Pentasa 500 mg Prolonged Release Tablets

  • Name:

    Pentasa 500 mg Prolonged Release Tablets

  • Company:
    info
  • Active Ingredients:

    Mesalazine

  • Legal Category:

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

Summary of Product Characteristics last updated on medicines.ie: 12/11/2019

Click on this link to Download PDF directly

Ferring Ireland Limited

Ferring Ireland Limited

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1 - 0 of 35 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 12 November 2019 SmPC

Reasons for updating

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

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

Free text change information supplied by the pharmaceutical company

Updates:

Section 4.4, to add sentence ‘Cases of nephrolithiasis have been reported with the use of mesalazine including stones with a 100% mesalazine content. It is recommended to ensure adequate fluid intake during treatment.’.

Section 4.8, to add column ‘Not known (cannot be estimated from the available data)’ and ‘Nephrolitiasis’ in Renal and urinary disorders section.

Updated on 25 January 2018 SmPC

Reasons for updating

  • New SmPC for new product

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

Updated on 25 January 2018 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose

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

Free text change information supplied by the pharmaceutical company

Section 4.4:

Sentence update: “Patients with pulmonary disease, in particular asthma, should be very carefully monitored during a course of treatment; please refer to section 4.8.”

 

Section 4.8

Photosensitivity” added as a rare side effect with the note “More severe reactions are reported in patients with pre-existing skin conditions such as atopic dermatitis and atopic eczema.

Other minor updates:

-          blood disorders” updated to “altered blood counts”

-          allergic exanthema” reworded to “dermatitis allergic” and relocated to section for skin and subcutaneous tissue disorders

-          increased liver enzymens, cholestasis parameters and bilirublin” reworded for clarification to “Increase in transaminases, increase in cholestasis parameters (e.g. alkaline phosphatase, gamma-glutamyltransferase and bilirubin),”

-          “lupus erythematosus-like reactions” reworded to “lupus erythematosus-like syndrome (systemic lupus erythematosus)”

-          “drug fever” moved to section for general disorders and administration site conditions.

 

Section 4.9

Most common symptoms of salicylate toxicity added for clarification as follows:

“But since PENTASA is an amino salicylate, symptoms of salicylate toxicity such as acid-base balance disorder, hyperventilation, pulmonary oedema, vomiting, dehydration and hypoglycaemia may occur. Symptoms of salicylate over dosage are well described in the literature”

Updated on 25 January 2018 PIL

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose

Free text change information supplied by the pharmaceutical company

Section 4.4:

Sentence update: “Patients with pulmonary disease, in particular asthma, should be very carefully monitored during a course of treatment; please refer to section 4.8.”

 

Section 4.8

Photosensitivity” added as a rare side effect with the note “More severe reactions are reported in patients with pre-existing skin conditions such as atopic dermatitis and atopic eczema.

Other minor updates:

-          blood disorders” updated to “altered blood counts”

-          allergic exanthema” reworded to “dermatitis allergic” and relocated to section for skin and subcutaneous tissue disorders

-          increased liver enzymens, cholestasis parameters and bilirublin” reworded for clarification to “Increase in transaminases, increase in cholestasis parameters (e.g. alkaline phosphatase, gamma-glutamyltransferase and bilirubin),”

-          “lupus erythematosus-like reactions” reworded to “lupus erythematosus-like syndrome (systemic lupus erythematosus)”

-          “drug fever” moved to section for general disorders and administration site conditions.

 

Section 4.9

Most common symptoms of salicylate toxicity added for clarification as follows:

“But since PENTASA is an amino salicylate, symptoms of salicylate toxicity such as acid-base balance disorder, hyperventilation, pulmonary oedema, vomiting, dehydration and hypoglycaemia may occur. Symptoms of salicylate over dosage are well described in the literature”

Updated on 24 June 2016 SmPC

Reasons for updating

  • 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

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

Free text change information supplied by the pharmaceutical company

Section 4.6:

New sentence: “The underlying condition itself (Inflammatory bowel disease (IBD) may increase risks for adverse pregnancy outcome.”

New text:  “There are no adequate and well controlled studies of Pentasa use in pregnant women. Limited published human data on mesalazine show no increase in the overall rate of congenital malformations.  Some data show an increased rate of preterm birth, stillbirth, and low birth weight; however, these adverse pregnancy outcomes are also associated with active inflammatory bowel disease. “

Deleted: “From several observational studies no teratogenic effects are reported and there is no evidence of significant risk of use in humans.”

Section 4.7:

Text updated from “No adverse effects” to “Treatment with Pentasa is unlikely to affect the ability to drive and/or use machines.”

