UCB Pharma Limited

Dipentum 250mg hard Capsules.

Each capsule contains 250mg olsalazine sodium.

For a full list of excipients, see section 6.1.

Capsule, hard

Beige, opaque, hard, gelatin size 1 capsule radially printed “DIPENTUM 250 mg” in black.

Treatment of mild to moderate acute ulcerative colitis with or without corticosteroids. The drug may also be used in the long term maintenance or remission of ulcerative colitis. It is particularly useful where patients cannot tolerate sulphazalazine because of sulpha intolerance.

To be taken in divided doses with meals

General

Olsalazine taken on an empty stomach may sometimes lead to loose stools or diarrhoea. By taking the drug at the end of a meal, this may be avoided.

Acute Mild Disease

Adults including the elderly: Commence on 1 g daily in divided doses taken at the end of meals. Depending on the patient's response, the dose may be titrated upwards over a period of one week to a maximum of 3g daily. Concomitant oral or rectal steroids may be used. In the event of drug related diarrhoea occurring, it may be transient. If it is not, dose may be reduced; where diarrhoea continues despite this reduction the drug should be stopped.

A single dose should not exceed 1 g.

Long-term maintenance of remission

Adults, including the elderly: Two capsules may be taken twice daily with food.

Children and infants: No specific recommendations are made.

Patients hypersensitive to olsalazine or other salicylates or any of the excipients. Severe renal impairment.

It is recommended to monitor patients with impaired kidney or liver function.

Patients suffering from severe allergy or asthma should be observed for signs of worsening of these conditions.

In -vitro and in-vivo laboratory studies do not suggest pharmacogenetic problems associated with the drug.

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 a suspicion or evidence of a blood dyscrasia.

The coadministration of salicylates and low molecular weight heparins or heparinoids may result in an increased risk of bleeding, more specifically hematomas following neuraxial anesthesia. Salicylates should be discontinued prior to the initiation of a low molecular weight heparin or heparinoid. If this is not possible, it is recommended to monitor patients closely for bleeding.

Increased prothrombin time in patients taking concomitant warfarin has been reported.

The coadministration of olsalazine and 6-mercaptopurine or thioguanine may result in an increased risk of myelosuppression. If coadministered with 6-mercaptopurine, it is recommended to use the lowest possible doses of each drug and to monitor the patient, especially for leukopenia. In case of coadministration with thioguanine, careful monitoring of blood counts is recommended.

It is recommended not to give salicylates for six weeks after the varicella vaccine to avoid a possible increased risk of developing Reye's syndrome.

Pregnancy:

Olsalazine has been shown to produce fetal developmental toxicity as indicated by reduced fetal weights, retarded ossifications and immaturity of the fetal visceral organs when given during organogenesis to pregnant rats in doses 5 to 20 times the human dose (100 to 400 mg/kg).

There are no adequate and well-controlled studies in pregnant women. Olsalazine should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.

Lactation:

Small amounts of the active metabolite of olsalazine (5-ASA) may pass into breast milk. Harmful infant effects (diarrhea) have been reported when 5-ASA was used during breastfeeding. Unless the benefit of the treatment outweighs the risks, olsalazine should not be taken by breast-feeding women, or patients should be advised to discontinue breastfeeding if using olsalazine.

On the basis of the pharmacodynamic profile and reported adverse events, olsalazine does not appear to produce any effects on ability to drive and use machines.

The most common side effect is diarrhoea which is usually transient.

In addition, the following undesirable effects have been reported:

General disorders and administration site conditions : headache, pyrexia

Blood and lymphatic system disorders : aplastic anaemia, eosinophilia, haemolytic anemia, leukopenia, neutropenia, pancytopenia, thrombocytopenia

Gastrointestinal disorders : abdominal pain upper, diarrhoea, dyspepsia, nausea, pancreatitis, vomiting

Hepatobiliary disorders : hepatic enzyme increased, hepatitis, increased bilirubin, pancreatitis

Skin and subcutaneous tissue disorders : alopecia, angioneurotic oedema, photosensitivity reaction, pruritus, rash, urticaria, paraesthesia

Cardiac disorders : myocarditis, palpitations, pericarditis, tachycardia

Renal and urinary disorders : interstitial nephritis

Respiratory, thoracic and mediastinal disorders : dyspnoea, interstitial lung disease

Musculoskeletal and connective tissue disorders : arthralgia, myalgia

Nervous system disorders : dizziness, paraesthesia, peripheral neuropathy

Psychiatric disorders: depression

Eye disorders : vision blurred

The knowledge of overdosage is limited. Possible overdose symptoms include nausea, vomiting and diarrhoea. It is recommended to check hematology, acid-base, electrolyte, liver and kidney status, and to provide supportive treatment. There is no specific antidote to Dipentum.

ATC Code: A07E C 03, Aminosalicylic acid and similar agents.

Olsalazine sodium was developed as a pro-drug for the release of 5- amonosalicylic acid in the colon by bacterial azo reduction. Neither substance is significantly absorbed, but the 5ASA which is taken up is largely acetylated in the gut wall, and urinary excretion is principally as the acetylated form. Olsalazine undergoes enterohepatic circulation with a T1/2 of 5-7 hours.

Non-clinical data reveal no special hazards for humans based on conventional studies of sdaety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential and toxicity to reproduction.

Magnesium stearate (E572)

Printing Ink

Shellac (E904)

Black iron oxide (E172)

Propylene glycol (E1520)

Or

Shellac (E904)

Black iron oxide (E172)

Propylene glycol (E1520)

Potassium Hydroxide

Capsule Shell

Caramel (E150)

Titanium dioxide (E171)

Gelatin

Not applicable.

5 years.

Do not store above 25°C. Keep the container tightly closed in order to protect from moisture.

White, HDPE bottle sealed by a foil inner-seal and tamper-evident LDPE cap, containing 112 capsules.

No special requirements for disposal.

UCB Pharma Limited

208 Bath Road

Slough

Berkshire,

SL1 3WE

United Kingdom

PA 365/82/1

Date of first authorisation: 12^th July 1995

Date of the latest renewal: 12^th July 2010

April 2011