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following estimates of incidence of adverse reactions are made are derived from experiences reported in the literature, unpublished clinical trials and voluntary reports since marketing of allopurinol began.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 experiences 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 <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 Allopac for 3-34 months (average >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 frequently <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, increased alkaline phosphatase and SGOT/SGPT.
Metabolic and Nutritional: Acute gout attacks.
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 >1%. The most frequent event observed was acute attacks of gout following the initiation of therapy. Analyses of current usage suggest that incidence of these adverse reactions is now <1%. The explanation for this decrease has not been determined, but it may be due to following recommended usage.
Incidence <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.
Skin and Appendages: Erythema multiforme exudativum (Stevens-Johnson syndrome), toxic epidermal necrosis (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 <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, decreased prothrombin, anemia, hemolytic anemia, reticulocytosis, lymphadenopathy, lymphocytosis.
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.