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Medication Safety Issues
Sound-alike/look-alike issues:
Sulfasalazine may be confused with salsalate, sulfaDIAZINE, sulfiSOXAZOLE
Azulfidine® may be confused with Augmentin®, azaTHIOprine
Pronunciation
(sul fa SAL a zeen)
U.S. Brand Names
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Management of ulcerative colitis; enteric coated tablets are also used for rheumatoid arthritis (including juvenile rheumatoid arthritis) in patients who inadequately respond to analgesics and NSAIDs
Use: Unlabeled/Investigational
Ankylosing spondylitis, collagenous colitis, Crohn's disease, psoriasis, psoriatic arthritis, juvenile chronic arthritis
Pregnancy Risk Factor
B/D (at term)
Lactation
Enters breast milk/use caution (AAP recommends use “with caution”)
Breast-Feeding Considerations
Sulfonamides are excreted in human breast milk and may cause kernicterus in the newborn. Although sulfapyridine has poor bilirubin-displacing ability, use with caution in women who are breast-feeding. The AAP classifies this agent to be used with caution since adverse effects have been reported in nursing infants.
Contraindications
Hypersensitivity to sulfasalazine, sulfa drugs, salicylates, or any component of the formulation; porphyria; GI or GU obstruction; pregnancy (at term)
Warnings/Precautions
Concerns related to adverse effects:
• CNS effects: Deaths from irreversible neuromuscular and central nervous system have been reported.
• Fibrosing alveolitis: Deaths from fibrosing alveolitis have been reported.
• Folate deficiency: May cause folate deficiency; consider providing 1 mg/day folate supplement.
• Oligospermia: In males, oligospermia (rare) has been reported.
• Sulfonamide allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonamide allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe.
Disease-related concerns:
• Allergies/asthma: Use with caution in patients with severe allergies or asthma.
• Blood dyscrasias: Use with caution in patients with blood dyscrasias; deaths from agranulocytosis, aplastic anemia, and other blood dyscrasias have been reported.
• G6PD deficiency: Use with caution in patients with G6PD deficiency.
• Hepatic impairment: Use with caution in patients with impaired hepatic function.
• Renal impairment: Use with caution in patients with renal impairment.
• Urinary obstruction: Use with caution in patients with urinary obstruction.
Special populations:
• Pediatrics: Safety and efficacy have not been established in children <2 years of age.
Adverse Reactions
>10%:
Central nervous system: Headache (33%)
Dermatologic: Photosensitivity
Gastrointestinal: Anorexia, nausea, vomiting, diarrhea (33%), gastric distress
Genitourinary: Reversible oligospermia (33%)
<3%:
Dermatologic: Urticaria/pruritus (<3%)
Hematologic: Hemolytic anemia (<3%), Heinz body anemia (<3%)
<0.1%: Alopecia, anaphylaxis, aplastic anemia, ataxia, convulsions, crystalluria, depression, drowsiness, epidermal necrolysis, exfoliative dermatitis, granulocytopenia, hallucinations, hearing loss, hematuria, hepatitis, insomnia, interstitial nephritis, jaundice, leukopenia, Lyell's syndrome, myelodysplastic syndrome, nephropathy (acute), neutropenic enterocolitis, pancreatitis, peripheral neuropathy, photosensitization, rhabdomyolysis, serum sickness-like reactions, skin discoloration, Stevens-Johnson syndrome, thrombocytopenia, thyroid function disturbance, tinnitus, urine discoloration, vasculitis, vertigo
Additional events reported with sulfonamides and/or 5-ASA derivatives: Cholestatic jaundice, eosinophilia pneumonitis, erythema multiforme, fibrosing alveolitis, hepatic necrosis, Kawasaki-like syndrome, SLE-like syndrome, pericarditis, seizure, transverse myelitis
Drug Interactions
Cardiac Glycosides: 5-ASA Derivatives may decrease the absorption of Cardiac Glycosides. Risk C: Monitor therapy
Methylfolate: Sulfasalazine may decrease the serum concentration of Methylfolate. Risk C: Monitor therapy
Thiopurine Analogs: 5-ASA Derivatives may decrease the metabolism of Thiopurine Analogs. Risk C: Monitor therapy
Varicella Virus-Containing Vaccines: 5-ASA Derivatives may enhance the adverse/toxic effect of Varicella Virus-Containing Vaccines. The primary concern is the potential development of Reye's Syndrome, a condition that has been associated with the use of salicylates in children with varicella infections. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Food: May impair folate absorption.
