Asacolon 500 mg Suppositories

  • Name:

    Asacolon 500 mg Suppositories

  • Company:
    info
  • Active Ingredients:

    Mesalazine

  • Legal Category:

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

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

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Tillotts Pharma GmbH

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 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

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

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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 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • 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

4.3       Contraindications

 

Hypersensitivity to the active substance or any of the excipients listed in section 6.1.

-  Known hypersensitivity to salicylates.

-  Known allergy to peanut or soya oil.

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

-  Severe liver impairment.

          - Children under 2 years of age.

 

 

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. Asacolon therapy should be stopped immediately if there is a suspicion or evidence of blood dyscrasia (signs of unexplained bleeding, bruising, purpura, anemia, persistent fever or sore throat), and patients should seek immediate medical advice. It is recommended that haematological investigation (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 treatment and then 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.

...

 

 

Hypersensitivity to Soya Oil

Patients with known allergy to peanut or soya oil should not take this medicine.

...

 

 

 

 

4.8       Undesirable effects

 

a)                  Summary of the safety profile

The Asacolon clinical trial database includes 246 patients treated with Asacolon 500 mg Suppositories. The mesalazine doses were in the range of 1.0 g/day to 1.5 g/day, the treatment duration varied between four weeks and twelve months.

Organ specific adverse drug reactions affecting the heart, lungs, liver, kidneys, pancreas, skin and subcutaneous tissue have been reported in association with oral or combined oral and rectal mesalazine administration. Most of these undesirable effects have not been reported following Asacolon 500 mg Suppositories monotherapy, but were observed with oral mesalazine administration. However, it cannot be excluded that these events can also occur with rectal mesalazine use alone.

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 four double-blind clinical studies and one open label clinical trial, 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 and < 1/10, uncommon:  ≥ 1/1,000 and < 1/100

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

 

Rare

(≥ 1/10,000 to

< 1/1,000)

Very rare

(< 1/10,000)

Frequency not known

Blood and lymphatic system disorders

--

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

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).

pleurisy

Gastrointestinal disorders

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

--

alopecia.

 

Musculoskeletal, connective tissue and bone disorders

--

myalgia, arthralgia.

 

Renal and urinary disorders

--

impairment of renal function including acute and chronic interstitial nephritis and renal insufficiency.

 

Reproductive system and breast disorders

--

oligospermia (reversible).

 

General disorders and administration site conditions

 

 

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

 

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 - use in children and adolescents
  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision

Updated on 26 May 2015 SPC

Reasons for updating

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

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

Free text change information supplied by the pharmaceutical company

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 1204/1/1
PA 2018/1/3

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 4.8 – Undesirable effects - how to report a side effect
  • 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 6.1 - List of excipients
  • Change to section 6.4 - Special precautions for storage
  • 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 suppository contains: Mesalazine 500 mg mesalazine.

 

Excipient(s) with known effect:

Each suppository contains 2.5 g hard fat containing lecithin derived from soya, see section 4.4.


For the
full list of excipients, see section 6.1.


 

4.1       Therapeutic Indications

 

This medication is indicated in adults for:

For the treatment of mild to moderate proctitis and proctosigmoiditis.

 

As an adjunct to oral therapy in severe generalised ulcerative colitis affecting the rectum or rectosigmoid colon.

4.2       Posology and method of administration

 

Rectal administration.

Posology

Adults:

One suppository to be inserted up to three times daily, after defaecation. The dosage is dependent upon the severity of the disease and it may be possible to reduce the dosage as the condition improves. In severe generalised ulcerative colitis affecting the rectum or rectosigmoid, and in cases slow to respond to oral therapy, one suppository may be used morning and evening, as an adjunct to oral therapy.

 

Renal impairment/hepatic impairment:

No data from controlled clinical studies are available warranting a specific dose adjustment in patients with mild to moderate renal or hepatic impairment. The maximum daily adult dose of 1.5 g mesalazine for rectal administration appears to carry little additional risk in these patients considering 4.0 g mesalazine being approved as maximum daily dose for oral administration (Asacolon tablets) to treat mild acute ulcerative colitis, see section 4.4. For severe renal or hepatic impairment, see section 4.3

 

The elderlyOlder people:

As for adults aboveThe normal adult dose can be used unless liver or renal function is severely impaired, (see section 4.3 and 4.4). No studies have been carried out in the elderlyolder people.

