Note: This document contains side effect information about sulfasalazine. Some dosage forms listed on this page may not apply to the brand name Azulfidine EN-tabs.

Summary

Common side effects of Azulfidine EN-tabs include: gastric distress, headache, nausea, oligospermia, vomiting, and anorexia. Other side effects include: fever. Continue reading for a comprehensive list of adverse effects.

Applies to sulfasalazine: oral tablets conventional and delayed-release.

Side effects include:

GI effects (anorexia, nausea, dyspepsia, vomiting, abdominal pain, gastric distress); headache; fever; rash; abnormal liver function test results; leukopenia; thrombocytopenia; reversible oligospermia. Rash occurs more frequently in patients with rheumatoid arthritis than in those with ulcerative colitis.

For Healthcare Professionals

Applies to sulfasalazine: compounding powder, oral delayed release tablet, oral tablet.

General

The most common side effects reported were anorexia, headache, nausea, vomiting, gastric distress, elevated temperature, erythema, pruritus, rash, loss of appetite, and reversible oligospermia. Less common side effects included urticaria, fever, Heinz body anemia, hemolytic anemia, and cyanosis. Frequency of side effects increased with daily doses of 4 g or more, or total serum sulfapyridine levels above 50 mcg/mL.

The use of enteric-coated preparations may decrease gastrointestinal side effects.

Gastrointestinal

Very common (10% or more): Nausea (up to 33%), vomiting (up to 33%), gastric distress (about 33%), dyspepsia (13%)

Common (1% to 10%): Abdominal pain, diarrhea, stomatitis

Frequency not reported: Impaired folic acid absorption, impaired digoxin absorption, neutropenic enterocolitis, hemorrhagic colitis, bloody diarrhea, necrotizing pancreatitis

Postmarketing reports: Pseudomembranous colitis, pancreatitis, worsening ulcerative colitis, parotitis^[Ref]

Nervous system

Transverse myelitis developed in 1 patient after receiving sulfasalazine (the active ingredient contained in Azulfidine EN-tabs) for 2 years. All symptoms resolved within 2 months after discontinuing sulfasalazine.^[Ref]

Very common (10% or more): Headache (up to 33%)

Common (1% to 10%): Dizziness, taste disorders, tinnitus

Uncommon (0.1% to 1%): Convulsions, vertigo

Frequency not reported: Meningitis, neuropathy, transverse myelitis, transient lesions of the posterior spinal column, cauda equina syndrome, Guillain-Barre syndrome, hearing loss, drowsiness, neurotoxicity, dysphasia, acute encephalopathy, monoparesis, cerebrospinal fluid abnormalities, altered taste, peripheral neuritis

Postmarketing reports: Aseptic meningitis, ataxia, encephalopathy, peripheral neuropathy, smell disorders^[Ref]

Metabolic

Hypoglycemia has been reported rarely in patients using sulfonamides.

Very common (10% or more): Anorexia (about 33%)

Rare (less than 0.1%): Hypoglycemia

Postmarketing reports: Folate deficiency, loss of appetite

Genitourinary

Diuresis has been reported rarely in patients using sulfonamides.

Infertility appeared to be reversible upon drug discontinuation.^[Ref]

Very common (10% or more): Reversible oligospermia (about 33%)

Common (1% to 10%): Proteinuria

Rare (less than 0.1%): Impotence, diuresis

Frequency not reported: Decreased motility, abnormal sperm penetration (sometimes resulted in infertility), urinary tract infections, urine discoloration

Postmarketing reports: Hematuria, crystalluria^[Ref]

Dermatologic

Very common (10% or more): Rash (up to 13%)

Common (1% to 10%): Pruritus, urticaria

Uncommon (0.1% to 1%): Alopecia

Frequency not reported: Toxic epidermal necrolysis (Lyell's syndrome), skin discoloration, erythema multiforme, parapsoriasis varioliformis acuta (Mucha-Haberman syndrome), generalized skin eruptions, petechiae

Postmarketing reports: Angioedema, purpura, epidermal necrolysis (Lyell's syndrome), Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms (DRESS), toxic pustuloderma, erythema, exanthema, exfoliative dermatitis, periorbital edema, lichen planus, photosensitivity^[Ref]

Angioedema was reported during postmarketing experience with the use of products containing or metabolized to mesalamine.

The risk of Stevens-Johnson syndrome or toxic epidermal necrolysis increased largely with the use of sulfonamides; however, these phenomena were rare as a whole.^[Ref]

Immunologic

Very common (10% or more): Immunoglobulin suppression (10%)

Frequency not reported: Drug-induced systemic lupus erythematosus (SLE)

Postmarketing reports: Kawasaki-like syndrome with hepatic function changes, induction of autoantibodies^[Ref]

Immunoglobulin suppression was slowly reversible and rarely accompanied by clinical findings.

In most cases of sulfasalazine-induced SLE, patients received the drug for greater than 1 year. Patients most commonly developed arthralgias and pleuritic chest pain. Generally, these patients had a positive ANA, anti-DNA antibody titer, and were slow acetylators of sulfonamides. Symptoms typically resolved over several weeks to several months.

At least 1 case of Kawasaki-like syndrome with hepatic function changes was reported during postmarketing experience with the use of products containing or metabolized to mesalamine.^[Ref]

Hepatic

Hepatitis associated with sulfasalazine (the active ingredient contained in Azulfidine EN-tabs) often developed 2 to 4 weeks after therapy was initiated, although hypersensitivity hepatitis has been reported after longer periods of therapy. Associated rash usually progressed to desquamation. Liver biopsy has shown necrosis and infiltration with moderate number of inflammatory cells. Noncaseating granulomas have also been seen. Hepatitis generally resolved over several weeks after therapy discontinuation, although some patients progressed to fulminant hepatic failure.

