Azulfidine Side Effects

Generic Name: sulfasalazine

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

Some side effects of Azulfidine may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

For the Consumer

Applies to sulfasalazine: oral tablet, oral tablet enteric coated

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
  • itching
  • skin rash
  • 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
  • troubled breathing with exertion
  • 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
  • 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
  • tightness in the chest
  • 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

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
  • Abdominal or stomach pain or upset
  • decreased weight
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 with sulfasalazine (the active ingredient contained in Azulfidine) were anorexia, headache, nausea, vomiting, gastric distress, and apparently reversible oligospermia; occurred in about one-third of patients. Less common side effects were skin rash, pruritus, urticaria, fever, Heinz body anemia, hemolytic anemia, and cyanosis; occurred in up to 1 in 30 patients. 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.

Hypersensitivity

The use of sulfonamides, including sulfasalazine (the active ingredient contained in Azulfidine) is associated with large increases in the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis, although these phenomena are rare as a whole.

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

Uncommon (0.1% to 1%): Erythema multiforme (Stevens-Johnson syndrome), exfoliative dermatitis, toxic 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, interstitial lung disease
Frequency not reported: Sulfasalazine-induced rash
Postmarketing reports: Anaphylaxis

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 (up to 8%), stomatitis (up to 4%)
Uncommon (0.1% to 1%): Pancreatitis, diarrhea (including bloody diarrhea), impaired folic acid absorption, impaired digoxin absorption, neutropenic enterocolitis
Rare (less than 0.1%): Pseudomembranous colitis (at least 1 case), necrotizing pancreatitis (at least 2 cases)
Frequency not reported: Altered taste, hemorrhagic colitis

Hepatic

Common (1% to 10%): Abnormal liver function tests (up to 4%)
Uncommon (0.1% to 1%): Hepatitis, hepatic failure
Postmarketing reports: Hepatotoxicity (some cases were fatal), including elevated liver function tests (SGOT/AST, SGPT/ALT, gamma-glutamyltransferase, lactate dehydrogenase, alkaline phosphatase, bilirubin), jaundice, cholestatic jaundice, cirrhosis, possible hepatocellular damage (including liver necrosis and liver failure); Kawasaki-like syndrome with hepatic function changes (at least 1 case)

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.

Hematologic

Common (1% to 10%): Hemolytic anemia (up to 3.3%), Heinz body anemia (up to 3.3%), leukopenia (up to 3%)
Uncommon (0.1% to 1%): Thrombocytopenia (up to 1%), agranulocytosis, aplastic anemia, purpura, hypoprothrombinemia, methemoglobinemia, congenital neutropenia, myelodysplastic syndrome, megaloblastic (macrocytic) anemia
Frequency not reported: Red cell aplasia

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.

Respiratory

Common (1% to 10%): Cyanosis (up to 3.3%)
Frequency not reported: Pulmonary infiltrates (frequently accompanied by eosinophilia), fibrosing alveolitis, bronchiolitis obliterans, lung toxicity (may mimic Wegener's granulomatosis)

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.

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

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.

Nervous system

Very common (10% or more): Headache (up to 33%)
Common (1% to 10%): Dizziness (4%)
Uncommon (0.1% to 1%): Meningitis (including aseptic meningitis), neuropathy (including peripheral neuropathy), transverse myelitis, convulsions, transient lesions of the posterior spinal column, cauda equina syndrome, Guillain-Barre syndrome, vertigo, hearing loss, ataxia, tinnitus, drowsiness
Frequency not reported: Neurotoxicity, dysphasia, acute encephalopathy, monoparesis, cerebrospinal fluid abnormalities

Transverse myelitis developed in 1 patient after receiving sulfasalazine for 2 years. All symptoms resolved within 2 months after discontinuing sulfasalazine.

Renal

Uncommon (0.1% to 1%): Toxic nephrosis with oliguria and anuria, nephritis (including interstitial nephritis), nephrotic syndrome, hemolytic uremic syndrome
Rare (less than 0.1%): Bilateral renal calculi composed of acetylsulfapyridine (at least 1 case), proteinase 3-ANCA positive necrotizing glomerulonephritis (at least 1 case)

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

Cardiovascular

Frequency not reported: Tachycardia

Genitourinary

Diuresis has been reported rarely in patients using sulfonamides.

Infertility appeared to be reversible upon drug discontinuation.

Very common (10% or more): Reversible oligospermia (about 33%)
Uncommon (0.1% to 1%): Urinary tract infections, hematuria, crystalluria, proteinuria, urine discoloration
Rare (less than 0.1%): Impotence, diuresis
Frequency not reported: Decreased motility, abnormal sperm penetration (sometimes resulted in infertility)

Dermatologic

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

Very common (10% or more): Skin rash (up to 13%)
Common (1% to 10%): Pruritus (up to 4%), urticaria (up to 3.3%)
Uncommon (0.1% to 1%): Skin discoloration
Rare (less than 0.1%): Lichen planus, toxic epidermal necrolysis (at least 2 cases)
Postmarketing reports: Angioedema

Psychiatric

Uncommon (0.1% to 1%): Mental depression, insomnia, hallucinations
Frequency not reported: Confusion, vivid dreams

Musculoskeletal

Frequency not reported: Myopathy

Other

Common (1% to 10%): Fever (up to 5%)
Frequency not reported: Malaise, false positive c-ANCAs

Ocular

Frequency not reported: Diplopia, blurred vision

Endocrine

Rare (less than 0.1%): Goiter production

Goiter production has been reported rarely in patients using sulfonamides.

Metabolic

Very common (10% or more): Anorexia (about 33%)
Rare (less than 0.1%): Hypoglycemia

Hypoglycemia has been reported rarely in patients using sulfonamides.

Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This material does not endorse drugs, diagnose patients, or recommend therapy. This information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate safety, effectiveness, or appropriateness for any given patient. Drugs.com does not assume any responsibility for any aspect of healthcare administered with the aid of materials provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the substances you are taking, check with your doctor, nurse, or pharmacist.

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