Asacolon 400 mg Gastro-Resistant Tablet

  • Name:

    Asacolon 400 mg Gastro-Resistant Tablet

  • Company:
    info
  • Active Ingredients:

    Mesalazine

  • Legal Category:

    Product subject to medical prescription which may be renewed (B)

Patient Information Leaflet Patient Information Leaflet last updated on medicines.ie: 30/10/19

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Summary of Product Characteristics last updated on medicines.ie: 30/10/2019

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Mareike Würz

Tillotts Pharma GmbH

Company Products

Medicine NameActive Ingredients
Medicine Name Asacolon 1600 mg modified-release tablets Active Ingredients Mesalazine
Medicine Name Asacolon 400 mg Gastro-Resistant Tablet Active Ingredients Mesalazine
Medicine Name Asacolon 500 mg Suppositories Active Ingredients Mesalazine
Medicine Name Asacolon 800 mg Gastro-Resistant Tablets Active Ingredients Mesalazine
Medicine Name Entocort CR 3mg Capsules Active Ingredients Budesonide
Medicine Name Vistaprep Powder for oral solution Active Ingredients Macrogol 3350, Potassium Chloride, Sodium Bicarbonate, Sodium Chloride
1 - 0 of 6 items.Total: Infinity pages

When a pharmaceutical company changes any document, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.

Updated on 30 October 2019 PIL

Reasons for updating

  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 4 - possible side effects

Free text change information supplied by the pharmaceutical company

Update the product information on the risk of ‘nephrolithiasis’ in line with the recent recommendation issued by the Pharmacovigilance Risk Assessment Committee (PRAC)

Updated on 30 October 2019

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects

Free text change information supplied by the pharmaceutical company

Update the product information on the risk of ‘nephrolithiasis’ in line with the recent recommendation issued by the Pharmacovigilance Risk Assessment Committee (PRAC)

Updated on 2 October 2018 PIL

Reasons for updating

  • Change to section 3 - dose and frequency

Updated on 2 October 2018

Reasons for updating

  • Change to section 4.2 - Posology and method of administration

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4.2       Posology and method of administration

Posology

Adults:

Ulcerative colitis:

Induction of remission:

2.4 g (6 tablets) per day once daily or in divided doses. If required the dose may be increased to 4.8 g (12 tablets) dailyper day in divided doses. Above 2.4 g daily in divided doses only.

The dosage can be adjusted in accordance with the response to the treatment.

 

Updated on 28 November 2017

Reasons for updating

  • New SmPC for new product

Legal category: Product subject to medical prescription which may be renewed (B)

Updated on 28 November 2017 SPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company


under Skin and subcutaneous tissue was added with frequency rare: photosensitivity

c) Description of selected adverse reactions

.... 

Photosensitivity

More severe reactions are reported in patients with pre-existing skin conditions such as atopic

dermatitis and atopic eczema.

Updated on 27 November 2017 PIL

Reasons for updating

  • New PIL for new product

Updated on 27 November 2017 PIL

Reasons for updating

  • Change to section 4 - possible side effects

Updated on 29 March 2017 SPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

4.4       Special warnings and precautions for use

Blood tests (differential blood count, liver function parameters such as ALT or AST; serum creatinine) and urinary status (dip sticks) should be determined prior to and during treatment, at the discretion of the treating physician. As a guideline, follow-up tests are recommended 14 days after commencement of treatment and then every 4 weeks for the following 12 weeks. If the findings are normal, follow-up tests should be carried out every three months. If additional signs appear, these tests should be performed immediately.

Renal impairment

Asacolon should not be used in patients with impaired renal function. Urinary status (dip sticks) should be determined prior to and during treatment, at the discretion of the treating physician. Caution should be exercised in patients with raised serum creatinine or proteinuria. The possibility of mesalazine-induced nephrotoxicity should be suspected in patients developing impairment of renal function during treatment.

 

It is recommended that all patients have an evaluation of their renal function prior to initiation of Asacolon therapy and repeatedly whilst on therapy. As a guideline, follow-up tests are recommended 14 days after commencement of treatment and then every 4 weeks for the following 12 weeks. Short monitoring intervals early after the start of Asacolon therapy will discover rare acute renal reactions. In the absence of an acute renal reaction monitoring intervals can be extended to every 3 months and then annually after 5 years. If additional laboratory or clinical signs of renal impairment appear, these tests should be performed immediately. Treatment with Asacolon should be stopped immediately if there is evidence of renal impairment and patients should seek immediate medical advice.

 

Blood dyscrasia

Serious blood dyscrasia has very rarely been reported. Treatment with Asacolon should be stopped immediately if there is a suspicion or evidence of blood dyscrasia, such as unexplained bleeding, haematoma, purpura, anaemia, persistent fever or sore throat, and patients should seek immediate medical advice. It is recommended that haematological investigations (differential blood count) are performed prior to initiation of Asacolon and whilst on therapy at the discretion of the treating physician. As a guideline, follow-up tests are recommended 14 days after initiation of therapy and then every 4 weeks for the following 12 weeks. If the results are normal, follow-up tests should be carried out every 3 months. If additional symptoms occur, these tests should be performed immediately.

 

Hepatic impairment

There have been reports of increased liver enzyme levels in patients taking preparations containing mesalazine. Caution is recommended if Asacolon is administered to patients with liver impairment. Blood tests (liver function parameters such as ALT or AST) should be performed prior to and during treatment, at the discretion of the treating physician. As a guideline, follow-up tests are recommended 14 days after commencement of treatment, then a further two to three tests at intervals of 4 weeks. If the findings are normal, follow-up tests should be carried out every 3 months. If additional symptoms occur, these tests should be performed immediately.
...

 

4.8       Undesirable effects

a) Summary of the safety profile

Organ specific adverse drug reactions affecting the heart, lungs, liver, kidneys, pancreas, skin and subcutaneous tissue have been reported.

Treatment must be stopped immediately if acute symptoms of intolerance occur such as abdominal cramps, acute abdominal pain, fever, severe headache and rash.

 

b) Tabulated summary of adverse reactions

Undesirable effects reported from clinical studies with patients treated with Asacolon 400 mg GR Tablets, and other sources are listed below.

 

Common:  ≥ 1/100 to < 1/10, uncommon:  ≥ 1/1,000 to < 1/100

Rare: ≥ 1/10,000 to < 1/1000, very rare: < 1/10,000 

Not known (cannot be estimated from the available data)

System Organ Class

Common

(≥ 1/100 to  < 1/10)

Uncommon

 (≥ 1/1,000 to < 1/100)

Rare

(≥ 1/10,000 to < 1/1,000)

Very rare

(< 1/10,000)

Frequency not known

Blood and lymphatic system disorders

--

eosinophilia

(as part of an allergic reaction).

--

altered blood counts (aplastic anemia, agranulocytosis, pancytopenia, neutropenia, leucopenia, thrombocytopenia).

