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Uses

Sulfasalazine is used for the management of mild to moderate ulcerative colitis in adults and children 2 years of age or older and also has been used in the management of Crohn's disease in adult and pediatric patients. In addition, sulfasalazine administered as delayed-release tablets is used for the management of rheumatoid arthritis in adults and for the management of polyarticular course juvenile rheumatoid arthritis in children 6-16 years of age.

Ulcerative Colitis

Sulfasalazine is used for the management of mild to moderate ulcerative colitis in conjunction with usual supportive and dietary measures. Corticosteroids are more effective than sulfasalazine in treating acute attacks and concomitant administration of corticosteroid retention enemas may be required. Patients who do not respond to concomitant sulfasalazine and topical corticosteroid therapy or who have extensive intestinal involvement may require systemic corticosteroids. Sulfasalazine is more effective than corticosteroids in reducing the frequency and severity of relapses, and usually is used for maintenance therapy. The manufacturers state that sulfasalazine also may be used as an adjunct in the treatment of severe ulcerative colitis. Controlled studies supporting this indication are lacking, and other treatment such as parenteral corticosteroids or surgery generally is required.

Crohn's Disease

Sulfasalazine has been used for the management of mildly to moderately active Crohn's disease, but its role in the management of this condition is not as well defined as in the symptomatic treatment of ulcerative colitis.

Sulfasalazine may be used as initial drug therapy in patients with mildly to moderately active disease, especially in those with ileocolonic or colonic involvement; the drug does not seem be effective in patients with small bowel disease. Many clinicians recommend that sulfasalazine be used in patients with left-sided disease, restricted to the colon. Limited data indicate that patients who have been previously treated with corticosteroids or have undergone surgical resection may fail to respond to sulfasalazine therapy, while those who have not received corticosteroids at initiation of sulfasalazine therapy or did not undergo surgery may respond substantially better to sulfasalazine than those receiving placebo. There also is some evidence that concomitant therapy with sulfasalazine and corticosteroids may not be more effective than either drug alone, but some subgroups of patients may have a better response to combined therapy (e.g., those with disease localized in the colon).

Sulfasalazine does not appear to be useful for maintenance therapy in Crohn's disease once a remission has been attained by drug therapy or following surgical resection. However, limited data indicate that sulfasalazine may be superior to placebo in delaying clinical flare-ups in patients with Crohn's disease involving the colon and/or rectum, although results have been conflicting.

For additional information on the management of Crohn's disease, .

Rheumatoid Arthritis in Adults

Sulfasalazine is used for the management of rheumatoid arthritis in adults whose symptoms progress despite an adequate regimen of nonsteroidal anti-inflammatory agents (NSAIAs) or those intolerant to an adequate trial of recommended dosages of one or more NSAIAs. Sulfasalazine is one of several disease-modifying antirheumatic drugs (DMARDs) that can be used when DMARD therapy is appropriate. (For further information on the treatment of rheumatoid arthritis, .) Usually used in conjunction with analgesic and/or NSAIA therapy, at least until the beneficial effects of sulfasalazine are apparent. Administration of sulfasalazine alone is not a complete treatment for rheumatoid arthritis, and the drug only should be used as one part of a comprehensive treatment program, including non-drug therapies such as rest and physical therapy. Unlike anti-inflammatory agents, sulfasalazine does not produce immediate response in patients with this condition.

Sulfasalazine has been used in combination with other DMARDs (e.g., azathioprine, gold compounds, hydroxychloroquine, methotrexate, penicillamine) and/or systemic corticosteroids. In patients with rheumatoid arthritis, sulfasalazine improves grip strength, decreases erythrocyte sedimentation rate, reduces joint tenderness, and decreases duration of early morning stiffness. Limited data indicate that sulfasalazine appears to be as effective as gold compounds, hydroxychloroquine, or penicillamine in the management of rheumatoid arthritis.

Juvenile Arthritis

Sulfasalazine is used for the management of the signs and symptoms of polyarticular course juvenile rheumatoid arthritis in children who have not responded adequately to NSAIAs. Safety and efficacy of sulfasalazine for the management of polyarticular course juvenile rheumatoid arthritis in children 6-16 years of age is supported by evidence from adequate and well-controlled studies in adults. Extrapolation of data from adults with rheumatoid arthritis to children with polyarticular course juvenile rheumatoid arthritis is based on similarities in disease and response to therapy in these patient populations and published studies. Because of the high frequency of adverse effects in children receiving sulfasalazine for the management of systemic course juvenile rheumatoid arthritis, use of the drug in children with this type of arthritis is not recommended.(See Pediatric Precautions.)

