Argonal: detailed information

Package leaflet: Information for the user

ARGONAL “400 mg gastro-resistant tablets”, “800 mg gastro-resistant tablets”

Mesalazine
Generic medicine
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 even if their symptoms are the same as yours.
If you experience any side effects, including any not listed in this leaflet, inform your doctor or pharmacist. See Section 4.

Contents of this leaflet:

What ARGONAL is and what it is used for
What you need to know before taking ARGONAL
How to take ARGONAL
Possible side effects
How to store ARGONAL
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 local anti-inflammatory action on the segments of intestinal mucosa affected by lesions.
This medicinal product is used in adults and children over 6 years of age for the treatment of ulcerative colitis and Crohn's disease (chronic inflammatory bowel diseases) as well as for unclassified inflammatory bowel disease (IBDU).
The medicine is indicated both for the treatment of active disease phases and for the prevention of relapses.
In severe active phases, concomitant corticosteroid therapy is recommended.
Oral pharmaceutical forms, such as tablets, allow adequate treatment of inflammatory bowel diseases at various sites.
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 ARGONAL

INFORM YOUR DOCTOR BEFORE USING mesalazine:

if you have ever developed a severe skin rash or skin peeling, blisters and/or mouth ulcers after taking mesalazine

Do not use ARGONAL:

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

Do not give ARGONAL tablets to children under 2 years of age. In children under 6 years of age,
the doctor will evaluate the need for treatment with tablets (see section “Children”).
Warnings and precautions:
Talk to your doctor or pharmacist before taking ARGONAL.
Before starting and during treatment with ARGONAL, your doctor may want to carry out blood tests,
liver enzyme tests (ALT – AST) and serum creatinine, as well as urine analyses, which you should perform
14 days after starting treatment and then every 4 weeks for 2 or 3 times.
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.
Be especially careful and inform your doctor if any of the following apply to you:

if you have particularly slow digestion or suffer from a condition causing narrowing of the lower part of the stomach (pyloric stenosis); this may lead to premature release of the active ingredient from the tablets in the stomach, causing gastric irritation and loss of product efficacy.
If you suffer or have suffered from kidney or liver diseases. If you have known renal dysfunction, treatment with ARGONAL should be avoided. Your doctor will assess kidney function in all patients before starting therapy and periodically during treatment, especially if kidney disease is present.
If you suffer from lung diseases, particularly asthma; in this case, you should be closely monitored during treatment with ARGONAL.
If you are being treated with oral hypoglycemic agents (used to reduce blood sugar levels), diuretics, coumarins (medicines used to make blood thinner and prevent clot formation), corticosteroids. If, following treatment with ARGONAL, you experience bleeding, bruising, red spots on the skin due to rupture of capillaries under the skin surface (purpura), decreased hemoglobin levels in blood (anemia), fever or sore throat, because rare cases of serious blood disorders (hematological dyscrasias) have been reported after treatment with mesalazine. If such a disorder is suspected, treatment with ARGONAL must be discontinued.
If you have heart conditions affecting the myocardium or 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 therapy. 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. In case of severe or recurrent headache, visual disturbances, ringing or buzzing in the ears, contact your doctor immediately.

Immediately discontinue treatment with ARGONAL if acute intolerance syndrome is suspected,
which may present with symptoms such as abdominal cramps, acute abdominal pain and bloody diarrhea,
fever, headache, and erythema.
Use of mesalazine may lead to 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.
Prolonged use of the product may lead to sensitization phenomena.
After stopping treatment or if treatment is inadequate, disease relapses may occur; in such cases, inform
your doctor.
For treatment of active phases of intestinal disease, your doctor may recommend additional therapy.
Children
ARGONAL is contraindicated in children under 2 years of age (see section “Do not use ARGONAL”).
ARGONAL gastro-resistant tablets are not recommended for use in children under 6 years of age unless
carefully evaluated by the doctor.
Other medicines and ARGONAL
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other
medicines, including those without 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:

lactulose (used as a laxative for constipation treatment) or other preparations that lower the pH of the colon, which may hinder the release of mesalazine
sulfonylureas (medicines used to lower blood sugar levels); their effect may be increased when taken concomitantly with mesalazine
coumarins (medicines used to make blood thinner and prevent clot formation), such as warfarin; their effect may decrease when taken concomitantly with mesalazine
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 concentration in blood)
sulfinpyrazone (used for prevention after myocardial infarction)
spironolactone (potassium-sparing diuretic)
furosemide (a diuretic medicine that increases urine production, used in case of fluid retention)
rifampicin (an antibiotic)
corticosteroids; concomitant use may increase gastrointestinal side effects
non-steroidal anti-inflammatory drugs (NSAIDs)
azathioprine or 6-mercaptopurine (anti-inflammatory and immunosuppressive drugs), as this may increase the risk of hematological dyscrasias
azathioprine or 6-mercaptopurine or thioguanine, as this may lead to increased myelosuppressive effects of these drugs.

ARGONAL with food and drink
Take ARGONAL tablets away from meals (see section 3).
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. In case of confirmed or suspected
pregnancy, take the medicine only if clearly needed 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 clearly necessary and under strict
medical supervision. If the newborn develops diarrhea, breastfeeding should be discontinued.
Driving and using machines
ARGONAL does not affect the ability to drive or operate machinery.
ARGONAL gastro-resistant tablets contain 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 exactly as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.
The dosage will be adjusted by your doctor according to the extent and severity of the disease.
At the beginning of treatment, it is advisable to gradually increase the dosage over a few days before reaching the maximum dosage.

Adults: 1-2 tablets of ARGONAL 400 mg or 1 tablet of ARGONAL 800 mg, three times daily.
The dosage may be increased up to 10 tablets of ARGONAL 400 mg or 5 tablets of ARGONAL 800 mg per day in severe cases, or as judged by the physician.

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

Children over 6 years of age:

Active disease phase: dosage to be individually determined, initially 30–50 mg/kg daily given in divided doses. The maximum dose is 75 mg/kg daily given in divided doses. The total daily dose must not exceed 4 g per day (maximum adult dose).
Maintenance treatment: dosage to be individually determined, starting with 15–30 mg/kg daily given in divided doses. The total daily dose must not exceed 2 g per day (recommended adult dose).

It is generally recommended to administer half the adult dose to children weighing up to 40 kg, and the full adult dose to children weighing more than 40 kg.

Swallow the tablets whole, without dividing or chewing them, preferably with a glass of water and away from meals.

At the beginning of treatment, it is advisable to reach the full dosage after a few days of treatment, gradually increasing the dose.

For active phases, the duration of treatment is typically 4–6 weeks and may vary, at the physician’s discretion, depending on the clinical course. 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 take more ARGONAL than you should
If you take an excessive dose of ARGONAL, inform your doctor immediately or go to the nearest hospital.
Data on cases of overdose are limited and do not indicate renal or hepatic toxicity.
There is no known specific antidote in case of overdose.

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

If you stop taking ARGONAL
Do not discontinue the medicine without first consulting your doctor.
After stopping treatment, symptoms may reappear (see section “Warnings and precautions”).

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

4. Possible side effects

Like all medicines, ARGONAL may cause side effects, although not everyone experiences them.

Stop treatment with mesalazine and contact your doctor immediately if you notice any of the following symptoms:

Allergic reactions (skin rashes, itching)
Episodes of acute intestinal intolerance with abdominal pain
Presence of blood in liquid stools (bloody diarrhoea)
Abdominal cramps
Headache (cephalalgia)
Fever
Skin rash
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 serious skin rashes may be preceded by fever and flu-like symptoms.

Inform your doctor immediately if you experience severe or recurrent headache, visual disturbances, ringing or buzzing in the ears. These could be symptoms of increased pressure inside the skull (idiopathic intracranial hypertension) [Frequency not known (frequency cannot be estimated based on available data)].