--

Immune system disorders

--

--

--

hypersensitivity reactions such as allergic exanthema, drug fever, lupus erythematosus syndrome, pancolitis.

--

Nervous system disorders

--

paresthesia.

headache, dizziness.

peripheral neuropathy.

--

Cardiac disorders

--

--

myocarditis,

pericarditis.

--

--

Respiratory, thoracic and mediastinal disorders

--

--

--

allergic and fibrotic lung reactions (including dyspnoea, cough, bronchospasm, alveolitis, pulmonary eosinophilia, lung infiltration, pneumonitis), interstitial pneumonia, eosinophilic pneumonia, lung disorder.

pleurisy

Gastrointestinal disorders

dyspepsia.

--

abdominal pain, diarrhoea, flatulence, nausea, vomiting.

acute pancreatitis

--

Hepato-biliary disorders

--

--

--

changes in liver function parameters (increase in transaminases and cholestasis parameters), hepatitis, cholestatic hepatitis.

--

Skin and subcutaneous tissue disorders

rash.

urticaria,

pruritus.

 

--

alopecia.

--

Musculoskeletal, connective tissue and bone disorders

--

--

--

myalgia, arthralgia.

lupus-like syndrome with pericarditis and pleuropericarditis as prominent symptoms as well as rash and arthralgia.

Renal and urinary disorders

--

--

--

impairment of renal function including acute and chronic interstitial nephritis and renal insufficiency, nephrotic syndrome, renal failure which may be reversible on early withdrawal.

--

Reproductive system and breast disorders

--

--

--

oligospermia (reversible).

--

General disorders and administration site conditions

--

pyrexia,

chest pain.

--

--

intolerance to mesalazine with C-reactive protein increased and/or exacerbation of symptoms of underlying disease

Investigations

--

--

--

--

blood creatinine increased, weight decreased, creatinine clearance decreased, amylase increased, red blood cell sedimentation rate increased, lipase increased, BUN increased.


 

 

Updated on 28 March 2017 PIL

Reasons for updating

  • Change to section 2 - what you need to know - contraindications
  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 2 - excipient warnings
  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision

Updated on 12 November 2015 SPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

In section 4.1 (therapeutic indications), moderate has been added.

Updated on 21 May 2015 SPC

Reasons for updating

  • Change to section 7 - Marketing authorisation holder
  • Change to section 8 - MA number

Legal category: Product subject to medical prescription which may be renewed (B)

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7.         MARKETING AUTHORISATION HOLDER

Tillotts Pharma Limited
United Drug House
Magna Drive
Magna Business Park
Citywest Road
Dublin 24
Tillotts Pharma GmbH

Warmbacher Strasse 80

79618 Rheinfelden

Germany

 

8.         MARKETING AUTHORISATION NUMBER

PA 1204/1/2
PA 2018/1/1

Updated on 19 May 2015 PIL

Reasons for updating

  • Change of manufacturer
  • Change of licence holder

Updated on 11 November 2014 SPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 5.3 - Preclinical safety data
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

 

 

2.         QUALITATIVE AND QUANTITATIVE COMPOSITION

 

Each gastro-resistant tablet contains: Mesalazine 400 mg.

 

Excipients with known effect: also contains 76.4 mg of lactose monohydrate, see section 4.4.for further details.

For the full list of excipients, see section 6.1.

 

4.         CLINICAL PARTICULARS

 

4.1       Therapeutic Indications

 

Asacolon is indicated in adults, children above 6 years and adolescents for:

For the treatment of mild acute ulcerative colitis. For the maintenance of remission of ulcerative colitis.

 

For the maintenance of surgically-induced remission of Crohn’s Disease.

 

4.2       Posology and Method of Administration

 

Posology

Adults:

Ulcerative colitis:

Induction of remission:

2.4 g (6 tablets) per day in divided doses. If required the dose may be increased to 4.8 g (12 tablets) daily.

The dosage can be adjusted in accordance with the response to the treatment.

 

Maintenance of remission:

1.2 to 2.4 g (3 to 6 tablets) per day once daily or in divided doses.

 

Crohn’s disease:

Maintenance of remission:

2.4 g (6 tablets) per day once daily or in divided doses.

 

Elderly populationOlder people

As for adults above unless liver or renal function is severely impaired (see section 4.3 and 4.4). No studies have been carried out in the elderly populationolder people.

 

Paediatric population

There is only limited documentation for an effect in children (age 6-18 years).

Method of administration: oral.

 

The tablets should must be swallowed whole preferably with some liquid before food intake. They must not be chewed, crushed or broken before swallowing.

If one or more doses have been missed, the next dose is to be taken as usual.

4.3       Contraindications

Asacolon is contraindicated in cases of:

 

History of hHypersensitivity to salicylates.

-  Hypersensitivity to mesalazine or any of the excipients (see section 6.1).

-  Severe renal impairment (GFR less than 30 mL/min/1.73 m2 per minute).

-  Severe liver impairment.

-  Children under the age of 2 years.

-  Gastric and duodenal ulcers

 

4.4       Special warnings and precautions for use

 

Renal impairment

Asacolon should not be used in patients with impaired renal function. Urinary status (dip sticks) should be determined prior to and during treatment, at the discretion of the treating physician. Not recommended for use in patients with renal impairment. Caution should be exercised in patients with raised blood ureaserum creatinine or proteinuria. The possibility of mesalazine-induced nephrotoxicity should be suspected in patients developing impairment of renal function during treatment.

 

It is recommended that all patients have an evaluation of their renal function prior to initiation of Asacolon therapy and periodically while on Asacolonrepeatedly whilst on therapy. As a guideline, follow-up tests are recommended 14 days of initiation of therapyafter commencement of treatment and then every 4 weeks for the following 12 weeks. Short monitoring intervals early after the start of Asacolon therapy will discover rare acute allergic impairment of renal functionreactions. In the absence of an acute allergic renal response reaction monitoring intervals can be extended to every 3 months and then annually after 5 years. If additional laboratory or clinical signs of illness renal impairment appear, these tests should be performed immediately. Treatment with Asacolon should be stopped immediately if there is evidence of renal impairment and patients should seek immediate medical advice.

 

Blood dyscrasia

Serious blood dyscrasia has very rarely been reported. Treatment with Asacolon should be stopped immediately if there is a suspicion or evidence of blood dyscrasia, such as unexplained bleeding, haematoma, purpura, anaemia, persistent fever or sore throat, and patients should seek immediate medical advice.  It is recommended that haematological investigations (differential blood count) are performed prior to initiation of Asacolon and whilst on therapy at the discretion of the treating physician. As a guideline, follow-up tests are recommended 14 days after initiation of therapy and then every 4 weeks for the following 12 weeks. If the results are normal, follow-up tests should be carried out every 3 months. If additional symptoms occur, these tests should be performed immediately.