Herb/Nutraceutical: Avoid dong quai, St John's wort (may also cause photosensitization)
Storage
Protect from light.
Mechanism of Action
Acts locally in the colon to decrease the inflammatory response and systemically interferes with secretion by inhibiting prostaglandin synthesis
Pharmacodynamics/Kinetics
Absorption: 10% to 15% as unchanged drug from small intestine
Distribution: Small amounts enter feces and breast milk
Metabolism: Via colonic intestinal flora to sulfapyridine and 5-aminosalicylic acid (5-ASA); following absorption, sulfapyridine undergoes N-acetylation and ring hydroxylation while 5-ASA undergoes N-acetylation
Half-life elimination: 5.7-10 hours
Excretion: Primarily urine (as unchanged drug, components, and acetylated metabolites)
Dosage
Oral:
Children ?2 years: Ulcerative colitis: Initial: 40-60 mg/kg/day in 3-6 divided doses; maintenance dose: 20-30 mg/kg/day in 4 divided doses
Children ?6 years: Juvenile rheumatoid arthritis: Enteric coated tablet: 30-50 mg/kg/day in 2 divided doses; Initial: Begin with 1/4 to 1/3 of expected maintenance dose; increase weekly; maximum: 2 g/day typically
Adults:
Ulcerative colitis: Initial: 1 g 3-4 times/day, 2 g/day maintenance in divided doses; may initiate therapy with 0.5-1 g/day
Rheumatoid arthritis: Enteric coated tablet: Initial: 0.5-1 g/day; increase weekly to maintenance dose of 2 g/day in 2 divided doses; maximum: 3 g/day (if response to 2 g/day is inadequate after 12 weeks of treatment)
Dosing interval in renal impairment:
Clcr 10-30 mL/minute: Administer twice daily
Clcr <10 mL/minute: Administer once daily
Dosing adjustment in hepatic impairment: Avoid use
Administration: Oral
GI intolerance is common during the first few days of therapy (give with meals).
Dietary Considerations
Since sulfasalazine impairs folate absorption, consider providing 1 mg/day folate supplement.
Patient Education
Inform prescriber of any allergies you have. Do not take any new medication during therapy without consulting prescriber. Take as directed, at regular intervals around-the-clock with food. Do not crush, chew, or dissolve coated tablets. Complete full course of therapy even if you are feeling better. Take a missed dose as soon as possible. If almost time for next dose, skip the missed dose and return to your regular schedule. Do not take a double dose. Maintain adequate hydration to prevent kidney damage unless instructed to restrict fluid intake. If you have diabetes, monitor glucose levels closely (may cause decreased effect of oral hypoglycemic agents). May cause dizziness or headache (use caution when driving or engaging in tasks requiring alertness until response to drug is known); photosensitivity (use sunblock, wear protective clothing and eyewear, and avoid direct sunlight); or nausea, vomiting, or loss of appetite (small, frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help). Report rash; persistent nausea, vomiting, or diarrhea; opportunistic infection (sore throat, fever, vaginal itching or discharge, unusual bruising or bleeding, fatigue); blood in urine or change in urinary pattern; swelling of face, lips, or tongue, tightness in chest, bad cough, blue skin color, or other persistent adverse effects. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.
