Sulfasalazine
Pronouncation: (SULL-fuh-SAL-uh-zeen)Class: Antirheumatic agent, GI agent
Trade Names:
Azulfidine
- Tablets 500 mg
Trade Names:
Azulfidine EN-tabs
- Tablets, delayed-release 500 mg
Salazopyrin (Canada)
Salazopyrin Desensitizing Kit (Canada)
Salazopyrin EN-tabs (Canada)
Pharmacology
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Feedback for Sulfasalazine
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Mode of action of sulfasalazine or its metabolites (5-aminosalicylic acid [5-ASA], sulfapyridine [SP]) is still under investigation. May be related to anti-inflammatory and/or immunomodulatory properties, to affinity for connective tissue, and/or to the relatively high concentrations reached in serous fluids, the liver, and intestinal walls.
Pharmacokinetics
Absorption
Bioavailability of sulfasalazine is less than 15%; T max is 6 h (range, 3 to 12 h). Approximately one third of a dose of sulfasalazine is absorbed from the small intestine. The remaining two thirds passes into the colon where it is split by bacteria into 5-ASA and SP. SP is well absorbed from the colon (estimated bioavailability 60%); 5-ASA is less well absorbed (estimated bioavailability 10% to 30%).
Distribution
Sulfasalazine is highly bound to albumin (more than 99.3%); Vd is approximately 7.5 L.
Metabolism
Sulfasalazine is extensively metabolized by intestinal bacteria to 5-ASA and SP. Primary route of metabolism of SP is via acetylation. 5-ASA is primarily metabolized in the liver and intestine via a non-acetylation, phenotype-dependent route.
Elimination
Absorbed SP and 5-ASA are primarily eliminated in the urine. Majority of 5-ASA stays within the colonic lumen and is excreted as 5-ASA and acetyl-5-ASA with the feces. Sulfasalazine t ½ (IV) is approximately 7.6 h; mean plasma t ½ of SP is 10.4 h (fast acetylators) and 14.8 h (slow acetylators). Sulfasalazine Cl following IV administration is approximately 1 L/h.
Special Populations
ElderlyElderly patients with rheumatoid arthritis showed a prolonged plasma t ½ for sulfasalazine, sulfinpyridine, and their metabolites. The clinical impact of this is unknown.
Acetylator statusSP metabolism is mediated by polymorphic enzymes such that 2 distinct populations of slow and fast metabolizer exist. Slow acetylator phenotype (approximately 60% of White patients) display a prolonged plasma t ½ and an accumulation of higher plasma levels of SP than fast aceytylators. The clinical implications of this are unclear; however, slow acetylators may experience a higher incidence of adverse reactions.
Indications and Usage
Tablets and delayed-release tabletsTreatment of mild to moderate ulcerative colitis; adjunctive therapy in severe ulcerative colitis; prolongation of the remission period between acute attacks of ulcerative colitis.
Delayed-release tabletsTreatment of rheumatoid arthritis in patients who have responded inadequately to salicylates or other NSAIDs; treatment of children with polyarticular-course juvenile rheumatoid arthritis who have responded inadequately to salicylates or other NSAIDs.
Unlabeled Uses
Ankylosing spondylitis, Crohn disease, granulomatous colitis, regional enteritis.
Contraindications
Patients with intestinal or urinary obstruction; porphyria; hypersensitivity to sulfasalazine, its metabolites, sulfonamides, or salicylates.
Dosage and Administration
Ulcerative ColitisAdults
Initial: PO 3 to 4 g/day in evenly divided doses. More than 4 g/day is associated with higher incidence of side effects. May begin with 1 to 2 g/day to lessen GI effects. Maintenance: PO 2 g/day in 4 divided doses.
Children at least 6 yr of ageInitial: PO 40 to 60 mg/kg/24 h in 3 to 6 divided doses. Maintenance: PO 30 mg/kg/24 h in 4 divided doses.
Rheumatoid ArthritisAdults
PO Delayed-release: 2ߙg/day in 2 evenly divided doses. May initiate therapy with a lower dosage (eg, 0.5 to 1 g/day) to reduce possible GI intolerance.
Children at least 6 yr of agePO Delayed-release: 30 to 50 mg/kg/day in 2 evenly divided doses. Initiate therapy with 25% to 33% of the planned maintenance dose to lessen GI effects; increase weekly until reaching maintenance dose at 1 mo. Max, 2 g/day.
General Advice
- Administer in evenly divided doses, preferably after meal or snack.
- Caution patient to swallow delayed-release tablets whole and not to crush, chew, or break.
- Administer each dose with a full glass of water.
- Encourage fluids between meals up to 2,000 mL/day to reduce risk of crystalluria and stone formation.
Storage/Stability
Store at controlled room temperature (59° to 86°F).
Drug Interactions
DigoxinAbsorption of digoxin may be decreased.
Folic acidSigns of folate deficiency have occurred, but specific symptoms related to deficiency have not been reported.
MethotrexateRisk of methotrexate-induced bone marrow suppression may be enhanced.
SulfonylureasIncreased sulfonylurea half-lives and hypoglycemia have occurred.
Laboratory Test Interactions
None well documented.
Adverse Reactions
CNS
Ataxia, cauda equine syndrome, convulsion, depression, drowsiness, Guillain-Barré syndrome, hallucinations, headache, hearing loss, insomnia, meningitis, peripheral neuropathy, tinnitus, transient lesions of the posterior spinal column, transverse myelitis, vertigo.
Dermatologic
Orange-yellow discoloration of skin.