 

Liver Hepatic impairment

There have been reports of increased liver enzyme levels in patients taking preparations containing mesalazine. Caution is recommended if Asacolon is administered to patients with liver impairment. Blood tests (liver function parameters such as ALT or AST) should be determined performed prior to and during treatment, at the discretion of the treating physician. As a guideline, follow-up tests are recommended 14 days after commencement of treatment, then a further two to three tests at intervals of 4 weeks. If the findings are normal, follow-up tests should be carried out every 3 months. If additional symptoms occur, these tests should be performed immediately.

 

Cardiac hypersensitivity reactions

Mesalazine-induced cardiac hypersensitivity reactions (myo- and pericarditis) have been reported rarely with Asacolon. In case of previous a suspected mesalazine-induced cardiac hypersensitivity Asacolon must not be reintroduced. Caution should be used taken in patients with previous myo- and pericarditis of allergic background regardless of its origin.

 

Pulmonary disease

Patients with pulmonary disease, in particular asthma, should be very carefully monitored during a course of treatment with Asacolon.

 

 

Hypersensitivity to Sulphasalazine

In patients with a history of hypersensitivity to sulphasalazine, therapy should be initiated only under close medical supervisionPatients with a history of adverse drug reactions to sulphasalazine therapy should be kept under close medical supervision. Treatment must be stopped immediately if acute symptoms of intolerance occur such as abdominal cramps, acute abdominal pain, fever, severe headache and rash.

 

Blood dyscrasia

Very rarely serious blood dyscrasia has been reported with this medicinal product. Treatment with Asacolon should be stopped immediately if there is a suspicion or evidence of blood dyscrasia, such as unexplained bleeding, haematoma, purpura, anaemia, persistent fever or sore throat, and patients should seek immediate medical advice.  Haematological investigations including a complete blood count should be performed prior to initiation and while on therapy at the discretion of the treating physician. As a guideline, follow-up tests are generally recommended 14 days after initiation of therapy and then every 4 weeks for the following 12 weeks. If the results are normal, follow-up tests should be carried out every 3 months. If additional symptoms occur, these tests should be performed immediately.

Gastric and duodenal ulcers

In case of existing gastric or duodenal ulcers treatment should begin with caution based on theoretical grounds.

 

Tablets in stool

A limited number of reports of intact tablets in stool have been received. What appear to be intact tablets may in some cases represent largely empty shells of the coated tablets. coating. Asacolon 400 mg Gastro-resistant Tablets release their content in the lower gut even if the coating does not dissolve entirely. Once pH 7.0 is reached, cracks in the coating are sufficient for the release of mesalazine from the tablets. This process is irreversible from here on and mesalazine will therefore be released continuously, independent of intestinal pH. If intact tablets are observed in the stool repeatedly, the patient should consult his/her physician.

 

Intolerance to carbohydrates

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

 

The elderlyOlder people

Use in the elderlyolder people should be handled with caution and the product should only be prescribed to patients having a normal or non-severely impaired liver and renal function, see section 4.3.

 

Paediatric population

There is only limited documentation for an effect in children (age 6-18 years), see section 4.2.

4.5       Interactions with other medicinal products and other forms of interactions

 

Specific interaction studies have not been performed.No interaction studies have been performed.

 

Sulphasalazine decreases the absorption of digoxin. There are no data on interaction of digoxin with mesalazine.

There is weak evidence that mesalazine might decrease the anticoagulant effect of warfarin.

 

In patients who are concomitantly treated with azathioprine, or 6-mercaptopurine or thioguanine, a possible increase in the myelosuppressive effects of azathioprine, or 6-mercaptopurine or thioguanine should be taken into account. As a result, Mesalazine can increase the myelosuppressive effects of azathioprine, or 6-mercaptopurine, or thioguanine. Llife-threatening infection can occur. Patients should be closely observed for signs of infection and myelosuppression. Haematological parameters, such asespecially leukocyte, thrombocyte and lymphocyte cell counts should be monitored regularly (weekly), especially at initiation of such combination therapy (see section 4.4). If white blood cells are stable after 1 month, testing every 4 weeks for the following 12 weeks followed by 3 monthly monitoring intervals appears to be justified.

 

The concurrent use of known nephrotoxic agents, such as NSAIDs, azathioprine, or methotrexate, may increase the risk of renal reactions. However, no adverse events proving such interactions have been reported (see section 4.4).

 

There is weak evidence that mesalazine might decrease the anticoagulant effect of warfarin.

 

Apart from purine antimetabolites interaction studies in adults and children, no other interaction studies in adults or paediatric patients have been performed.

 

4.6       Fertility, pregnancy and lactation

 

Pregnancy

There are no adequate data on the use of Asacolon in pregnant women. However, data from a limited number (627) of exposed pregnancies indicate no adverse effect of mesalazine on the pregnancy or on the health of the fetus/newborn child., but more frequent pre-term births cannot be excluded. To date no other relevant epidemiologic data are available.

 

In one single case after long-term use of a high dose of mesalazine (2-4 g, orally) during pregnancy, renal failure in a neonate was reported.

 

Animal studies on oral mesalazine do not indicate direct or indirect harmful effects with respect to pregnancy, embryonic/fetal development, parturition or postnatal development.

Mesalazine crosses the placental barrier. Asacolon should only be used during pregnancy if the potential benefit outweighs the possible risk. Caution should be exercised when using high doses of mesalazine.

 

Breast-feeding

N-acetyl-5-aminosalicylic acid and to a lesser degree mesalazine are excreted in breast milk. The clinical significance of this has not been determined. Only limited experience during lactation in women is available to date. Hypersensitivity reactions such as diarrhoea in the infant cannot be excluded. Therefore, Asacolon should only be used during breast-feeding, if the potential benefit outweighs the possible risk. If the infant develops diarrhoea, breast-feeding should be discontinued.

 

Fertility

No effects on fertility have been observed.

 

4.7       Effects on ability to drive and use machines

 

No effects on the ability to drive and use machines have been observed.Asacolon has no or negligible influence on the ability to drive and use machines.

 

4.8       Undesirable effects

 

a) Summary of the safety profile

Organ specific adverse drug  reactions affecting the heart, lungs, liver, kidneys, pancreas, skin and subcutaneous tissue have been reported.

Treatment must be stopped immediately if acute symptoms of intolerance occur such as abdominal cramps, acute abdominal pain, fever, severe headache and rash.

 

b) Tabulated summary of adverse reactions

Undesirable effects relevant for the labelling reported from eight (8) double-blind and five (5) open label clinical studies with 739 patients treated with Asacolon 400 mg GR tTablets, and other sources  information from spontaneous reporting, the literature and the EU Mesalazine Core Safety Profile of 07 April 2011 is listed below. The frequency of some reactions cannot be reliably estimated due to the limitation of the reporting sources.

 

Common:  ≥ 1/100 to < 1/10, uncommon:  ≥ 1/1,000 to < 1/100

Rare: ≥ 1/10,000 to < 1/1000, very rare: < 1/10,000 

Not known (cannot be estimated from the available data)

 

The Asacolon clinical trial database includes 651 patients treated with Asacolon 400 mg GR Tablets. The mesalazine doses were in the range of 0.8 to 4.8 g/day, the average treatment duration varied between four weeks and four years.