Section 4.8

Adverse events updated, see SPC for full updated list.

 

Section 4.9

New sentences:

“But since Pentasa is an amino salicylate, symptoms of salicylate toxicity may occur.  Symptoms of salicylate over dosage are well described in the literature.  “

“There is no specific antidote and the management of overdose is supportive and symptomatic. The treatment at hospital includes close monitoring of renal function.”

 

Deleted text:

“There is no specific antidote and treatment is symptomatic and supportive.”

Management of overdose in man:

Symptomatic treatment at hospital. Close monitoring of renal function. Intravenous infusion of electrolytes may be used to promote diuresis.”

 

Section 5.1

Deleted:It is thought to act locally on the gut wall in inflammatory bowel disease, although its precise mechanism of action has not been fully elucidated.”

New sections:

“It has been established that mesalazine is the active component of sulphasalazine which is used for the treatment of ulcerative colitis and Crohn’s disease.  Based on clinical results, the therapeutic value of mesalazine after oral as well as rectal administration appears to be due to local effect on the inflamed intestinal tissue, rather than to systemic effect.  There is information suggesting that severity of colonic inflammation in ulcerative colitis patients treated with mesalazine is inversely correlated with mucosal concentrations of mesalazine. “

 

The mechanism of action of mesalazine is not fully understood although mechanisms such as activation of the γ-form of peroxisome proliferator-activated receptors (PPAR-γ) and inhibition of nuclear factor-kappa B (NF-κB) in the intestinal mucosa has been implicated.  “

 

Sections 5.2 and 5.3

Full updates, see SPC for text.

Updated on 24 June 2016 PIL

Reasons for updating

  • 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

Free text change information supplied by the pharmaceutical company

Section 4.6:

New sentence: “The underlying condition itself (Inflammatory bowel disease (IBD) may increase risks for adverse pregnancy outcome.”

New text:  “There are no adequate and well controlled studies of Pentasa use in pregnant women. Limited published human data on mesalazine show no increase in the overall rate of congenital malformations.  Some data show an increased rate of preterm birth, stillbirth, and low birth weight; however, these adverse pregnancy outcomes are also associated with active inflammatory bowel disease. “

Deleted: “From several observational studies no teratogenic effects are reported and there is no evidence of significant risk of use in humans.”

Section 4.7:

Text updated from “No adverse effects” to “Treatment with Pentasa is unlikely to affect the ability to drive and/or use machines.”

Section 4.8

Adverse events updated, see SPC for full updated list.

 

Section 4.9

New sentences:

“But since Pentasa is an amino salicylate, symptoms of salicylate toxicity may occur.  Symptoms of salicylate over dosage are well described in the literature.  “

“There is no specific antidote and the management of overdose is supportive and symptomatic. The treatment at hospital includes close monitoring of renal function.”

 

Deleted text:

“There is no specific antidote and treatment is symptomatic and supportive.”

Management of overdose in man:

Symptomatic treatment at hospital. Close monitoring of renal function. Intravenous infusion of electrolytes may be used to promote diuresis.”

 

Section 5.1

Deleted:It is thought to act locally on the gut wall in inflammatory bowel disease, although its precise mechanism of action has not been fully elucidated.”

New sections:

“It has been established that mesalazine is the active component of sulphasalazine which is used for the treatment of ulcerative colitis and Crohn’s disease.  Based on clinical results, the therapeutic value of mesalazine after oral as well as rectal administration appears to be due to local effect on the inflamed intestinal tissue, rather than to systemic effect.  There is information suggesting that severity of colonic inflammation in ulcerative colitis patients treated with mesalazine is inversely correlated with mucosal concentrations of mesalazine. “

 

The mechanism of action of mesalazine is not fully understood although mechanisms such as activation of the γ-form of peroxisome proliferator-activated receptors (PPAR-γ) and inhibition of nuclear factor-kappa B (NF-κB) in the intestinal mucosa has been implicated.  “

 

Sections 5.2 and 5.3

Full updates, see SPC for text.

Updated on 26 May 2015 PIL

Reasons for updating

  • Change to Section 4.8 – Undesirable effects - how to report a side effect

Free text change information supplied by the pharmaceutical company

Update to include new HPRA contact information

Updated on 26 May 2015 SmPC

Reasons for updating

  • Change to Section 4.8 – Undesirable effects - how to report a side effect

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

Free text change information supplied by the pharmaceutical company

Update to include new HPRA contact information

Updated on 15 July 2014 PIL

Reasons for updating

  • Change to section 1 - Name of medicinal product
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 10 - Date of revision of the text

Free text change information supplied by the pharmaceutical company

1.         TRADE NAME OF MEDICINAL PRODUCT

Pentasa 500 mg500mg Prolonged-release Tablets


2.         QUALITATIVE AND QUANTITATIVE COMPOSITION     

Each tablet contains mesalazine 500 mg.