Other Uses

Sulfasalazine has been used with some success in the treatment of granulomatous colitis and scleroderma, and was reportedly beneficial in the treatment of collagenous colitis in one patient.

Dosage and Administration

Administration

Sulfasalazine conventional and delayed-release tablets are administered orally. The total daily dosage should be divided into equally divided doses, and, if possible, doses should be administered after meals.

Delayed-release sulfasalazine tablets should be swallowed whole.

Dosage

Ulcerative Colitis

For the management of ulcerative colitis, the interval between doses of sulfasalazine given as conventional or delayed-release tablets should not exceed 8 hours. The response to sulfasalazine in ulcerative colitis patients can be evaluated by clinical criteria (e.g., presence of fever, weight changes, degree and frequency of diarrhea and bleeding) as well as by sigmoidoscopy and evaluation of biopsy samples. Continuation of sulfasalazine therapy may be necessary even when clinical symptoms, including diarrhea, have been controlled. When endoscopic examination confirms satisfactory improvement, sulfasalazine dosage may be decreased to a maintenance dosage. If diarrhea recurs, dosage should be increased to previously effective dosage. Patients with ulcerative colitis should be advised that the disease rarely remits completely, and that continued use of maintenance dosages of sulfasalazine may decrease the risk of relapse.

The usual initial adult dosage of sulfasalazine given as conventional or delayed-release tablets for the management of ulcerative colitis is 3-4 g daily given in equally divided doses. In some patients, it may be advantageous to initiate therapy with a dosage of 1-2 g daily to lessen adverse GI effects. Although dosage as high as 12 g daily has been given, dosage exceeding 4 g daily is accompanied by an increased incidence of adverse effects. Some clinicians recommend that dosage exceeding 4 g daily be avoided unless the serum concentration of total sulfapyridine and the phenotype of the patient are known. The usual adult maintenance dosage is 2 g daily in 4 divided doses, although some clinicians advocate a lower maintenance dosage of 1-1.5 g daily when possible to prevent adverse effects. The efficacy of maintenance therapy appears to be dose related, but the potential value of dosages greater than 2 g daily must be weighed against the risks of increased adverse effects and the necessity for more careful monitoring of the patient.

When sulfasalazine is given as conventional or delayed-release tablets for the management of ulcerative colitis in children 6 years of age or older, the usual initial dosage is 40-60 mg/kg daily in 3-6 divided doses and the usual maintenance dosage is 30 mg/kg daily in 4 divided doses.

Crohn's Disease

When sulfasalazine is used for the management of mildly to moderately active Crohn's disease, a daily dosage of 3-6 g, given in divided doses as conventional or delayed-release tablets, has been recommended for adults. Sulfasalazine (1.5-3 g daily), given as conventional or delayed-release tablets also has been used for maintenance therapy in Crohn's disease, although such dosages do not appear to be more effective than placebo when used in patients with medically-induced remission.

Sulfasalazine, given as an initial dosage of 25-40 mg/kg daily and increased to 50-75 mg/kg daily (maximum daily dosage of 4 g), has been used in a limited number of pediatric patients with Crohn's disease (i.e., mild ileal, ileocecal, ileocolonic, or colonic disease). Limited data from a retrospective comparative study indicate that efficacy in maintaining remission of Crohn's disease is similar in children receiving sulfasalazine to those receiving oral mesalamine delayed-release tablets. However, some patients preferred mesalamine to sulfasalazine because of ease and frequency of administration and better tolerance.

Rheumatoid Arthritis in Adults

For the management of rheumatoid arthritis, the interval between doses of sulfasalazine given as delayed-release tablets usually is 12 hours.

The usual adult dosage of sulfasalazine given as delayed-release tablets for the management of rheumatoid arthritis is 2-3 g daily given in equally divided doses. It may be advantageous to initiate therapy with a dosage of 0.5-1 g daily to lessen adverse GI effects. The manufacturers recommend that patients receive 0.5 g every evening the first week of therapy, 0.5 g twice daily (morning and evening) the second week, 0.5 g every morning and 1 g every evening the third week, and 1 g twice daily (morning and evening) thereafter. A response to sulfasalazine (manifested by improvement in the number and extent of actively inflamed joints) may not occur until after 4-12 weeks of therapy. Patients receiving sulfasalazine dosages exceeding 2 g daily should be carefully monitored.