 

Paediatric population

There is little experience and only limited documentation for an effect in children.

 

Method of administration: rectal.

The suppositories are for rectal use and must not be swallowed. 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 hypersensitivity to salicylates.

-  Hypersensitivity to mesalazine the active substance or any of the excipients listed in (see section 6.1).

-  Known hypersensitivity to salicylates.

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

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 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 after initiation of therapycommencement 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 renal impairment appearsymptoms occur, 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. Asacolon therapy should be stopped immediately if there is a suspicion or evidence of blood dyscrasia (signs of unexplained bleeding, bruising, purpura, anemia, persistent fever or sore throat), and patients should seek immediate medical advice. It is recommended that haematological investigation (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 treatment and then 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.

 

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 rarely reported rarely with Asacolon. In case of previous 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 toAdverse drug reactions to Sulphasalazine

In pPatients with a history of hypersensitivity adverse drug reactions to sulphasalazine, therapy should be initiated onlykept 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.

 

Hypersensitivity to Soya Oil

Patients with known allergy to peanut or soya oil should not take this medicine.

 

Blood dyscrasia

Very rarely serious blood dyscrasia has been reported with this medicinal product.  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 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 are recommended should be carried out every 3 months. If additional symptoms occur, these tests should be performed immediately.. This procedure is to be followed especially, if a patient develops signs and symptoms suggestive of blood dyscrasia during treatment, such as unexplained bleeding, haematoma, purpura, anaemia, persistent fever or sore throat. Treatment with Asacolon should be stopped immediately if there is a suspicion or evidence of blood dyscrasia and patients should seek immediate medical advice.

Gastric and duodenal ulcers

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

 

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 little experience and only limited documentation for an effect in children.

 

4.5       Interaction with other medicinal products and other forms of interaction

 

Specific No interaction studies have not been performed.

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 Mesalazine can increase the myelosuppressive effects of azathioprine and or 6-mercapto-purine, or thioguanine should be taken into account. As a result, Llife-threatening infection can occur. Patients should be closely observed for signs of infection and myelosuppression. Haematological parameters, such asespecially the 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.

 

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       PFertility, 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 foetus/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/feoetal 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

The Asacolon clinical trial database includes 246 patients treated with Asacolon 500 mg Suppositories. The mesalazine doses were in the range of 1.0 g/day to 1.5 g/day, the treatment duration varied between four weeks and twelve months.

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

Organ specific adverse drug reactions affecting the heart, lungs, liver, kidneys, pancreas, skin and subcutaneous tissue have been reported in association with oral or combined oral and rectal mesalazine administration. Most of these undesirable effects have not been reported following Asacolon 500 mg Suppositories monotherapy, but were observed with oral mesalazine administration. However, it cannot be excluded that these events can also occur with rectal mesalazine use alone.

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 four double-blind clinical studies and one open label clinical trial, 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 and < 1/10, uncommon:  ≥ 1/1,000 and < 1/100

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

 

 

Rare

(≥ 1/10,000 to

< 1/1,000)

Very rare

(< 1/10,000)

Blood and lymphatic system disorders

--

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

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).

Gastrointestinal disorders

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

--

alopecia.

Musculoskeletal, connective tissue and bone disorders

--

myalgia, arthralgia.

Renal and urinary disorders

--

impairment of renal function including acute and chronic interstitial nephritis and renal insufficiency.

Reproductive system and breast disorders

--

oligospermia (reversible).

 

Blood and lymphatic system disorders

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

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.

Very rare:

Not known:

acute pancreatitis.

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., blood bilirubin increased.

 

Skin and subcutaneous tissue disorders

Very rare:

alopecia.

 

Musculoskeletal, connective tissue and bone disorders

Very rare:

Not known:

myalgia, arthralgia.

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 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)

 

c)      Description of selected adverse reactions

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.

 

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).

 

Under Cco-administration of myelosuppressive immunosuppressive drugs such as azathioprine, or 6-MP or thioguanine can precipitate leucopenialife-threatening infection can occur, (see section 4.5).