 

For full list of excipients, see section 6.1.

 

3.         PHARMACEUTICAL FORM

Prolonged-release tablet.

 

White-grey to pale brown, speckled, round, prolonged release tablets, scored and marked '500mg' on one side and 'PENTASA’ on the reverse side.


4.         CLINICAL  PARTICULARS

           

4.1       Therapeutic indications

For the treatment of mild to moderate ulcerative colitis and Crohn's disease.

 

4.2       Posology and method of administration

 

Ulcerative Colitis

Adults:

Acute TreatmentActive treatment:  Individual dosage, up to 4 g mesalazine once daily or in two or three divided doses.

 

Maintenance treatment:  Recommended dosage, 2 g mesalazine once daily.

 

Children:

Individual dosage, recommended starting dose is 20-30 mg/kg bodyweight daily in two or three divided doses.

 

Crohn’s Disease

Adults:

Acute TreatmentActive treatment:  Individual dosage, up to 4 g mesalazine daily in two or three divided doses.

 

Maintenance treatment:  Individual dosage, up to 4 g mesalazine daily in two or three divided doses.

 

Paediatric population

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

 

Ulcerative colitis

Treatment of active disease:

Children:

Individual dosage, recommended  6 years of age and older:  To be determined individually, starting dose is 20-with 30-50 mg/kg bodyweight daily in two or three/day in divided doses. Maximum dose: 75 mg/kg/day in divided doses. The total dose should not exceed 4 g/day (maximum adult dose).

 

Maintenance treatment:

Children 6 years of age and older:  To be determined individually, starting with 15-30 mg/kg/day in divided doses. The total dose should not exceed 2 g/day (recommended adult dose).

 

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.

 

Crohn’s disease

Treatment of active disease:

Children 6 years of age and older:  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 g/day (maximum adult dose).

 

Maintenance treatment:

Children 6 years of age and older:  To be determined individually, starting with 15-30 mg/kg/day in divided doses. The total dose should not exceed 2 g/day (recommended adult dose).

 

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.

 

 

Method of Administration

Pentasa tablets must not be chewed.  To facilitate swallowing the tablets may be dispersed in 50 ml of cold water. Stir and drink immediately.

 

 

4.3       CONTRAINDICATIONS

           

Hypersensitivity to mesalazine, any of the excipients, or salicylates

Severe liver and/or renal impairment

Children under the age of 2 years

 

 

 

4.8       Undesirable effects

The most frequent adverse reactions seen in clinical trials are diarrhoea, nausea, abdominal pain, headache, vomiting and rash.  Hypersensitivity reactions and drug fever may occasionally occur.

 

Frequency of adverse effects, based on clinical trials and reports from post-marketing surveillance.


                    <No changes to ADR table>

 

* The mechanism of mesalazine induced myocarditis, pericarditis, pancreatitis, nephritis and hepatitis is unknown, but it might be of allergic origin.

It is important to note that several of these disorders can also be attributed to be the inflammatory bowel disease itself.

 

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 IMB Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971;  Fax: +353 1 6762517.

Website: www.imb.ie; e-mail: imbpharmacovigilance@imb.ie

5.         PHARMACOLOGICAL PROPERTIES

5.1       Pharmacodynamic Properties

Pharmacotherapeutic group: Intestinal anti-inflammatory agents.

ATC Code: A07 EC02

 

Mechanism of action and pharmacodynamic effects:

Mesalazine is recognised as the active moiety of sulphasalazine in the treatment of ulcerative colitis. It is thought to act locally on the gut wall in inflammatory bowel disease, although its precise mechanism of action has not been fully elucidated.

 

Increased leucocyte migration, abnormal cytokine production, increased production of arachidonic acid metabolites, particularly leukotriene B4 and increased free radical formation in the inflamed intestinal tissue are all present in patients with inflammatory bowel disease. Mesalazine has in-vitro and in-vivo pharmacological effects that inhibit leucocyte chemotaxis, decrease cytokine and leukotriene production and scavenge for free radicals. It is currently unknown which, if any of these mechanisms play a predominant role in the clinical efficacy of mesalazine.