Juvenile Arthritis

The usual dosage of sulfasalazine given as delayed-release tablets for the management of polyarticular course juvenile rheumatoid arthritis in children 6 years of age and older is 30-50 mg/kg daily in 2 equally divided doses; the maximum dosage usually is 2 g daily. To reduce GI intolerance, the manufacturers recommend that sulfasalazine therapy in children be initiated with ¼ to (1/3) of the planned maintenance dosage, and that dosage be increased at weekly intervals until the planned maintenance dosage is achieved (usually at week 4).

Cautions

Onset of adverse effects generally occurs within a few days to 12 weeks following initiation of sulfasalazine therapy, especially if dosage exceeds 4 g daily.

Clinical experience to date indicates that the incidence of sulfasalazine-induced adverse effects in patients with ulcerative colitis generally is similar to that reported in patients with rheumatoid arthritis, although there is a greater incidence of some reactions.

The most frequent adverse effects associated with sulfasalazine therapy in patients with ulcerative colitis are anorexia, headache, nausea, vomiting, gastric distress, and apparently reversible oligospermia. Other adverse effects reported in patients with ulcerative colitis include pruritus, urticaria, rash, fever, Heinz body anemia, hemolytic anemia, and cyanosis.

Adverse effects reported in patients with rheumatoid arthritis receiving sulfasalazine include nausea, dyspepsia, headache, abdominal pain, vomiting, fever, dizziness, stomatitis, rash, pruritus, abnormal liver function test results, leukopenia, and thrombocytopenia; reversible immunoglobulin suppression, rarely accompanied by clinical findings, has been observed in sulfasalazine-treated patients with rheumatoid arthritis. It appears that there are no drug-induced adverse effects that are specific to patients with rheumatoid arthritis; however, rash occurs more frequently in patients with rheumatoid arthritis than in those with ulcerative colitis, occurring in 13 or 3.3% of patients with rheumatoid arthritis or ulcerative colitis, respectively.

An increased incidence of adverse effects has been reported in patients receiving sulfasalazine daily dosages of 4 g or more or those with serum total sulfapyridine concentrations exceeding 50 mcg/mL. The ability to acetylate sulfasalazine may influence the onset and severity of adverse effects. In one study, 86% of patients exhibiting adverse effects were slow acetylators of sulfapyridine.

GI Effects

Nausea, vomiting, gastric distress, and anorexia occur in 8-33% of patients receiving sulfasalazine. Diarrhea, bloody diarrhea, neutropenic enterocolitis, hepatitis, hepatic failure, and pancreatitis have also been reported with sulfasalazine or other sulfonamides.

GI symptoms occurring after the first few days of sulfasalazine therapy are probably secondary to high serum concentrations of total sulfapyridine and may be alleviated by halving the dose and gradually increasing it over several days. If symptoms persist, the drug should be discontinued for 5-7 days, and therapy reinstituted at a lower daily dosage.

There have been isolated reports of sulfasalazine delayed-release tablets passing intact through the GI tract of some patients, possibly because of a lack of intestinal esterases capable of disintegrating the enteric coating. The drug should be discontinued immediately in such patients.

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions, including erythema multiforme (Stevens-Johnson syndrome), exfoliative dermatitis, epidermal necrolysis (Lyell's syndrome) with corneal damage, rash with eosinophilia and systemic symptoms (DRESS), anaphylaxis, serum sickness syndrome, interstitial lung disease, pneumonitis with or without eosinophilia, vasculitis, fibrosing alveolitis, pleuritis, pericarditis with or without tamponade, allergic myocarditis, polyarteritis nodosa, lupus erythematosus-like syndrome, hepatitis and hepatic necrosis with or without immune complexes, fulminant hepatitis sometimes leading to liver transplantation, parapsoriasis varioliformis aculta (Mucha-Haberman syndrome), rhabdomyolysis, photosensitization, arthralgia, periorbital edema, conjunctival and scleral injection, and alopecia, have been reported with sulfasalazine or other sulfonamides.

Sulfasalazine should be used with caution in patients with severe allergy or bronchial asthma.

If a hypersensitivity reaction occurs during sulfasalazine therapy, the drug should be discontinued immediately.

Desensitization

Desensitization to sulfasalazine has been used when reinstitution of sulfasalazine therapy is considered necessary in patients who have had a hypersensitivity reaction to the drug; however, desensitization should not be attempted in patients with a history of agranulocytosis, toxic epidermal necrolysis, fibrosing alveolitis, or anaphylactoid reaction while receiving sulfasalazine.

