Sulfasalazine adverse effects

Sulfasalazine is associated with various adverse effects, most of which are thought to be due to the sulfapyridine component. Common adverse effects that may be dose related include headache, dyspepsia, nausea, vomiting, and fatigue.19 Idiosyncratic effects include bone marrow suppression, reduction in sperm counts in males, hepatitis, and pulmonitis. Hypersensitivity reactions may occur in patients allergic to sulfonamide-containing medications. 

The use of non-sulfapyridine-based aminosalicylates has led to greater tolerability. Although the adverse effects are similar to those of sulfasalazine, they occur at a much lower rate. Olsalazine, in particular, is associated with a higher incidence of secretory diarrhea. These agents can also be used safely in patients with a reported sulfonamide allergy. 

Oral sulfasalazine or mesalamine is effective in maintaining remission in patients with more extensive disease.1,26 Lower daily doses (e.g., 2 to 4 g sulfasalazine or 1.6 to 2.4 g mesalamine) may be used for disease maintenance. As with distal UC, oral corticosteroids are not effective for maintaining remission and should be avoided due to the high incidence of adverse effects. 

Sulfasalazine use is often limited by adverse effects. Antirheumatic effects should be seen in 2 months. 

Sulfasalazine is an antiinflammatory agent that inhibits 5-lipoxygenase. It is used selectively as an alternative treatment, particularly in patients with concurrent psoriatic arthritis. When used alone, it is not as effective as methotrexate, PUVA, or acitretin. However, it has a relatively high margin of safety. The usual oral dose is 3 to 4 g/day for 8 weeks. Its adverse effects are similar to other sulfonamide antibiotics. 

Non-dose-related adverse effects of sulfasalazine include rash, fever, or hepatotoxicity most commonly, as well as relatively uncommon but serious reactions such as bone marrow suppression, thrombocytopenia, pancreatitis, pneumonitis, interstitial nephritis, and hepatitis. 

Oral mesalamine derivatives may impose a lower frequency of adverse effects compared with sulfasalazine. Up to 90% of patients who are intolerant to sulfasalazine will tolerate oral mesalamine derivatives. Olsalazine may cause watery diarrhea in up to 25% of patients. 

Tanaka, E., Taniguchi, A., Urano, W., et al. (2002) Adverse effects of sulfasalazine in patients with rheumatoid arthritis are associated with diplotype configuration at the iV-acetyltransferase 2 gene. Journal of Rheumatology. 29, 2492-2499. 

Maintenance therapy with sulfasalazine reduces relapse rate. However a considerable number of patients experience adverse effects which are by the sulfa component of sulfasalazine. Then preparations of 5-aminosalicylic acid can be used. 

Newer aminosalicylate preparations appear superior to placebo but differ little in efficacy from sulfasalazine SASP. Potential advantages in reduced adverse effects from removal of the sulfa moiety nevertheless may exist. 

The systemic adverse effects of corticosteroids make them inappropriate as maintenance treatments and the first line treatments are the aminosalicylates. The original drug sulfasalazine is a chemical combination of sulfapyridine and 5 aminosalicylic acid. Following the discovery that the active... 

With the combination of traditional DMARDs complete remissions are obtained in 30% of early RA over a period of 5 years. These remissions last on average less than 10 months. After 5 years only half of the patients continue with MTX and less than 25% stay on other DMARDs. After 5 years non-compliance is mostly due to adverse effects and lack of efficacy of NSAIDs, hydroxychloroquine, sulfasalazine, prednisone, d-penicillamine, azafhio-prine, and gold salts. Only MTX retains some efficacy. With these therapeutic modalities joint erosions progress to permanent joint destruction, deformities and disability. 

Leflunomide (Arava) is an isoxazole derivative approved for the treatment of rheumatoid arthritis in 1998. Limited data suggest that it is comparable in efficacy to sulfasalazine and produces fewer adverse effects. It has a faster onset of action (4 weeks) than other DMARDs. 