 

The risk of colorectal cancer (CRC) is slightly increased in ulcerative colitis. Observed effects of mesalazine in experimental models and patient biopsies support the role of mesalazine in prevention of colitis-associated CRC, with down regulation of both inflammation dependent and non-inflammation dependent signalling pathways involved in the development of colitis-associated CRC. However data from meta-analyses, including both referral and non-referral populations, provide inconsistent clinical information regarding the benefit of mesalazine in the carcinogenesis risk associated with ulcerative colitis.


10.       DATE OF REVISION OF THE TEXT

August 2013June 2014

Updated on 15 July 2014 SmPC

Reasons for updating

  • Change to section 1 - Name of medicinal product
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • 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

1.         TRADE NAME OF MEDICINAL PRODUCT

Pentasa 500 mg500mg Prolonged-release Tablets


2.         QUALITATIVE AND QUANTITATIVE COMPOSITION     

Each tablet contains mesalazine 500 mg.

 

For full list of excipients, see section 6.1.

 

3.         PHARMACEUTICAL FORM

Prolonged-release tablet.

 

White-grey to pale brown, speckled, round, prolonged release tablets, scored and marked '500mg' on one side and 'PENTASA’ on the reverse side.


4.         CLINICAL  PARTICULARS

           

4.1       Therapeutic indications

For the treatment of mild to moderate ulcerative colitis and Crohn's disease.

 

4.2       Posology and method of administration

 

Ulcerative Colitis

Adults:

Acute TreatmentActive treatment:  Individual dosage, up to 4 g mesalazine once daily or in two or three divided doses.

 

Maintenance treatment:  Recommended dosage, 2 g mesalazine once daily.

 

Children:

Individual dosage, recommended starting dose is 20-30 mg/kg bodyweight daily in two or three divided doses.

 

Crohn’s Disease

Adults:

Acute TreatmentActive treatment:  Individual dosage, up to 4 g mesalazine daily in two or three divided doses.

 

Maintenance treatment:  Individual dosage, up to 4 g mesalazine daily in two or three divided doses.

 

Paediatric population

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

 

Ulcerative colitis

Treatment of active disease:

Children:

Individual dosage, recommended  6 years of age and older:  To be determined individually, starting dose is 20-with 30-50 mg/kg bodyweight daily in two or three/day in divided doses. Maximum dose: 75 mg/kg/day in divided doses. The total dose should not exceed 4 g/day (maximum adult dose).

 

Maintenance treatment:

Children 6 years of age and older:  To be determined individually, starting with 15-30 mg/kg/day in divided doses. The total dose should not exceed 2 g/day (recommended adult dose).

 

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.

 

Crohn’s disease

Treatment of active disease:

Children 6 years of age and older:  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 g/day (maximum adult dose).

 

Maintenance treatment:

Children 6 years of age and older:  To be determined individually, starting with 15-30 mg/kg/day in divided doses. The total dose should not exceed 2 g/day (recommended adult dose).

 

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.

 

 

Method of Administration

Pentasa tablets must not be chewed.  To facilitate swallowing the tablets may be dispersed in 50 ml of cold water. Stir and drink immediately.

 

 

4.3       CONTRAINDICATIONS

           

Hypersensitivity to mesalazine, any of the excipients, or salicylates

Severe liver and/or renal impairment

Children under the age of 2 years

 

 

 

4.8       Undesirable effects

The most frequent adverse reactions seen in clinical trials are diarrhoea, nausea, abdominal pain, headache, vomiting and rash.  Hypersensitivity reactions and drug fever may occasionally occur.

 

Frequency of adverse effects, based on clinical trials and reports from post-marketing surveillance.


                    <No changes to ADR table>

 

* The mechanism of mesalazine induced myocarditis, pericarditis, pancreatitis, nephritis and hepatitis is unknown, but it might be of allergic origin.

It is important to note that several of these disorders can also be attributed to be the inflammatory bowel disease itself.

 

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 IMB Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971;  Fax: +353 1 6762517.

Website: www.imb.ie; e-mail: imbpharmacovigilance@imb.ie

5.         PHARMACOLOGICAL PROPERTIES

5.1       Pharmacodynamic Properties

Pharmacotherapeutic group: Intestinal anti-inflammatory agents.

ATC Code: A07 EC02

 

Mechanism of action and pharmacodynamic effects:

Mesalazine is recognised as the active moiety of sulphasalazine in the treatment of ulcerative colitis. It is thought to act locally on the gut wall in inflammatory bowel disease, although its precise mechanism of action has not been fully elucidated.

 

Increased leucocyte migration, abnormal cytokine production, increased production of arachidonic acid metabolites, particularly leukotriene B4 and increased free radical formation in the inflamed intestinal tissue are all present in patients with inflammatory bowel disease. Mesalazine has in-vitro and in-vivo pharmacological effects that inhibit leucocyte chemotaxis, decrease cytokine and leukotriene production and scavenge for free radicals. It is currently unknown which, if any of these mechanisms play a predominant role in the clinical efficacy of mesalazine.

 

The risk of colorectal cancer (CRC) is slightly increased in ulcerative colitis. Observed effects of mesalazine in experimental models and patient biopsies support the role of mesalazine in prevention of colitis-associated CRC, with down regulation of both inflammation dependent and non-inflammation dependent signalling pathways involved in the development of colitis-associated CRC. However data from meta-analyses, including both referral and non-referral populations, provide inconsistent clinical information regarding the benefit of mesalazine in the carcinogenesis risk associated with ulcerative colitis.


10.       DATE OF REVISION OF THE TEXT

August 2013June 2014

Updated on 30 August 2013 PIL

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 5.1 - Pharmacodynamic properties

Free text change information supplied by the pharmaceutical company

Section 4.1:
Updated to “For the treatment of mild to moderate ulcerative colitis and Crohn's disease."

 

 

Section 4.2:
“Ulcerative Colitis, Adults: Acute Treatment: Individual dosage, up to 4 g mesalazine once daily or in two or three divided doses”

 Crohn’s Disease, Adults: Maintenance treatment: Individual dosage, up to 4 g recommended starting dose is 1500mg mesalazine daily in two or three divided doses."

Section 5.1:
ATC code added (A07 EC02)

Updated on 30 August 2013 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 5.1 - Pharmacodynamic properties

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

Free text change information supplied by the pharmaceutical company

Section 4.1:
Updated to “For the treatment of mild to moderate ulcerative colitis and Crohn's disease."

 

 

Section 4.2:
“Ulcerative Colitis, Adults: Acute Treatment: Individual dosage, up to 4 g mesalazine once daily or in two or three divided doses”

 Crohn’s Disease, Adults: Maintenance treatment: Individual dosage, up to 4 g recommended starting dose is 1500mg mesalazine daily in two or three divided doses."

Section 5.1:
ATC code added (A07 EC02)

Updated on 3 August 2012 SmPC

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 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose
  • Change to section 6.4 - Special precautions for storage

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

Free text change information supplied by the pharmaceutical company

Section 4.2

- addition of sentence: “Pentasa tablets must not be chewed. To facilitate swallowing the tablets may be dispersed in 50ml of cold water. Stir and drink immediately.”

 

Section 4.3:
Removed two contraindications: active peptic ulcer and coagulopathy.

Section 4.4:

Most patients who are intolerant or hypersensitive to sulphasalazine are able to take Pentasa without risk of similar reactions. However, caution is recommended when treating patients allergic to sulphasalazine (risk of allergy to salicylates). Haematological investigations should be performed if the patient develops unexplained bleeding, bruising, purpura, anaemia, fever or sore throat.  In case of acute intolerance reactions such as abdominal cramps, acute abdominal pain, fever, severe headache and rash, therapy should be discontinued immediately.

 

Caution is recommended in patients with impaired liver function. Liver function parameters like ALT or AST should be assessed prior to and during treatment, at the discretion of the treating physician.

 

It is recommended that mesalazine be used with extreme caution in patients with mild to moderate renal impairment. (See section 4.3, Contraindications).

 

Patients on any oral formulation of mesalazine should have renal function monitored, with serum creatinine levels measured prior to treatment start, every 3 months for the first year, then 6 monthly for the next 4 years and annually thereafter.  Treatment with mesalazine should be discontinued if renal function deteriorates.

 

If a patient develops dehydration while on treatment with mesalazine, normal electrolyte levels and fluid balance should be restored as soon as possible.

 

The drug is not recommended for use in patients with renal impairment. The renal function should be monitored regularly (e.g. serum creatinine), especially during the initial phase of treatment. Urinary status (dip sticks) should be determined prior to and during treatment at the discretion of the treating physician. Mesalazine induced nephrotoxicity should be suspected in patients developing renal dysfunction during treatment. The concurrent use of other known nephrotoxic agents should increase monitoring frequency of renal function.

 

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

 

Mesalazine induced cardiac hypersensitivity reactions (myocarditis and pericarditis) have been reported rarely. Serious blood dyscrasias have been reported very rarely with mesalazine. Blood test for differential blood count is recommended prior to and during treatment, at the discretion of the treating physician. As stated in the interaction section 4.5, concomitant treatment with mesalazine can increase the risk of blood dyscrasia in patients receiving azathioprine, or 6-mercaptopurine or thioguanine. Treatment should be discontinued on suspicion or evidence of these adverse reactions.