Specialized references should be consulted for specific information on desensitization procedures and dosage. Although various desensitization procedures have been reported to be effective, many regimens use an initial sulfasalazine dosage of 50-250 mg daily which is then doubled every 4-7 days until the desired therapeutic dosage is attained. If manifestations of sensitivity recur, the drug should be discontinued.

Other Adverse Effects

A few cases of pulmonary eosinophilia and at least one fatality from fibrosing alveolitis have been reported in patients receiving sulfasalazine.

Sulfasalazine may impart an orange-yellow color to alkaline urine and skin, and patients should be advised of this effect.

Precautions and Contraindications

Sulfasalazine shares the toxic potentials of the sulfonamides, and the usual precautions of sulfonamide therapy should be observed.

Sulfasalazine should be used in patients with hepatic or renal damage or with blood dyscrasias only after critical appraisal. Fatalities related to hypersensitivity reactions, blood dyscrasias (e.g., agranulocytosis, aplastic anemia), renal and liver damage, irreversible neuromuscular and CNS changes, and fibrosing alveolitis have been reported in patients receiving the drug.

The presence of clinical signs such as sore throat, fever, pallor, purpura, or jaundice may indicate myelosuppression, hemolysis, or hepatotoxicity.

Complete blood cell counts (CBCs), with differentials, and liver function tests should be performed prior to initiation of sulfasalazine therapy and every 2 weeks during the first 3 months of therapy. These tests should then be performed once monthly during the second 3 months of therapy and once every 3 months thereafter and as clinically indicated. In addition urinalysis (with microscopic examination) should be done frequently and other renal function tests should be evaluated periodically during sulfasalazine therapy. The drug can be discontinued while awaiting results of blood tests.

Adequate fluid intake must be maintained during sulfasalazine therapy to reduce the risk of crystalluria and stone formation.

Patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency should be monitored closely for signs of hemolytic anemia; this adverse effect frequently is dose related.

Sulfasalazine is contraindicated in individuals hypersensitive to sulfasalazine, its metabolites, sulfonamides, or salicylates. The drug also is contraindicated in individuals with intestinal or urinary tract obstruction or porphyria.

Pediatric Precautions

Safety and efficacy of sulfasalazine conventional or delayed-release tablets in children younger than 2 years of age with ulcerative colitis have not been established.

Safety and efficacy of sulfasalazine delayed-release tablets for the management of polyarticular course juvenile rheumatoid arthritis in children 6-16 years of age is supported by evidence from adequate and well-controlled studies in adults. Adverse effects observed in children receiving sulfasalazine for the management of juvenile rheumatoid arthritis generally are similar to those observed in adults with rheumatoid arthritis. However, sulfasalazine therapy is associated with a high frequency of serum sickness-like syndrome in children with systemic course juvenile rheumatoid arthritis. This syndrome, which frequently is severe, presents as fever, nausea, vomiting, headache, rash, and abnormalities in liver function test results. Therefore, use of sulfasalazine in patients with systemic course juvenile rheumatoid arthritis is notrecommended.

Sulfasalazine, given as an initial dosage of 25-40 mg/kg daily and increased to 50-75 mg/kg daily (maximum daily dosage of 4 g), has been used in a limited number of pediatric patients with Crohn's disease (i.e., mild ileal, ileocecal, ileocolonic, or colonic disease). Limited data from a retrospective comparative study indicate that efficacy in maintaining remission of Crohn's disease is similar in children receiving sulfasalazine to those receiving oral mesalamine delayed-release tablets. However, some patients preferred mesalamine to sulfasalazine because of ease and frequency of administration and better tolerance.

Geriatric Precautions

Prolonged plasma elimination half-lives of sulfasalazine, sulfapyridine, and their metabolites have been reported in geriatric patients with rheumatoid arthritis. The clinical importance of these effects are not known.

Mutagenicity and Carcinogenicity

In carcinogenicity studies evaluating sulfasalazine in rats and mice, an increased incidence of urinary bladder transitional cell papillomas was observed in male rats and transitional cell papilloma of the kidney was observed in some female rats. In addition, an increased incidence of hepatocellular adenoma or carcinoma was observed in male and female mice.

Sulfasalazine was not mutagenic in the Ames test or in a mouse lymphoma cell assay; however, the drug showed equivocal mutagenic response in some other tests, including the micronucleus assay of mouse and rat bone marrow and mouse peripheral red blood cell, and the sister chromatid exchange, chromosomal aberration, and micronucleus assays in human lymphocytes.