 

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

 

d) Paediatric population

There is only limited safety experience with the use of Asacolon Suppositories in the paediatric population. It is expected that the target organs of possible adverse reactions in the paediatric population are the same as for adults (heart, lungs, liver, kidneys, pancreas, skin and subcutaneous tissue).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Irish Medicines Board, Pharmacovigilance Section, Fax: +353 1 6767836; e-mail: imbpharmacovigilance@imb.ie; www.imb.ie.

 

4.9       Overdose

 

There is littleare 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.

 

 

5.         PHARMACOLOGICAL PROPERTIES

 

5.1       Pharmacodynamic properties

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

 

Mechanism of action

Asacolon 500 mg Suppositories contains mesalazine [ATC A07EC02], also 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. Mesalazine inhibits migration of polymorph nuclear leucocytes and lipoxygenase 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. Under trial conditions mesalazine has also 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). Recently mMesalazine has been shown to activate PPAR-γ receptors which counteract nuclear activation of intestinal inflammatory responses.

 

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

Clinical studies in patients with mild to moderate proctitis and proctosigmoiditis.

Induction of remission of mild to moderate proctitis and proctosigmoiditis.

Two prospective, double-blind, placebo controlled studies including 156 patients provided evidence of clinical efficacy for Asacolon 500 mg Suppositories for the induction of remission of mild to moderate proctitis and proctosigmoiditis.

In one study, 94 patients with mild to moderate distal proctosigmoiditis (<20 cm) were enrolled. The primary endpoint included clinical, endoscopic and histologic remission rates at one month. Clinical remission was achieved in 22 of 32 (69%) in the 1 g Asacolon group, in 23 of 31 (74%) in the 1.5 g Asacolon group versus 7 of 31 (39%) with placebo.

 

A second study included 62 patients with mild to moderate ulcerative colitis localized at the distal rectosigmoid region. The primary endpoint included clinical, endoscopic and histologic remission rates at one month. The clinical outcome of either remission or improvement was achieved in 28 of 32 (88%) in the 500 mg t.i.d Asacolon group versus 10 of 30 (33%) with placebo.

 

Maintenance of remission of mild to moderate proctitis.

The clinical development of Asacolon 500 mg Suppositories included one comparative bioavailability study, one small scale tolerability and four double-blind clinical studies. The bioavailability study showed an acceptable profile in comparison to another licensed mesalazine suppository. The tolerability and clinical studies provided data supporting the safe and efficacious use. Evidence of clinical efficacy showed a statistically significant improvement in clinical, sigmoidoscopic and histological indices of disease.

Clinical study in patients with quiescent ulcerative proctitis.

A prospective, double-blind, multicentre trial studied the efficacy and tolerability of Asacolon 500 mg Suppositories in 111 patients with quiescent ulcerative proctitis limited to the rectum (≤ 15 cm from anus) for one year. Clinical outcome assessment was based on cumulative relapse rates at 12 months which were: 3 of 32 (10%) in the 1.0 g/day Asacolon group, 11 of 35 (32%) in the 0.5 g/day Asacolon group and 14 of 29 (47%) in the placebo group.

 

 

5.2       Pharmacokinetic properties

 

Absorption

As with the tablets, oOnly a proportion of mesalazine contained in the suppositories is absorbed and available to the systemic circulation. The mode of action of mesalazine is local rather than systemic. Acetylation of mesalazine to N-acetyl mesalazine occurs in the gastrointestinal wall and in the liver. N-acetyl mesalazine is predominantly excreted in the urine. After a single dose of Asacolon 500 mg Suppositories in healthy volunteers the mean Cmax and Tmax were 211 ng/mL and 2.0 hours for mesalazine and 443 ng/mL and 3.0 hours for N-acetyl mesalazine, respectively. Mesalazine and the main metabolite N-acetyl mesalazine were reported to have biological half-lives of 4.97 hours and 8.32 hours, respectively. About 43% of mesalazine and about 78% of N-acetyl mesalazine are bound to plasma proteins.

 

Distribution

Low concentrations of mesalazine and its N-acetyl metabolite 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.

