Sulfasalazine therapy

When given orally, usually 4 g/day, up to 8 g/day of sulfasalazine is required to attain control of active inflammation. Sulfasalazine therapy should be instituted at 500 mg/day and increased every few days up to 4 g/ day or the maximum tolerated. 

Sulfasalazine (Azulfidine) is approved for the treatment of rheumatoid arthritis and ulcerative colitis. It is also used to treat ankylosing spondylitis and Crohn s disease. Comparisons of sulfasalazine with other DMARDs suggest that it is more effective than hydroxychloroquine, azathioprine, and oral gold compounds. It is at least as effective as intramuscular gold and penicillamine. It has a greater degree of toxicity than hydroxychloroquine but less than gold compounds and penicillamine. After 5 years, approximately 75% of patients have discontinued sulfasalazine therapy, primarily because of a lack of efficacy as opposed to intolerable side effects. 

Space drug doses around the clock and continue sulfasalazine therapy for the full... 

Inform the dentist or surgeon of sulfasalazine therapy if he or she will have dental or other surgical procedures... 

Sulfasalazine, commonly used in the treatment of inflammatory bowel disease and rheumatoid arthritis, is selectively used as an alternative treatment, particularly in patients with concurrent psoriatic arthritis. Sulfasalazine is an anti-inflammatory agent that inhibits 5-lipoxygenase. When used as a single agent in the treatment of psoriasis, it is not as effective as is therapy with methotrexate, PUVA, or acitretin. One possible advantage of sulfasalazine therapy compared with other systemic treatments is its relatively high margin of safety. The usual dose of oral sulfasalazine is 3 to 4 g/day for 8 weeks. ... 

Vitamin status also may be affected by drugs (Table 135-15). For example, sulfasalazine therapy has been noted to cause a decrease in folic acid, isoniazid therapy causes pyridoxine deficiency, and furosemide therapy may result in decreased thiamin concentrations. Furthermore, some drug therapy outcomes may be affected by vitamin intake. The ingestion of megadoses of folic acid may decrease methotrexate s therapeutic effect, whereas changes in an individual s usual vitamin K intake may cause variability in warfarin s anticoagulation effects. 

Engler R, Squire E, Benson P (1995) Chronic sulfasalazine therapy in the treatment of delayed pressure urticaria and angioede-ma. Ann Allergy 74 155-159... 

Gupta R, Hennebry TA, Kinasewitz GT. Pleuropericardial effusion after 37 years of sulfasalazine therapy. J Cardiovasc Med Hagerst... 

Other adverse reactions that may occur during therapy include nausea, vomiting, diarrhea, abdominal pain, chills, fever, and stomatitis (inflammation of the mouth). In some instances, these may be mild. Other times they may cause serious problems requiring discontinuation of the drug. Sulfasalazine may cause the urine and skin to be an orange-yellow color this is not abnormal. 

For patients with more extensive disease extending proximal to the splenic flexure, oral sulfasalazine or any of the newer oral mesalamine products is considered first-line therapy.1 Doses should provide 4 to 6 g of sulfasalazine or 4.8 g of mesalamine. While little differences in efficacy exist between... 

Oral corticosteroids may be used for patients who are unresponsive to sulfasalazine or mesalamine. Prednisone doses of 40 to 60 mg per day (or equivalent) are recommended.1 Azathioprine or 6-MP is used for patients unresponsive to corticosteroids or those who become steroid-dependent. Over a 12-month period, these agents have been shown to reduce the relapse rate to 36% versus 59% seen with placebo.1 Infliximab 5 mg/kg may also be used for patients who are unresponsive to conventional oral therapies and may reduce the need for colectomy after 3 months of treatment.35... 

Azathioprine, mycophenolate mofetil, and enteric-coated MPA are not metabolized through the CYP isozyme system therefore, they do not experience the same DDI profiles as cyclosporine, tacrolimus, and sirolimus. Azathioprine s major DDIs involve allopurinol, angiotensin-converting enzyme (ACE) inhibitors, aminosalicylates (e.g., mesalamine and sulfasalazine), and warfarin.11 The interaction with allopurinol is seen frequently and has clinical significance. Allopurinol inhibits xanthine oxidase, the enzyme responsible for metabolizing azathioprine. Combination of azathioprine and allopurinol has resulted in severe toxicities, particularly myelosuppression. It is recommended that concomitant therapy with azathioprine and allopurinol be avoided, but if combination therapy is necessary, the azathioprine doses must be reduced to one-third or one-fourth of the current dose. Use of azathioprine with the ACE inhibitors or aminosalicylates also can result in enhanced myelosuppression.11 Some case reports exist demonstrating that warfarin s therapeutic effects may be decreased by azathioprine.43-45... 

In addition to relying on safety and efficacy data, the initial DMARD choice depends on disease severity, patient characteristics (i.e., comorbidities, likelihood of adherence), cost, and clinician experience with the medication.1,7 Methotrexate alone or in combination therapy is the initial treatment of choice for patients with aggressive disease. Patients with early, mild disease may receive monotherapy with sulfasalazine or hydroxychloroquine. Agents such as azathioprine, D-penicillamine, and gold salts are used rarely today because of concerns about toxicity and reduced efficacy.1,15... 