 

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 three months. If additional symptoms occur, these tests should be performed immediately.

 

 

 

 

 

 

 

 

 


Section 4.5:
Section update from

 

“The concurrent use of mesalazine with other known nephrotoxic agents, such as NSAIDs and azathioprine, may increase the risk of renal reaction (See section 4.4, Special warnings and precautions for use).”

 

to

 

“Combination therapy with Pentasa and azathioprine, or 6-mercaptopurine or thioguanine have in several studies shown a higher frequency of myelosuppressive effects, and an interaction seems to exist, however, the mechanism behind the interaction is not fully established. Regular monitoring of white blood cells is recommended and dosage regime of thiopurines should be adjusted accordingly.

 

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

 

 


Section 4.6:

Section update as follows:

 

“Experience of use during pregnancy is limited. Pentasa should be used with caution during pregnancy and lactation and only if the potential benefit outweighs the possible hazards in the opinion of the physician

 

Mesalazine is known to cross the placental barrier, but the limited data available on its use in pregnant women do not allow assessment of possible adverse effects. No teratogenic effects have been observed in animal studies. and its concentration in umbilical cord plasma is one tenth of the concentration in maternal plasma. The metabolite acetyl-mesalazine is found in the same concentration in umbilical cord and maternal plasma. From several observational studies no teratogenic effects are reported and there is no evidence of significant risk of use in humans. Animal studies on oral mesalazine do not indicate direct or indirect harmful effects with respect to pregnancy, embryonic/foetal development, parturition or postnatal development. Blood disorders (pancytopenia, leucopenia, thrombocytopenia, anaemia) have been reported in new-borns of mothers being treated with Pentasa.

 

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.

 

Mesalazine is excreted in breast milk. The mesalazine concentration in breast milk is lower than in maternal blood, whereas the metabolite, acetyl mesalazine appears in similar or increased concentrations. No adverse effects in suckling babies of mothers treated with Pentasa have been reported, but the data are very limited. There is limited experience of the use of oral mesalazine in lactating women. No controlled studies with Pentasa during breast-feeding have been carried out. Hypersensitivity reactions like diarrhoea in the infant can not be excluded. If the infant develops diarrhoea, breast-feeding should be discontinued.

 

 

Animal data on mesalazine show no effect on male and female fertility.

Oligospermia (reversible) has been reported after use of mesalazine, see section 4.8.

 


Section 4.8
addition of the subheading: "Frequency of adverse effects, based on clinical trials and reports from post-marketing surveillance"

updates to adverse events as follows:
    -Blood and the lymphatic system disorders, Very rare: "eosinophilia (as part of an allergic reaction), altered blood counts (anaemia, aplastic anaemia, leucopenia (incl granulocytopenia and neutropenia)), thrombocytopenia, agranulocytosis, pancytopenia"
    - Immune system disorders, Very rare: "pancolitis, hypersensitivity reactions such as allergic exanthema"
    - Nervous system disorders, Rare: "dizziness"
    - Resiratory, thoracic adn mediastinal disorders, Very rare: "Allergic and fibrotic lung reactions (incl dyspnoea, coughing, bronchospasm, allergic alveolitis, pulmonary eosinophilia, interstitial lung disease, pulmonary infiltration, pneumonitis)
    - Gastrointestinal disorders, Rare: "Increased amylase, acute pancreatitis*, flatulence"
    - Hepato-biliary disorders, Very rare: "Increased liver enzymes, cholestatis parameters adn bilirubin, hepatotoxicity incl hepatitis*, cholestatic hepatitis, cirrhosis, hepatic failure)
    - Skin and subcutaneous tissue disorders, Very rare: "Reversible alopecis, bullous skin reactions including erythema multidorme adn Stevens Johnson Syndrome"
    - Renal and urinary disorders, Very rare: "Renal function abnormal impairment (incl. acute and chronic interstitial nephritis*, nephrotic syndrome, renal insufficiency), Urine discolouration"

    - Reproductive system disorders, Very rare: "Oligospermia (reversible)"


Section 4.9
'Human experience' section updated from “No cases of overdose have been reported.” to "There is limited clinical experience with overdose of Pentasa which does not indicate renal or hepatic toxicity. There is no specific antidote and treatment is symptomatic and supportive. There have been reports of patients taking daily doses of 8 grams for a month without any adverse events."

 

 

Section 6.4

Following sentence included: “Store in the original package as the product is sensitive to light.”