 

Elimination

The elimination of mesalazine is essentially faecal and urinary in the form of mesalazine and its N-acetyl metabolite. Mesalazine and the main metabolite N-acetyl mesalazine were reported to have biological half-lives of 4.97 hours and 8.32 hours, respectively, following the use of Asacolon 500 mg Suppositories in healthy volunteers.

 

Linearity/non-linearity

No specific studies have been performed.

 

Pharmacokinetic/pharmacodynamic 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.


6.1       List of excipients

Hard Fat.

Lecithin, derived from soya oil.

 

6.4       Special precautions for storage

Do not store above 25 °C. Do not refrigerate or freeze. Store in a dry place protected from direct heat. Store in the original package in order to protect from light.

6.6              Special precautions for disposal and other handling

No special requirements. Any unused product or waste material should be disposed of in accordance with local requirements.

 


10.       DATE OF REVISION OF THE TEXT

October 2013September 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 further information section
  • Change to date of revision

Updated on 14 October 2013 PIL

Reasons for updating

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

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

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

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Old

New

4.2       Posology and method of administration

 

4.2       Posology and method of administration

 

Children:

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

 

Paediatric population:

There is little experience and only limited documentation for an effect in children.

 

4.4       Special warnings and precautions for use

 

4.4       Special warnings and precautions for use

 

Children

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

 

Paediatric population

There is little experience and only limited documentation for an effect in children.

 

10.       DATE OF REVISION OF THE TEXT

 

10.       DATE OF REVISION OF THE TEXT

 

November 2011

 

October 2013

 

Updated on 22 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 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

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

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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. 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 after 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 symptoms occur, 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.  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 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 are recommended should be carried out every 3 months. If additional symptoms occur, these tests should be performed immediately.. This procedure is to be followed especially, if a patient develops signs and symptoms suggestive of blood dyscrasia during treatment, such as unexplained bleeding, haematoma, purpura, anaemia, persistent fever or sore throat. Treatment with Asacolon should be stopped immediately if there is a suspicion or evidence of blood dyscrasia and patients should seek immediate medical advice.

 

 

The elderly

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

 

Children

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

 

4.5       Interaction with other medicinal products and other forms of interaction

 

Specific interaction studies have not been performed.

 

Mesalazine can increase the myelosuppressive effects of azathioprine and 6-mercapto-purine, 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.

 

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       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/foetal 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 246 patients treated with Asacolon 500 mg Suppositories. The mesalazine doses were in the range of 1.0 g/day to 1.5 g/day, the treatment duration varied between four weeks and twelve months.

Undesirable effects relevant for the labelling reported from four double-blind and one open clinical study  and information from spontaneous reporting and 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

Very rare:          altered blood counts (aplastic anemia, 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

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.

Very rare

Not known:

acute pancreatitis.

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, blood bilirubin increased.

 

Skin and subcutaneous tissue disorders

Very rare:

alopecia.

 

Musculoskeletal, connective tissue and bone disorders

Very rare:

Not known:

myalgia, arthralgia.

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 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.

 

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       Overdose

 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 2010

 

Updated on 23 May 2011 PIL

Reasons for updating

  • Addition of manufacturer

Updated on 16 August 2010 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

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

Free text change information supplied by the pharmaceutical company

4.2       Posology and method of administration

new: 

Renal impairment/hepatic impairment:

No data from controlled clinical studies are available warranting a specific dose adjustment in patients with mild to moderate renal or hepatic impairment. The maximum daily adult dose of 1.5 g mesalazine for rectal administration appears to carry little additional risk in these patients considering 4.0 g mesalazine being approved as maximum daily dose for oral administration (Asacolon tablets) to treat mild acute ulcerative colitis, see section 4.4. For severe renal or hepatic impairment, see section 4.3

 

The elderly: only the word severely has been added

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

 

4.4       Special warnings and precautions for use

Renal impairment

deleted: Not recommended for use in patients with renal impairment.  