 

Undesirable effects relevant for the labelling reported from nine double-blind and six open clinical studies and information from spontaneous reporting or the literature is listed below. The latter was reported from a population of unknown size. Their frequency is not known.

System Organ Class

Common

(≥ 1/100 to  < 1/10)

Uncommon

 (≥ 1/1,000 to < 1/100)

Rare

(≥ 1/10,000 to < 1/1,000)

Very rare

(< 1/10,000)

Frequency not known

Blood and lymphatic system disorders

--

eosinophilia

(as part of an allergic reaction).

--

altered blood counts (aplastic anemia, agranulocytosis, pancytopenia, neutropenia, leucopenia, thrombocytopenia).

--

Immune system disorders

--

--

--

hypersensitivity reactions such as allergic exanthema, drug fever, lupus erythematosus syndrome, pancolitis.

--

Nervous system disorders

--

paresthesia.

headache, dizziness.

peripheral neuropathy.

--

Cardiac disorders

--

--

myocarditis,

pericarditis.

--

--

Respiratory, thoracic and mediastinal disorders

--

--

--

allergic and fibrotic lung reactions (including dyspnoea, cough, bronchospasm, alveolitis, pulmonary eosinophilia, lung infiltration, pneumonitis), interstitial pneumonia, eosinophilic pneumonia, lung disorder.

--

Gastrointestinal disorders

dyspepsia.

--

abdominal pain, diarrhoea, flatulence, nausea, vomiting.

acute pancreatitis

--

Hepato-biliary disorders

--

--

--

changes in liver function parameters (increase in transaminases and cholestasis parameters), hepatitis, cholestatic hepatitis.

 

--

Skin and subcutaneous tissue disorders

rash.

urticaria,

pruritus.

 

--

alopecia.

--

Musculoskeletal, connective tissue and bone disorders

--

--

--

myalgia, arthralgia.

lupus-like syndrome with pericarditis and pleuropericarditis as prominent symptoms as well as rash and arthralgia.

Renal and urinary disorders

--

--

--

impairment of renal function including acute and chronic interstitial nephritis and renal insufficiency, nephrotic syndrome, renal failure which may be reversible on early withdrawal.

--

Reproductive system and breast disorders

--

--

--

oligospermia (reversible).

--

General disorders and administration site conditions

--

pyrexia,

chest pain.

--

--

--

Investigations

--

--

--

--

blood creatinine increased, weight decreased, creatinine clearance decreased, amylase increased, red blood cell sedimentation rate increased, lipase increased, BUN increased.

Blood and lymphatic system disorders

Uncommon:    : anaemia.eosinophilia (as part of an allergic reaction).

Very rare:        :altered blood counts (aplastic anaemia, agranulocytosis, pancytopenia,

                          neutropenia, leucopenia, thrombocytopenia)., bone marrow depression,

                          eosinophilia, blood disorder.

 

Immune system disorders

Very rare:        : hypersensitivity reactions such as allergic exanthema, drug fever, lupus

                          erythematosus syndrome, pancolitis.

 

Nervous system disorders

Uncommon:    : tinnitus, paresthesia.

Rare:                : headache, dizziness.

Very rare:        : peripheral neuropathy.

 

Cardiac disorders

Rare:                : myocarditis, pericarditis.

 

Respiratory, thoracic and mediastinal disorders

Very rare:        : allergic and fibrotic lung reactions (including dyspnoea, cough,  

                          bronchospasm, alveolitis, pulmonary eosinophilia, lung infiltration,  

                          pneumonitis), pneumonia, interstitial pneumonia, eosinophilic pneumonia,

                          lung disorder.

 

Gastrointestinal disorders

Common:          dyspepsia.

Rare:                : abdominal pain, diarrhoea, flatulence, nausea, vomiting, dyspepsia.

Very rare:        : acute pancreatitis.

Not known      : exacerbation of the symptoms of colitis.

 

Hepato-biliary disorders

Very rare:        : changes in liver function parameters (increase in transaminases and

                          cholestasis parameters), hepatitis, cholestatic hepatitis.

 

Skin and subcutaneous tissue disorders

Common:        : rash.

Uncommon:    : pruritus, urticaria.

Very rare:        : alopecia.

 

Musculoskeletal and connective tissue disorders

Very rare:        : myalgia, arthralgia.

Not known:     : lupus-like syndrome with pericarditis and pleuropericarditis as

                          prominent symptoms as well as rash and arthralgia.

 

Renal and urinary disorders

Very Rare:       : impairment of renal function including acute and chronic interstitial

                          nephritis and renal insufficiency, nephrotic syndrome, renal failure which

                          may be reversible on early withdrawal.

 

Reproductive system and breast disorders

Very rare:        oligospermia (reversible).

 

 

General disorders and administration site conditions

Common         : drug fever.

Uncommon:    : pyrexia, chest pain. drug ineffective.

Very rare         : chest pain.

 

Investigations

Not known:       blood creatinine increased, weight decreased, creatinine clearance decreased, amylase increased, red blood cell sedimentation rate increased, lipase increased, BUN increased.

 

Very common:  ≥ 1/10, common:  ≥ 1/100 and < 1/10, uncommon:    1/1,000 and < 1/100, rare:    1/10,000 and < 1/1,000, very rare:  < 1/10,000, not known (cannot be estimated from the available data)

4.9       Overdosage

 There are rareis little data on overdose (e.g. intended suicide with high oral doses of mesalazine), which do not indicate renal or hepatic toxicity. There is no specific antidote and treatment is symptomatic and supportive.

 

 

5.         PHARMACOLOGICAL PROPERTIES

 

5.1       Pharmacodynamic properties

Pharmacotherapeutic group: Intestinal anti-inflammatory agents, ATC code: A07EC02

 

Mechanism of Action

Asacolon 400 mg Gastro-resistant Tablets contains mesalazine [ATC A07EC02], oralso known as 5-aminosalicylic acid, which has an anti-inflammatory effect through a mechanism that has not yet been fully clarified. Mesalazine has been shown to inhibit LTB4-stimulated migration of intestinal macrophages and thus may reduce intestinal inflammation by restricting migration of macrophages to inflamed areas. The production of pro-inflammatory leukotrienes (LTB4 and 5-HETE) in macrophages of the intestinal wall is inhibited. Mesalazine has been shown to activate PPAR-γ receptors which counteract nuclear activation of intestinal inflammatory responses. Mesalazine inhibits migration of polymorph nuclear leukocytes and lipooxygenase of cells at concentrations reached in the large intestine during treatment. The production of pro-inflammatory leukotrienes (LTB4 and 5-HETE) in macrophages of the intestinal wall is then inhibited. In trial conditions mesalazine has also inhibited cyclo-oxygenase and thus, the release of thromboxane B2 and prostaglandin E2, but the clinical meaning of this effect is still unclear. Mesalazine inhibits formation of platelet activating factor (PAF). Mesalazine is also an antioxidant; it has been shown to decrease formation of reactive oxygen products and to capture free radicals. Furthermore, mesalazine inhibits secretion of water and chloride and increases the re-absorption of sodium in the intestine in experimental colitis in test animals.

