Pentasa 1 G Suspension

PENTASA u00c6 1 g ENEMA is indicated for the treatment of ulcerative proctosigmoiditis and left-sided colitis.

PENTASA u00c6 1 g ENEMA should be inserted into the rectum. It should not be taken by mouth. Ulcerative proctosigmoiditis and left-sided colitis: One enema should be administered at bedtime. A visit to the toilet is recommended before administration. Shake the enema container well before use. The enema is protected by an aluminium foil bag and should be used immediately after opening the bag. See separate instructions for use in the enclosed Patient Information Leaflet.

• Hypersensitivity to any of the components of PENTASA u00c6 1 g ENEMA and salicylates.
• Severe liver and/or renal impairment.

Caution is recommended when treating patients allergic to sulphasalazine (risk of allergy to salicylates). Caution is recommended in patients with impaired liver function. Liver function parameters such as ALT or AST should be assessed prior to and during treatment, at regular intervals. PENTASA u00c6 1 g ENEMA 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. 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. Mesalazine-induced cardiac hypersensitivity reactions (myo- and pericarditis) have been reported. Serious blood dyscrasias have been reported with PENTASA u00c6 1 g ENEMA. Blood test for differential blood count is recommended prior to and during treatment, at regular intervals. Concomitant treatment with PENTASA u00c6 1 g ENEMA can increase the risk of blood dyscrasia in patients receiving azathioprine or 6-mercaptopurine (see INTERACTIONS). PENTASA u00c6 1 g ENEMA treatment should be discontinued on suspicion or evidence of these adverse reactions. PENTASA u00c6 1 g ENEMA should be inserted into the rectum. It should not be taken by mouth.

Combination therapy with PENTASA u00c6 1 g ENEMA and azathioprine or 6-mercaptopurine have shown a higher frequency of leucopenia, and an interaction seems to exist. Regular monitoring of white blood cells is recommended and the dosage requirements of thiopurines should be adjusted accordingly.

Safety in pregnancy and lactation has not been established. Hypersensitivity reactions to mesalazine in breast milk, like diarrhoea, have been reported in the suckling infant. 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. Blood disorders (pancytopenia, leucopenia, thrombocytopenia, anaemia) have been reported in newborns of mothers being treated with PENTASA u00c6 1 g ENEMA. Women receiving PENTASA u00ae 1g ENEMA should not breastfeed their infants.

It is unknown if treatment with PENTASA u00c6 1 g ENEMA affects the ability to drive and/or use machines.

The most frequent adverse reactions seen in clinical trials were 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 faecal urge may occur.

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

MedDRA Organ Class

• Common (1 - 10 %)
• Rare (0,01 - 0,1 %)
• Very rare (<0,01 %)
• Post marketing- (frequency unknown)

Blood and the lymphatic system disorders: eosinophilia (as part of an allergic reaction), anaemia, aplastic anaemia, leucopenia (incl. granulocytopenia and neutropenia), thrombocytopenia, agranulocytosis, pancytopenia

Immune system disorders: Hyper-sensitivity reaction, anaphylaxis

Nervous system disorders: Headache, peripheral neuropathy

Cardiac disorders: Myocarditis* and pericarditis*

Respiratory, thoracic and mediastenal disorders: Allergic and fibrotic lung reactions (incl. dyspnoea, coughing, allergic alveolitis, pulmonary eosinophilia, interstitial lung disease, pulmonary infiltration, pneumonitis)

Gastrointestinal disorders: diarrhoea, abdominal pain, nausea, vomiting, increased amylase, pancreatitis*, flatulence

Hepato-biliary disorders: increased liver enzymes, and bilirubin, hepatotoxicity (incl. hepatitis*, cirrhosis, hepatic failure)

Skin and subcutaneous tissue disorders: rash (incl. urticaria, erythematous rash), Reversible alopecia, lupus erythematosus-like reactions

Musculo-skeletal, myalgia, arthralgia connective tissue and bone disorders

Renal and urinary disorders: Renal function impairment (incl. interstitial nephritis*, nephrotic syndrome, renal insufficiency), urine discolouration

General disorders and administration site conditions: Drug Fever

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

Treatment is symptomatic and supportive in a hospital. Close monitoring of renal function is advised.