sulfasalazine

Absorption: 10–15% absorbed after oral administration.

Distribution: Widely distributed; crosses the placenta and enters breast milk.

Protein Binding: 99%.

Metabolism/Excretion: Split by intestinal bacteria into sulfapyridine and 5-aminosalicylic acid. Some absorbed sulfasalazine is excreted by bile back into intestines; 15% excreted unchanged by the kidneys. Sulfapyridine also excreted mostly by the kidneys.

Half-Life: 6 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	1 hr	1.5–6 hr	6–12 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity reactions to sulfonamides, salicylates, or sulfasalazine;
Cross-sensitivity with furosemide, sulfonylurea hypoglycemic agents, or carbonic anhydrase inhibitors may exist;
Glucose-6–phosphate dehydrogenase deficiency (↑ risk of hemolysis);
Hypersensitivity to bisulfites (mesalamine enema only);
Urinary tract or intestinal obstruction;
Porphyria.

Use Cautiously in:

Severe hepatic impairment;
Severe renal impairment;
History of porphyria;
Blood dyscrasias;
OB: Neural tube defects have been reported; use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Lactation: May compete with bilirubin for binding sites on plasma proteins in the newborn and cause kernicterus; bloody stools or diarrhea reported in breastfed infants;
Pedi: Children 2 yr (safety and effectiveness not established).

Adv. Reactions/Side Effects ⬆ ⬇

Derm: rash, ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), EXFOLIATIVE DERMATITIS, photosensitivity, STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN), yellow discoloration

GI: anorexia, diarrhea, nausea, vomiting, drug-induced hepatitis

GU: crystalluria, infertility, oligospermia, orange-yellow discoloration of urine, renal impairment

Hemat: AGRANULOCYTOSIS, APLASTIC ANEMIA, blood dyscrasias, eosinophilia, hemolytic anemia, megaloblastic anemia, thrombocytopenia

Neuro: headache, peripheral neuropathy

Resp: pneumonitis

Misc: fever, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA)

Interactions ⬆ ⬇

Drug-drug:

May ↑ action/risk of toxicity from oral hypoglycemic agents, phenytoin, methotrexate, zidovudine, or warfarin.
↑risk of drug-induced hepatitis with other hepatotoxic agents.
↑risk of crystalluria with methenamine.
May ↓ metabolism and ↑ effects/toxicity of mercaptopurine or thioguanine.

May ↓ iron and folic acid absorption.

Route/Dosage ⬆ ⬇

Ulcerative Colitis

PO (Adults ): 1 g every 6–8 hr (may start with 500 mg every 6–12 hr), followed by maintenance dose of 500 mg every 6 hr.
PO (Children >2 yr): Initial: 6.7–10 mg/kg every 4 hr or 10–15 mg/kg every 6 hr or 13.3–20 mg/kg every 8 hr. Maintenance: 7.5 mg/kg every 6 hr (not to exceed 2 g/day).

Rheumatoid Arthritis

PO (Adults ): 500 mg–1 g/day (as delayed-release tablets) for 1 wk, then ↑ by 500 mg/day every wk up to 2 g/day in 2 divided doses; if no benefit seen after 12 wk, ↑ to 3 g/day in 2 divided doses.
PO (Children ≥6 yr): 30–50 mg/kg/day in 2 divided doses (as delayed-release tablets); initiate therapy at 25% of planned maintenance dose and ↑ every 7 days until maintenance dose is reached (not to exceed 2 g/day).

Availability ⬆ ⬇

(Generic available)

Tablets: 500 mg
Delayed-release (enteric-coated) tablets (Azulfidine EN-tabs): 500 mg

Assessment ⬆ ⬇

Assess patient for allergy to sulfonamides and salicylates. Discontinue therapy if rash, difficulty breathing, swelling of face or lips, or fever occur.
Monitor intake and output ratios. Fluid intake should be sufficient to maintain a urine output of at least 1200–1500 mL daily to prevent crystalluria and stone formation.
Assess for rash periodically during therapy. May cause SJS, TEN, and DRESS. Discontinue therapy if severe or if accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis, and/or eosinophilia.
Ulcerative Colitis: Assess abdominal pain and frequency, quantity, and consistency of stools at the beginning of and during therapy.
Rheumatoid Arthritis: Assess range of motion and degree of swelling and pain in affected joints before and periodically during therapy.

Lab Test Considerations:

Monitor urinalysis, BUN, and serum creatinine before and periodically during therapy. May cause crystalluria and urinary cell calculi formation. Discontinue sulfasalazine if renal function declines.
Monitor CBC with differential and liver function tests before and every 2nd wk during first 3 mo of therapy, monthly during the 2nd 3 mo, and every 3 mo thereafter or as clinically indicated. Discontinue sulfasalazine if blood dyscrasias occur.
Serum sulfapyridine levels may be monitored; concentrations >50 Μg/mL may be associated with increased incidence of adverse reactions.
Higher than recommended doses can interfere with a variety of lab assays that use nicotinamide adenine dinucleotide or nicotinamide adenine dinucleotide phosphate (CK, AST/ALT, ammonia, thyroxine, glucose).

Implementation ⬆ ⬇

Do not confuse sulfasalazine with cefuroxime or sulfadiazine.
- Varying dosing regimens of sulfasalazine may be used to minimize GI side effects.
PO: Administer after meals or with food to minimize GI irritation, with a full glass of water. DNC: Swallow enteric-coated tablets whole; do not crush or chew.

Patient/Family Teaching ⬆ ⬇

Instruct patient on the correct method of administration. Advise patient to take medication as directed, even if feeling better. Take missed doses as soon as remembered unless almost time for next dose.
May cause dizziness. Caution patient to avoid driving or other activities that require alertness until response to medication is known.
Advise patient to notify health care professional if skin rash, sore throat, fever, mouth sores, unusual bleeding or bruising, wheezing, fever, or hives occur.
Caution patient to use sunscreen and protective clothing to prevent photosensitivity reactions.
Inform patient that this medication may cause orange-yellow discoloration of urine and skin, which is not significant. May permanently stain contact lenses yellow.
Instruct patient to notify health care professional if symptoms worsen or do not improve. If symptoms of acute intolerance (cramping, acute abdominal pain, bloody diarrhea, fever, headache, rash) occur, discontinue therapy and notify health care professional immediately.
Rep: May cause fetal harm. Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected, and to avoid breastfeeding during therapy. Neural tube defects have been reported in infants of women taking sulfasalazine during pregnancy. Monitor newborns for kernicterus if mother taking sulfasalazine; monitor breastfed infants for bloody stool or diarrhea. Inform male patient that sulfasalazine may cause infertility; usually reversible.
Instruct patient to notify health care professional if symptoms do not improve after 1–2 mo of therapy.

Evaluation/Desired Outcomes ⬆ ⬇

Decrease in diarrhea and abdominal pain.
Return to normal bowel pattern in patients with ulcerative colitis. Effects may be seen within 3–21 days. The usual course of therapy is 3–6 wk.
Maintenance of remission in patients with ulcerative colitis.
Decrease in pain and inflammation and increase in mobility in patients with rheumatoid arthritis.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