 

Pharmacodynamic effects

Under trial conditions mesalazine inhibited the cyclooxygenase and thus, the release of thromboxane B2 and prostaglandin E2, but the clinical meaning of this effect is still unclear. Mesalazine inhibits the formation of platelet activating factor (PAF). Mesalazine is also an antioxidant; it has been shown to decrease formation of reactive oxygen products and to capture free radicals.

 

Epidemiological data indicate that continued long-term mesalazine maintenance treatment may reduce the risk of colon cancer.

 

Clinical efficacy and safety

Mild to moderate acute ulcerative colitis

This indication was also investigated in seven controlled and three open label clinical trials. A total of 787 patients were enrolled, of whom 559 received Asacol 400 mg GR Tablets. Three studies were placebo-controlled, one of which also compared the efficacy of Asacol to another proprietary oral mesalazine product. Five studies were performed without comparator. The studies included dose ranging of Asacol. One study compared the efficacy of mesalazine versus sulfasalazine. The studies included dose ranging of Asacol from 1.2 - 4.8 g/day. One study used computerised morphometry to assess the efficacy of Asacol compared with a prednisolone enema. These studies established the safety and efficacy of Asacol for the treatment of mild to moderate acute UC at daily doses of 2.4 – 4.8 g mesalazine.

This indication was investigated in a double blind, randomised study with 229 patients. In the full analysis set (n=225), the UC-DAI reductions calculated between initiation and end of therapy after 8 weeks treatment were 1.5 in the 2.4 g/day Asacolon 400 group, 2.9 in the 3.6 g/day Asacolon 400 group, 1.3 in the 2.25 g/day active comparator group and 0.3 in the placebo group. Treatment with 3.6 g/day Asacolon 400 was superior to 2.25 g/day mesalazine comparator drug (P=0.003). No significant differences were seen in the safety profiles of all treatments.

 

 

Maintenance of remission of ulcerative colitis

The efficacy of Asacolon 400 was investigated in a double-blind randomised placebo-controlled study including 264 patients. Treatment success in the two Asacolon 400 (0.8 g/day) and 1.6 g/day) was compared by endoscopic evaluation at the 6-month endpoint with the placebo group by using the Fischer exact test. In the intention-to-treat analysis of all patients, 42 of 87 patients (48.3%) in the placebo group had treatment success compared to 57 of the 90 patients (63.3% [CI, 52.8% to 73.8%]) in the group receiving 0.8 g/day (P= 0.050) and 61 of the 87 patients (70.1% [CI, 59.9% to 80.3%]) in the group receiving 1.6 g/day (P= 0.005). Asacolon 400 mg GR Tablets were safe and effective in maintaining remission in quiescent ulcerative colitis.

 

This indication was studied in five controlled and two open label clinical trials involving 677 patients, of whom 406 received Asacol 400 mg GR Tablets. Asacol treatment was compared to sulfasalazine in three studies, to another proprietary oral mesalazine product in one study, and to placebo in one study. The dosage varied from 0.8 - 4.4 g mesalazine per day. These studies established the safety and efficacy of Asacol for the maintenance of remission of UC at daily doses of 1.6 – 2.4 g mesalazine.

 

Maintenance of remission of Crohn’s ileo-colitisMaintenance of surgically-induced remission of Crohn’s Disease

 

One open-label study in 15 Italian collaborating centres enrolled 110 CD patients operated for Crohn’s disease by first intestinal resection, of which 47 evaluable patients treated with Asacolon 400 (2.4 g/day) were compared to 48 patients given no treatment. The cumulative proportion of recurrence at 6, 12 and 24 months was significantly lower in the mesalazine group than in the untreated group (P=0.002). At 24 months the cumulative proportions of endoscopic recurrence were 0.52 (±0.12) (±S.E.M.) and 0.85 (±0.07), respectively. The cumulative proportions of severe recurrence was also significantly lower in the Asacolon 400 group 0.17 (±0.09) vs. 0.38 (±0.09); P=0.021. The results of the study indicate that Asacolon 400 mg GR Tablets are safe and delay the recurrence and lessens the severity of the disease at 2 years.

This indication was studied in one double blind, one retrospective and two open label clinical studies involving 336 patients, of whom 159 received Asacol 400 mg GR Tablets. Asacol treatment was compared to sulfasalazine in one study and to placebo or no specific treatment in three studies. Two studies confirmed efficacy in preventing post-operative recurrence of Crohn’s disease. These studies support the safety and efficacy of Asacol in the treatment of quiescent Crohn's disease of the terminal ileum and colon including post-operative patients at a daily dose of 2.4 g mesalazine.

 

 

5.2       Pharmacokinetic properties

Absorption

Asacolon 400 mg Gastro-resistant Tabletstablets are coated with a pH responsive polymer [EudragitTM S] which allows the active principle to be releasedenables the release of mesalazine only at a pH above 7, i.e. when the intraluminal pH is above 7, that is within the terminal ileum and colon, which are the main sites of inflammation in IBD. After any initial disruption of the coating mesalazine will continue to be released irrespective of the pH. Asacolon tablets have been designed to minimise absorption of mesalazine in the digestive tract.

 

After a single dose of 2.4 g of mesalazine (6 Asacolon 400 mg GR Tablets) in healthy volunteers under fasting conditions quantifiable amounts (> 2.00 ng/mL) of mesalazine were observed in plasma after 4.5 h (median tlag). The geometric mean Cmax –value of mesalazine was 722.11 ng/mL with a median tmax of about 9.5 h, whereas that of N-acetyl mesalazine was 1437.90 ng/mL with a median tmax of 12.0 h.

Based on the recovery of unchanged mesalazine and the main metabolite N-acetyl mesalazine in collected urine after fasted oral administration approximately 25% of the dose (more than 95 % as metabolite) was excreted renally within 60 h.

Following concomitant food intake in the same study a single dose of 2.4 g of mesalazine resulted in quantifiable amounts of mesalazine after 9.0 h (median tlag). The geometric mean Cmax –value of mesalazine was 1725.93 ng/mL with a median tmax of about 22.0 h, whereas that of N-acetyl mesalazine was 2235.32 ng/mL with a median tmax of 24.0 h.

Based on the recovery of unchanged mesalazine and the main metabolite N-acetyl mesalazine in collected urine after fed oral administration approximately 30% of the dose (about 90 % as metabolite) was excreted renally within 60 h.

Following concomitant food intake the Cmax-values of mesalazine increased 2.39-fold, and the extent of exposure (AUC0-tlast) increased 1.57-fold. Concerning N-acetyl mesalazine after concomitant food intake the Cmax-values increased 1.55-fold, whereas its extent of exposure increased about 1.1-fold only.

