FDA label 2ca799ba-56af-4fa6-ac9c-44f736ef1a02

WARNINGS ALLOPURINOL SHOULD BE DISCONTINUED AT THE FIRST APPEARANCE OF SKIN RASH OR OTHER SIGNS WHICH MAY INDICATE AN ALLERGIC REACTION. In some instances a skin rash may be followed by more severe hypersensitivity reactions such as exfoliative, urticarial and purpuric lesions as well as Stevens-Johnson Syndrome (erythema multiforme exudativum) and/or generalized vasculitis, irreversible hepatotoxicity and on rare occasions, death. In patients receiving mercaptopurine or azathioprine, the concomitant administration of 300 to 600 mg of allopurinol per day will require a reduction in dose to approximately one-third to one-fourth of the usual dose of mercaptopurine or azathioprine. Subsequent adjustment of doses of mercaptopurine or azathioprine should be made on the basis of therapeutic response and the appearance of toxic effects (see CLINICAL PHARMACOLOGY ). A few cases of reversible clinical hepatotoxicity have been noted in patients taking allopurinol, and in some patients asymptomatic rises in serum alkaline phosphatase or serum transaminase have been observed. If anorexia, weight loss or pruritus develop in patients on allopurinol, evaluation of liver function should be part of their diagnostic workup. In patients with pre-existing liver disease, periodic liver function tests are recommended during the early stages of therapy. Due to the occasional occurrence of drowsiness, patients should be alerted to the need for due precaution when engaging in activities where alertness is mandatory. The occurrence of hypersensitivity reactions to allopurinol may be increased in patients with decreased renal function receiving thiazides and allopurinol concurrently. For this reason, in this clinical setting, such combinations should be administered with caution and patients should be observed closely.

ADVERSE REACTIONS 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following estimates of incidence of adverse reactions are made are derived from experiences reported in the literature, unpublished clinical trials and voluntary reports since marketing of allopurinol began.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* 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 (see ADVERSE REACTIONS introduction, INDICATIONS AND USAGE , PRECAUTIONS and DOSAGE AND ADMINISTRATION ). 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 T o report SUSPECTED ADVERSE EVENTS, contact Actavis at 1-800-272-5525 or FDA at 1-800- FDA-1088 or h tt p : // w w w . f d a.gov/ for voluntary reporting of adverse reactions.