Allopurinol is not known to alter the accuracy of laboratory tests.
Reproductive studies have been performed in rats and rabbits at doses up to twenty times the usual human dose (5 mg/kg per day), and it was concluded that there was no impaired fertility or harm to the fetus due to allopurinol. There is a published report of a study in pregnant mice given 50 or 100 mg/kg allopurinol intraperitoneally on gestation days 10 or 13. There were increased numbers of dead fetuses in dams given 100 mg/kg allopurinol but not in those given 50 mg/kg. There were increased numbers of external malformations in fetuses at both doses of allopurinol on gestation day 10 and increased numbers of skeletal malformations in fetuses at both doses on gestation day 13. It cannot be determined whether this represented a fetal effect or an effect secondary to maternal toxicity. There are, however, no adequate or well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Experience with allopurinol during human pregnancy has been limited partly because women of reproductive age rarely require treatment with allopurinol. There are two unpublished reports and one published paper of women giving birth to normal offspring after receiving allopurinol during pregnancy.
Allopurinol and oxipurinol have been found in the milk of a mother who was receiving allopurinol. Since the effect of allopurinol on the nursing infant is unknown, caution should be exercised when allopurinol is administered to a nursing woman.
Allopurinol is rarely indicated for use in children with the exception of those with hyperuricemia secondary to malignancy or to certain rare inborn errors of purine metabolism (see INDICATIONS AND USAGE and DOSAGE AND ADMINISTRATION).
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following estimates of incidence of adverse reactions are made are derived from experiences reported in the literature, unpublished clinical trials and voluntary reports since marketing of allopurinol began.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 (see PRECAUTIONS and DOSAGE AND ADMINISTRATION).
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 (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 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 (see PRECAUTIONS).
Most Common Reactions 1 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.
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 (see PRECAUTIONS).
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.
- 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 (see ADVERSE REACTIONS introduction, INDICATIONS AND USAGE, PRECAUTIONS, and DOSAGE AND ADMINISTRATION).
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