Absorption by the oral route is approximately 26 %.  Consequently, 74 % of the administered dose remain within the terminal ileum, colon, and rectum, being available to exert a topical anti-inflammatory effect. Mesalazine is metabolised both by the liver and the intestinal mucosa to an inactive derivative, N-acetyl-5-aminosalicylic acid. Mesalazine has an elimination half-life between 9 hours (single dose) and 11 hours (steady state). The elimination of mesalazine is essentially faecal and urinary, in the form of mesalazine and its N-acetyl metabolite.

 

Distribution

About 43% mesalazine and about 78% N-acetyl mesalazine are bound to plasma proteins.

Approximately 75 % of the administered dose remains in the gut lumen and the mucosal tissue.

The mean apparent volume of distribution per kg of body weight (Vdw) was 59.07 L/kg (geometric mean: 48.86 L/kg) after a single dose of 2.40 g of mesalazine (6 GR tablets of Asacolon 400 mg) in healthy volunteers under fasting conditions. Based upon the absorption of 24.8% of the administered dose, this parameter is equal to 14.65 L/kg (geometric mean: 12.12 L/kg).

Low concentrations of mesalazine and N-acetyl mesalazine have been detected in human breast milk. The clinical significance of this has not been determined.

 

Biotransformation

Mesalazine is metabolised both by the intestinal mucosa and the liver to the inactive metabolite N-acetyl mesalazine. At least 90% of the drug recovered in the urine after oral administration is found as the main metabolite N-acetyl-mesalazine.

 

Elimination

The elimination of mesalazine is essentially urinary and faecal in the form of mesalazine and its N-acetyl metabolite. The geometric mean of total apparent clearance of mesalazine after administration of 2.40 g of mesalazine (6 GR tablets of Asacolon 400 mg) in healthy volunteers under fasting conditions was about 135 L/h (geometric mean, CV% = 61.43%, intersubject). The median elimination half-life was 20 h ranging from 5 to 77 h.

About 25% of the total dose administered was recovered in the urine within 60 h after fasted administrationmainly as N-acetyl mesalazine and as the parent compound (about 1 %).

 

Linearity/non-linearity

In a cross-over design with 3 test periods and 3 ascending oral doses of Asacolon 400 mg GR Tablets administered 6 hourly over 4 consecutive doses (total daily dose of mesalazine: 3200, 4800, 6400 mg) it was shown that the absorption and elimination kinetics for mesalazine are dose independent for the 3 doses evaluated.  For each dose, about ¾ of the dose was available for the therapeutic activity for the colon. Only about ¼ of each dose was absorbed and excreted in the urine, primarily as the metabolite. Based on urine drug excretion, plasma drug Cmax’s and the combined plasma AUC’s, there was a linear dose response for the 3 Asacolon tablet doses. The clinical performance of Asacol 400 should be similar for the range of doses evaluated in this study.

 

Pharmacokinetic/pharmacodynamics relationship(s)

No specific studies have been performed.

 

5.3       Preclinical safety data

Effects in non-clinical studies were observed only at exposures considered sufficiently in excess of the maximum human exposure indicating little relevance to clinical use.

Toxicity of mesalazine after oral administration has been investigated in several studies with both single and repeated doses. When a dose of 1g/kg body weight/day was administered repeatedly to rats, it caused damage in kidneys and the gastro-intestinal tract.

 

10.       DATE OF REVISION OF THE TEXT

October 2013 September 2014

 

 

Updated on 6 November 2014 PIL

Reasons for updating

  • Change to, or new use for medicine
  • Change to warnings or special precautions for use
  • Change of contraindications
  • Change to instructions about overdose
  • Change to storage instructions
  • Change to side-effects
  • Change to drug interactions
  • Change to information about drinking alcohol
  • Change to information about pregnancy or lactation
  • Change to information about driving or using machinery
  • Change to how the medicine works
  • Change to date of revision

Updated on 14 October 2013 SPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 10 - Date of revision of the text

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OLD

CURRENTLY APPROVED

4.2       Posology and Method of Administration

 

4.2       Posology and Method of Administration

 

Children

There is no dose recommendation for children (see 4.3 and 4.4).

 

Paediatric population

There is only limited documentation for an effect in children (age 6-18 years).

 

Children 6 years of age and older

·        Active disease: To be determined individually, starting with 30-50 mg/kg/day in divided doses. Maximum dose: 75 mg/kg/day in divided doses. The total dose should not exceed 4.0 g/day.

·        Maintenance treatment: To be determined individually, starting with 15-30 mg/kg/day in divided doses. The total dose should not exceed 2.0 g/day.

 

It is generally recommended that half the adult dose may be given to children up to a body weight of 40 kg; and the normal adult dose to those above 40 kg.

 

4.4       Special warnings and precautions for use

 

4.4       Special warnings and precautions for use

 

Children

Safety and effectiveness of Asacolon tablets in children have not been established.

 

Paediatric population

There is only limited documentation for an effect in children (age 6-18 years), see section 4.2.

 

10.       DATE OF REVISION OF THE TEXT

 

10.       DATE OF REVISION OF THE TEXT

 

August 2012

October 2013

 

Updated on 14 October 2013 PIL

Reasons for updating

  • Change to, or new use for medicine
  • Change to further information section

Updated on 9 October 2012 SPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

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Section 4.2


Adults:

Ulcerative colitis:

Induction of remission:

2.4 g (6 tablets) per day in divided doses. If required the dose may be increased to 4 g (10 tablets) 4.8 g (12 tablets) daily.

The dosage can be adjusted in accordance with the response to the treatment.

Maintenance of remission:

1.2 to 2.4 g (3 to 6 tablets) per day once daily or in divided doses.

 

Crohn’s disease:

Maintenance of remission:

2.4 g (6 tablets) per day once daily or in divided doses.

 

Section 10

November 2011

August 2012

Updated on 25 September 2012 PIL

Reasons for updating

  • Change to, or new use for medicine
  • Change to date of revision

Updated on 16 November 2011 SPC

Reasons for updating

  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose
  • Change to section 10 - Date of revision of the text

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4.3       Contraindications

Asacolon is contraindicated in cases of:

 

-  History of hypersensitivity to salicylates.

-  Hypersensitivity to mesalazine or any of the excipients (see section 6.1).

-  Severe renal impairment (GFR less than 30 mL per minute).

-  Severe liver impairment.

-  Gastric and duodenal ulcers

-  Children under 2 years of age.

 

4.4       Special warnings and precautions for use

 

Renal impairment

Urinary status (dip sticks) should be determined prior to and during treatment, at the discretion of the treating physician. Not recommended for use in patients with renal impairment. Caution should be exercised in patients with raised blood urea or proteinuria. The possibility of mesalazine-induced nephrotoxicity should be suspected in patients developing impairment of renal function during treatment.