The following side effects may occur during treatment with ARGONAL:

Common (may affect up to 1 in 10 people):

Headache
Increased blood pressure (hypertension)
Skin rashes
Nausea
Diarrhoea
Abdominal distension
Weakness (asthenia)
Fever (pyrexia)

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

Itching
Upper abdominal pain
Presence of blood in liquid stools (haematochezia)
Abdominal cramps and pain
Drowsiness
Tremor
Increased heart rate (tachycardia)
Decreased blood pressure (hypotension)
Fatigue
Swelling (oedema) of the face

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

Dizziness
Excess 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 disorders 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), decreased number of granulocytes (a specific type of white blood cells) (agranulocytosis), reduction in blood cells (pancytopenia)
Hypersensitivity reactions such as blisters and vesicles (allergic exanthema), drug fever, reactions similar to systemic lupus erythematosus, an autoimmune disease affecting the body's natural defence system (lupus-like syndrome), inflammation of the colon (pancolitis)
Peripheral nervous system damage manifesting as numbness or weakness in arms and legs (peripheral neuropathy)
Liver inflammation (hepatitis)
Liver inflammation caused by impaired bile excretion (cholestatic hepatitis)
Changes in certain liver parameters (increased transaminase levels and cholestasis)
Inflammation of the pancreas (pancreatitis and acute pancreatitis)
Formation of stones within the biliary system (cholelithiasis)
Kidney inflammation (acute and chronic interstitial nephritis), kidney and urinary tract disorders (nephrotic syndrome), and reduced kidney function (renal failure)
Inflammation of the lower respiratory tract (eosinophilic pneumonia), inflammation of the interstitial lung tissue (interstitial pneumonia)
Allergic and fibrotic lung reactions such as difficulty breathing (dyspnoea), cough, bronchial constriction (bronchospasm), inflammation of the lung alveoli (alveolitis), lung inflammation (pulmonary infiltration, pneumonia, eosinophilic and interstitial pneumonia)
Hair and scalp hair loss (alopecia)
Muscle pain (myalgia) and joint pain (arthralgia)
Reduced number of spermatozoa in the ejaculate (oligospermia), reversible
High fever (hyperpyrexia)

Frequency not known (frequency cannot be estimated based on available data):

Swelling of the skin and mucous membranes (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 contact 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 ARGONAL

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack and blister after 'Exp'.
The expiry date refers to the last day of that month.
Do not store above 25°C.
Do not use the product if the packaging shows visible signs of deterioration.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. 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 substance: 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 substance: 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 contents of the pack
ARGONAL “400 mg gastro-resistant tablets”: 50 gastro-resistant tablets in blister packs
ARGONAL “800 mg gastro-resistant tablets”: 24 gastro-resistant tablets in blister packs
ARGONAL “800 mg gastro-resistant tablets”: 60 gastro-resistant tablets in blister packs

Marketing Authorisation Holder and Manufacturer
MARKETING AUTHORISATION HOLDER
Dicofarm S.p.A. - Via del Casale della Marcigliana, 29 - 00138 Rome, Italy
MANUFACTURER
Special Product’s Line S.p.A. – Via Fratta Rotonda Vado Largo, 1, 03012 Anagni (FR), Italy

Package leaflet: information for the user

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

Mesalazine
Equivalent medicine
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 effects, including those not listed in this leaflet, contact your doctor or pharmacist. See Section 4.

Contents of this leaflet:

What ARGONAL is and what it is used for
What you need to know before using ARGONAL
How to use ARGONAL
Possible side effects
How to store ARGONAL
Contents of the pack and other information

1. What ARGONAL is and what it is used for

ARGONAL contains the active substance mesalazine, a compound with local anti-inflammatory action on the segments of intestinal mucosa affected by lesions.
This medicinal product is used in adults and children over 2 years of age for the treatment of ulcerative colitis (a chronic inflammatory bowel disease affecting the distal portion 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 treatment with corticosteroids 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 ARGONAL

INFORM YOUR DOCTOR BEFORE USING mesalazine:

if you have ever developed a severe skin rash or skin peeling, blisters and/or mouth ulcers after taking mesalazine

Do not use ARGONAL:

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

Warnings and precautions:
Talk to your doctor or pharmacist before using ARGONAL.
Before starting and during treatment with ARGONAL, your doctor may want to carry out blood tests, tests to assess liver enzyme levels (ALT or AST) and serum creatinine, as well as urine tests. These should be performed 14 days after starting treatment and then at 4-week intervals for 2 or 3 times.
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 occurring between mesalazine and bleach.
Be especially careful and inform your doctor if any of the following apply to you:

If you suffer or have suffered from kidney or liver disorders: if you have known renal dysfunction, treatment with ARGONAL should be avoided. Your doctor will assess renal function in all patients before starting therapy and periodically during treatment, particularly if kidney disease is present.
If you suffer from lung diseases, especially asthma, you should be closely monitored during treatment with ARGONAL.
If you are being treated with oral hypoglycemic agents (used to reduce blood sugar levels), diuretics, coumarins (medicines used to make blood more fluid and prevent clot formation), or corticosteroids.
If you have heart conditions affecting the myocardium or pericardium (myocarditis or pericarditis).
If, following treatment with ARGONAL, you develop bleeding, bruising, red spots on the skin due to rupture of capillaries beneath the skin surface (purpura), decreased hemoglobin levels in the blood (anemia), fever, or sore throat, as rare cases of serious blood disorders (haematological dyscrasias) have been reported after treatment with mesalazine. If such a disorder is suspected, treatment with ARGONAL must be discontinued.
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. 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. In case of severe or recurrent headache, vision disturbances, ringing or buzzing in the ears, contact your doctor immediately.

Immediately discontinue treatment with ARGONAL if acute intolerance syndrome is suspected, which may present with symptoms such as abdominal cramps, acute abdominal pain and bloody diarrhea, fever, headache, and erythema.
The use of mesalazine may lead to 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.
Prolonged use of the product may lead to sensitization phenomena.
After stopping treatment or if treatment is inadequate, disease relapses may occur; in such cases, inform your doctor.
Children
ARGONAL is contraindicated in children under 2 years of age (see section “Do not use ARGONAL”).
Other medicines and ARGONAL
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those without a prescription.
Mesalazine may affect the action of other medicines, and these may in turn 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 when taken concomitantly with mesalazine
coumarins (medicines used to make blood more fluid and prevent clot formation), such as warfarin; their effect may decrease when taken concomitantly with mesalazine
methotrexate (a medicine used in patients with psoriasis, Crohn's disease, rheumatoid arthritis, and in the treatment of certain tumors)
probenecid (used to reduce blood uric acid concentration)
sulfinpyrazone (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)
corticosteroids; concomitant use may increase gastrointestinal side effects
non-steroidal anti-inflammatory drugs (NSAIDs)
azathioprine or 6-mercaptopurine (anti-inflammatory and immunosuppressive medicines), as this may increase the risk of haematological dyscrasias
azathioprine, 6-mercaptopurine, or thioguanine, as an increase in the immunosuppressive effects of these medicines may occur.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, ask your doctor or pharmacist for advice before taking this medicine. In confirmed or suspected pregnancy, take the medicine only if clearly needed 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 clearly needed and under strict medical supervision. If the newborn develops diarrhea, breastfeeding should be discontinued.
Driving and using machines
ARGONAL does not affect 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 exactly as directed by your doctor. 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.

Adults: On average, 1 enema of 2 g/50 ml, 1–2 times daily, in the morning and/or evening before going to bed; or 1 enema of 4 g/100 ml once daily (preferably in the evening before bedtime).

Use in children and adolescents

Children over 2 years of age: Proportionally reduced doses as determined by the physician; for example, ½ enema of 2 g/50 ml, 1–2 times daily.

Shake well before use to obtain a homogeneous suspension, then remove the cap from the rectal cannula. To administer, lie on your left side, keeping the left leg straight and bending the right leg. Gently insert the cannula into the anal orifice and squeeze the bottle with gradual and constant pressure until the entire contents have been expelled. After administration, turn several times from side to side to facilitate better distribution of the medication, and remain lying down for at least 30 minutes. Optimal effectiveness is achieved by retaining the medication as long as possible, preferably leaving it in place overnight. For this reason, it is advisable that at least one daily application is performed before bedtime.

The recommended duration of treatment during active phases is generally 4–6 weeks, but 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 use more ARGONAL than you should

If you use more ARGONAL than the recommended single dose, inform your doctor immediately or go to the nearest hospital.

Cases of overdose following rectal administration are not expected.