Pregnancy, Fertility, and Lactation

Reproduction studies in rats and rabbits using sulfasalazine dosages up to 6 times the usual human dosage have not revealed evidence of harm to the fetus.

Sulfasalazine has been used for the treatment of inflammatory bowel disease, including Crohn's disease and ulcerative colitis, during pregnancy. Although fetal abnormalities occasionally have been reported in infants born to women with inflammatory bowel disease who received sulfasalazine alone or combined with corticosteroids during pregnancy, most evidence indicates that sulfasalazine is not associated with a substantial risk of teratogenicity and that the potential benefits of therapy with the drug generally appear to outweigh the possible risks in pregnant women with this disease. Although most experience with the use of sulfasalazine in pregnancy has been in women with inflammatory bowel disease, safety of the drug in pregnant women with rheumatoid arthritis is not expected to differ from that in inflammatory bowel disease and sulfasalazine therapy generally can be continued in pregnant women with rheumatoid arthritis. Some clinicians consider sulfasalazine the disease-modifying antirheumatic drug (DMARD) of choice in women who are planning to become pregnant or who are pregnant.

The risk of sulfasalazine-induced kernicterus in neonates born to women who received the drug during the last trimester appears to be low. Agranulocytosis has been reported in an infant whose mother received sulfasalazine and corticosteroid therapy throughout pregnancy. The effect of the drug on subsequent growth development and functional maturation in children whose mothers received sulfasalazine during pregnancy has not been determined.

Because there are no adequate and controlled studies to date using sulfasalazine in pregnant women, the drug should be used during pregnancy only when clearly needed.

Impairment of male fertility was observed in reproduction studies in rats using sulfasalazine dosages of 800 mg/kg daily. Oligospermia, abnormal sperm forms, impaired sperm motility, and infertility have occurred in men receiving sulfasalazine; however, these effects appear to be reversible following discontinuance of the drug. These effects appear to be caused by effects of sulfapyridine, not 5-aminosalicylic acid (mesalamine), on sperm maturation.

Sulfasalazine should be used with caution in nursing women since sulfonamides are distributed into milk.

Drug Interactions

Sulfasalazine shares the potential drug interactions of the sulfonamides. In addition, sulfasalazine may interact with other agents.

It has been postulated that concomitant use of anti-infectives may alter the action of sulfasalazine by altering intestinal flora and consequently sulfasalazine metabolism.

Digoxin

Concomitant use of sulfasalazine and digoxin may result in decreased absorption of digoxin.

Folic Acid

Sulfasalazine inhibits folic acid absorption, interferes with folic acid metabolism, and may result in decreased serum folic acid concentrations and possibly folic acid deficiency in some patients. Several mechanisms appear to be involved, including inhibition of hepatic folate metabolism, intestinal transport of folic acid, and jejunal brush-border folate conjugase.

Some clinicians suggest that folic acid deficiency may be prevented in patients receiving sulfasalazine by increased dietary intake of folic acid, taking the drug between meals, and/or by administration of folic acid supplements.

Iron

Sulfasalazine chelates iron, altering distribution of sulfasalazine in the intestinal lumen, interfering with its absorption and resulting in lower blood concentrations of sulfasalazine.

Methotrexate

Concomitant use of sulfasalazine and methotrexate in patients with rheumatoid arthritis does not appear to affect the pharmacokinetics of either drug. However, results of 2 controlled studies in patients with rheumatoid arthritis have shown an increased incidence of adverse GI effects (mainly nausea) in patients receiving concomitant therapy with sulfasalazine (2 g daily) and methotrexate (7.5 mg weekly) when compared with such incidence associated with administration of either drug alone.

Pharmacokinetics

Absorption

About 10-15% of a dose of sulfasalazine is absorbed as unchanged drug from the small intestine. Part of the absorbed sulfasalazine is apparently excreted via the bile into the intestine. The remainder of an oral dose of sulfasalazine passes intact into the colon where the azo-linkage is cleaved by intestinal flora to form sulfapyridine and 5-aminosalicylic acid (mesalamine). Sulfapyridine is rapidly absorbed from the colon. Only a small portion of the 5-aminosalicylic acid present in the colon is absorbed.