 

It is recommended that all patients have an evaluation of their renal function prior to initiation of Asacolon therapy and periodically while on Asacolon therapy. As a guideline, follow-up tests are recommended 14 days of initiation of therapy and then every 4 weeks for the following 12 weeks. Short monitoring intervals early after the start of Asacolon therapy will discover rare acute allergic impairment of renal function. In the absence of an acute allergic renal response monitoring intervals can be extended to every 3 months and then annually after 5 years. If additional signs of illness appear, these tests should be performed immediately. Treatment with Asacolon should be stopped immediately if there is evidence of renal impairment and patients should seek immediate medical advice.

 

Liver impairment

There have been reports of increased liver enzyme levels in patients taking preparations containing mesalazine. Caution is recommended if Asacolon is administered to patients with liver impairment. Blood tests (liver function parameters such as ALT or AST) should be determined prior to and during treatment, at the discretion of the treating physician. As a guideline, follow-up tests are recommended 14 days after commencement of treatment, then a further two to three tests at intervals of 4 weeks. If the findings are normal, follow-up tests should be carried out every 3 months. If additional symptoms occur, these tests should be performed immediately.

 

Cardiac hypersensitivity reactions

Mesalazine-induced cardiac hypersensitivity reactions (myo- and pericarditis) have been reported rarely with Asacolon. In case of previous mesalazine-induced cardiac hypersensitivity Asacolon must not be reintroduced. Caution should be used in patients with previous myo- and pericarditis of allergic background regardless of its origin.

 

Pulmonary disease

Patients with pulmonary disease, in particular asthma, should be very carefully monitored during a course of treatment with Asacolon.

 

 

Hypersensitivity to Sulphasalazine

In patients with a history of hypersensitivity to sulphasalazine, therapy should be initiated only under close medical supervision. Treatment must be stopped immediately if acute symptoms of intolerance occur such as abdominal cramps, acute abdominal pain, fever, severe headache and rash.

 

Blood dyscrasia

Very rarely serious blood dyscrasia has been reported with this medicinal product. Treatment with Asacolon should be stopped immediately if there is a suspicion or evidence of blood dyscrasia, such as unexplained bleeding, haematoma, purpura, anaemia, persistent fever or sore throat, and patients should seek immediate medical advice.  Haematological investigations including a complete blood count should be performed prior to initiation and while on therapy at the discretion of the treating physician. As a guideline, follow-up tests are generally recommended 14 days after initiation of therapy and then every 4 weeks for the following 12 weeks. If the results are normal, follow-up tests should be carried out every 3 months. If additional symptoms occur, these tests should be performed immediately.

 

Tablets in stool

A limited number of reports of intact tablets in stool have been received. What appear to be intact tablets may in some cases represent largely empty shells of the tablet coating. Asacolon 400 mg Gastro-resistant Tablets release their content in the lower gut even if the coating does not dissolve entirely. Once pH 7.0 is reached, cracks in the coating are sufficient for the release of mesalazine from the tablets. This process is irreversible from here on and mesalazine will therefore be released continuously, independent of intestinal pH. If tablets are observed in the stool repeatedly, the patient should consult his/her physician.

 

Intolerance to carbohydrates

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

 

The elderly

Use in the elderly should be handled with caution and the product should only be prescribed to patients having a normal renal function.

 

Children

Safety and effectiveness of Asacolon tablets in children have not been established.

 

4.5       Interactions with other medicinal products and other forms of interactions

 

Specific interaction studies have not been performed.

 

Sulphasalazine decreases the absorption of digoxin. There are no data on interaction of digoxin with mesalazine.

 

Mesalazine can increase the myelosuppressive effects of azathioprine, or 6-mercaptopurine, or thioguanine. Life-threatening infection can occur. Patients should be closely observed for signs of infection and myelosuppression. Haematological parameters, such as leukocyte and lymphocyte cell counts should be monitored regularly (weekly), especially at initiation of such combination therapy (see section 4.4). If white blood cells are stable after 1 month, testing every 4 weeks for the following 12 weeks followed by 3 monthly monitoring intervals appears to be justified.

 

The concurrent use of known nephrotoxic agents, such as NSAIDs, azathioprine, or methotrexate, may increase the risk of renal reactions. However, no adverse events proving such interactions have been reported (see section 4.4).

 

There is weak evidence that mesalazine might decrease the anticoagulant effect of warfarin.

 

Apart from purine antimetabolites interaction studies in adults and children, no other interaction studies in adults or paediatric patients have been performed.

 

4.6       Fertility, pregnancy and lactation

 

There are no adequate data on the use of Asacolon in pregnant women. However, data from a limited number (627) of exposed pregnancies indicate no adverse effect of mesalazine on the pregnancy or on the health of the fetus/newborn child, but more frequent pre-term births cannot be excluded. To date no other relevant epidemiologic data are available.

 

In one single case after long-term use of a high dose of mesalazine (2-4 g, orally) during pregnancy, renal failure in a neonate was reported.

 

Animal studies on oral mesalazine do not indicate direct or indirect harmful effects with respect to pregnancy, embryonic/fetal development, parturition or postnatal development.

Mesalazine crosses the placental barrier. Asacolon should only be used during pregnancy if the potential benefit outweighs the possible risk. Caution should be exercised when using high doses of mesalazine.

 

N-acetyl-5-aminosalicylic acid and to a lesser degree mesalazine are excreted in breast milk. The clinical significance of this has not been determined. Only limited experience during lactation in women is available to date. Hypersensitivity reactions such as diarrhoea in the infant cannot be excluded. Therefore, Asacolon should only be used during breast-feeding, if the potential benefit outweighs the possible risk. If the infant develops diarrhoea, breast-feeding should be discontinued.

 

4.7       Effects on ability to drive and use machines

 

No effects on the ability to drive and use machines have been observed.

 

4.8       Undesirable effects

 

The Asacolon clinical trial database includes 651 patients treated with Asacolon 400 mg GR Tablets. The mesalazine doses were in the range of 0.8 to 4.8 g/day, the average treatment duration varied between four weeks and four years.

 

Undesirable effects relevant for the labelling reported from nine double-blind and six open clinical studies and information from spontaneous reporting or the literature is listed below. The latter was reported from a population of unknown size. Their frequency is not known.

 

Blood and lymphatic system disorders

Uncommon     : anaemia.

Very rare         :altered blood counts (aplastic anaemia, agranulocytosis, pancytopenia,

                          neutropenia, leucopenia, thrombocytopenia), bone marrow depression,

                          eosinophilia, blood disorder.

 

Immune system disorders

Very rare         : hypersensitivity reactions such as allergic exanthema, drug fever, lupus

                          erythematosus syndrome, pancolitis.

Nervous system disorders

Uncommon     : tinnitus, paresthesia.

Rare                 : headache, dizziness.

Very rare         : peripheral neuropathy.

 

Cardiac disorders

Rare                 : myocarditis, pericarditis.

