Allopurinol Side Effects

Brand Names: Zyloprim

Please note - some side effects for Allopurinol may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).

Side Effects of Allopurinol - for the consumer

Allopurinol

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Allopurinol:

Diarrhea; nausea.

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blood in urine or painful urination; dark urine; fever, chills, or sore throat; irritation of the eyes; joint pain; loss of appetite; red, swollen, blistered, or peeling skin; stomach pain; unexplained weight loss; unusual bruising or bleeding; unusual muscle pain or weakness; yellowing of the skin or eyes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch .

For the professional

Allopurinol

Data upon which the following estimates of incidence of adverse reactions are made are derived from experiences reported in the literature, unpublished clinical trials and voluntary reports since marketing of Allopurinol began. Past experience suggested that the most frequent event following the initiation of Allopurinol treatment was an increase in acute attacks of gout (average 6% in early studies). An analysis of current usage suggests that the incidence of acute gouty attacks has diminished to less than 1%. The explanation for this decrease has not been determined but may be due in part to initiating therapy more gradually.

The most frequent adverse reaction to Allopurinol is skin rash. Skin reactions can be severe and sometimes fatal. Therefore, treatment with Allopurinol should be discontinued immediately if a rash develops. Some patients with the most severe reaction also had fever, chills, arthralgias, cholestatic jaundice, eosinophilia and mild leukocytosis or leukopenia. Among 55 patients with gout treated with Allopurinol for 3 to 34 months (average greater than 1 year) and followed prospectively, Rundles observed that 3% of patients developed a type of drug reaction which was predominantly a pruritic maculopapular skin eruption, sometimes scaly or exfoliative. However, with current usage, skin reactions have been observed less frequently than 1%. The explanation for this decrease is not obvious. The incidence of skin rash may be increased in the presence of renal insufficiency. The frequency of skin rash among patients receiving ampicillin or amoxicillin concurrently with Allopurinol has been reported to be increased.

Most Common Reactions*
Probably Causally Related

Gastrointestinal: diarrhea, nausea, alkaline phosphatase increase, SGOT/ SGPT increase

Metabolic and Nutritional: acute attacks of gout

Skin and Appendages: rash, maculopapular rash

*Early clinical studies and incidence rates from early clinical experience with Allopurinol suggested that these adverse reactions were found to occur at a rate of greater than 1%. The most frequent event observed was acute attacks of gout following the initiation of therapy. Analyses of current usage suggest that the incidence of these adverse reactions is now less than 1%. The explanation for this decrease has not been determined, but it may be due to following recommended usage.

Incidence Less Than 1%
Probably Causally Related

Body as a whole: ecchymosis, fever, headache

Cardiovascular: necrotizing angiitis, vasculitis

Gastrointestinal: hepatic necrosis, granulomatous hepatitis, hepatomegaly, hyperbilirubinemia, cholestatic jaundice, vomiting, intermittent abdominal pain, gastritis, dyspepsia

Hemic and Lymphatic: thrombocytopenia, eosinophilia, leukocytosis, leukopenia

Musculoskeletal: myopathy, arthralgias

Nervous: peripheral neuropathy, neuritis, paresthesia, somnolence

Respiratory: epistaxis

Skin and Appendages: erythema multiforme exudativum (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome), hypersensitivity vasculitis, purpura, vesicular bullous dermatitis, exfoliative dermatitis, eczematoid dermatitis, pruritus, urticaria, alopecia, onycholysis, lichen planus

Special Senses: taste loss/perversion

Urogenital: renal failure, uremia

Incidence Less Than 1%
Causal Relationship Unknown

Body as a whole: malaise

Cardiovascular: pericarditis, peripheral vascular disease, thrombophlebitis, bradycardia, vasodilation

Endocrine: infertility (male), hypercalcemia, gynecomastia (male)

Gastrointestinal: hemorrhagic pancreatitis, gastrointestinal bleeding, stomatitis, salivary gland swelling, hyperlipidemia, tongue edema, anorexia

Hemic and Lymphatic: aplastic anemia, agranulocytosis, eosinophilic fibrohistiocytic lesion of bone marrow, pancytopenia, prothrombin decrease, anemia, hemolytic anemia, reticulocytosis, lymphadenopathy, lymphocytosis

Musculoskeletal: myalgia

Nervous: optic neuritis, confusion, dizziness, vertigo, foot drop, decrease in libido, depression, amnesia, tinnitus, asthenia, insomnia

Respiratory: bronchospasm, asthma, pharyngitis, rhinitis

Skin and appendages: furunculosis, facial edema, sweating, skin edema

Special Senses: cataracts, macular retinitis, iritis, conjunctivitis, amblyopia

Urogenital: nephritis, impotence, primary hematuria, albuminuria

By body system

General side effects

In general, the side effects of allopurinol have been more likely and more severe in patients with reduced renal function.

Dermatologic side effects

Dermatologic side effects have included skin rash, pruritus, and alopecia. Severe skin reactions have rarely included exfoliative dermatitis, vesicular bullous eruptions, and erythema multiforme.

Allopurinol-induced rash may be followed by more severe hypersensitivity reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, vasculitis, nephrotoxicity, and hepatotoxicity. Such hypersensitivity syndromes have been fatal in some cases.