Approximately 30% of patients using sulfasalazine discontinue the drug because of toxicity. Common adverse effects include nausea, vomiting, headache, and rash. Hemolytic anemia and methemoglobinemia also occur, but rarely. Neutropenia occurs in 1-5% of patients, while thrombocytopenia is very rare. Pulmonary toxicity and positive double-stranded DNA are occasionally seen, but drug-induced lupus is rare. Reversible infertility occurs in men, but sulfasalazine does not affect fertility in women. The drug does not appear to be teratogenic. 

Sulfasalazine has a high incidence of adverse effects, most of which are attributable to systemic effects of the sulfapyridine molecule. Slow acetylators of sulfapyridine have more frequent and more severe adverse effects than fast acetylators. Up to 40% of patients cannot tolerate therapeutic doses of sulfasalazine. The most common problems are dose-related and include nausea, gastrointestinal upset, headaches, arthralgias, myalgias, bone marrow suppression, and malaise. Hypersensitivity to sulfapyridine (or, rarely, 5-ASA) can result in fever, exfoliative dermatitis, pancreatitis, pneumonitis, hemolytic anemia, pericarditis, or hepatitis. Sulfasalazine has also been associated with oligospermia, which reverses upon discontinuation of the drug. Sulfasalazine impairs folate absorption and processing hence, dietary supplementation with 1 mg/d folic acid is recommended. 

A 74-year-old woman with seronegative rheumatoid arthritis was given sulfasalazine followed by methotrexate, both of which were withdrawn because of adverse effects. She also took prednisone 10 mg/day. She developed acute abdominal pain and fever (38.7° C) with no chills. Her serum amylase was 269 IU/1, serum lipase... 

Crossover studies have shown that mesalazine has about a 10-fold lower potential than sulfasalazine for inducing allergic reactions or causing intolerance. Adverse effects with all aminosalicylates include (generally more frequent with sulfasalazine) headache, nausea, abdominal pain, dyspepsia, fatigue, rash, fever, rarely exacerbation of the disease, pancreatitis, pericarditis, pneumonitis, liver disease, nephritis, and bone marrow depression. Watery diarrhea is an adverse effect unique to olsalazine, while anorexia, folate malabsorption, hemolysis, neutropenia, agranulocytosis, male infertility, and neuropathy are unique to sulfasalazine. 

The adverse effects of sulfasalazine 2-3 g/day and mesalazine 1.2-2.4 g/day in 685 patients have been reviewed for a median follow-up period of 7 and 5 years respectively (18). Adverse effects were observed overall in 20% of patients taking sulfasalazine and 6.5% of those taking mesalazine. The commonest adverse effects due to sulfasalazine (reported by more than 10% of patients) were dyspepsia, rash, and headache, while the commonest due to mesalazine were rash, diarrhea, headache, fever, abdominal pain, impaired renal function, dyspepsia, and edema. Fertility was affected in aU 42 male patients taking sulfasalazine who were assessed, but improved when they changed to mesalazine. 

Pregnant colitic patients generally fare better if they continued to take aminosalicylates. Though sulfasalazine crosses the placenta, competes for albumin-binding sites with bilirubin, and can be detected in breast milk, no adverse effects on offspring have been detected. 

Because sulfonamides are subject to polymorphic metabolism by N-acetyltransferase (NAT2), some of the adverse effects of sulfasalazine are more common in slow acetylators. Gastrointestinal adverse reactions occur more commonly in slow acetylators, and they should use lower doses. 

Oral enteric-coated mesalazine is well tolerated in children aged 4—19 years and in adults who are intolerant of sulfasalazine. The most common adverse effects are headache, gas, nausea, diarrhea, and dyspepsia. The adverse effects can be severe enough to require withdrawal of the drug in up to 11% of patients. 

In 30 patients aged 18 8 years with chronic colitis, characterized by vague lower abdominal pain, rectal bleeding, diarrhea, and palpable tender descending and sigmoid colons, Boswellia serrata (900 mg/day for 6 weeks) produced remission in 14 of 20 patients, and sulfasalazine (3 g/day for 6 weeks) in 4 of 10 patients (4). There were few adverse effects. 

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