 

Respiratory, thoracic and mediastinal disorders

Very rare         : allergic and fibrotic lung reactions (including dyspnoea, cough,  

                          bronchospasm, alveolitis, pulmonary eosinophilia, lung infiltration,  

                          pneumonitis), pneumonia, interstitial pneumonia, eosinophilic pneumonia,

                          lung disorder.

 

Gastrointestinal disorders

Rare                 : abdominal pain, diarrhoea, flatulence, nausea, vomiting, dyspepsia.

Very rare         : acute pancreatitis.

Not known      : exacerbation of the symptoms of colitis.

 

Hepato-biliary disorders

Very rare         : changes in liver function parameters (increase in transaminases and

                          cholestasis parameters), hepatitis, cholestatic hepatitis.

 

Skin and subcutaneous tissue disorders

Common         : rash.

Uncommon     : pruritus, urticaria.

Very rare         : alopecia.

 

Musculoskeletal and connective tissue disorders

Very rare         : myalgia, arthralgia.

Not known      : lupus-like syndrome with pericarditis and pleuropericarditis as

                          prominent symptoms as well as rash and arthralgia.

 

Renal and urinary disorders

Very Rare        : impairment of renal function including acute and chronic interstitial

                          nephritis and renal insufficiency, nephrotic syndrome, renal failure which

                          may be reversible on withdrawal.

 

Reproductive system and breast disorders

Very rare:       oligospermia (reversible).

 

General disorders and administration site conditions

.

Uncommon     : drug ineffective.

Very rare         : chest pain.

 

Very common:  ≥ 1/10, common:  ≥ 1/100 and < 1/10, uncommon:  ≥  1/1,000 and < 1/100, rare:  ≥  1/10,000 and < 1/1,000, very rare:  < 1/10,000, not known (cannot be estimated from the available data)

 

An unknown number of the above undesirable effects are probably associated to the underlying IBD rather than Asacolon/mesalazine medication. This holds true especially for gastrointestinal undesirable effects and arthralgia.

 

Mesalazine‑induced nephrotoxicity, which may be reversible on withdrawal, should be suspected in patients developing renal dysfunction during treatment (see section 4.4).

 

To avoid blood dyscrasia resulting from developing bone marrow depression patients should be monitored with care (see section 4.4).

 

Co-administration of myelosuppressive drugs such as azathioprine, or 6-MP, or thioguanine can precipitate leucopenia (see section 4.5).

 

Concurrent use of NSAIDs, azathioprine, or methotrexate may increase the risk of renal reactions (see section 4.5).

 

4.9       Overdosage

 There are rare data on overdose (e.g. intended suicide with high oral doses of mesalazine), which do not indicate renal or hepatic toxicity. There is no specific antidote and treatment is symptomatic and supportive.

 

 

 

 

10.       DATE OF REVISION OF THE TEXT

November 2011

Updated on 15 November 2011 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to side-effects
  • Change to date of revision

Updated on 23 May 2011 PIL

Reasons for updating

  • Addition of manufacturer

Updated on 1 March 2011 SPC

Reasons for updating

  • Change to section 6.1 - List of excipients

Legal category: Product subject to medical prescription which may be renewed (B)

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6. PHARMACEUTICAL PARTICULARS

 

6.1. List of Excipients

 

Lactose, granular

Sodium starch glycollate

Magnesium stearate (E572)

Talc (E553b)

Povidone

 

Film Coating

Methacrylic acid-methyl methacrylate copolymer (1:2)

Talc

Dibutyl phthalate Triethyl citrate

Yellow pigment (ferric oxide) (E172)

Macrogol 6000

Red pigment (ferric oxide) (E172)

 

 

Updated on 24 February 2011 SPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 6.1 - List of excipients
  • Change to section 9 - Date of renewal of authorisation
  • Change to section 10 - Date of revision of the text

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2.         QUALITATIVE AND QUANTITATIVE COMPOSITION

Each gastro-resistant tablet contains: Mesalazine 400mg.

 

Excipients: also contains 76.4mg of lactose monohydrate, see section 4.4.for further details.

For full list of excipients, see section 6.1.

 

 

6.         PHARMACEUTICAL PARTICULARS

 

6.1       List of excipients

Sodium starch glycolate (Type A)

 

9.         DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION

Date of first authorisation:     11th December 1990

Date of last renewal:              11th December 2010

 

 

10.       DATE OF REVISION OF THE TEXT

February 2011

 

Updated on 23 February 2011 PIL

Reasons for updating

  • Change to further information section
  • Change to date of revision

Updated on 14 December 2009 PIL

Reasons for updating

  • Change due to user-testing of patient information
  • Correction of spelling/typing errors
  • Improved electronic presentation

Updated on 18 November 2009 SPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose
  • Change to section 5.3 - Preclinical safety data
  • Change to section 10 - Date of revision of the text
  • Correction of spelling/typing errors
  • Improved electronic presentation
  • Change to improve clarity and readability

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

In section 4.2 (posology and method of administration) wording of headings have been changed from Geriatric patients to The elderly and from Paediatric patients to Children.
In section 4.3 (contraindications): gastric and duodenal ulcers have been added.
In section 4.4 (special warnings and precautions for use) subsection renal impairment has been rewritten for better understanding, subsection cardiac hypersensitivity reactions has been added, subsection lung function impairment has been removed, subsection Sensitivity to Sulphasalazine has been renamed with Hypersensitivity to Sulphasalazine, in subsection blood dyscrasia new wording, in subsection Intolerance to carbohydrates new wording, subsection Geriatric patients has been renamed The elderly and new wording, subsection Paediatric patients replaced by Children.
In section 4.5 (Interaction with other medicinal products and other forms of interactions) new wording.
In section 4.6 (Pregnancy and lactation) new wording.
In section 4.7 (Effects on ability to drive and use machines): Asacolon tablets have no or negligible influence on the ability to drive and use machines, or negligible removed.
In section 4.8 (Undesirable effects): new wording and:
Blood and lymphatic system disorder: eosinophilia added.
Nervous system disorder: peripheral neuropathy added.
Hepato-biliary disorders: liver function test abnormal, blood bilirubin increase added.
Removed: Investigations: blood bilirubin increase, liver function test abnormal.
Section 4.9 (Overdose) has been rewritten.
Section 5.3 (Preclinical safety data) has been rewritten.

Updated on 23 September 2008 PIL

Reasons for updating

  • Change of manufacturer

Updated on 8 May 2008 SPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 6.4 - Special precautions for storage
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Update of section 2, 4.4 6.4 and 10.

Updated on 31 October 2007 SPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 5.3 - Preclinical safety data
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

For details of the changes please refer to the following link:
 

Updated on 27 April 2006 SPC

Reasons for updating

  • New SPC for medicines.ie

Legal category: Product subject to medical prescription which may be renewed (B)

Updated on 27 April 2006 PIL

Reasons for updating

  • New PIL for medicines.ie