If you forget to use ARGONAL

Do not use a double dose of ARGONAL to make up for a missed application.

If you stop using ARGONAL

Do not discontinue treatment with this medicine without first consulting your doctor.

After stopping treatment, symptoms may reappear (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 may cause side effects, although not everybody experiences them.
Stop treatment with mesalazine and contact your doctor immediately if you notice any of the
following symptoms:

Allergic reactions (skin rash, itching).
Episodes of acute intestinal intolerance with abdominal pain.
Presence of blood in liquid stools (bloody diarrhoea).
Abdominal cramps.
Headache.
Fever.
Skin rash.
Flat, red, target-shaped or circular patches on the trunk, often with central blisters, skin peeling, mouth, throat, nose, genital or eye ulcers, widespread skin 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, visual disturbances, ringing or buzzing in the ears. These could be symptoms of increased pressure inside the skull (idiopathic intracranial hypertension) [Frequency not known (frequency cannot be estimated based on available data)].
During treatment with ARGONAL, the following side effects may occur:
Common (may affect up to 1 in 10 people):

Headache
Increased blood pressure (hypertension)
Skin rash
Nausea
Diarrhoea
Abdominal distension
Weakness (asthenia)
Fever (pyrexia)

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

Itching
Upper abdominal pain
Presence of blood in liquid stools (haemorrhagic diarrhoea)
Abdominal cramps and pain
Drowsiness
Tremor
Increased heart rate (tachycardia)
Decreased blood pressure (hypotension)
Fatigue
Swelling (oedema) of the face

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

Dizziness
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).
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), decrease in the number of granulocytes (a specific type of white blood cells) (agranulocytosis), reduction in blood cells (pancytopenia).
Hypersensitivity reactions such as blisters and eruptions (allergic exanthema), drug fever, reactions similar to systemic lupus erythematosus, an autoimmune disease affecting the body's natural defence system (lupus-like syndrome), inflammation of the colon (pancolitis).
Peripheral nervous system damage manifesting as numbness or weakness in arms and legs (peripheral neuropathy).
Inflammation of the liver (hepatitis).
Liver inflammation caused by blockage of bile excretion (cholestatic hepatitis).
Changes in certain liver parameters (increased transaminase levels and cholestasis).
Inflammation of the pancreas (pancreatitis and acute pancreatitis).
Formation of stones within the biliary system (cholelithiasis).
Kidney inflammation (acute and chronic interstitial nephritis), kidney and urinary tract disorders (nephrotic syndrome), and reduced kidney function (renal failure).
Inflammation of the lower respiratory tract (eosinophilic pneumonia), inflammation of the lung interstitial tissue (interstitial pneumonia).
Allergic and fibrotic lung reactions such as difficulty breathing (dyspnoea), cough, narrowing of the bronchi (bronchospasm), inflammation of the lung alveoli (alveolitis), inflammation of the lungs (pulmonary infiltration, pneumonia, eosinophilic and interstitial pneumonia).
Loss of hair and body hair (alopecia).
Muscle pain (myalgia) and joint pain (arthralgia).
Reduced number of sperm in the ejaculate (oligospermia), reversible.
High fever (hyperpyrexia).

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

Swelling of the skin and mucous membranes (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 contact 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 ARGONAL

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging and on the blister after 'Exp'.
The expiry date refers to the product stored in its original, undamaged packaging and kept under
appropriate storage conditions.
Do not store above 25°C.
Do not use the product if the packaging shows any signs of deterioration.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of
medicines no longer required. This will help protect the environment.

6. Package contents and other information

What ARGONAL contains
ARGONAL 2 g/50 ml rectal suspension
One single-dose container of 50 ml contains:
Active substance: Mesalazine 2 g
ARGONAL 4 g/100 ml rectal suspension
One single-dose container of 50 ml contains:
Active substance: Mesalazine 4 g
The other components are: tragacanth gum, xanthan gum, edetate sodium, 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 carton contains 7 single-dose containers of 50 ml ready-to-use rectal suspension.
ARGONAL 4 g/100 ml rectal suspension:
One carton contains 7 single-dose containers of 100 ml ready-to-use rectal suspension.

