FDA label 5accbac8-8f3d-400b-98b5-b80312efe379

WARNINGS ALLOPURINOL SHOULD BE DISCONTINUED AT THE FIRST APPEARANCE OF SKIN RASH OR OTHER SIGNS WHICH MAY INDICATE AN ALLERGIC REACTION. In some instances with oral allopurinol, 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 sodium for injection 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 PRECAUTIONS - Drug Interactions ). A few cases of reversible clinical hepatotoxicity have been noted in patients taking oral 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. Thus, in patients with decreased renal function, such combinations should be administered with caution.

ADVERSE REACTIONS In an uncontrolled, compassionate plea protocol, 125 of 1,378 patients reported a total of 301 adverse reactions while receiving allopurinol sodium for injection. Most of the patients had advanced malignancies or serious underlying diseases and were taking multiple concomitant medications. Side effects directly attributable to allopurinol sodium for injection were reported in 19 patients. Fifteen of these adverse experiences were allergic in nature (rash, eosinophilia, local injection site reaction). One adverse experience of severe diarrhea and one incidence of nausea were also reported as being possibly attributable to allopurinol sodium for injection. Two patients had serious adverse experiences (decreased renal function and generalized seizure) reported as being possibly attributable to allopurinol sodium for injection. A listing of the adverse reactions regardless of causality reported from clinical trials follows: Incidence Greater Than 1%: Cutaneous/Dermatologc: rash (1.5%) Genitourinary: renal failure/insufficiency (1.2%) Gastrointestinal: nausea (1.3%), vomiting (1.2%) Incidence Less Than 1%: Body as Whole: fever, pain, chills, alopecia, infection, sepsis, enlarged abdomen, mucositis/pharyngitis, blast crisis, cellulitis, hypervolemia Cardiovascular: heart failure, cardiorespiratory arrest, hypertension, pulmonary embolus, hypotension, decreased venous pressure, flushing, headache, stroke, septic shock, cardiovascular disorder, ECG abnormality, hemorrhage, bradycardia, thrombophlebitis, ventricular fibrillation Cutaneous/Dermatologic: urticaria, pruritus, local injection site reaction Gastrointestinal: diarrhea, gastrointestinalbleeding, hyperbilirubinemia, splenomegaly, hepatomegaly, intestinal obstruction, jaundice, flatulence, constipation, liver failure, proctitis Genitourinary: hematuria, increased creatinine, oliguria, kidney function abnormality, urinary tract infection Hematologic: leukopenia, marrow aplasia, thrombocytopenia, eosinophilia,neutropenia, anemia, pancytopenia, ecchymosis, bone marrow suppression, disseminated intravascular coagulation Metabolic: hypocalcemia, hyperphosphatemia, hypokalemia, hyperuricemia, electrolyte abnormality, hypercalcemia, hyperglycemia, hypernatremia, hyponatremia, metabolic acidosis, edema, glycosuria, hyperkalemia, lactic acidosis, water intoxication, hypomagnesemia Neurologic: seizure, status epilepticus, myoclonus, twitching, agitation, mental status changes, cerebral infarction, coma, dystonia, paralysis, tremor Pulmonary: respiratory failure/insufficiency, ARDS, increased respiration rate, apnea Musculoskeletal: arthralgia Other: hypotonia, diaphoresis, tumor lysis syndrome The most frequent adverse reaction to oral allopurinol is skin rash. Skin reactions can be severe and sometimes fatal. Therefore, treatment with allopurinol sodium for injection should be discontinued immediately if a rash develops (see WARNINGS ). For further details on hypersensitivity reactions to treatment with oral allopurinol, refer to the package insert for allopurinol tablets.

<table> <col width="46%"/> <col width="54%"/> <tbody> <tr> <td styleCode="Toprule "> <paragraph> <content styleCode="bold">Incidence Greater Than 1%:</content> </paragraph> </td> <td styleCode="Toprule "/> </tr> <tr> <td> <paragraph>Cutaneous/Dermatologc:</paragraph> </td> <td> <paragraph>rash (1.5%)</paragraph> </td> </tr> <tr> <td> <paragraph>Genitourinary:</paragraph> </td> <td> <paragraph>renal failure/insufficiency (1.2%)</paragraph> </td> </tr> <tr> <td> <paragraph>Gastrointestinal:</paragraph> </td> <td> <paragraph>nausea (1.3%), vomiting (1.2%)</paragraph> </td> </tr> <tr> <td> <paragraph> <content styleCode="bold">Incidence Less Than 1%:</content> </paragraph> </td> <td/> </tr> <tr> <td> <paragraph>Body as Whole:</paragraph> </td> <td> <paragraph>fever, pain, chills, alopecia, infection, sepsis, enlarged abdomen, mucositis/pharyngitis, blast crisis, cellulitis, hypervolemia</paragraph> </td> </tr> <tr> <td> <paragraph>Cardiovascular:</paragraph> </td> <td> <paragraph>heart failure, cardiorespiratory arrest, hypertension, pulmonary embolus, hypotension, decreased venous pressure, flushing, headache, stroke, septic shock, cardiovascular disorder, ECG abnormality, hemorrhage, bradycardia, thrombophlebitis, ventricular fibrillation</paragraph> </td> </tr> <tr> <td> <paragraph>Cutaneous/Dermatologic:</paragraph> </td> <td> <paragraph>urticaria, pruritus, local injection site reaction</paragraph> </td> </tr> <tr> <td> <paragraph>Gastrointestinal:</paragraph> </td> <td> <paragraph>diarrhea, gastrointestinalbleeding, hyperbilirubinemia, splenomegaly, hepatomegaly, intestinal obstruction, jaundice, flatulence, constipation, liver failure, proctitis</paragraph> </td> </tr> <tr> <td> <paragraph>Genitourinary:</paragraph> </td> <td> <paragraph>hematuria, increased creatinine, oliguria, kidney function abnormality, urinary tract infection </paragraph> </td> </tr> <tr> <td> <paragraph>Hematologic:</paragraph> </td> <td> <paragraph>leukopenia, marrow aplasia, thrombocytopenia, eosinophilia,neutropenia, anemia, pancytopenia, ecchymosis, bone marrow suppression, disseminated intravascular coagulation </paragraph> </td> </tr> <tr> <td> <paragraph>Metabolic:</paragraph> </td> <td> <paragraph>hypocalcemia, hyperphosphatemia, hypokalemia, hyperuricemia, electrolyte abnormality, hypercalcemia, hyperglycemia, hypernatremia, hyponatremia, metabolic acidosis, edema, glycosuria, hyperkalemia, lactic acidosis, water intoxication, hypomagnesemia</paragraph> </td> </tr> <tr> <td> <paragraph>Neurologic:</paragraph> </td> <td> <paragraph>seizure, status epilepticus, myoclonus, twitching, agitation, mental status changes, cerebral infarction, coma, dystonia, paralysis, tremor</paragraph> </td> </tr> <tr> <td> <paragraph>Pulmonary:</paragraph> </td> <td> <paragraph>respiratory failure/insufficiency, ARDS, increased respiration rate, apnea</paragraph> </td> </tr> <tr> <td> <paragraph>Musculoskeletal:</paragraph> </td> <td> <paragraph>arthralgia</paragraph> </td> </tr> <tr> <td styleCode="Botrule "> <paragraph>Other:</paragraph> </td> <td styleCode="Botrule "> <paragraph>hypotonia, diaphoresis, tumor lysis syndrome</paragraph> </td> </tr> </tbody> </table>