The incidence of skin rash may be increased in patients with renal dysfunction.

Hypersensitivity side effects

A case study suggests cell-mediated immunity to allopurinol and oxypurinol is involved in allopurinol-induced hypersensitivity reactions.

A first of a kind case report, allopurinol hypersensitivity syndrome, elevations in pancreatic exocrine enzyme level, and new-onset type 1 diabetes mellitus have been reported in a 58-year-old Cambodian female.

Allopurinol-induced hypersensitivity reactions tend to occur more often in the presence of renal insufficiency and/or concomitant thiazide diuretic therapy.

Hypersensitivity side effects have included hypersensitivity maculopapular rash (1% to 3%). Rash, eosinophilia, and fever have been reported in 0.3% of patients. Rare, but potentially fatal, reactions have included arthralgias, hepatitis, acute interstitial nephritis, vasculitis, and severe skin reactions. Stevens-Johnson syndrome, toxic epidermal necrolysis, and toxic pustuloderma have been reported rarely. At least 3 cases of allopurinol hypersensitivity syndrome have also been reported.

Hepatic side effects

Hepatic side effects have included elevations in serum transaminases and alkaline phosphatase. Cholestatic jaundice, hepatic necrosis, granulomatous hepatitis, and hepatomegaly have been reported rarely.

Hypersensitivity appears to play a role in allopurinol-induced hepatotoxicity. Hepatitis is usually accompanied by fever, rash, and occasionally hepatomegaly. Liver biopsies in cases of hepatitis have revealed mild portal inflammation and acute centrilobular necrosis, consistent with hypersensitivity reactions.

Gastrointestinal side effects

Gastrointestinal side effects including diarrhea, nausea, and vomiting have been reported in less than 1% of patients. At least one case of steatorrhea has also been reported, in addition to a case of elevations in pancreatic exocrine enzyme level.

A first of a kind case report, elevations in pancreatic exocrine enzyme level, new-onset type 1 diabetes mellitus, and allopurinol hypersensitivity syndrome have been reported in a 58-year-old Cambodian female.

Hematologic side effects

A 43-year-old female with chronic kidney disease developed fever, generalized morbilliform rash, leukocytosis with marked eosinophilia, and hepatic dysfunction 3 weeks after starting allopurinol therapy (300 mg/day for 3 days followed by 200 mg/day) for hyperuricemia and arthritis. Pure red cell aplasia was suspected due to progressive worsening of anemia with reticulocytopenia. Treatment with recombinant human erythropoietin was initiated in addition to prednisolone 15 mg daily. Eleven days later (approximately 7 weeks after allopurinol was discontinued), both the hemoglobin level and reticulocyte count began to rise.

Hematologic side effects including bone marrow suppression, resulting in severe anemia, thrombocytopenia, and leukopenia have been reported in 0.2% of patients. In addition, aplastic anemia, sometimes fatal, and hemolytic anemia have been reported. At least one case of pure red cell aplasia has also been reported.

Renal side effects

Studies of patients with allopurinol-induced crystalluria and nephrolithiasis have revealed both urate and allopurinol/oxypurinol (allopurinol metabolite) calculi. Biopsies in cases of suspected allopurinol-associated acute renal failure have revealed vasculitis, interstitial nephritis, and rare cases of granulomatous nephritis.

Renal side effects have included crystalluria and stone formation as well as elevations in blood urea nitrogen. Acute interstitial nephritis due to hypersensitivity and granulomatous nephritis have also been reported.

Nervous system side effects

Allopurinol-induced aseptic meningitis has been reported in two isolated cases where 60-year-old Caucasian men developed high fevers soon after taking an initial dose of 300 mg allopurinol, and when rechallenged, with quick improvement after allopurinol was stopped.

There is a case report of a patient with no history of psychiatric disease whose allopurinol-associated catatonia, rash, and fever responded to steroids.

Nervous system side effects have been reported extremely rarely and included case reports of peripheral neuropathy, catatonia, and cerebral vasculitis associated with allopurinol hypersensitivity. At least two cases of allopurinol-induced aseptic meningitis have also been reported.

Ocular side effects

Ocular side effects have included cataract formation. Macular retinitis, iritis, conjunctivitis, and amblyopia have also been reported, although causality is unknown.

Anterior lens thinning is associated with cataract formation, and is more common among patients on allopurinol therapy.

Immunologic side effects

Immunologic side effects have included at least one case of ANCA-positive vasculitis.

Antineutrophil cytoplasmic antibodies (ANCA) against human neutrophil elastase as well as against myeloperoxidase were documented in a 47-year-old man who developed vasculitis during allopurinol therapy for gout. Clinical improvement and decline in antibodies were noted upon discontinuation of allopurinol.

Metabolic side effects

Metabolic side effects including at least one case of new-onset type 1 diabetes mellitus have been reported.

A first of a kind case report, new-onset type 1 diabetes mellitus, elevations in pancreatic exocrine enzyme level, and allopurinol hypersensitivity syndrome have been reported in a 58-year-old Cambodian female.

Musculoskeletal side effects

Musculoskeletal side effects have included acute attacks of gout.

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