Sulfasalazine Side Effects

It is possible that some side effects of sulfasalazine may not have been reported. These can be reported to the FDA here. Always consult a healthcare professional for medical advice.

For the Consumer

Applies to sulfasalazine: oral tablet, oral tablet enteric coated

As well as its needed effects, sulfasalazine may cause unwanted side effects that require medical attention.

If any of the following side effects occur while taking sulfasalazine, check with your doctor immediately:

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
  • 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 sulfasalazine side effects may not need any medical attention. As your body gets used to the medicine these side effects may disappear. Your health care professional may be able to help you prevent or reduce these side effects, but do check with them if any of the following side effects continue, or if you are concerned 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 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

Nervous system

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

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

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

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

Diuresis has been reported rarely in patients using sulfonamides.

Infertility appeared to be reversible upon drug discontinuation.

Dermatologic

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.

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

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

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.

Hepatic

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.

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

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

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

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.

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

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

Psychiatric

Common (1% to 10%): Insomnia
Uncommon (0.1% to 1%): Depression
Frequency not reported: Confusion, vivid dreams
Postmarketing reports: Hallucinations

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

Ocular

Common (1% to 10%): Conjunctival and scleral injection
Frequency not reported: Diplopia, blurred vision, corneal damage

Hypersensitivity

Frequency not reported: Hypersensitivity reactions, drug-induced rash, lupus erythematosus-like syndrome, anaphylactoid reactions
Postmarketing reports: Anaphylaxis, serum sickness

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.

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

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

Endocrine

Rare (less than 0.1%): Goiter production

Goiter production has been reported rarely in patients using sulfonamides.

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