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Pentasa 1g SuppositoriesMesalazine
Table of Contents
1. NAME OF THE MEDICINAL PRODUCT
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
3. PHARMACEUTICAL FORM
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
4.2 Posology and method of administration
4.3 Contraindications
4.4 Special warnings and precautions for use
4.5 Interaction with other medicinal products and other forms of interaction
4.6 Pregnancy and lactation
4.7 Effects on ability to drive and use machines
4.8 Undesirable effects
4.9 Overdose
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
5.2 Pharmacokinetic properties
5.3 Preclinical safety data
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
6.2 Incompatibilities
6.3 Shelf life
6.4 Special precautions for storage
6.5 Nature and contents of container
6.6 Special precautions for disposal and other handling
7. MARKETING AUTHORISATION HOLDER
8. MARKETING AUTHORISATION NUMBER(S)
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
10. DATE OF REVISION OF THE TEXT
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Each suppository contains mesalazine 1g.
For full list of excipients, see section 6.1.
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Suppository
White to tan, spotted, oblong suppository.
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For the treatment of Ulcerative proctitis.
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Adults:
Acute treatment:
The recommended dosage is one suppository twice daily for two to four weeks.
Maintenance treatment:
1000-2000mg mesalazine daily.
Children:
20-30mg mesalazine per kilogram body weight daily, divided into several doses when possible.
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1. Use in patients hypersensitive to salicylates
2. Use in children under the age of 2 years.
3. Use in patients with active peptic ulcer
4. Use in patients with coagulopathy
5. Use in patients with severe liver and/or renal impairment
6. Use in patients allergic to any of the ingredients
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Serious blood dyscrasias have been reported rarely with mesalazine. Haematological investigations should be performed if the patient develops unexplained bleeding, bruising, purpura, anaemia, fever or sore throat. Treatment should be stopped if there is suspicion or evidence of blood dyscrasia.
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). Caution is recommended in patients with impaired liver function.
It is recommended that mesalazine is used with extreme caution in patients with mild to moderate renal impairment. (See section 4.3, Contraindications).
If a patient develops dehydration while on treatment with mesalazine, normal electrolyte levels and fluid balance should be restored as soon as possible.
Mesalazine induced nephrotoxicity should be suspected in patients developing renal dysfunction during treatment.
Mesalazine induced cardiac hypersensitivity reactions (myocarditis and pericarditis) have been reported rarely. Treatment should be discontinued on suspicion or evidence of these reactions.
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The concurrent use of mesalazine with other known nephrotoxic agents, such as NSAIDs and azathioprine, may increase the risk of renal reactions (see section 4.4, Special warnings and precautions for use)
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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.
Mesalazine is excreted in breast milk. The concentration 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.
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The most frequent adverse reactions seen in clinical trials are diarrhoea (3%), nausea (3%), abdominal pain (3%), headache (3%), vomiting (1%) and rash (1%). Hypersensitivity reactions and drug fever may occasionally occur. Following rectal administration, local reactions such as pruritus, rectal discomfort and urge may occur.
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Common
 1/100 to < 1/10
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Rare
1/10,000 to  1/1,000
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Very rare
1/10,000
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Blood and the lymphatic system disorders
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Eosinophilia (as part of an allergic reaction)
Anaemia
Aplastic anaemia
Leukopenia (incl. granulocytopenia)
Thrombocytopenia
Agranulocytosis
Pancytopenia
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Nervous System Disorders
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Headache
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Peripheral neuropathy
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Cardiac disorders
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Myocarditis*
Pericarditis*
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Respiratory, thoracic and mediastinal disorders
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Allergic lung reactions (incl. dyspnoea, coughing, allergic alveolitis, pulmonary eosinophilia, pulmonary infiltration, pneumonitis)
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Gastrointestinal disorders
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Diarrhoea
Abdominal pain
Nausea
Vomiting
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Increased amylase, pancreatitis*
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Hepato-biliary disorders
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Increased liver enzymes and bilirubin, hepatotoxicity (incl. hepatitis*, cirrhosis, hepatic failure)
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Skin and subcutaneous tissue disorders
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Rash (incl. urticaria, erythematous rash)
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Reversible alopecia
Bullous skin reactions including erythema multiforme and Stevens Johnson Syndrome
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Musculoskeletal, connective tissue and bone disorders
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Myalgia
Arthralgia
Isolated reports of lupus erythematosus-like reactions
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Renal and urinary disorders
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Abnormal renal function (incl. interstitial nephritis*, nephrotic syndrome, urine discolouration)
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* 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.
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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:
No cases of overdose have been reported.
Management of overdose in man:
Symptomatic treatment at hospital. Close monitoring of renal function. Intravenous infusion of electrolytes may be used to promote diuresis.
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Pharmacotherapeutic group: Intestinal anti-inflammatory agents.
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.
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General characteristics of the active substance:
Disposition and local availability:
Pentasa suppositories are designed to provide the distal part of the intestinal tract with high concentrations of mesalazine and a low systemic absorption. They are used to treat the rectum.
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, but 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 x 2), approximately 10% of the dose is adsorbed after administration of suppositories.
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 pure mesalazine 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:
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.
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There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
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Povidone
Macrogol 6000
Magnesium Stearate
Talc
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Do not store above 25ºC. Store in the original package.
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Each suppository is individually packed in double aluminium foil and presented in cartons of 28 suppositories.
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Ferring Ireland Ltd
United Drug House
Magna Drive
Magna Business Park
Citywest Road
Dublin 24
Ireland
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Date of first authorisation: 21 December 1992
Date of last renewal: 21 December 2007
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