What it's for (Indications)
- Sulphasalazine is primarily indicated for the treatment of mild to moderate ulcerative colitis (UC), and as an adjunctive therapy in severe cases.
- It is also used for the management of Crohn's disease, particularly in active disease to induce remission, though its role in maintenance for Crohn's is less prominent than in UC.
- Beyond inflammatory bowel disease, sulphasalazine is a well-established disease-modifying anti-rheumatic drug (DMARD) for the treatment of active rheumatoid arthritis (RA) in adults who have responded inadequately to non-steroidal anti-inflammatory drugs (NSAIDs) and/or other DMARDs.
- Additionally, it is prescribed for polyarticular course juvenile idiopathic arthritis (JIA) when other therapies have failed.
- Its broad anti-inflammatory and immunomodulatory properties make it a valuable agent in these chronic inflammatory conditions, targeting symptomatic relief and disease progression and aiming to reduce the need for corticosteroid use.
Dosage Information
| Type | Guideline |
|---|---|
| Standard | The dosage of sulphasalazine is highly individualized and depends on the specific indication, patient tolerance, and response to therapy, typically starting with a lower dose and gradually increasing to a maintenance dose. For ulcerative colitis and Crohn's disease in adults, therapy usually commences with 1 to 2 grams daily, divided into multiple doses, increasing slowly over several weeks to a maintenance dose of 3 to 4 grams daily, not exceeding 6 grams daily in severe cases. In rheumatoid arthritis, the adult starting dose is commonly 500 mg daily for the first week, escalating by 500 mg increments weekly to a maintenance dose of 2 grams daily, usually divided into two doses. Pediatric dosing for juvenile idiopathic arthritis is based on weight, starting with 10 mg/kg/day and gradually increasing to 30-50 mg/kg/day, not exceeding 2 grams daily. All doses should be taken with food or after meals to minimize gastrointestinal upset, and patients should be advised to maintain adequate hydration to prevent crystalluria. Enteric-coated formulations, such as Salazodine EC 500 mg, are often preferred to reduce upper gastrointestinal side effects. |
Safety & Warnings
Common Side Effects
- Sulphasalazine is associated with a range of side effects, some of which can be significant and warrant close monitoring.
- Common adverse reactions include gastrointestinal disturbances such as nausea, vomiting, dyspepsia, abdominal pain, and diarrhea, which are often dose-dependent and can be mitigated by enteric-coated formulations or dose reduction.
- Other frequent side effects include headache, rash, anorexia, dizziness, and reversible oligospermia in males.
- More serious, albeit less common, adverse events include hematologic abnormalities such as agranulocytosis, aplastic anemia, leukopenia, thrombocytopenia, hemolytic anemia (especially in G6PD deficient patients), and methemoglobinemia.
- Hepatic toxicity, manifesting as hepatitis, cholestatic jaundice, or even hepatic necrosis, can occur.
- Renal complications like crystalluria, nephrolithiasis, and interstitial nephritis are also reported.
- Hypersensitivity reactions, including severe dermatologic conditions like Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) are critical concerns.
- Patients may also experience folate deficiency due to interference with absorption, requiring supplementation.
- Discoloration of urine, skin, and contact lenses to an orange-yellow hue is an expected, harmless side effect.
Serious Warnings
- Black Box Warning: **WARNING: SEVERE HYPERSENSITIVITY REACTIONS, BLOOD DYSCRASIAS, AND HEPATIC DAMAGE.** Sulphasalazine has been associated with severe, potentially fatal, hypersensitivity reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS). These reactions require immediate discontinuation of the drug upon recognition. Fatalities have been reported with these severe skin and systemic reactions. Furthermore, severe blood dyscrasias, including agranulocytosis, aplastic anemia, leukopenia, thrombocytopenia, and hemolytic anemia, have occurred with the use of sulphasalazine, some with fatal outcomes. Cases of hepatic damage, ranging from hepatitis to fulminant hepatic necrosis, also resulting in fatalities, have been reported. Due to these significant risks, complete blood counts, including differential white blood cell counts, and liver function tests (e.g., AST, ALT, alkaline phosphatase, bilirubin) must be performed prior to the initiation of sulphasalazine therapy and at frequent intervals throughout treatment (e.g., every two weeks for the first three months, then monthly for the next three months, and quarterly thereafter) to monitor for early signs of these adverse effects. The benefits of sulphasalazine should be carefully weighed against the potential risks, especially in patients with a history of allergies or asthma, who may be at an increased risk for hypersensitivity reactions. Immediate discontinuation and medical attention are warranted if any signs or symptoms suggestive of these severe reactions develop.
- Patients receiving sulphasalazine require close monitoring due to the potential for severe adverse reactions.
- Regular complete blood counts with differential white blood cell counts, and liver and renal function tests are imperative before initiating therapy and at frequent intervals throughout treatment to detect myelosuppression, hepatotoxicity, or renal impairment promptly.
- This medication should be used with extreme caution in patients with a history of severe allergy, bronchial asthma, or those with known hypersensitivity to sulfonamides, salicylates, or any component of sulphasalazine, as severe and potentially fatal hypersensitivity reactions can occur.
- Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency are at an increased risk of hemolytic anemia, and appropriate monitoring is crucial.
- Adequate hydration is essential to prevent crystalluria and stone formation, particularly in patients with pre-existing renal impairment.
- Folate supplementation is often necessary to prevent megaloblastic anemia and other complications associated with folate deficiency due to its inhibitory effect on folate absorption.
- Any signs of rash, sore throat, fever, pallor, or jaundice necessitate immediate discontinuation of the drug and thorough medical evaluation.
- Patients should be advised about potential photosensitivity and to use sun protection.
How it Works (Mechanism of Action)
Sulphasalazine functions as a prodrug, undergoing cleavage by colonic bacteria within the large intestine into two primary components: sulfapyridine (SP) and 5-aminosalicylic acid (5-ASA), also known as mesalamine. The 5-ASA moiety is considered the therapeutically active component for inflammatory bowel disease, exerting its anti-inflammatory effects primarily topically within the colon. It acts by inhibiting the synthesis of prostaglandins and leukotrienes, which are potent inflammatory mediators, and by scavenging free radicals and reactive oxygen species. Additionally, 5-ASA may modulate local immune responses by inhibiting neutrophil chemotaxis, reducing the production of inflammatory cytokines like TNF-alpha, and interfering with the nuclear factor-kappa B (NF-κB) pathway. Sulfapyridine is largely responsible for the systemic effects, including many of the observed side effects and potentially contributing to the anti-inflammatory or immunomodulatory actions in systemic diseases such as rheumatoid arthritis, although its precise mechanism in these conditions is less clearly defined than 5-ASA's in IBD. This dual-component action allows for targeted topical anti-inflammatory effects in the gut and systemic immunomodulation.
Commercial Brands (Alternatives)
No other brands found for this formula.