GI
Abdominal pain, anorexia, bloody diarrhea, diarrhea, impaired folic acid absorption, gastric distress, nausea, pancreatitis, pseudomembranous enterocolitis, stomatitis, vomiting.
Genitourinary
Crystalluria, elevated creatinine, hematuria, hemolytic-uremic syndrome, nephritis, nephrotic syndrome, orange-yellow urine, proteinuria, toxic nephrosis with oliguria and anuria, UTI.
Hematologic
Agranulocytosis, aplastic anemia, congenital neutropenia, Heinz body anemia, hemolytic anemia, hypoprothrombinemia, leukopenia, megaloblastic (macrocytic) anemia, methemoglobinemia, myelodysplastic syndrome, purpura, thrombocytopenia.
Hepatic
Hepatocellular necrosis; cholestatic jaundice, cirrhosis, elevated LFTs, jaundice, Kawasaki-like syndrome, possible hepatocellular damage including liver necrosis and failure (postmarketing).
Hypersensitivity
Allergic myocarditis, alopecia, anaphylactoid reactions, arthralgia, epidermal necrolysis with or without corneal damage, erythema multiforme of Stevens-Johnson type, exfoliative dermatitis, fibrosing alveolitis, fulminant hepatitis, hepatic necrosis, hepatitis, generalized skin eruptions, lupus erythematosus phenomenon, parapsoriasis varioliformis acuta, pericarditis with or without tamponade, periorbital edema, photosensitization, pleuritis, polyarteritis nodosa, pruritus, rhabdomyolysis, serum sickness, transient pulmonary changes with eosinophilia and decreased pulmonary function, urticaria.
Respiratory
Cyanosis, pulmonary infiltrates.
Miscellaneous
Arthralgia, chills, drug fever, myalgia, periarteritis nodosum, pyrexia.
Precautions
MonitorObtain CBC with differential and LFTs before starting therapy and every 2 wk during first 3 mo of therapy, then every month during the next 3 mo, then every 3 mo thereafter, and as clinically indicated. Urinalysis with microscopic examination and assessment of renal function should be done periodically. Serum SP levels may be useful because concentrations above 50 mcg/mL appear to be associated with an increased incidence of adverse reactions. |
Pregnancy
Category B .
Lactation
Excreted in breast milk.
Children
Safety and efficacy not established for children younger than 2 yr of age with ulcerative colitis. Safety and efficacy of delayed-release tablets not established for children younger than 6 yr of age with rheumatoid arthritis.
Renal Function
Use with caution.
Hepatic Function
Use with caution.
Fertility
Oligospermia and infertility have been observed in men treated with sulfasalazine; effects appear to be reversible when drug is withdrawn.
Allergy or asthma
Use with caution.
Contact lenses
May permanently stain soft contact lenses yellow.
Delayed-release tablets
Isolated instances of delayed-release tablets being passed undisintegrated. Immediately discontinue use of this doseform if noted.
Fluid intake
Maintain adequate fluid intake to prevent crystalluria and stone formation.
Glucose-6-phosphate dehydrogenase deficiency
Can produce clinically significant hemolysis in patients with G-6-PD deficiency.
Porphyria
May precipitate acute attacks of porphyria.
Severe reactions
Reactions, including death, have been associated with hypersensitivity reactions, agranulocytosis, aplastic anemia, other blood dyscrasias, and renal and hepatic damage. Irreversible neuromuscular and CNS changes and fibrosing alveolitis may occur.
Sulfonamides
There are chemical similarities to some goitrogens, diuretics (acetazolamide and thiazides), and oral hypoglycemic agents. Goiter production, diuresis, and hypoglycemia have occurred rarely in patients receiving sulfonamides. Cross-sensitivity may exist.
Overdosage
Symptoms
Abdominal pain, anuria, drowsiness, gastric distress, nausea, seizures, vomiting.
Patient Information
- Instruct patient to take exactly as prescribed and not to change the dose or discontinue therapy unless advised by health care provider.
- Advise patient to take in equally divided doses, with a full glass of water, preferably after meal or snack.
- Caution patient using delayed-release tablets to swallow tablets whole and not to crush, chew, break, or cut tablets.
- Advise patient that medication may cause an orange-yellow discoloration of the skin and urine but it is of no concern. Caution patient that soft contact lenses may be permanently stained yellow by this same effect.
- Advise patient that drug may cause dizziness and to use caution driving or performing other hazardous tasks until tolerance is determined.
- Instruct patient to notify health care provider if symptoms of condition being treated (ulcerative colitis or arthritis) do not appear to improve or worsen.
- Advise patient to discontinue therapy and immediately notify health care provider if any of the following occur: fever, paleness, red or purple spots under the skin, skin rash or other signs of allergic reaction, sore throat, yellowing of the skin or eyes.
- Advise patient to avoid unnecessary exposure to direct and indirect sunlight or tanning lamps, and to use sunscreen and wear protective clothing to avoid photosensitivity reactions during therapy. Advise patient to discontinue therapy and notify health care provider if any of the following occur following exposure to sunlight or artificial ultraviolet light (eg, sunlamp): blistering, rash or itching, redness, sensation of skin burning, swelling.
- Advise patient to report any other bothersome side effects to health care provider.
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More Sulfasalazine resources:
Azulfidine EN-tabs Delayed-Release Tablets
Sulfasalazine - Includes detailed dosage instructions.
Sulfasalazine Drug Interactions
Rheumatoid Arthritis, Crohn's Disease -- Maintenance, Ulcerative Colitis, Crohn's Disease -- Acute, Ulcerative Colitis -- Active, Ulcerative Colitis -- Maintenance, Uveitis
