- 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
- Administrative data
- 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
|Common (≥1% and <10%)||Gastrointestinal disorders: Nausea, vomiting, diarrhoea, abdominal pain Skin disorders: Rash (including urticaria and erythematous rash) General: Headache|
|Rare (≥0.01% and < 0.1%)||Blood disorders: Leucopenia (including granulocytopenia), neutropenia, agranulocytosis, aplastic anaemia, thrombocytopenia Nervous system disorders: Peripheral neuropathy Cardiac disorders: Myocarditis, pericarditis Respiratory disorders: Allergic lung reactions (including dyspnoea, coughing, allergic alveolitis, pulmonary eosinophilia, pulmonary infiltration, pneumonitis) Gastrointestinal disorders: Pancreatitis, increased amylase Liver: Abnormalities of hepatic function and hepatotoxicity (including hepatitis, cirrhosis, hepatic failure) Urogenital: Abnormal renal function (including interstitial nephritis, nephrotic syndrome), urine discolouration (*see additional text). Collagen disorders: Lupus erythematosus-like reactions|
|Very rare (<0.01% )||Blood disorders: Anaemia, eosinophilia (as part of an allergic reaction) and pancytopenia Liver: Increased liver enzymes and bilirubin Skin disorders: Reversible alopecia, bullous skin reactions including erythema multiforme and Stevens-Johnson syndrome Musculo-skeletal disorders: Myalgia, arthralgia Allergic reactions: Hypersensitivity reactions, drug fever.|
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.
Disposition and local availability:PENTASA enemas are designed to provide the distal part of the intestinal tract with high concentrations of mesalazine and a low systemic absorption. The enemas have 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, 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), about 15-20% of the dose is absorbed after administration of enemas.
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:The systematic absorption following administration of PENTASA enemas 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.
Ferring Pharmaceuticals Ltd
Drayton Hall, Church Road, West Drayton, UB7 7PS, UK
+44 (0)844 931 0051
+44 (0)844 931 0050