excretion (cholestatic hepatitis).
• Changes in some liver parameters (increased transaminase levels and cholestasis).
• Inflammation of the pancreas (pancreatitis and acute pancreatitis).
• Formation of stones within the biliary system (cholelithiasis).
• Inflammation of the kidneys (acute and chronic interstitial nephritis), pathology at the renal and urinary level (nephrotic syndrome) and reduced kidney function (renal insufficiency).
• Inflammation of the lower respiratory tract (eosinophilic pneumonia), inflammation at the interstitial lung tissue level (interstitial pneumonia).
• Allergic and fibrotic reactions of the lungs such as difficulty breathing (dyspnea), cough, narrowing of the bronchi (bronchospasm), inflammation of the lung alveoli (alveolitis), inflammation of the lungs (in- filtration of the lungs, pneumonia, eosinophilic and interstitial pneumonia).
• Hair loss (alopecia).
• Muscle pain (myalgia) and joint pain (arthralgia).
• Reduced number of sperm in the ejaculate (oligospermia), reversible.
• High fever (hyperpyrexia).

Not known(the frequency cannot be estimated based on available data)

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

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through 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 ARGONAL

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date indicated on the packaging and on the blister after 'Scad'. The
expiry date refers to the product in intact packaging, correctly stored.
Do not store at a temperature above 25°C.
During the warm season, it may be necessary to immerse the suppository container in cold water to
consolidate suppositories that have become soft.
Do not use the product if the packaging shows visible signs of deterioration.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to dispose of
medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What ARGONAL contains
ARGONAL “500 mg suppositories”
One suppository contains
Active ingredient: Mesalazine 500 mg
Other components: Semisynthetic glycerides

Description of the appearance of ARGONAL and contents of the pack
Box of 20 suppositories

Marketing Authorisation Holder and Manufacturer
HOLDER
Dicofarm S.p.A. - Via del Casale della Marcigliana, 29 - 00138 Rome

MANUFACTURER
Special Product’s Line S.p.A. – Via Fratta Rotonda Vado Largo, 1, 03012 Anagni (FR)
LAMP SAN. PROSPERO S.p.A. - Via della Pace, 25/A - 41030 Modena