Salicylate-sulphonamides (DMARDs) .

Sulfasalazine [sulphasalazine] - rheumatoid arthritis

Sulfasalazine EP 500mg

Yellow film-coated, ovoid gastro-resistant tablets embossed “Kph” on one side and “102” on the other

a) Induction and maintenance of remission of ulcerative colitis; treatment of active Crohn's Disease.

b) Treatment of rheumatoid arthritis which has failed to respond to non-steroidal anti-inflammatory drugs (NSAIDs).

EN-Tablets should be used where there is gastro-intestinal intolerance of plain tablets. They should not be crushed or broken.

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

Elderly Patients: No special precautions are necessary.

a) Ulcerative colitis

Adults

Severe Attack: Salazopyrin 2-4 tablets four times a day may be given in conjunction with steroids as part of an intensive management regime. Rapid passage of the tablets may reduce effect of the drug.

Night-time interval between doses should not exceed 8 hours.

Moderate Attack: 2-4 tablets four times a day may be given in conjunction with steroids.

Mild Attack: 2 tablets four times a day with or without steroids.

Maintenance Therapy: With induction of remission reduce the dose gradually to 4 tablets 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 risk of relapse.

Children

The dose is reduced in proportion to body weight.

Acute Attack or relapse: 40- 60mg/kg per day

Maintenance Dosage: 20 - 30mg/kg per day

Salazopyrin Suspension may provide a more flexible dosage form.

b) Crohn 's Disease

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

c) Rheumatoid Arthritis

Patients with rheumatoid arthritis, and those treated over a long period with NSAIDs, may have sensitive stomachs and for this reason enteric-coated Salazopyrin (EN-Tabs) are recommended for this disease, as follows:

The patient should start with one tablet daily, increasing his dosage by a tablet a day each week until one tablet four times a day, or two three times a day are reached, according to tolerance and response. Onset of effect is slow and a marked effect may not be seen for six weeks. A reduction in ESR and C-reactive protein should accompany an improvement in joint mobility. NSAID_s may be taken concurrently with Salazopyrin.

Not recommended.

Sulfasalazine is contraindicated in:

Infants under the age of 2 years.

Patients with a known hypersensitivity to sulfasalazine, its metabolites or any of the excipients as well as sulfonamides or salicylates.

Patients with porphyria.

Precautions: Haematological and hepatic side effects may occur. Differential white cell, red cell and platelet counts should be performed initially and at least monthly for a minimum of the first three months of treatment. The patient should also be counselled to report immediately with any sore throat, fever, malaise or unexpected non-specific illness. Treatment should be stopped immediately if there is suspicion or laboratory evidence of a potentially serious blood dyscrasia.

Liver function tests should be carried out at monthly intervals for the first three months of treatment. Patients with liver disease should be treated with caution.

The kidney function should be checked initially and at regular intervals during the treatment. Since sulfasalazine may cause haemolytic anaemia, it should be used with caution in patients with G-6-PD deficiency.

Changes in the blood picture (e.g. macrocytosis and pancytopenia) due to folic acid deficiency can be normalised by administration of folic acid or folinic acid (leucovorin).

Reduced absorption of digoxin, resulting in non-therapeutic serum levels, has been reported when used concomitantly with oral sulfasalazine.

Sulfonamides bear certain chemical similarities to some oral hypoglycemic agents. Hypoglycemia has occurred in patients receiving sulfonamides. Patients receiving sulfasalazine and hypoglycemic agents should be closely monitored.

Due to inhibition of thiopurine methyltransferase by salazopyrin, bone marrow suppression and leucopenia have been reported when the thiopurine 6-mercaptopurine or its prodrug, azathioprine, and oral salazopyrin were used concomitantly.

Due to inhibition of thiopurine methyltransferase by salazopyrin, bone marrow suppression and leucopenia have been reported when the thiopurine 6-mercaptopurine or its prodrug, azathioprine, and oral salazopyrin were used concomitantly.

Coadministration of oral sulfasalazine and methotrexate to rheumatoid arthritis patients did not alter the pharmacokinetic disposition of the drugs. However, an increased incidence of gastrointestinal adverse events, especially nausea, was reported.

Overall, about 75% of ADRs occur within 3 months of starting therapy, and over 90% by 6 months. Some undesirable effects are dose-dependent and symptoms can often be alleviated by reduction of the dose.

General

Sulfasalazine 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 following reactions have been recorded in patients taking sulfasalazine:

Haematological. Potentially fatal leucopenia, neutropenia, agranulocytosis, aplastic anaemia and thrombocytopenia. Leucopenia, which is normally mild and transient, may occur in up to 1.5% of patients and agranulocytosis in up to one in 700 patients during the second month of therapy.

The risk of sulfasalazine associated blood disorders is substantially higher in patients treated for rheumatoid arthritis than it is for patients treated for inflammatory bowel disease.

Heinz body anaemia, methaemoglobinaemia, hypoprothrombinaemia, haemolytic anaemia, megaloblastic anaemia.

Hypersensitivity reactions

Generalised skin eruptions, Stevens-Johnson Syndrome, exfoliative dermatitis, epidermal necrolysis, pruritis, urticaria, photosensitisation, anaphylaxis, serum sickness, drug fever, lymphadenopathy, periorbital oedema, conjuctivial and scleral polyarteritis nodosa, LE-phenomenon and lung complications with dyspnoea, fever, cough, eosinophilia, fibrosing alveolitis, pericarditis, vasculitis, nephritis, alopecia.

Gastro-intestinal reactions

Stomatitis, parotitis, pancreatitis, hepatitis.

CNS Reactions

Vertigo, tinnitus, peripheral neuropathy, aseptic meningitis, ataxia, convulsions, insomnia, mental depression and hallucinations.

Fertility

Oligospermia, reversible on discontinuance of drug.

Renal Reactions

Crystalluria, haematuria, proteinuria and nephrotic syndrome.

Pharmacia Limited

(POM)

22 June 2009