Pentasa 10 mg/ml Rectal Suspension

  • Name:

    Pentasa 10 mg/ml Rectal Suspension

  • 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

Company Products

Medicine NameActive Ingredients
Medicine Name Cortiment 9mg prolonged release tablets Active Ingredients Budesonide
Medicine Name DDAVP Desmopressin 100 micrograms/ml Nasal drops,solution Active Ingredients Desmopressin Acetate
Medicine Name DDAVP/Desmopressin 4 micrograms/ml Solution for Injection Active Ingredients Desmopressin Acetate
Medicine Name Desmospray, Desmopressin Nasal Spray Active Ingredients Desmopressin Acetate
Medicine Name Desmotabs Melt 120 micrograms oral lyophilisate Active Ingredients Desmopressin Acetate
Medicine Name Desmotabs Melt 240 micrograms oral lyophilisate Active Ingredients Desmopressin Acetate
Medicine Name Desmotabs Melt 60 micrograms oral lyophilisate Active Ingredients Desmopressin Acetate
Medicine Name FIRMAGON 120 mg powder and solvent for solution for injection Active Ingredients degarelix acetate
Medicine Name FIRMAGON 80 mg powder and solvent for solution for injection Active Ingredients degarelix acetate
Medicine Name Glypressin 1 mg Powder and Solvent for Solution for Injection Active Ingredients Terlipressin acetate
Medicine Name Glypressin 1 mg/ 8.5 ml solution for injection Active Ingredients Terlipressin acetate
Medicine Name Gonapeptyl Depot 3.75 mg powder and solvent for suspension for injection Active Ingredients triptorelin acetate
Medicine Name Lutinus 100 mg Vaginal Tablets Active Ingredients Progesterone
Medicine Name Menopur 1200IU powder and solvent for solution for injection Active Ingredients Menotrophin
Medicine Name Menopur 600IU powder and solvent for solution for injection Active Ingredients Menotrophin
Medicine Name Menopur 75IU Powder and Solvent for Solution for Injection. Menotrophin (HMG) Active Ingredients Menotrophin
Medicine Name Noqturina 25 microgram oral lyophilisate Active Ingredients Desmopressin Acetate
Medicine Name Noqturina 50 microgram oral lyophilisate Active Ingredients Desmopressin
Medicine Name Nordurine 0.1 mg Tablets Active Ingredients Desmopressin Acetate
Medicine Name Nordurine 0.2mg Tablets Active Ingredients Desmopressin Acetate
Medicine Name Pabal 100 micrograms/ml solution for injection Active Ingredients Carbetocin
Medicine Name Pentasa 1 g Prolonged-release Tablets Active Ingredients Mesalazine
Medicine Name Pentasa 1 g Suppositories Active Ingredients Mesalazine
Medicine Name Pentasa 10 mg/ml Rectal Suspension Active Ingredients Mesalazine
Medicine Name Pentasa 500 mg Prolonged Release Tablets Active Ingredients Mesalazine
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 29 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 29 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.

- “anal discomfort and irritation at the application site, pruritus tenesmus” updated to “anal discomfort and irritation at the application site, pruritus (anal), rectal tenesmus”

 

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 29 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.

- “anal discomfort and irritation at the application site, pruritus tenesmus” updated to “anal discomfort and irritation at the application site, pruritus (anal), rectal tenesmus”

 

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
  • Change to section 6.6 - Special precautions for disposal and other handling

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.

 

Section 6.6:

New sentence:The rectal suspension may colour the linen and toilet.”

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
  • Change to section 6.6 - Special precautions for disposal and other handling

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.

 

Section 6.6:

New sentence:The rectal suspension may colour the linen and toilet.”

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 17 July 2014 PIL

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 10 - Date of revision of the text

Free text change information supplied by the pharmaceutical company

1. NAME OF THE MEDICINAL PRODUCT

Pentasa 10 mg/ml Rectal Suspension

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each bottle of rectal suspension contains mesalazine 1g in 100ml

.

 

For a full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Rectal suspension

White to slightly yellow suspension

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Pentasa Rectal Suspension is indicated in the management of active ulcerative colitis.

4.2 Posology and method of administration

Adults:

The recommended dosage is 1 g mesalazine (100 ml Rectal Suspension) at bedtime.

Paediatric population:

There is little experience and only limited documentation

for 2  3 weeksan effect in children.

Children

 

:

 

Reduced dose based on body weight.

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

4.4 Special warnings and precautions for use

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). 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.

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, 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.

4.5 Interaction with other medicinal products and other forms of interaction

Combination therapy with Pentasa and azathioprine, 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.

4.6 Fertility, pregnancy and lactation

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 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. 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.

4.7 Effects on ability to drive and use machines

No adverse effects.

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. Following rectal administration, local reactions such as pruritus, rectal discomfort and urge may occur.

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

<No changes to AE 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

4.9 Overdose

Acute experience in animals

:

 

Single oral doses of mesalazine of up to 5gkg in pigs or a single intravenous dose of mesalazine at 920mgkg in rats were not lethal.

Human experience

:

:

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.

Management of overdose in man

:

:

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

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Intestinal antiinflammatory agents (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.

5.2 Pharmacokinetic properties

General characteristics of the active substance

Disposition and local availability:

Pentasa Rectal Suspension are designed to provide the distal part of the intestinal tract with high concentrations of mesalazine and a low systemic absorption. The Rectal Suspension has been shown to reach and cover the descending colon.

Biotransformation:

Mesalazine is metabolised both presystemically by the intestinal mucosa and systemically in the liver to Nacetyl mesalazine (acetyl mesalazine). The acetylation seems to be independent of the acetylator phenotype of the patient. Some acetylation also occurs through the action of colonic bacteria.

Acetyl mesalazine is thought to be clinically as well as toxicologically inactive, although this remains to be confirmed.

Absorption:

The absorption following rectal administration is low, and depends on the dose, the formulation and the extent of spread. Based on urine recoveries in healthy volunteers under steady-state conditions given a daily dose of 2g (1g - 2), about 15-20% of the dose is absorbed after administration of Rectal Suspensions.

Distribution:

Mesalazine and acetyl mesalazine do not cross the blood brain barrier. Protein binding of mesalazine is approximately 50% and of acetyl mesalazine about 80%.

Elimination:

The plasma half-life of mesalazine following i.v. administration is approximately 40 minutes and for acetyl mesalazine approximately 70 minutes. Both substances are excreted in urine and faeces. The urinary excretion consists mainly of acetyl mesalazine.

Characteristics in patients:

The systematic absorption following administration of Pentasa Rectal Suspension has been shown to be significantly decreased in patients with active ulcerative colitis compared to those in remission.

In patients with impaired liver and kidney functions, the resultant decrease in the rate of elimination and increased systemic concentration of mesalazine may constitute an increased risk of nephrotoxic adverse reactions.

5.3 Preclinical safety data

Definitive nephrotoxicity and possible gastrointestinal toxicity is demonstrated in all species examined, and nephrotoxicity is evident with doses 5-10 times those used in humans.

In-vitro test systems and in-vivo studies showed no evidence of mutagenic effects. Studies on the tumorigenic potential carried out in rats showed no evidence of any substance-related increase in the incidence of tumours.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Disodium edetate.

Sodium metabisulfite (E223)

Sodium acetate.

Hydrochloric acid (for pH adjustment)

Purified water.

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

Before opening individual foil pack: 3 years

After opening individual foil pack: Use immediately

6.4 Special precautions for storage

Store below 25°C. Do not freeze.

Store in the original package in order to protect from light.

6.5 Nature and contents of container

Polyethylene bottles fitted with a tip containing a back valve for rectal administration. The bottles are supplied in nitrogen-filled aluminium foil bags. Presented in cartons containing 7 x 100ml bottles. A plastic sleeve bearing administration instructions is provided for each Rectal Suspension bottle. The sleeve also facilitates hygienic application of the Rectal Suspension and disposal after use

.

 

6.6 Special Precautions for disposal of a used medicinal product or waste materials derived from such medicinal product and other handling of the product.

Shake the Rectal Suspension bottle well before use.

7. MARKETING AUTHORISATION HOLDER

Ferring Ireland Ltd.,

United Drug House,

Magna Drive,

Magna Business Park,

Citywest Road,

Dublin 24,

Ireland

8. MARKETING AUTHORISATION NUMBER

PA 1009/6/3

9. DATE OF FIRST AUTHORISATION  RENEWAL OF AUTHORIZATION

Date of first authorisation: 2

nd February 1989

 

Date of last renewal: 2

nd February 2009

 

10. DATE OF REVISION OF THE TEXT

October 2013June 2014




Updated on 17 July 2014 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 10 - Date of revision of the text

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

Free text change information supplied by the pharmaceutical company

1. NAME OF THE MEDICINAL PRODUCT

Pentasa 10 mg/ml Rectal Suspension

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each bottle of rectal suspension contains mesalazine 1g in 100ml

.

 

For a full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Rectal suspension

White to slightly yellow suspension

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Pentasa Rectal Suspension is indicated in the management of active ulcerative colitis.

4.2 Posology and method of administration

Adults:

The recommended dosage is 1 g mesalazine (100 ml Rectal Suspension) at bedtime.

Paediatric population:

There is little experience and only limited documentation

for 2  3 weeksan effect in children.

Children

 

:

 

Reduced dose based on body weight.

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

4.4 Special warnings and precautions for use

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). 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.

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, 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.

4.5 Interaction with other medicinal products and other forms of interaction

Combination therapy with Pentasa and azathioprine, 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.

4.6 Fertility, pregnancy and lactation

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 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. 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.

4.7 Effects on ability to drive and use machines

No adverse effects.

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. Following rectal administration, local reactions such as pruritus, rectal discomfort and urge may occur.

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

<No changes to AE 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

4.9 Overdose

Acute experience in animals

:

 

Single oral doses of mesalazine of up to 5gkg in pigs or a single intravenous dose of mesalazine at 920mgkg in rats were not lethal.

Human experience

:

:

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.

Management of overdose in man

:

:

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

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Intestinal antiinflammatory agents (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.

5.2 Pharmacokinetic properties

General characteristics of the active substance

Disposition and local availability:

Pentasa Rectal Suspension are designed to provide the distal part of the intestinal tract with high concentrations of mesalazine and a low systemic absorption. The Rectal Suspension has been shown to reach and cover the descending colon.

Biotransformation:

Mesalazine is metabolised both presystemically by the intestinal mucosa and systemically in the liver to Nacetyl mesalazine (acetyl mesalazine). The acetylation seems to be independent of the acetylator phenotype of the patient. Some acetylation also occurs through the action of colonic bacteria.

Acetyl mesalazine is thought to be clinically as well as toxicologically inactive, although this remains to be confirmed.

Absorption:

The absorption following rectal administration is low, and depends on the dose, the formulation and the extent of spread. Based on urine recoveries in healthy volunteers under steady-state conditions given a daily dose of 2g (1g - 2), about 15-20% of the dose is absorbed after administration of Rectal Suspensions.

Distribution:

Mesalazine and acetyl mesalazine do not cross the blood brain barrier. Protein binding of mesalazine is approximately 50% and of acetyl mesalazine about 80%.

Elimination:

The plasma half-life of mesalazine following i.v. administration is approximately 40 minutes and for acetyl mesalazine approximately 70 minutes. Both substances are excreted in urine and faeces. The urinary excretion consists mainly of acetyl mesalazine.

Characteristics in patients:

The systematic absorption following administration of Pentasa Rectal Suspension has been shown to be significantly decreased in patients with active ulcerative colitis compared to those in remission.

In patients with impaired liver and kidney functions, the resultant decrease in the rate of elimination and increased systemic concentration of mesalazine may constitute an increased risk of nephrotoxic adverse reactions.

5.3 Preclinical safety data

Definitive nephrotoxicity and possible gastrointestinal toxicity is demonstrated in all species examined, and nephrotoxicity is evident with doses 5-10 times those used in humans.

In-vitro test systems and in-vivo studies showed no evidence of mutagenic effects. Studies on the tumorigenic potential carried out in rats showed no evidence of any substance-related increase in the incidence of tumours.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Disodium edetate.

Sodium metabisulfite (E223)

Sodium acetate.

Hydrochloric acid (for pH adjustment)

Purified water.

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

Before opening individual foil pack: 3 years

After opening individual foil pack: Use immediately

6.4 Special precautions for storage

Store below 25°C. Do not freeze.

Store in the original package in order to protect from light.

6.5 Nature and contents of container

Polyethylene bottles fitted with a tip containing a back valve for rectal administration. The bottles are supplied in nitrogen-filled aluminium foil bags. Presented in cartons containing 7 x 100ml bottles. A plastic sleeve bearing administration instructions is provided for each Rectal Suspension bottle. The sleeve also facilitates hygienic application of the Rectal Suspension and disposal after use

.

 

6.6 Special Precautions for disposal of a used medicinal product or waste materials derived from such medicinal product and other handling of the product.

Shake the Rectal Suspension bottle well before use.

7. MARKETING AUTHORISATION HOLDER

Ferring Ireland Ltd.,

United Drug House,

Magna Drive,

Magna Business Park,

Citywest Road,

Dublin 24,

Ireland

8. MARKETING AUTHORISATION NUMBER

PA 1009/6/3

9. DATE OF FIRST AUTHORISATION  RENEWAL OF AUTHORIZATION

Date of first authorisation: 2

nd February 1989

 

Date of last renewal: 2

nd February 2009

 

10. DATE OF REVISION OF THE TEXT

October 2013June 2014




Updated on 24 October 2013 PIL

Reasons for updating

  • Change to section 6.4 - Special precautions for storage

Free text change information supplied by the pharmaceutical company

Section 6.4: Storage conditions updated from

"Do not store above 25°C. Store in the original package to protect from light." to: "Store below 25C. Do not freeze. Store in the original package in order t protect from light."

Updated on 24 October 2013 SmPC

Reasons for updating

  • 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 6.4: Storage conditions updated from

"Do not store above 25°C. Store in the original package to protect from light." to: "Store below 25C. Do not freeze. Store in the original package in order t protect from light."

Updated on 15 August 2012 SmPC

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 4.6 - Pregnancy and lactation
  • 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:

- addition of the sentence: "In case of acute intolerance reactions such as abdominal cramps, acute abdominal pain, fever, severe headache and rash, therapy should be discontinued immediately."
- addition of the sentence: "Urinary status (dip sticks) should be determined prior to and during treatment at the discretion of the treating physician."

- addition of the sentence: “Patients with pulmonary disease, in particular asthma, should be very carefully monitored during a course of treatment.”
- inclusion of 'thioguanine' in the sentence "As stated in the interaction section 4.5, concomitant treatment with mesalazine can increase the risk of blood dyscrasia in patients receiving azathioprine, 6-mercaptopurine or thioguanine."
- addition of the following sentences: "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:
- sentence update: "Combination therapy with Pentasa and azathioprine, or  6-mercaptopurine or thioguanine, have in several studies shown a higher frequency of leucopenia myelosuppressive effects, and an interaction seems to exist, however, the mechanism behind the interaction is not fully established."
- addition of the sentence: "There is weak evidence that mesalazine might decrease the anticoagulant effect of warfarin."


Section 4.6:

- addition of the sentence: "Animal studies on oral mesalazine do not indicate direct or indirect harmful effects with respect to pregnancy, embryonic/foetal development, parturition or postnatal development."

- deletion of the sentence: "In animal studies no teratogenic or mutagenic effects have been observed".
- addition of the sentences:
"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."
"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:
    - Deletion of the column 'Not known'. The two 'Not known' events of hypersensitivity reaction and drug fever were changed to 'Very rare' frequency, as described below.

    -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 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."

Updated on 15 August 2012 PIL

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 4.6 - Pregnancy and lactation
  • 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:

- addition of the sentence: "In case of acute intolerance reactions such as abdominal cramps, acute abdominal pain, fever, severe headache and rash, therapy should be discontinued immediately."
- addition of the sentence: "Urinary status (dip sticks) should be determined prior to and during treatment at the discretion of the treating physician."

- addition of the sentence: “Patients with pulmonary disease, in particular asthma, should be very carefully monitored during a course of treatment.”
- inclusion of 'thioguanine' in the sentence "As stated in the interaction section 4.5, concomitant treatment with mesalazine can increase the risk of blood dyscrasia in patients receiving azathioprine, 6-mercaptopurine or thioguanine."
- addition of the following sentences: "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:
- sentence update: "Combination therapy with Pentasa and azathioprine, or  6-mercaptopurine or thioguanine, have in several studies shown a higher frequency of leucopenia myelosuppressive effects, and an interaction seems to exist, however, the mechanism behind the interaction is not fully established."
- addition of the sentence: "There is weak evidence that mesalazine might decrease the anticoagulant effect of warfarin."


Section 4.6:

- addition of the sentence: "Animal studies on oral mesalazine do not indicate direct or indirect harmful effects with respect to pregnancy, embryonic/foetal development, parturition or postnatal development."

- deletion of the sentence: "In animal studies no teratogenic or mutagenic effects have been observed".
- addition of the sentences:
"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."
"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:
    - Deletion of the column 'Not known'. The two 'Not known' events of hypersensitivity reaction and drug fever were changed to 'Very rare' frequency, as described below.

    -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 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."

Updated on 2 June 2010 PIL

Reasons for updating

  • Change to section 3 - Pharmaceutical form

Free text change information supplied by the pharmaceutical company

Section 3: The visual description of the product has been updated from 'Colourless to slightly yellow suspension' to 'White to slightly yellow suspension'.  The actual appearance of the product has not changed.

Updated on 2 June 2010 SmPC

Reasons for updating

  • Change to section 3 - Pharmaceutical form

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

Free text change information supplied by the pharmaceutical company

Section 3: The visual description of the product has been updated from 'Colourless to slightly yellow suspension' to 'White to slightly yellow suspension'.  The actual appearance of the product has not changed.

Updated on 12 March 2010 PIL

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 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose

Free text change information supplied by the pharmaceutical company

Section 4.3: removed the following contraindications: active peptic ulcer, coagulopathy, concurrent use of lactulose and other agents which lower stool pH

Section 4.4: Text updated.  The following sentences added:
    -    'Liver function parameters like ALT or AST should be assessed prior to and during treatment, at the discretion of the treating physician.'
    -    'The renal function should be monitored regularly (e.g. serum creatinine), especially during the initial phase of treatment.'
    -    'The concurrent use of other known nephrotoxic agents should increase monitoring of renal function.'
    -    'Blood test for differential blood count is recommended prior to and during treatment, at the discretion of the treating physician.'

Section 4.5:  Updated to: 'Combination therapy with PENTASA and azathioprine or 6-mercaptopurine have in several studies shown a higher frequency of leucopenia, 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.'


Section 4.6:  Updated to: '

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 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 umbilican 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.  In animal studies no teratogenic or mutagenic effects have been observed. 

Blood disorders (pancytopenia, leucopenia, thrombocytopenia, anaemia) have been reported in new-borns of mothers being treated with PENTASA.

                                                  

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. 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.'

 

 

Section 4.8:  Addition of undesirable effect: very rare - interstitial lung disease

Section 4.9: Updated 'Human experience' section to: 'There is limited clinical experience with overdose of PENTASA. There have been reports of patients taking daily doses of 8 grams for a month without any adverse events.'

