Sulcolon

Induction and maintenance of remission of ulcerative colitis and treatment of active Crohn's disease.

The dose is adjusted according to the severity of the disease and the patient's tolerance of the drug, as detailed below.

A) Ulcerative Colitis

Adults and the Elderly

Severe attacks: 20 to 40 ml four times a day may be given in conjunction with steroids as part of an intensive management regime. Rapid passage of the suspension may reduce the effect of the drug.

The night time interval between doses should not exceed 8 hours.

Moderate attacks: 20 ml four times a day may be taken with or without steroids.

Maintenance therapy: With induction of remission, reduce the dose gradually to 40 ml per day. This dosage should be continued indefinitely, since discontinuance even several years after an acute attack is associated with a four-fold increase in relapse.

Children

The dose is reduced in proportion to body weight.

Acute attack or relapse: 0.8 - 1.2 ml/kg/day.

Maintenance dosage: 0.4 - 0.6 ml/kg/day.

B) Crohn's Disease

In active Crohn's Disease, Sulcolone should be administered as in attacks of ulcerative colitis (see above).

Sulcolone is contraindicated in:

- Infants under the age of two years.

- Patients with a known hypersensitivity to Sulcolone, its metabolites or any of the excipients as well as sulfonamides, salicylates or the sodium benzoate preservative.

- Patients with porphyria.

Complete blood counts, including differential white cell count and liver function tests, should be performed before starting Sulcolone, and every second week during the first three months of therapy. During the second three months, the same tests should be done once monthly and thereafter once every three months, and as clinically indicated. Assessment of renal function (including urinalysis) should be performed in all patients initially and at least monthly for the first three months of treatment. Thereafter, monitoring should be performed as clinically indicated.

The patient should also be counselled to report immediately with any sore throat, fever, malaise, pallor, purpura, jaundice or unexpected non-specific illness during Sulcolone treatment, this may indicate myelosuppression, haemolysis or hepatoxicity. Treatment should be stopped immediately while awaiting the results of blood tests.

Sulcolone should not be given to patients with impaired hepatic or renal function or with blood dyscrasias, unless the potential benefit outweighs the risk.

Sulcolone should be given with caution to patients with severe allergy or bronchial asthma.

Use in children with the concomitant condition systemic onset juvenile rheumatoid arthritis may result in a serum sickness like reaction; therefore Sulcolone is not recommended in these patients.

Since Sulcolone may cause haemolytic anaemia, it should be used with caution in patients with glucose-6-phosphate dehydrogenase deficiency.

Oral Sulcolone inhibits the absorption and metabolism of folic acid and may cause folic acid deficiency potentially resulting in serious blood disorders (e.g. macrocytosis and pancytopenia), this can be normalised by administration of folic acid or folinic acid (leucovorin).

Because Sulcolone causes crystalluria and kidney stone formation, adequate fluid intake should be ensured during treatment.

Oligospermia and infertility may occur in men treated with Sulcolone. Discontinuation of the drug appears to reverse these effects within 2 to 3 months.

Life-threatening cutaneous reactions Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with the use of Sulcolone. Patients should be advised of the signs and symptoms and monitored closely for skin reactions. The highest risk for occurrence of SJS or TEN is within the first weeks of treatment. If symptoms or signs of SJS or TEN (e.g. progressive skin rash often with blisters or mucosal lesions) are present, Sulcolone treatment should be discontinued. The best results in managing SJS and TEN come from early diagnosis and immediate discontinuation of any suspect drug. Early withdrawal is associated with a better prognosis. If the patient has developed SJS or TEN with the use of Sulcolone, Sulcolone must not be re-started in this patient at any time.

Sulcolone may colour the urine orange-yellow.

Excipient warnings

This product contains small amounts of ethanol (alcohol), less than 100mg per 5ml.

No specific effects.

Overall, about 75% of ADRs occur within three months of treatment and over 90% by six months. Some unwanted effects are dose-dependent and symptoms can often be alleviated by reduction of the dose.

General

Sulcolone is split by intestinal bacteria to sulfapyridine and 5-amino salicylate so ADRs to either sulfonamide or salicylate are possible. Patients with slow acetylator status are more likely to experience ADRs related to sulfapyridine. The most commonly encountered ADRs are nausea, headache, rash, loss of appetite and raised temperature.

Specific

The adverse reactions observed during clinical studies conducted with Sulcolone have been provided in a single list below by class and frequency (very common (>1/10); common (>1/100 to< 1/10); uncommon (>1/1000 to < 1/100); rare (>1/10,000 to <1/1000); very rare (<1/10,000)). Where an adverse reaction was seen at different frequencies in clinical studies, it was assigned to the highest frequency reported.

Additional reactions reported from post-marketing experience are included as frequency Not known (cannot be estimated from the available data) in the list below.