Marketing Authorization Holder and Manufacturer
MARKETING AUTHORIZATION 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)

Package leaflet: information for the user

ARGONAL “500 mg suppositories”

Mesalazine
Generic medicine
Please 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 give it to others, even if their symptoms are the same as yours, as it could be harmful.
If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See Section 4.

Contents of this leaflet:

What ARGONAL is and what it is used for
What you need to know before using ARGONAL
How to use ARGONAL
Possible side effects
How to store ARGONAL
Contents of the pack and other information

1. What ARGONAL is and what it is used for

ARGONAL contains the active substance mesalazine, a compound with local anti-inflammatory action on the segments of intestinal mucosa affected by lesions.
This medicinal product is used in adults and children over 2 years of age for the treatment of ulcerative colitis (a chronic inflammatory bowel disease affecting the distal portion 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 corticosteroid therapy 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 ARGONAL

INFORM YOUR DOCTOR BEFORE USING mesalazine:

if you have ever developed a severe skin rash or skin peeling, blisters and/or mouth ulcers after taking mesalazine

Do not use ARGONAL:

If you are allergic to the active substance mesalazine or to any of the other ingredients of this medicinal product (listed in section 6);
If you are allergic to other chemically related medicines, particularly salicylates;
If you suffer from kidney diseases (severe nephropathies);
If you have severe impairment of liver or kidney function;
If you suffer from active gastric ulcers or duodenal ulcers;
If you have a particular predisposition to bleeding (hemorrhagic 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:
Talk to your doctor or pharmacist before using ARGONAL.
Before starting and during treatment with ARGONAL, your doctor may want to carry out blood tests, tests to assess liver enzyme levels (ALT or AST) and serum creatinine, and urine analyses, which you will need to perform 14 days after starting treatment and subsequently at 4-week intervals for 2 or 3 times.
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 occurring between mesalazine and bleach.
Pay special attention and inform your doctor if any of the following apply to you:

If you suffer or have suffered from kidney or liver disorders. If you have known renal dysfunction, treatment with ARGONAL should be avoided. Your doctor will evaluate renal function in all patients before starting therapy and periodically during treatment, especially if kidney disease is present.
If you suffer from lung diseases, particularly asthma, you should be closely monitored during treatment with ARGONAL.
If you are being treated with oral hypoglycemic agents (used to reduce blood sugar levels), diuretics, coumarins (medicines used to make blood more fluid and prevent clot formation), corticosteroids;
If you have heart conditions affecting the myocardium and pericardium (myocarditis or pericarditis).
If, following treatment with ARGONAL, you experience bleeding, bruising, red spots on the skin due to capillary rupture beneath the skin surface (purpura), decreased hemoglobin levels in the blood (anemia), fever, or sore throat, as rare cases of serious blood disorders (hematological dyscrasias) have been reported after treatment with mesalazine. If such a disorder is suspected, treatment with ARGONAL must be discontinued.
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. In case of severe or recurrent headache, visual disturbances, ringing or buzzing in the ears, contact your doctor immediately.

Immediately discontinue treatment with ARGONAL if acute intolerance syndrome is suspected, which may present with symptoms such as cramps, acute abdominal pain and bloody diarrhea, fever, headache (migraine), and erythema.
The use of mesalazine may lead to 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.
Prolonged use of the product may lead to sensitization phenomena.
After stopping treatment or if treatment is inadequate, disease relapses may occur; in such cases, inform your doctor.
Children
ARGONAL is contraindicated in children under 2 years of age (see section “Do not use ARGONAL”).
Other medicines and ARGONAL
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those 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 when taken concomitantly with mesalazine
coumarins (medicines used to make blood more fluid and prevent clot formation), such as warfarin; their effect may decrease when taken concomitantly with mesalazine
methotrexate (a medicine used in patients with psoriasis, Crohn's disease, rheumatoid arthritis, and in the treatment of certain cancers)
probenecid (used to reduce uric acid concentration in the blood)
sulfinpyrazone (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)
corticosteroids; concomitant use may increase gastrointestinal side effects
non-steroidal anti-inflammatory drugs (NSAIDs)
azathioprine or 6-mercaptopurine (anti-inflammatory and immunosuppressive drugs), as this may increase the risk of hematological 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 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 strictly necessary and under close 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 strictly necessary and under close medical supervision. If the newborn 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 exactly as directed by your doctor. 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.
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 of age: reduced doses proportionally, as judged by the doctor.
To achieve the best therapeutic effect, it is important that the suppository is retained for at least 30 minutes, or preferably for longer periods (e.g. overnight).
The duration of treatment during active phases is generally 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 evolution.
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 expected.
If you forget to use ARGONAL
Do not use a double dose of ARGONAL to make up for a missed dose.
If you stop using ARGONAL
Do not stop taking this medicine without first consulting your doctor.
After stopping treatment, symptoms may reappear (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 may cause side effects, although not everybody gets them.
Stop treatment with mesalazine and contact your doctor immediately if you notice any of the following
symptoms:

Allergic reactions (skin rashes, itching).
Episodes of acute intestinal intolerance with abdominal pain.
Presence of blood in liquid stools (bloody diarrhoea).
Abdominal cramps.
Headache.
Fever.
Skin rash.
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 reactions may be preceded by fever and flu-like symptoms.

Inform your doctor immediately if you experience severe or recurrent headache, visual disturbances, ringing or
buzzing in the ears. These could be symptoms of increased pressure inside the skull (idiopathic intracranial
hypertension) [Frequency not known (frequency cannot be estimated from the available data)].
The following side effects may occur during treatment with ARGONAL:
Common (may affect up to 1 in 10 people):

Headache
Increased blood pressure (hypertension)
Skin rashes
Nausea
Diarrhoea
Abdominal distension
Weakness (asthenia)
Fever (pyrexia)

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

Itching
Upper abdominal pain
Presence of blood in liquid stools (haemorrhagic diarrhoea)
Abdominal cramps and pain
Drowsiness
Tremor
Increased heart rate (tachycardia)
Decreased blood pressure (hypotension)
Fatigue
Swelling (oedema) 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).
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), decrease in the number of granulocytes (a specific type of white blood cells) (agranulocytosis), reduction in blood cells (pancytopenia).
Hypersensitivity reactions such as blisters and vesicles (allergic exanthema), drug fever, reactions similar to systemic lupus erythematosus, an autoimmune disease affecting the body's natural defence system (lupus-like syndrome), inflammation of the colon (pancolitis).
Damage to the peripheral nervous system manifesting as numbness or weakness in arms and legs (peripheral neuropathy).
Inflammation of the liver (hepatitis).
Liver inflammation caused by blockage of bile excretion (cholestatic hepatitis).
Changes in some liver parameters (increase in transaminase and cholestasis parameters).
Inflammation of the pancreas (pancreatitis and acute pancreatitis).
Formation of stones within the biliary system (cholelithiasis).
Kidney inflammation (acute and chronic interstitial nephritis), kidney and urinary tract disorders (nephrotic syndrome), and reduced kidney function (renal failure).
Inflammation of the lower respiratory tract (eosinophilic pneumonia), inflammation of the interstitial lung tissue (interstitial pneumonia).
Allergic and fibrotic lung reactions such as difficulty breathing (dyspnoea), cough, narrowing of the bronchi (bronchospasm), inflammation of the lung alveoli (alveolitis), lung inflammation (pulmonary infiltration, 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 (frequency cannot be estimated from the available data):

Swelling of the skin and mucous membranes (angioedema).
Kidney stones and associated renal pain (see also section 2).

Reporting of side effects
If you experience any side effects, 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 ARGONAL

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging and on the blister after 'Exp'. The
expiry date refers to the product in its original, unopened packaging, correctly stored.
Do not store above 25°C.
During hot seasons, it may be necessary to immerse the container of suppositories in cold water to
re-solidify suppositories that may have softened.
Do not use the product if the packaging shows 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. Contents of the pack and other information

What ARGONAL contains
ARGONAL "500 mg suppositories"
One suppository contains
Active substance: Mesalazine 500 mg
Other components: Semisynthetic glycerides

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

Marketing Authorisation Holder and Manufacturer
MARKETING AUTHORISATION 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)