Azulfidine Side Effects

Generic name: sulfasalazine

Medically reviewed by Philip Thornton, DipPharm. Last updated on Jul 22, 2024.

Note: This document provides detailed information about Azulfidine Side Effects associated with sulfasalazine. Some dosage forms listed on this page may not apply specifically to the brand name Azulfidine.

Applies to sulfasalazine: oral tablet, oral tablet enteric coated.

Serious side effects of Azulfidine

Along with its needed effects, sulfasalazine (the active ingredient contained in Azulfidine) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking sulfasalazine:

More common

• aching of joints
• fever
• headache (continuing)
• increased sensitivity of the skin to sunlight
• skin rash or itching
• vomiting

Less common

• back, leg, or stomach pains
• bleeding gums
• bluish color of the fingernails, lips, skin, palms, or nail beds
• chills
• dark urine
• difficulty breathing
• fever
• general body swelling
• headache
• loss of appetite
• nausea
• nosebleeds
• pale skin
• sore throat
• trouble breathing
• unusual bleeding or bruising
• unusual tiredness or weakness
• yellowing of the eyes or skin

Less common or rare

• aching of muscles
• black, tarry stools
• blistering, peeling, or loosening of the skin
• bloating
• blood in the urine or stools
• bloody diarrhea
• bluish fingernails, lips, or skin
• chest pain or tightness
• constipation
• cough
• difficulty with swallowing
• dizziness
• fainting spells
• fast heartbeat
• general feeling of discomfort or illness
• general tiredness and weakness
• hives
• indigestion
• inflammation of the joints
• irregular heartbeat
• light-colored stools
• muscle aches
• muscle cramps or spasms
• muscle pain or stiffness
• painful or difficult urination
• pains in the stomach, side, or abdomen, possibly radiating to the back
• pinpoint red spots on the skin
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• rash
• red skin lesions, often with a purple center
• red, irritated eyes
• redness, blistering, peeling, or loosening of the skin
• sores, ulcers, or white spots in the mouth or on the lips
• swollen or painful glands
• upper right abdominal or stomach pain

Incidence not known

• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs

Other side effects of Azulfidine

Some side effects of sulfasalazine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• decreased weight
• stomach upset

Less common

• welts

Less common or rare

• discoloration of the skin or urine
• hair loss or thinning of the hair
• swelling or inflammation of the mouth

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

• 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]

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

Metabolic

• Very common (10% or more): Anorexia (about 33%)
• Rare (less than 0.1%): Hypoglycemia
• Postmarketing reports: Folate deficiency, loss of appetite

Hypoglycemia has been reported rarely in patients using sulfonamides.

Genitourinary

• 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]

Diuresis has been reported rarely in patients using sulfonamides.

Infertility appeared to be reversible upon drug discontinuation.^[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

• 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]

Hepatitis associated with sulfasalazine 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]

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]

Further information

Azulfidine side effects can vary depending on the individual. Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.

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