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Pronunciation
(sul fa SAL a zeen)
Generic Available (U.S.)
Yes
Index Terms
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of mild-to-moderate ulcerative colitis or as adjunctive therapy in severe ulcerative colitis; enteric coated tablets are also used for rheumatoid arthritis (including juvenile idiopathic arthritis [JIA]) in patients who inadequately respond to analgesics and NSAIDs
Use: Unlabeled/Investigational
Ankylosing spondylitis, Crohn's disease, psoriasis, psoriatic arthritis
Pregnancy Risk Factor
B
Pregnancy Considerations
Adverse events have not been observed in animal reproduction studies. Sulfasalazine and sulfapyridine cross the placenta; a potential for kernicterus in the newborn exists. Agranulocytosis was noted in an infant following maternal use of sulfasalazine during pregnancy. Based on available data, an increase in fetal malformations has not been observed following maternal use of sulfasalazine for the treatment of inflammatory bowel disease or ulcerative colitis.
Lactation
Enters breast milk/use caution (AAP recommends use “with caution”; AAP 2001 update pending)
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.
Contraindications
Hypersensitivity to sulfasalazine, sulfa drugs, salicylates, or any component of the formulation; porphyria; GI or GU obstruction
Warnings/Precautions
Concerns related to adverse effects:
• Blood dyscrasias: Fatalities associated with severe reactions including agranulocytosis, aplastic anemia, and other blood dyscrasias have occurred; discontinue use at first sign of rash or signs of serious adverse reactions. Use with extreme caution in patients with blood dyscrasias.
• CNS effects: Deaths from irreversible neuromuscular and central nervous system changes have been reported.
• Dermatologic reactions: Fatalities associated with severe reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis have occurred with sulfonamides; discontinue use at first sign of rash.
• Fibrosing alveolitis: Deaths from fibrosing alveolitis have been reported.
• Folate deficiency: May cause folate deficiency; consider providing 1 mg/day folate supplement.
• GI effects: Nausea, vomiting, and abdominal discomfort commonly occur; titration of dose and/or using the enteric coated formulation may decrease GI adverse effects.
• Hepatic necrosis: Fatalities associated with hepatic damage have occurred; discontinue use at first sign of jaundice or hepatotoxicity.
• Oligospermia: In males, oligospermia (rare) has been reported; usually reverses upon discontinuation.
• 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.
• G6PD deficiency: Use with caution in patients with G6PD deficiency; hemolytic anemia may occur.
• Hepatic impairment: Use with extreme caution in patients with impaired hepatic function.
• Renal impairment: Use with extreme caution in patients with renal impairment. Maintain adequate hydration to prevent crystalluria.
Special populations:
• Slow acetylators: Patients classified as slow acetylators may be at increased risk for adverse reactions due to a prolonged half-life of sulfapyrazine (metabolite of sulfasalazine).
Adverse Reactions
>10%:
Central nervous system: Headache
Dermatologic: Rash
Gastrointestinal: Anorexia, dyspepsia, gastric distress, nausea, vomiting
Genitourinary: Oligospermia (reversible)
1% to 10%:
Cardiovascular: Cyanosis
Central nervous system: Dizziness, fever
Dermatologic: Pruritus, urticaria
Gastrointestinal: Abdominal pain, stomatitis
Hematologic: Heinz body anemia, hemolytic anemia, leukopenia, thrombocytopenia
Hepatic: Liver function tests abnormal
<1%, postmarketing, and/or case reports (includes reactions reported with mesalamine or other sulfonamides): Agranulocytosis, alopecia, anaphylaxis, aplastic anemia, arthralgia, ataxia, cholestatic jaundice, cirrhosis, crystalluria, depression, diarrhea, drowsiness, drug rash with eosinophilia and systemic symptoms (DRESS), eosinophilia, epidermal necrolysis, exfoliative dermatitis, fibrosing alveolitis, fulminant hepatitis, Guillain-Barré syndrome, hallucinations, hearing loss, hemolytic-uremic syndrome, hematuria, hepatic failure, hepatic necrosis, hepatitis, hypoglycemia, hypoprothrombinemia, insomnia, interstitial lung disease, interstitial nephritis, jaundice, Kawasaki-like syndrome (single case report), lupus-like syndrome, megaloblastic anemia, meningitis, methemoglobinemia, myelitis, myelodysplastic syndrome, myocarditis (allergic), nephropathy (acute), nephrotic syndrome, neutropenia (congenital), neutropenic enterocolitis, pancreatitis, pericarditis, periorbital edema, peripheral neuropathy, photosensitization, pleuritis, pneumonitis, polyarteritis nodosa, proteinuria, purpura, rhabdomyolysis, seizure, serum sickness-like reactions, skin discoloration, Stevens-Johnson syndrome, thyroid function disturbance, tinnitus, urine discoloration, vasculitis, vertigo
Drug Interactions
Cardiac Glycosides: 5-ASA Derivatives may decrease the serum concentration of Cardiac Glycosides. Risk C: Monitor therapy
Heparin: 5-ASA Derivatives may enhance the adverse/toxic effect of Heparin. Specifically, the risk for bleeding/bruising may be increased. Risk C: Monitor therapy
