PHARMACOLOGY

Pharmacotherapeutic Group: DMARD

 Pharmacodynamic Properties:Sulfasalazine or its metabolites, 5-aminosalicylic acid (5ASA) and sulfapyridine (SP), is still under investigation, but may be related to the anti-inflammatory and/or immunomodulatory properties that have been observed in animal and in vitro models, to its affinity for connective tissue, and/or to the relatively high concentration it reaches in serous fluids, the liver and intestinal walls, as demonstrated in autoradiographic studies in animals.

 Pharmacokinetic Properties:

Absorption:15% of the dose is absorbed from small intestine, the rest reaches the colon where the azo bond is cleaved by the intestinal flora, producing sulfapyridine and 5-aminosalicylic acid (mesalazine). 60% of the sulfapyridine and 10-30% of the 5-aminosalicylic acid is absorbed from the colon.

Distribution: Following intravenous injection, the calculated volume of distribution (Vdss) for SSZ was 7.5 ± 1.6 L. SSZ is highly bound to albumin (>99.3%) while SP is only about 70% bound to albumin. Acetylsulfapyridine (AcSP), the principal metabolite of SP, is approximately 90% bound to plasma proteins.

Metabolism: Absorbed sulfapyridine undergoes extensive metabolism by acetylation, hydroxylation, and glucuronidation. Slow acetylators are 2-3 times more likely to experience adverse effects from sulfapyridine compared to fast acetylators. Absorbed 5-aminosalicylic acid undergoes acetylation.

Excretion: Via urine, as unchanged sulfasalazine (15%), sulfapyridine and its metabolites (60%), and 5-aminosalicylic acid and its metabolites (20-33%). Renal clearance was estimated to account for 37% of total clearance.

 INDICATIONS

Rheumatoid Arthritis,  Ulcerative Colitis, Inflammatory Bowel Disease

 DOSAGE & ADMINISTRATION

Adults: 

For Rheumatoid Arthritis: Delayed-release tablets: 1000 mg orally twice a day

For Ulcerative Colitis: 3 to 4 g/day orally in evenly divided doses.

Maintenance: 2 g/day orally in evenly divided doses

For Crohn's Disease:3 to 6 g/day orally in divided doses

Paediatrics( Children, six years of age and older): 

For Ulcerative Colitis

40 to 60 mg/kg body weight in each 24-hour period, divided into 3 to 6 doses. Maintenance therapy: 30 mg/kg/day orally divided into 4 doses

For Juvenile Rheumatoid Arthritis

Delayed-release tablets:
30 to 50 mg/kg/day orally in 2 equally divided doses
Maximum dose: 2 g/day (normally)

ADVERSE DRUG REACTIONS

Headache, anorexia, nausea, vomiting, diarrhoea, abdominal discomfort, photosensitivity, crystalluria, reversible oligospermia, yellow-orange staining of contact lens, skin, urine and other body fluids, alopoecia.
Potentially Fatal: Severe hypersensitivity reactions, blood dyscrasias, renal and hepatic toxicity, fibrosing alveolitis.

 PRECAUTIONS

Sulfasalazine tablets should be given with caution to patients with severe allergy or bronchial asthma. Adequate fluid intake must be maintained in order to prevent crystalluria and stone formation. Patients with glucose-6 phosphate dehydrogenase deficiency should be observed closely for signs of hemolytic anemia. This reaction is frequently dose related. If toxic or hypersensitivity reactions occur, the drug should be discontinued immediately.

 DRUG INTERACTIONS

Plasma levels reduced by rifampicin and ethambutol. Interferes with absorption of folic acid. Additive leucopaenia with gold therapy for rheumatoid arthritis. Increased haematological toxicity with azathioprine. Reduced serum levels of digoxin.

 CONTRAINDICATIONS

Patients with intestinal or urinary obstruction, porphyria,  hypersensitive to sulfasalazine, its metabolites, sulfonamides, or salicylates.

 PRESENTATION

SULFAZ: Each box contains 10 Blister of 10 Tablets per strip