Body System	Adverse drug reactions
Infections and infestations
Not known	Pseudomembranous colitis
Blood and Lymphatic System Disorders
Common	Leukopenia
Uncommon	Thrombocytopenia*
Not known	Agranulocytosis, aplastic anemia, haemolytic anemia, Heinz body anaemia, hypoprothrombinaemia, lymphadenopathy, macrocytosis, megaloblastic anemia, methaemoglobinaemina, neutropenia, pancytopenia
Immune System Disorders:
Not known	Anaphylaxis, polyarteritis nodosa, serum sickness
Metabolism and Nutrition Disorders:
Not known	Loss of appetite
Psychiatric Disorders:
Common	Insomnia
Uncommon	Depression
Not known	Hallucinations
Nervous System Disorders:
Common	Dizziness, headache, taste disorders
Uncommon	Convulsions
Not known	Aseptic meningitis, ataxia, encephalopathy, peripheral neuropathy, smell disorders
Ear and Labyrinth Disorders:
Common	Tinnitus
Uncommon	Vertigo
Eye Disorders:
Common	Conjuctivial and scleral injection
Cardiac Disorders:
Not known	Allergic myocarditis, cyanosis, pericarditis
vascular Disorders:
Uncommon	Vasculitis
Respiratory, Thoracic and Mediastinal Disorders:
Common	Cough
Uncommon	Dyspnoea
Not known	Fibrosing alveolitis, eosinophilic infiltration, interstitial lung disease
Gastrointestinal Disorders:
Very Common	Gastric distress, nausea
Common	Abdominal pain, diarrhoea, vomiting, stomatitis
Not known	Aggravation of ulcerative colitis, pancreatitis, parotitis
Hepato-biliary Disorders:
Not known	Hepatic failure, fulminant hepatitis, hepatitis*
Skin and Subcutaneous Tissue Disorders:
Common	Pruritus
Uncommon	Alopecia, urticaria
Very rare	Severe cutaneous adverse reactions (SCARs): Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported
Not known	Epidermal necrolysis (Lyell's syndrome), Drug rash with eosinophilia and systemic symptoms (DRESS), toxic pustuloderma, erythema, exanthema, exfoliative dermatitis, periorbital oedema, lichen planus, photosensitivity
Musculoskeletal and Connective Tissue Disorders:
Common	Arthralgia
Not known	Systemic lupus erythematosus
Renal and Urinary Disorders:
Common	Proteinuria
Not known	Nephrotic syndrome, interstitial nephritis, crystalluria*, haematuria
Reproductive System and Breast Disorders:
Not known	Reversible oligospermia*
General Disorders and Administration Site Conditions:
Common	Fever
Uncommon	Facial oedema
Not known	Yellow discoloration of skin and body fluids
Investigations:
Uncommon	Elevation of liver enzymes
Not known	Induction of autoantibodies 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 the Yellow Card Scheme at www.mhra.gov.uk/yellowcard. Overdose The drug has low acute per oral toxicity in the absence of hypersensitivity. There is no specific antidote and treatment should be supportive. Pharmacodynamic properties Sulcolone has beneficial effects in the treatment of ulcerative colitis and maintenance of remission, and in the treatment of acute Crohn's disease. Around 90% of a dose reaches the colon where bacteria split the drug into sulpyapyridine and mesalazine. These are active, and the unsplit Sulcolone is also active on a variety of systems. Most sulfapyridine is absorbed, hydroxylated or glucuronidated and a mix of unchanged and metabolised sulfapyridine appears in the urine. Some mesalazine is taken up and acetylated in the colon wall, such that renal excretion is mainly acetyl-mesalazine. Sulcolone is excreted unchanged in the bile and urine. Overall the drug and its metabolites exert immunomodulatory effects, antibacterial effects, effects on the arachidonic acid cascade and alteration of activity of certain enzymes. The net result clinically is a reduction in activity of the inflammatory bowel disease. The enteric coated Sulcolone is registered for the treatment of rheumatoid arthritis, where the effect resembles penicillamine or gold. Pharmacokinetic properties With regard to the use of Sulcolone in bowel disease there is no evidence that systemic levels are of any relevance other than with regard to ADR incidence. Here levels of sulfapyridine over about 50µg/ml are associated with a substantial risk of ADRs, especially in slow acetylators. For Sulcolone given as a single 3g oral dose, peak serum levels of Sulcolone occurred in 3-5 hours, elimination half life was 5.7 ±0.7 hours, lag time 1.5 hours. During maintenance therapy renal clearance of Sulcolone was 7.3 ±1.7ml/min, for sulfapyridine 9.9 ±1.9 and acetyl-mesalazine 100 ±20. Free Sulcolone first appears in plasma in 4.3 hours after a single dose with an absorption half life of 2.7 hours. The elimination half life was calculated as 18 hours. For mesalazine, only acetyl-mesalazine (not free mesalazine) was demonstrable, the acetylation probably largely achieved in the colon mucosa. After 3g Sulcolone dose lag time was 6.1 ±2.3 hours and plasma levels kept below 2µg/ml total mesalazine. Urinary excretion half life was 6.0 ±3.1 hours and absorption half life based on these figures 3.0 ±1.5 hours. Renal clearance constant was 125 ml/min corresponding to the GFR. Studies in volunteers suggest that Sulcolone is handled in a similar manner whether given as suspension or tablets. Pharmacotherapeutic group R52.1 – Chronic intractable pain R52.2 – Other chronic pain R52.9 – Unspecified pain Incompatibilities None relevant Special precautions for disposal and other handling Take the suspension with food. Available in countries Indonesia A-Z index: ABCDEFGHIJKLMNOPQRSTUVYZ