 

 

 

 

Updated on 12 March 2010 SmPC

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 4.8 - 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 4.3: removed the following contraindications: active peptic ulcer, coagulopathy, concurrent use of lactulose and other agents which lower stool pH

Section 4.4: Text updated.  The following sentences added:
    -    'Liver function parameters like ALT or AST should be assessed prior to and during treatment, at the discretion of the treating physician.'
    -    'The renal function should be monitored regularly (e.g. serum creatinine), especially during the initial phase of treatment.'
    -    'The concurrent use of other known nephrotoxic agents should increase monitoring of renal function.'
    -    'Blood test for differential blood count is recommended prior to and during treatment, at the discretion of the treating physician.'

Section 4.5:  Updated to: 'Combination therapy with PENTASA and azathioprine or 6-mercaptopurine have in several studies shown a higher frequency of leucopenia, 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.'


Section 4.6:  Updated to: '

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 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 umbilican 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.  In animal studies no teratogenic or mutagenic effects have been observed. 

Blood disorders (pancytopenia, leucopenia, thrombocytopenia, anaemia) have been reported in new-borns of mothers being treated with PENTASA.

                                                  

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. 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.'

 

 

Section 4.8:  Addition of undesirable effect: very rare - interstitial lung disease

Section 4.9: Updated 'Human experience' section to: 'There is limited clinical experience with overdose of PENTASA. There have been reports of patients taking daily doses of 8 grams for a month without any adverse events.'

 

 

 

 

Updated on 3 November 2009 PIL

Reasons for updating

  • Change to section 1 - Name of medicinal product
  • Change to section 4.8 - Undesirable effects
  • Change to section 6.4 - Special precautions for storage

Free text change information supplied by the pharmaceutical company

Section 1:  Name of the product changed from 'Pentasa Enema 10mg/ml' to 'Pentasa 10mg/ml Rectal Suspension'
Section 4.8:  Table updated to MedDra format.  Very rare undesirable effects added: pneumonitis, peripheral neuropathy, urine discolouration
Section 6.4:  Storage conditions updated to read 'Store in the original package to protect from light'

Updated on 3 November 2009 SmPC

Reasons for updating

  • Change to section 1 - Name of medicinal product
  • Change to section 4.8 - Undesirable effects
  • 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 1:  Name of the product changed from 'Pentasa Enema 10mg/ml' to 'Pentasa 10mg/ml Rectal Suspension'
Section 4.8:  Table updated to MedDra format.  Very rare undesirable effects added: pneumonitis, peripheral neuropathy, urine discolouration
Section 6.4:  Storage conditions updated to read 'Store in the original package to protect from light'

Updated on 27 August 2007 PIL

Reasons for updating

  • Correction of spelling/typing errors

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 June 2005 SmPC

Reasons for updating

  • Change to section 6.2 - Incompatibilities
  • Change to section 6.4 - Special precautions for storage
  • Change to section 6.6 - Special precautions for disposal and other handling
  • 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 27 June 2005 PIL

Reasons for updating

  • Change to section 6.2 - Incompatibilities
  • Change to section 6.4 - Special precautions for storage
  • Change to section 6.6 - Special precautions for disposal and other handling
  • 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 20 June 2005 PIL

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 6.1 - List of excipients
  • Change to section 6.2 - Incompatibilities
  • Change to section 6.3 - Shelf life
  • Change to section 6.4 - Special precautions for storage
  • Change to section 6.6 - Special precautions for disposal and other handling
  • 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 20 June 2005 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 6.1 - List of excipients
  • Change to section 6.2 - Incompatibilities
  • Change to section 6.3 - Shelf life
  • Change to section 6.4 - Special precautions for storage
  • Change to section 6.6 - Special precautions for disposal and other handling
  • 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 27 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 27 June 2003 PIL

Reasons for updating

  • New SPC for medicines.ie