Hepatitis has been reported in patients with sulfasalazine hypersensitivity. Some of these cases were fatal.

Side effects listed as postmarketing reports were reported during postmarketing experience with the use of products containing or metabolized to mesalamine.^[Ref]

Common (1% to 10%): Abnormal liver function tests

Uncommon (0.1% to 1%): Elevated liver enzymes

Frequency not reported: Hepatic necrosis

Postmarketing reports: Hepatotoxicity (some cases were fatal), including elevated liver function tests (SGOT/AST, SGPT/ALT, GGT, LDH, alkaline phosphatase, bilirubin), jaundice, cholestatic jaundice, cirrhosis, cholestatic hepatitis, cholestasis, possible hepatocellular damage (including liver necrosis and liver failure); Kawasaki-like syndrome with hepatic function changes; fulminant hepatitis; hepatitis; hepatic failure^[Ref]

Hematologic

Common (1% to 10%): Hemolytic anemia, Heinz body anemia, leukopenia

Uncommon (0.1% to 1%): Thrombocytopenia

Frequency not reported: Red cell aplasia, congenital neutropenia, myelodysplastic syndrome

Postmarketing reports: Pseudomononucleosis, lymphadenopathy, macrocytosis, neutropenia, pancytopenia, agranulocytosis, aplastic anemia, hypoprothrombinemia, methemoglobinemia, megaloblastic (macrocytic) anemia^[Ref]

Agranulocytosis has generally occurred during the first 1 to 3 months of therapy. Patients often presented with fever and sore throat. A few also presented with a rash. Bone marrow hypoplasia or aplasia was usually confined to the myeloid series, but may be accompanied by erythroid hypoplasia and marrow plasmacytosis. In one review of 62 cases of sulfasalazine-induced agranulocytosis, 6.5% of patients died. Recovery of granulocytes was generally seen within 1 to 2 weeks after drug discontinuation, and leukocyte counts and differential returned to normal in 1 to 3 weeks. Some cases of agranulocytosis were treated with colony stimulating factor, which appeared to increase the time to recovery.^[Ref]

Respiratory

Common (1% to 10%): Cough

Uncommon (0.1% to 1%): Dyspnea

Frequency not reported: Pulmonary infiltrates (frequently accompanied by eosinophilia), pneumonitis (with or without eosinophilia), pleuritis, bronchiolitis obliterans, lung toxicity (may mimic Wegener's granulomatosis)

Postmarketing reports: Oropharyngeal pain, fibrosing alveolitis, eosinophilic infiltration, interstitial lung disease^[Ref]

Patients often presented after several weeks or months of therapy with fever, malaise, shortness of breath, and nonproductive cough. Eosinophilic infiltrates have been seen. Respiratory changes generally resolved over a few weeks, however, fatal reactions involving fibrosing alveolitis have been reported.^[Ref]

Cardiovascular

Common (1% to 10%): Cyanosis

Uncommon (0.1% to 1%): Vasculitis

Frequency not reported: Tachycardia

Postmarketing reports: Myocarditis, allergic myocarditis, pallor, polyarteritis nodosa, pericarditis^[Ref]

Psychiatric

Common (1% to 10%): Insomnia

Uncommon (0.1% to 1%): Depression

Frequency not reported: Confusion, vivid dreams

Postmarketing reports: Hallucinations^[Ref]

Musculoskeletal

Common (1% to 10%): Arthralgia

Frequency not reported: Myopathy, rhabdomyolysis, Sjogren's syndrome

Postmarketing reports: Systemic lupus erythematosus

Other

Common (1% to 10%): Fever

Uncommon (0.1% to 1%): Facial edema

Frequency not reported: Malaise, false positive c-ANCAs, elevated temperature, petechiae and drug fever, LE phenomenon

Postmarketing reports: Yellow discoloration of skin and body fluids^[Ref]

Ocular

Common (1% to 10%): Conjunctival and scleral injection

Frequency not reported: Diplopia, blurred vision, corneal damage^[Ref]

Hypersensitivity

Frequency not reported: Hypersensitivity reactions, drug-induced rash, lupus erythematosus-like syndrome, anaphylactoid reactions

Postmarketing reports: Anaphylaxis, serum sickness^[Ref]

The following side effects have been reported as hypersensitivity reactions: erythema multiforme (Stevens-Johnson syndrome), exfoliative dermatitis, epidermal necrolysis (Lyell's syndrome) with corneal damage, drug rash with eosinophilia and systemic symptoms (DRESS), anaphylaxis, serum sickness syndrome, 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 acuta (Mucha-Haberman syndrome), rhabdomyolysis, photosensitization, arthralgia, periorbital edema, conjunctival and scleral injection, alopecia, and interstitial lung disease.

Anaphylaxis was reported during postmarketing experience with the use of products containing or metabolized to mesalamine.^[Ref]

Renal

Frequency not reported: Toxic nephrosis with oliguria and anuria, nephritis, hemolytic uremic syndrome, bilateral renal calculi composed of acetylsulfapyridine, proteinase 3-ANCA positive necrotizing glomerulonephritis

Postmarketing reports: Nephrolithiasis, nephrotic syndrome, interstitial nephritis^[Ref]

At least 1 patient developed bilateral renal calculi composed of acetylsulfapyridine, a metabolite of sulfasalazine.^[Ref]

Endocrine

Rare (less than 0.1%): Goiter production^[Ref]

Goiter production has been reported rarely in patients using sulfonamides.^[Ref]