Allopurinol

5.4 Hepatotoxicity Cases of reversible clinical hepatotoxicity have occurred in patients taking allopurinol tablets, 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 tablets, evaluate liver enzymes. In patients with pre-existing liver disease, monitor liver enzymes periodically. Discontinue allopurinol tablets in patients with elevated liver enzymes.

5.5 Myelosuppression Myelosuppression, manifested by anemia, leukopenia or thrombocytopenia, has been reported in patients receiving allopurinol tablets. The cytopenias have occurred as early as 6 weeks up to 6 years after the initiation of therapy of allopurinol tablets. Concomitant use of allopurinol tablets with cytotoxic drugs associated with myelosuppression may increase the risk of myelosuppression. Monitor blood counts more frequently when cytotoxic drugs are used concomitantly [see Drug Interactions (7.2) ] . Concomitant use with allopurinol increases the exposure of either mercaptopurine or azathioprine which may increase the risk of myelosuppression. Reduce the dosage of mercaptopurine or azathioprine as recommended in their respective prescribing information when used concomitantly with allopurinol tablets [see Drug Interactions (7.2) ] .

5.6 Potential Effect on Driving and Use of Machinery Drowsiness, somnolence and dizziness have been reported in patients taking allopurinol tablets [see Adverse Reactions (6) ] . Inform patients also that the central nervous system depressant effects of allopurinol tablets may be additive to those of alcohol and other CNS depressants. Advise patients to avoid operation of automobiles or other dangerous machinery and activities made hazardous by decreased alertness when starting allopurinol tablets or increasing the dose, until they know how the drug affects them.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Skin Rash and Hypersensitivity [see Warnings and Precautions (5.1) ] Nephrotoxicity [see Warnings and Precautions (5.3) ] Hepatoxicity [see Warnings and Precautions (5.4) ] Myelosuppression [see Warnings and Precautions (5.5) ] Potential Effect on Driving and Use of Machinery [see Warnings and Precautions (5.6) ] The following adverse reactions associated with the use of allopurinol tablets were identified in literature, unpublished clinical trials or post marketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The most frequent adverse reaction to allopurinol tablets is skin rash. Most Common Adverse Reactions (≥ 1%) Gastrointestinal : Diarrhea, nausea, alkaline phosphatase increase, AST/ALT increase. Metabolic and Nutritional : Acute attacks of gout. Skin and Appendages : Rash, maculopapular rash. Less Common Adverse Reactions (< 1%) Body As a Whole : Ecchymosis, fever, headache, malaise. Cardiovascular : Necrotizing angiitis, vasculitis, pericarditis, peripheral vascular disease, thrombophlebitis, bradycardia, vasodilation. Gastrointestinal : Hepatic necrosis, granulomatous hepatitis, hepatomegaly, hyperbilirubinemia, cholestatic jaundice, vomiting, intermittent abdominal pain, gastritis, dyspepsia, hemorrhagic pancreatitis, gastrointestinal bleeding, stomatitis, salivary gland swelling, hyperlipidemia, tongue edema, anorexia. Hemic and Lymphatic: Thrombocytopenia, eosinophilia, leukocytosis, leukopenia, aplastic anemia, agranulocytosis, eosinophilic fibrohistiocytic lesion of bone marrow, pancytopenia, prothrombin decrease, anemia, hemolytic anemia, reticulocytosis, lymphadenopathy, lymphocytosis. Musculoskeletal: Myopathy, arthralgias, myalgia. Nervous: Peripheral neuropathy, neuritis, paresthesia, somnolence, optic neuritis, confusion, dizziness, vertigo, foot drop, decrease in libido, depression, amnesia, tinnitus, asthenia, insomnia. Respiratory: Epistaxis, bronchospasm, asthma, pharyngitis, rhinitis. 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, furunculosis, facial edema, sweating, skin edema. Special Senses : Taste loss/perversion, cataracts, macular retinitis, iritis, conjunctivitis, amblyopia. Urogenital: Renal failure, uremia, nephritis, impotence, primary hematuria, albuminuria. Endocrine: Infertility (male), hypercalcemia, gynecomastia (male). Most common adverse reactions (incidence > 1%) are nausea, diarrhea, and increase in liver function tests. (6) To report SUSPECTED ADVERSE REACTIONS, contact Leading Pharma, LLC at 1-844-740-7500 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch