Allopurinol Sodium

5 WARNINGS AND PRECAUTIONS Skin Rash and Hypersensitivity: Discontinue Allopurinol Sodium for Injection at the first appearance of skin rash or other signs which may indicate a hypersensitivity reaction. Allopurinol has been associated with serious and sometimes fatal dermatologic reactions. ( 5.1 ) Renal Function Impairment: Patients with decreased renal function require lower doses of allopurinol. ( 5.2 ) Hepatotoxicity: If signs and symptoms of hepatotoxicity develop, liver function evaluation should be performed. ( 5.3 ) Myelosuppression: Bone marrow suppression has been reported with allopurinol. ( 5.4 ) Drowsiness: Drowsiness has been reported in patients taking Allopurinol Sodium for Injection. ( 5.5 ) 5.1 Skin Rash and Hypersensitivity Serious and sometimes fatal dermatologic reactions, including toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported in patients taking allopurinol [see Adverse Reactions (6.1) ] . These reactions occur in approximately 5 in 10,000 (0.05%) patients taking allopurinol. Other serious hypersensitivity reactions that have been reported include exfoliative, urticarial and purpuric lesions; generalized vasculitis; and irreversible hepatotoxicity. Discontinue Allopurinol Sodium for Injection at the first appearance of skin rash or other signs which may indicate a hypersensitivity reaction. The HLA-B*58:01 allele is a genetic marker for severe skin reactions indicative of hypersensitivity to allopurinol. Patients who carry the HLA-B*58:01 allele are at a higher risk of allopurinol hypersensitivity syndrome (AHS), but hypersensitivity reactions have been reported in patients who do not carry this allele. The frequency of this allele is higher in individuals of African, Asian (e.g., Han Chinese, Korean, Thai), and Native Hawaiian/Pacific Islander ancestry [see Clinical Pharmacology (12.5) ] . The use of Allopurinol Sodium for Injection is not recommended in HLA-B*58:01 positive patients unless the benefits clearly outweigh the risks. Prior to starting Allopurinol Sodium for Injection, consider testing for the HLA-B*58:01 allele in genetically at-risk populations. Screening is generally not recommended in patients from populations in which the prevalence of HLA-B*58:01 is low, or in current allopurinol users, as the risk of SJS/TEN/DRESS is largely confined to the first few months of therapy, regardless of HLA-B*58:01 status. Hypersensitivity reactions to Allopurinol Sodium for Injection may be increased in patients with decreased renal function receiving thiazide diuretics and Allopurinol Sodium for Injection concurrently. In addition, concomitant use of the following drugs may increase the risk of skin rash, which may be severe: bendamustine, thiazide diuretics, ampicillin and amoxicillin [see Drug Interactions (7.1) ] . Patients should stop Allopurinol Sodium for Injection and seek medical attention if they develop a rash. 5.2 Renal Function Impairment Treatment with Allopurinol Sodium for Injection may result in renal impairment due to formation of xanthine calculi or due to precipitation of urates in patients receiving concomitant uricosuric agents. Patients with pre-existing renal disease, including renal impairment or history of kidney stones, may be at increased risk for worsening renal impairment due to xanthine calculi or precipitation of urates while receiving treatment with Allopurinol Sodium for Injection. Monitor serum creatinine at least daily during the early stages of allopurinol administration. Maintain fluid intake sufficient to yield a urinary output of at least 2 liters per day in adults. In patients with severely impaired renal function or increase in uric acid concentration associated with decreased urate clearance, reduce the dosage of Allopurinol Sodium for Injection [see Use In Specific Populations (8.6) and Dosage and Administration (2.1 , 2.2) ] . 5.3 Hepatotoxicity Cases of reversible clinical hepatotoxicity have been noted in patients taking oral allopurinol. 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, evaluate liver enzymes. In patients with pre-existing liver disease, monitor liver enzymes periodically during the early stages of therapy. Discontinue Allopurinol Sodium for Injection in patients with elevated liver enzymes. 5.4 Myelosuppression Myelosuppression, manifested by anemia, leukopenia or thrombocytopenia, has been reported in patients receiving allopurinol [see Adverse Reactions (6.1) ] . The cytopenias have occurred from as early as 6 weeks to as late as 6 years after the initiation of allopurinol therapy. Discontinue use of Allopurinol Sodium for Injection in patients with unexplained cytopenias. Concomitant use with allopurinol with cytotoxic drugs associated with myelosuppression may increase the risk of myelosuppression. Monitor blood counts more frequently [see Drug Interactions (7) ] . 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 the respective prescribing information when used concomitantly with Allopurinol Sodium for Injection. [see Drug Interactions (7) ] . 5.5 Drowsiness Drowsiness has been reported in patients taking Allopurinol Sodium for Injection [see Adverse Reactions (6.1) ] . Advise patients to avoid operation of automobiles or other dangerous machinery and activities made hazardous by decreased alertness when starting Allopurinol Sodium for Injection or increasing the dose until they know how the drug affects them. Advise patients that the central nervous system depressant effects of Allopurinol Sodium for Injection may be additive to those of alcohol and other CNS depressants.