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made are derived from experiences reported in the literature, unpublished clinical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 ZYLOPRIM (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 (see PRECAUTIONS and DOSAGE
The most frequent adverse reaction to ZYLOPRIM (allopurinol) is skin rash. Skin reactions
can be severe and sometimes fatal. Therefore, treatment with ZYLOPRIM (allopurinol) should
be discontinued immediately if a rash develops (see WARNINGS). 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 ZYLO-PRIM 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 pru-ritic maculopapular skin
eruption, sometimes scaly or exfolia-tive. 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 ZYLOPRIM (allopurinol) has been reported to be
increased (see PRECAUTIONS).
Most Common Reactions* Probably Causally Related:
Gastrointestinal: Diarrhea, nausea, alkaline phosphatase 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 ZYLOPRIM (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 (see ADVERSE REACTIONS introduction, INDICATIONS
AND USAGE, PRECAUTIONS, and DOSAGE
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,
Musculoskeletal: Myopathy, arthralgias.
Nervous: Peripheral neuropathy, neuritis, paresthesia, somnolence.
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 (see PRECAUTIONS).
Incidence Less Than 1% Causal Relationship Unknown:
Body As a Whole: Malaise.
Cardiovascular: Pericarditis, peripheral vascular disease, thrombophlebitis,
Endocrine: Infertility (male), hypercalcemia, gynecomastia (male).
Gastrointestinal: Hemorrhagic pancreatitis, gastrointestinal
bleeding, stomatitis, salivary gland swelling, hyperlipidemia, tongue edema,
Hemic and Lymphatic: Aplastic anemia, agranulocytosis, eosinophilic
fibrohistiocytic lesion of bone marrow, pancyto-penia, prothrombin decrease,
anemia, hemolytic anemia, reticu-locytosis, 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
Special Senses: Cataracts, macular retinitis, iritis, conjunctivitis,
Urogenital: Nephritis, impotence, primary hematuria, albu-minuria.