Heparin (Low Molecular Weight): 5-ASA Derivatives may enhance the adverse/toxic effect of Heparin (Low Molecular Weight). Specifically, the risk for bleeding/bruising may be increased. 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
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
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: ≤15% as unchanged drug from small intestine
Distribution: Small amounts enter feces
Metabolism: Via colonic intestinal flora to sulfapyridine and 5-aminosalicylic acid (5-ASA). Following absorption, sulfapyridine undergoes acetylation to form AcSP and ring hydroxylation while 5-ASA undergoes N-acetylation (non-acetylation phenotype dependent process); rate of metabolism via acetylation dependent on acetylation phenotype
Bioavailability: Sulfasalazine: <15%; sulfapyridine: ~60%; 5-aminosalicylic acid: ~10% to 30%
Half-life elimination: 5.7-10 hours (prolonged in elderly); sulfapyridine half-life prolonged in slow acetylators (14.8 hours)
Time to peak: Sulfasalazine: 3-12 hours (mean: 6 hours); metabolites: ~10 hours
Excretion: Primarily urine (as unchanged drug, components, and acetylated metabolites)
Dosage
Oral:
Children ≥6 years:
Ulcerative colitis: Initial: 40-60 mg/kg/day in 3-6 divided doses; maintenance dose: 30 mg/kg/day in 4 divided doses
Juvenile idiopathic arthritis (JIA): 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: 3-4 g/day in evenly divided doses at ≤8-hour intervals. Note: American College of Gastroenterology guideline recommendations: Titrate to 4-6 g/day in 4 divided doses (Kornbluth, 2010).
Maintenance dose: 2 g/day in evenly divided doses at ≤8-hour intervals; may initiate therapy with 1-2 g/day to reduce GI intolerance
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: Use not recommended; weigh risk vs benefit
Dosing adjustment in hepatic impairment: Use not recommended; weigh risk vs benefit
Administration: Oral
GI intolerance is common during the first few days of therapy (give with meals). Do not crush enteric coated tablets.
Monitoring Parameters
CBC with differential and liver function tests (prior to therapy, then every other week for first 3 months of therapy, followed by every month for the second 3 months, then once every 3 months thereafter); periodic urinalysis and renal function tests; stool frequency; signs of infection
Dietary Considerations
Since sulfasalazine impairs folate absorption, consider providing 1 mg/day folate supplement.
Patient Education
Take with food, at regular intervals. Do not crush, chew, or dissolve coated tablets. Maintain adequate hydration to prevent kidney damage, unless instructed to restrict fluid intake. May cause dizziness, headache, nausea, vomiting, or loss of appetite. Report rash; persistent nausea, vomiting, diarrhea, or GI pain; 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; or tightness in chest, bad cough, or blue skin color.
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 use-related cautions and allergy history prior to starting therapy (sulfa drugs, salicylates). Monitor for blood dyscrasias, photosensitivity, gastrointestinal disturbance, anemia, jaundice, hematuria, or CNS changes.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, oral: 500 mg
Azulfidine®: 500 mg [scored]
Tablet, delayed release, enteric coated, oral: 500 mg
Azulfidine EN-tabs®: 500 mg
Pricing: U.S. (www.drugstore.com)
Tablet, EC (Azulfidine EN-tabs)
500 mg (100): $82.99
Tablet, EC (Sulfasalazine)
500 mg (100): $37.99
Tablet, EC (Sulfazine EC)
500 mg (60): $24.99
Tablets (Azulfidine)
500 mg (100): $68.99
Tablets (Sulfasalazine)
500 mg (100): $18.99
Extemporaneously Prepared
A 100 mg/mL oral suspension may be made with tablets. Place twenty 500 mg tablets in a mortar and add a small amount of a 1:1 mixture of Ora-Sweet® and Ora-Plus® to cover the tablets. Let soak for 20-30 minutes. Crush the tablets and mix to a uniform paste; mix while adding the vehicle in equal proportions to almost 100 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add sufficient quantity of vehicle to make 100 mL. Label "shake well". Stable 91 days under refrigeration or at room temperature.
Lingertat-Walsh K, Walker SE, Law S, et al, "Stability of Sulfasalazine Oral Suspension," Can J Hosp Pharm, 2006, 59(4):194-200.
References
American Academy of Pediatrics Committee on Drugs, "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.
Haas RM, Li P, and Chu JW, “Glucose-Lowering Effects of Sulfasalazine in Type 2 Diabetes,” Diabetes Care, 2005, 28(9):2238-9.
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.
Kornbluth A and Sachar DB, “Ulcerative Colitis Practice Guidelines in Adults: American College of Gastroenterology, Practice Parameters Committee,” Am J Gastroenterol, 2010, 105(3):501-23.
Lichtenstein GR, Hanauer SB, and Sandborn WJ, “Management of Crohn's Disease in Adults,” Am J Gastroenterol, 2009, 104(2):465-83.
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.
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 May 2011
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