 

 

 

Updated on 3 August 2012 PIL

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 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose
  • Change to section 6.4 - Special precautions for storage

Free text change information supplied by the pharmaceutical company

Section 4.2

- addition of sentence: “Pentasa tablets must not be chewed. To facilitate swallowing the tablets may be dispersed in 50ml of cold water. Stir and drink immediately.”

 

Section 4.3:
Removed two contraindications: active peptic ulcer and coagulopathy.

Section 4.4:

Most patients who are intolerant or hypersensitive to sulphasalazine are able to take Pentasa without risk of similar reactions. However, caution is recommended when treating patients allergic to sulphasalazine (risk of allergy to salicylates). Haematological investigations should be performed if the patient develops unexplained bleeding, bruising, purpura, anaemia, fever or sore throat.  In case of acute intolerance reactions such as abdominal cramps, acute abdominal pain, fever, severe headache and rash, therapy should be discontinued immediately.

 

Caution is recommended in patients with impaired liver function. Liver function parameters like ALT or AST should be assessed prior to and during treatment, at the discretion of the treating physician.

 

It is recommended that mesalazine be used with extreme caution in patients with mild to moderate renal impairment. (See section 4.3, Contraindications).

 

Patients on any oral formulation of mesalazine should have renal function monitored, with serum creatinine levels measured prior to treatment start, every 3 months for the first year, then 6 monthly for the next 4 years and annually thereafter.  Treatment with mesalazine should be discontinued if renal function deteriorates.

 

If a patient develops dehydration while on treatment with mesalazine, normal electrolyte levels and fluid balance should be restored as soon as possible.

 

The drug is not recommended for use in patients with renal impairment. The renal function should be monitored regularly (e.g. serum creatinine), especially during the initial phase of treatment. Urinary status (dip sticks) should be determined prior to and during treatment at the discretion of the treating physician. Mesalazine induced nephrotoxicity should be suspected in patients developing renal dysfunction during treatment. The concurrent use of other known nephrotoxic agents should increase monitoring frequency of renal function.

 

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

 

Mesalazine induced cardiac hypersensitivity reactions (myocarditis and pericarditis) have been reported rarely. Serious blood dyscrasias have been reported very rarely with mesalazine. Blood test for differential blood count is recommended prior to and during treatment, at the discretion of the treating physician. As stated in the interaction section 4.5, concomitant treatment with mesalazine can increase the risk of blood dyscrasia in patients receiving azathioprine, or 6-mercaptopurine or thioguanine. Treatment should be discontinued on suspicion or evidence of these adverse reactions.

 

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 three months. If additional symptoms occur, these tests should be performed immediately.

 

 

 

 

 

 

 

 

 


Section 4.5:
Section update from

 

“The concurrent use of mesalazine with other known nephrotoxic agents, such as NSAIDs and azathioprine, may increase the risk of renal reaction (See section 4.4, Special warnings and precautions for use).”

 

to

 

“Combination therapy with Pentasa and azathioprine, or 6-mercaptopurine or thioguanine have in several studies shown a higher frequency of myelosuppressive effects, and an interaction seems to exist, however, the mechanism behind the interaction is not fully established. Regular monitoring of white blood cells is recommended and dosage regime of thiopurines should be adjusted accordingly.

 

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

 

 


Section 4.6:

Section update as follows:

 

“Experience of use during pregnancy is limited. Pentasa should be used with caution during pregnancy and lactation and only if the potential benefit outweighs the possible hazards in the opinion of the physician

 

Mesalazine is known to cross the placental barrier, but the limited data available on its use in pregnant women do not allow assessment of possible adverse effects. No teratogenic effects have been observed in animal studies. and its concentration in umbilical cord plasma is one tenth of the concentration in maternal plasma. The metabolite acetyl-mesalazine is found in the same concentration in umbilical cord and maternal plasma. From several observational studies no teratogenic effects are reported and there is no evidence of significant risk of use in humans. Animal studies on oral mesalazine do not indicate direct or indirect harmful effects with respect to pregnancy, embryonic/foetal development, parturition or postnatal development. Blood disorders (pancytopenia, leucopenia, thrombocytopenia, anaemia) have been reported in new-borns of mothers being treated with Pentasa.

 

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.

 

Mesalazine is excreted in breast milk. The mesalazine concentration in breast milk is lower than in maternal blood, whereas the metabolite, acetyl mesalazine appears in similar or increased concentrations. No adverse effects in suckling babies of mothers treated with Pentasa have been reported, but the data are very limited. There is limited experience of the use of oral mesalazine in lactating women. No controlled studies with Pentasa during breast-feeding have been carried out. Hypersensitivity reactions like diarrhoea in the infant can not be excluded. If the infant develops diarrhoea, breast-feeding should be discontinued.