The elderly: only the word non-severely has been added

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

10.       DATE OF REVISION OF THE TEXT new date has been added

July 2010

 

Updated on 11 August 2010 PIL

Reasons for updating

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

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 5.1 - 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
  • 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

Section 4.2 (posology and method of administration) has been changed for better understanding and readability.
Section 4.3 (Contraindications): has been changed for better understanding and readability, and 'use in patients with haemorrhagic tendency' has been removed.   
Section 4.4 (Special warnings and precautions for use) has been changed for better understanding and readability, 'Patients with lung function impairment, especially asthma, should be very closely monitored' has been removed. New subsections (Renal impairment, liver impairment, cardia hypersensitivity reactions, the elderly and children) have been added.
Section 4.5 (Interaction with other medicinal products and other forms of interaction) has been changed for better understanding and readability, 'the uricosuric activity of sulfinpyrazone, the diuretic effect of furosemide may be reduced' has been removed, 'Apart from purine antimetabolites interactions studies in adults and children, no other interaction studies in adults or paediatric patients have been performed' has been added.
Section 4.6 (Pregnancy and lactation) has been changed for better understanding and readability.
Section 4.7 (Effects on ability to drive and use machines): 'No known effect' has been replaced by 'Asacolon suppositories have no influence on the ability to drive and use machines'.
Section 4.8 (Undesirable effects): has been changed for better understanding and readability. Introduction added, information on the frequency of undesirable effects (common, uncommon, not known) added, some AE terms renamed and allocation corrected to System Organ Class, Addition and Deletion of undesirable effects based on post-marketing experience and published undesirable effects cases.
Section 4.9 (Overdose): has been changed for better understanding and readability.
Section 5.1 (Pharmacodynamic properties): has been changed for better understanding and readability, new pharmacodynamic properties added.
Section 5.2 (Pharmacokinetic properties): has been changed for better understanding and readability, new pharmcokinetic properties added.
Section 5.3 (Preclinical safety data): has been changed for better understanding and readability, new preclinical safety data added.

Updated on 18 November 2009 PIL

Reasons for updating

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

Updated on 23 September 2008 PIL

Reasons for updating

  • Change of manufacturer

Updated on 6 December 2007 PIL

Reasons for updating

  • Correction of spelling/typing errors
  • Change to side-effects
  • Change to storage instructions
  • Change to date of revision

Updated on 28 August 2007 SPC

Reasons for updating

  • 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 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose
  • Change to section 5.1 - Pharmacodynamic properties
  • Correction of spelling/typing errors

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

Free text change information supplied by the pharmaceutical company

 

Section 4.4 (Special warnings and precautions for use):

Removed paragraph ‘Organic or functional obstruction in the upper gastrointestinal tract will delay onset of action of the product’.

Section 4.5 (Interaction with other medicinal products and other forms of interaction):

Removed paragraph ‘Mesalazine decreases the absorption of digoxin’.

Added paragraph ‘Concurrent use of known nephrotoxic agents including non steroidal anti-inflammatory drugs and azathioprine may increase the risk of renal impairment’.

Added ‘Haematological parameters, especially the white cell and lymphocyte cell counts should be monitored…’.

Replaced ‘Haematological parameters … should be monitored repeatedly …’ by ‘Haematological parameters … should be monitored regularly …’.

Removed ‘The uricosuric activity of probenecid and the activity of spironolactone may be reduced’.

Removed paragraph ‘Gastrointestinal side effects of glucocorticoids may be increased’.

Removed paragraph ‘Mesalazine may affect the action of antineoplastics by inhibition of thiopurine methyltransferase’.

Removed paragraph ‘Mesalazine may inhibit the action of warfarin; prothrombin time should be closely monitored if this combination is essential’.

Removed paragraph ‘In theory, interaction with antacids may occur due to pH imbalance, but this has not been shown experimentally’.

Section 4.8 (Undesirable effects):

This section has been widely amended according to the EC SPC guideline of October 2005. All undesirable effects are now grouped according to system organ classes and the frequency of occurrence has been added.

Section 4.9 (Overdose):

Removed ‘Gastric lavage’.

Section 5.1 (Pharmacodynamic properties):

Paragraph one: Replacement of  ‘… active component which is delivered directly to the distal colon by  the suppositories’ by ‘… active component which is delivered directly to the rectum and sigmoid colon by the suppositories’.

Updated on 27 April 2006 PIL

Reasons for updating

  • New PIL for medicines.ie

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)