Geriatric Considerations
Adjust dose for renal function.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Dizziness is common; sulfonamides reported to cause restlessness, irritability, depression, euphoria, disorientation, panic, hallucinations, and delusions
Mental Health: Effects on Psychiatric Treatment
Photosensitivity is common; use caution with concurrent psychotropics; may cause leukopenia; caution with clozapine and carbamazepine
Nursing: Physical Assessment/Monitoring
Assess for allergy history prior to starting therapy (sulfa drugs, salicylates). Assess potential for interactions with other pharmacological agents patient may be taking (eg, increased or decreased levels/effects of concurrently administered drugs). Evaluate therapeutic effectiveness (reduced clinical symptoms) and adverse reactions (eg, photosensitivity, gastrointestinal disturbance [nausea, vomiting, anorexia], anemia, jaundice, hematuria). Caution patients with diabetes to monitor glucose levels closely (may cause altered effect of oral hypoglycemic agents). Teach patient proper use, possible side effects/appropriate interventions, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: 500 mg
Azulfidine®, Sulfazine: 500 mg
Tablet, delayed release, enteric coated: 500 mg
Azulfidine® EN-tabs®, Sulfazine EC: 500 mg
Pricing: U.S. (www.drugstore.com)
Tablet, EC (Azulfidine EN-tabs)
500 mg (100): $69.29
Tablet, EC (Sulfasalazine)
500 mg (100): $37.99
Tablet, EC (Sulfazine EC)
500 mg (60): $24.99
Tablets (Azulfidine)
500 mg (100): $57.73
Tablets (Sulfasalazine)
500 mg (100): $18.99
References
“American Academy of Pediatrics Committee on Drugs. The Transfer of Drugs and Other Chemicals Into Human Milk,” Pediatrics, 2001, 108(3):776-89.
American College of Rheumatology Ad Hoc Committee on Clinical Guidelines, “Guidelines for the Management of Rheumatoid Arthritis,” Arthritis Rheum, 1996, 39(5):713-22.
Ardizzone S and Porro GB, “A Practical Guide to the Management of Distal Ulcerative Colitis,” Drugs, 1998, 55(4):519-42.
Gabay C, DeBandt M, and Palazzo E, “Sulfasalazine-Related Life-threatening Side Effects: Is N-acetylcysteine of Therapeutic Value?” Clin Exp Rheumatol, 1993, 11(4):417-20.
Giannini EH and Cawkwell GD, “Drug Treatment in Children With Juvenile Rheumatoid Arthritis,” Pediatr Clin North Am, 1995, 42(5):1099-125.
Haines JD, Jr, “Hepatotoxicity After Treatment With Sulfasalazine,” Postgrad Med, 1986, 79(6):193-4, 197-8.
Jick H, Myers MW, and Dean AD, “The Risk of Sulfasalazine- and Mesalazine-Associated Blood Disorders,” Pharmacotherapy, 1995, 15(2):176-81.
Jullien D, Wokenstein P, Roupie E, et al, “Toxic Epidermal Necrolysis After Sulfasalazine Treatment of Mild Psoriatic Arthritis: Warning on the Use of Sulfasalazine for a New Indication,” Arthritis Rheum, 1995, 38(4):573.
Kirschner BS, “Inflammatory Bowel Disease in Children,” Pediatr Clin North Am, 1988, 35(1):189-208.
O'Dell JR, “Triple Therapy With Methotrexate, Sulfasalazine, and Hydroxychloroquine in Patients With Rheumatoid Arthritis,” Rheum Dis Clin North Am, 1998, 24(3):465-77.
Peppercorn MA, “Sulfasalazine: Pharmacology, Clinical Use, Toxicity, and Related New Drug Development,” Ann Intern Med, 1984, 101(3):377-86.
van Rossum MA, Fiselier TJ, Franssen MJ, et al, “Sulfasalazine in the Treatment of Juvenile Chronic Arthritis: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study. Dutch Juvenile Chronic Arthritis Study Group,” Arthritis Rheum, 1998, 41(5):808-16.
Veale DJ, Ho M, and Morley KD, “Sulfasalazine-Induced Lupus in Psoriatic Arthritis,” Br J Rheumatol, 1995, 34(4):383-4.
International Brand Names
Lexi-Comp.com
Last full review/revision July 2009
Content last modified July 2009
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