Systemic therapies are seldom used for mild to moderate psoriasis, and are generally reserved for patients with moderate to severe psoriasis.17 29 Oral agents include sulfasalazine, acitretin, methotrexate, cyclosporine, mycophenolate mofetil, azathioprine, tacrolimus, and hydroxyurea. Parenteral agents include the biologic response modifiers alefacept, efalizumab, etanercept, infliximab, and many others, currently at various stages of research or approval for psoriasis. 

Sulfasalazine has variable efficacy and is of limited potency. However, its side-effect profile is better than other systemic therapies and it is sometimes tried as an initial systemic agent for moderate to severe psoriasis. Usual doses are 2 to 4 g/day in divided doses.10... 

Combination therapy with two or more DMARDs may be effective when single-DMARD treatment is unsuccessful. Combinations that are particularly effective include (1) MTX plus cyclosporine, and (2) MTX plus sulfasalazine and hydroxychloroquine. 

The first line of drug therapy for the patient with mild to moderate colitis is oral sulfasalazine or an oral mesalamine derivative, or topical mesalamine or steroids for distal disease (Fig. 26-1). 

Ulcerative colitis In the treatment of mild to moderate ulcerative colitis, and as adjunctive therapy in severe ulcerative colitis for the prolongation of the remission period between acute attacks of ulcerative colitis (refer to the sulfasalazine monograph in the Gl chapter). 

Monitoring Perform complete blood counts, including differential white cell count and liver function tests before starting sulfasalazine and every second week during the first 3 months of therapy. During the second 3 months, perform the same tests once monthly and, thereafter, once every 3 months and as clinically indicated. Also perform urinalysis and assess renal function periodically during treatment. 

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. 

Outcome measurements used in the evaluation of the outcome of treatment of RA with sulfasalazine, parenteral gold salts, D-penicillamine, hydroxychloroquine, prednisolone, MTX, cyclophosphamide (CyC), and azathioprine in single drug therapy cannot be compared with endpoints used in SBC-5-lMNs and biological-DMARDs combined with MTX. 

The most recent treatment paradigm calls for earher, more aggressive treatment of rheumatoid arthritis. DMARDs are frequently employed along with NSAIDs in the initial treatment of the disease. The COX-2 inhibitors are often used because they are less likely to cause serious GI toxicity than are the nonspecihc COX inhibitors. The usual DMARD of choice for patients with mild rheumatoid arthritis is hydroxychloroquine or sulfasalazine methotrexate is used for those with moderate to serious disease. Other DMARDs are used if these agents are poorly tolerated or do not produce suf-hcient response. Combination therapy of methotrexate and another agent is also used to treat disease that is not responsive to individual DMARDs. 

Sulfasalazine treatment results in an 85% remission rate in mild to moderate ulcerative colitis. Termination of therapy leads to an 80% relapse within the next year. In Crohn s disease, sulfasalazine acts primarily on involved colonic mucosa, although remission of ileal disease also has been reported. The National Cooperative Crohn s Disease Study found sulfasalazine to be better in the treatment of colonic disease, while corticosteroids were judged better in the treatment of small bowel disease. Since sulfasalazine does not prevent relapse of Crohn s disease once remission is achieved, maintenance therapy is not characteristically used. 

Since sulfasalazine inhibits the absorption of folic acid, patients may become folate deficient during longterm therapy. Sulfasalazine decreases the bioavailabiUty of digoxin. Cholestyramine reduces the metabolism of sulfasalazine. Sulfasalazine causes a reversible decrease in sperm counts. Sulfasalazine is safe in pregnancy. 

C. The information provided suggests the patient has mild to moderate disease. Initial therapy should be a 5-ASA containing product, which includes sulfasalazine and mesalamine. However, the patient has a sulfa allergy, precluding the use of sulfasalazine. Metronidazole is useful in the treatment of some patients with Crohn s disease. Cyclosporine has been used in patients with fulminant ulcerative colitis. Prednisone may have to be added to this patient s therapy, but only if he fails to respond to the mesalamine. It should not be used initially. 

When added to methotrexate background therapy, cyclosporine, chloroquine, hydroxychloroquine, leflunomide, infliximab, adalimumab, rituximab, and etanercept have all shown improved efficacy. In contrast, azathioprine, auranofin, or sulfasalazine plus methotrexate results in no additional therapeutic benefit. Other combinations have occasionally been used, including the combination of intramuscular gold with hydroxychloroquine. 

Penicillamine (Cuprimine), a derivative of penicillin, is officially classified as a chelating agent that is often used in the treatment of heavy metal intoxication (e.g., lead poisoning). In addition, this drug has been used in patients with severe rheumatoid arthritis, and seems to be as effective as other DMARDs such as methotrexate, sulfasalazine, and gold therapy.68 98 Penicillamine, however, tends to be substantially more toxic than other DMARDs, and is therefore used rarely in the treatment of specific patients with rheumatoid arthritis.68... 

Te use of NSAIDS and other anti-inflammatory therapies are similar to those used in other autoimmune arthritic disorders. Corticosteroid injections for severe pain and inflammation at specific joints are standard therapy. For severe forms of the disease immunomoduladng and-rheumatic drugs such as methodexate and sulfasalazine are effecdve. As with other similar disorders, the biologic TNF a inhibitors are currently prescribed for severe Reiter s synchome. 

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