 

 

Animal data on mesalazine show no effect on male and female fertility.

Oligospermia (reversible) has been reported after use of mesalazine, see section 4.8.

 


Section 4.8
addition of the subheading: "Frequency of adverse effects, based on clinical trials and reports from post-marketing surveillance"

updates to adverse events as follows:
    -Blood and the lymphatic system disorders, Very rare: "eosinophilia (as part of an allergic reaction), altered blood counts (anaemia, aplastic anaemia, leucopenia (incl granulocytopenia and neutropenia)), thrombocytopenia, agranulocytosis, pancytopenia"
    - Immune system disorders, Very rare: "pancolitis, hypersensitivity reactions such as allergic exanthema"
    - Nervous system disorders, Rare: "dizziness"
    - Resiratory, thoracic adn mediastinal disorders, Very rare: "Allergic and fibrotic lung reactions (incl dyspnoea, coughing, bronchospasm, allergic alveolitis, pulmonary eosinophilia, interstitial lung disease, pulmonary infiltration, pneumonitis)
    - Gastrointestinal disorders, Rare: "Increased amylase, acute pancreatitis*, flatulence"
    - Hepato-biliary disorders, Very rare: "Increased liver enzymes, cholestatis parameters adn bilirubin, hepatotoxicity incl hepatitis*, cholestatic hepatitis, cirrhosis, hepatic failure)
    - Skin and subcutaneous tissue disorders, Very rare: "Reversible alopecis, bullous skin reactions including erythema multidorme adn Stevens Johnson Syndrome"
    - Renal and urinary disorders, Very rare: "Renal function abnormal impairment (incl. acute and chronic interstitial nephritis*, nephrotic syndrome, renal insufficiency), Urine discolouration"

    - Reproductive system disorders, Very rare: "Oligospermia (reversible)"


Section 4.9
'Human experience' section updated from “No cases of overdose have been reported.” to "There is limited clinical experience with overdose of Pentasa which does not indicate renal or hepatic toxicity. There is no specific antidote and treatment is symptomatic and supportive. There have been reports of patients taking daily doses of 8 grams for a month without any adverse events."

 

 

Section 6.4

Following sentence included: “Store in the original package as the product is sensitive to light.”

 

 

 

Updated on 22 June 2009 PIL

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.8 - Undesirable effects

Free text change information supplied by the pharmaceutical company

Section 4.2:  A change in the recommended dose for maintenance of Ulcerative Colitis to '2g once daily'
Section 4.8:  Addition of undesirable effects: peripheral neuropathy, pneumonitis and urine discolouration.  Table updated to MedDRA format.

Updated on 22 June 2009 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.8 - Undesirable effects

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

Free text change information supplied by the pharmaceutical company

Section 4.2:  A change in the recommended dose for maintenance of Ulcerative Colitis to '2g once daily'
Section 4.8:  Addition of undesirable effects: peripheral neuropathy, pneumonitis and urine discolouration.  Table updated to MedDRA format.

Updated on 19 August 2008 PIL

Reasons for updating

  • Change to section 3 - Pharmaceutical form
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 10 - Date of revision of the text

Free text change information supplied by the pharmaceutical company

Section 3  Tablet colour changed from 'white to light grey' to 'white-grey to pale brown'.
Section 6.6  'No special precautions requried' changed to 'No special requirements'
Section 10  Changed Date of Revision of Text to August 2008

Updated on 19 August 2008 SmPC

Reasons for updating

  • Change to section 3 - Pharmaceutical form
  • 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

Section 3  Tablet colour changed from 'white to light grey' to 'white-grey to pale brown'.
Section 6.6  'No special precautions requried' changed to 'No special requirements'
Section 10  Changed Date of Revision of Text to August 2008

Updated on 27 August 2007 SmPC

Reasons for updating

  • Correction of spelling/typing errors

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

Updated on 27 August 2007 PIL

Reasons for updating

  • Correction of spelling/typing errors

Updated on 27 June 2005 PIL

Reasons for updating

  • Change to section 7 - Marketing authorisation holder
  • Change to section 9 - Date of renewal of authorisation
  • Change to section 10 - Date of revision of the text

Updated on 27 June 2005 SmPC

Reasons for updating

  • Change to section 7 - Marketing authorisation holder
  • Change to section 9 - Date of renewal of authorisation
  • Change to section 10 - Date of revision of the text

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

Updated on 26 June 2003 SmPC

Reasons for updating

  • New SPC for medicines.ie

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

Updated on 26 June 2003 PIL

Reasons for updating

  • New SPC for medicines.ie