SULFASALAZINE

Gastro-resistant 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. 1.

Ulcerative colitis:

Adults : • Severe attacks: 2-4 tablets four times a day, which 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 attacks: 2-4 tablets four times a day may be given in conjunction with steroids • Mild attacks: 2 tablets four times a day with or without steroids • Maintenance therapy: With induction of remission gradually reduce dose to 4 tablets per day.

The dosage should be continued indefinitely to avoid relapse, since discontinuation even several years after an acute attack is associated with a four-fold increase in risk of relapse.

Paediatric population (Children):

The dose is reduced in proportion to body weight. • Acute attack or relapse: 40-60 mg/kg per day • Maintenance therapy: 20-30 mg/kg per day Sulfasalazine suspension may provide a more flexible dosage form. 2. Crohn’s disease In active Crohn’s disease, sulfasalazine should be administered as in attacks of ulcerative colitis (see above) 3.

Rheumatoid arthritis:

Patients with rheumatoid arthritis, and those treated over a long period with NSAIDs, may have sensitive stomachs and for this reason gastro-resistant sulfasalazine tablets are recommended for this disease, as follows: The patient should start with one tablet daily for one week, thereafter increasing the dose by one tablet 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. NSAIDs may be taken concurrently with sulfasalazine.

Route of administration:

Oral

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 adverse effects due 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 Sulfasalazine 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).

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.

4 for further information 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.

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Serious infections associated with myelosuppression, including sepsis and pneumonia, have been reported. Patients who develop a new infection while undergoing treatment with sulfasalazine should be monitored closely. Administration of sulfasalazine should be discontinued if a patient develops a serious infection.

Caution should be exercised when considering the use of sulfasalazine in patients with a history of recurring or chronic infections or with underlying conditions which may predispose patients to infections. Complete blood counts, including differential white cell, red cell and platelet counts and liver function tests should be performed before starting sulfasalazine, 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 at monthly intervals for a minimum of the first three months of treatment.

For patients with baseline renal impairment, treatment with sulfasalazine should only be initiated if the benefits are considered to outweigh risk. Thereafter, periodic renal function monitoring should be performed as clinically indicated, especially in the early months of treatment.

Treatment should be discontinued if renal function deteriorates. Patients should be counselled to report immediately any development of sore throat, fever, malaise, pallor, purpura, jaundice, or non-specific illness, this may indicate myelosuppression, haemolysis or hepatoxicity; a Patient Information Leaflet should also be supplied to warn patients of this requirement, and of the risks of serious blood dyscrasias.

Treatment should be stopped immediately while awaiting the results of blood tests. 4 “Interference with laboratory testing” for Interference with laboratory testing. Sulfasalazine should not be given to patients with impaired hepatic or renal function or with blood dyscrasias, unless the potential benefit outweighs the risk.

Patients with severe allergy or bronchial asthma should be treated with caution. , pseudomononucleosis), hematological abnormalities (including hematophagic histiocytosis), and/or pneumonitis including eosinophilic infiltration. Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of sulfasalazine.

Patients appear to be at highest risk for these events early in the course of therapy, the onset of the event occurring in the majority of cases within the first month of treatment. Sulfasalazine should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Severe, life-threatening, systemic hypersensitivity reactions such as Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) have been reported in patients taking various drugs including sulfasalazine. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident.

If such signs or symptoms are present, the patient should be evaluated immediately. Sulfasalazine should be discontinued if an alternative etiology for the signs or symptoms cannot be established. Use in children with the concomitant condition systemic onset juvenile rheumatoid arthritis may result in a serum sickness like reaction; therefore sulfasalazine is not recommended in these patients.

Patients with glucose-6-phosphate dehydrogenase deficiency should be closely observed for signs of haemolytic anaemia (Heinz body anaemia). , macrocytosis and pancytopenia), this can be normalised by administration of folic acid or folinic acid (leucovorin).

Because sulfasalazine causes crystalluria and kidney stone formation, adequate fluid intake should be ensured during treatment. Oligospermia and infertility may occur in men treated with sulfasalazine. Discontinuation of the drug appears to reverse these effects within 2 to 3 months.

Interference with laboratory testing Several reports of possible interference with measurements, by liquid chromatography, of urinary normetanephrine causing a false-positive test result have been observed in patients exposed to sulfasalazine or its metabolite, mesalamine/mesalazine.

Sulfasalazine or its metabolites may interfere with ultraviolet absorbance, particularly at 340 nm, and may cause interference with some laboratory assays that use NAD(H) or NADP(H) to measure ultraviolet absorbance around that wavelength.

Examples of such assays may include urea, ammonia, LDH, α-HBDH and glucose. It is possible that alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase-muscle/brain (CK- MB), glutamate dehydrogenase (GLDH), or thyroxine may also show interference when sulfasalazine treatment is given at high doses.

Consult with the testing laboratory regarding the methodology used. Caution should be exercised in the interpretation of these laboratory results in patients who are receiving sulfasalazine. Results should be interpreted in conjunction with clinical findings.

Sulfasalazine is contraindicated in; • patients with a known hypersensitivity to sulfasalazine, its metabolites or any of the excipients, as well as salicylate and sulfonamide hypersensitivity; • children under the age of 2 years; • patients with porphyria