Following administration of a single 2-g oral dose of sulfasalazine to healthy adults, peak serum sulfasalazine concentrations occur within 1.5-6 hours and average 14 mcg/mL. Peak serum sulfapyridine concentrations occur within 6-24 hours and average 21 mcg/mL. Following administration of a single 2-g oral dose of delayed-release sulfasalazine, peak serum sulfasalazine concentrations occur within 3-12 hours and average 6 mcg/mL, and peak sulfapyridine concentrations occur within 12-24 hours and average 13 mcg/mL. Peak plasma concentrations of sulfapyridine and 5-aminosalicylic acid usually occur about 10 hours after dosing; the longer time to achieve peak plasma concentrations of the metabolites versus the parent drug probably is associated with GI transit time to the lower intestine where metabolism of sulfasalazine occurs.

The mean serum concentration of total sulfapyridine (sulfapyridine and its metabolites) tends to be greater in patients who are slow acetylator phenotypes than in fast acetylator phenotypes. In one study of colitis patients receiving sulfasalazine in doses ranging from 3-6 g daily, mean steady-state serum concentrations in fast acetylators were 17.6 mcg of sulfasalazine per mL, 31 mcg of total sulfapyridine per mL, and 1 mcg of 5-aminosalicylic acid per mL. In slow acetylators, mean steady-state serum concentrations were 18.7 mcg of sulfasalazine per mL, 53.7 mcg of total sulfapyridine per mL, and 1 mcg of 5-aminosalicylic acid per mL.

Serum concentrations of total sulfapyridine in excess of 50 mcg/mL appear to correlate with adverse effects, while concentrations of 20-50 mcg of total sulfapyridine per mL appear to correlate with clinical improvement.

Serum concentrations of 5-aminosalicylic acid range from 0-4 mcg/mL in patients with ulcerative colitis receiving sulfasalazine.

Distribution

In animals, relatively high concentrations of sulfasalazine are present in serous fluid, liver, and the intestinal wall. Sulfapyridine is distributed to most body tissues. The apparent steady-state volume of distribution of sulfasalazine following IV administration reportedly is about 7.5 L. Only very small amounts of unchanged sulfasalazine are distributed into milk, but sulfapyridine concentrations in milk are about 30-60% of those in serum. Unchanged sulfasalazine, sulfapyridine and its metabolites, and 5-aminosalicylic acid and its acetylated metabolite cross the placenta.

Sulfasalazine, sulfapyridine, and acetylsulfapyridine (principal metabolite of sulfapyridine) are about 99, 70, and 90% bound, respectively, to plasma proteins, mainly albumin.

Elimination

In one study in healthy individuals receiving 4-g doses of sulfasalazine, the mean serum half-life of sulfasalazine was reported to be 5.7 hours following a single dose and 7.6 hours following multiple doses. The half-life of sulfapyridine was reported to be 8.4 hours following a single dose, and 10.4 hours following multiple doses of sulfasalazine.

Sulfasalazine is cleaved by intestinal flora in the colon to form sulfapyridine and 5-aminosalicylic acid. (See Pharmacokinetics: Absorption.) Following absorption, sulfapyridine undergoes hepatic N-acetylation (to form acetylsulfapyridine) and ring hydroxylation followed by conjugation with glucuronic acid. The rate of metabolism of sulfapyridine and acetylsulfapyridine depends on the acetylator phenotype of the patient. The mean plasma half-life of sulfapyridine in fast acetylators or slow acetylators is 10.4 or 14.8 hours, respectively. Sulfapyridine also can be metabolized to 5-hydroxy-sulfapyridine and N-acetyl-5-hydroxy-sulfapyridine. A small portion of 5-aminosalicylic acid is absorbed and undergoes N-acetylation in the liver and intestine; the major portion is excreted in the feces.

In geriatric patients with rheumatoid arthritis, the half-life of sulfasalazine and its metabolites may be increased.

Most of a dose of sulfasalazine is excreted in the urine. Generally, unchanged sulfasalazine accounts for up to 15%, sulfapyridine and its metabolites account for about 60%, and 5-aminosalicylic acid and its metabolites account for 20-33% of a dose. One study has shown urinary excretion of total sulfapyridine to be higher in patients in remission as compared with unimproved patients. Although total fecal excretion of sulfasalazine and its metabolites depends on GI transit time and the activity of the intestinal bacteria, one study has shown fecal excretion to account for about 5% of a daily dose (primarily as sulfapyridine metabolites).

Following IV administration, the calculated clearance of sulfasalazine is about 17 mL/minute; renal clearance of the drug is approximately 37% of the total clearance.