Allopurinol: uses, appearance and warnings

Allopurinol Tablets is indicated for: The management of adults with signs and symptoms of primary or secondary gout (acute attacks, tophi, joint destruction, uric acid lithiasis, and/or nephropathy) The management of adult and pediatric patients with leukemia, lymphoma and solid tumor malignancies who are receiving cancer therapy which causes elevations of serum and urinary uric acid levels The management of adult patients with recurrent calcium oxalate calculi whose daily uric acid excretion exceeds 800 mg/day in male patients and 750 mg/day in female patients, despite lifestyle changes (such as reduction of dietary sodium, non-dairy animal protein, oxylate rich foods, refined sugars and increases in oral fluids and fruits and vegetables) Limitations of Use Allopurinol Tablets is not recommended for the treatment of asymptomatic hyperuricemia. Allopurinol Tablets is a xanthine oxidase inhibitor indicated for the management of: Adult patients with signs and symptoms of primary or secondary gout (acute attacks, tophi, joint destruction, uric acid lithiasis, and/or nephropathy) ( 1 ) Adult and pediatric patients with leukemia, lymphoma and solid tumor malignancies who are receiving cancer therapy which causes elevations of serum and urinary uric acid levels ( 1 ) Adult patients with recurrent calcium oxalate calculi whose daily uric acid excretion exceeds 800 mg/day in male patients and 750 mg/day in female patients, despite lifestyle changes ( 1 ) Limitations of Use Allopurinol Tablets is not recommended for the treatment of asymptomatic hyperuricemia. ( 1 )

Allopurinol Tablets tablets have functional scoring and are available in the following strengths: 100 mg: Round, flat, off-white, scored tablet, debossed “0524” over “0405”.. 300 mg: Round, convex, off-white tablet, debossed “AL3”. Tablets: 100 mg, and 300 mg, functionally scored

How Supplied Allopurinol Tablets (allopurinol) is available in multiple tablet strengths with functional scoring and package sizes (bottles with child-resistant caps) as listed in Table 4. TABLE 4: Allopurinol Tablets Presentations 100 mg; round, flat, off-white, scored tablet, debossed “0524” over “0405”. Bottles of 100 NDC 55111-729-01 Bottles of 1000 NDC 55111-729-10 300 mg; round, convex, off-white tablet, debossed “AL3”. Bottles of 100 NDC 55111-730-01 Bottles of 500 NDC 55111-730-05 Storage and Handling Store at 15°-30°C (59°-86°F) and protect from moisture. QUESTIONS OR COMMENTS? Call toll free 1-888-375-3784. You may report side effects to FDA at 1-800-FDA-1088.

Allopurinol Tablets is contraindicated in patients with a history of hypersensitivity reaction to allopurinol or to any of the ingredients of Allopurinol Tablets. Known hypersensitivity to allopurinol or to any of the ingredients of Allopurinol Tablets.

Skin Rash and Hypersensitivity: Allopurinol has been associated with serious and sometimes fatal dermatological reactions. Discontinue Allopurinol Tablets at the first appearance of skin rash or other signs of hypersensitivity reaction. ( 5.1 ) Gout Flares: May occur during initiation of treatment. Concurrent prophylactic treatment with colchicine or anti-inflammatory agents is recommended. ( 5.2 ) Nephrotoxicity: Allopurinol may affect kidney function. Patients with decreased kidney function require lower doses of Allopurinol Tablets. ( 5.3 ) Hepatoxicity: Cases of reversible hepatotoxicity have occurred. If signs and symptoms of hepatotoxicity develop, evaluate liver function. ( 5.4 ) Myelosuppression: Bone marrow suppression has been reported with allopurinol. ( 5.5 ) Potential Effect on Driving and Use of Machinery: Drowsiness, somnolence and dizziness have been reported in patients taking Allopurinol Tablets. ( 5.6 ) 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) ]. 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 Tablets permanently 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 Tablets is not recommended in HLA- B*58:01 positive patients unless the benefits clearly outweigh the risks. Consider screening for HLA-B*5801 before starting treatment with Allopurinol Tablets in patients from populations in which the prevalence of this HLA-B*5801 allele is known to be high. 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 Tablets may be increased in patients with decreased kidney function receiving thiazide diuretics and Allopurinol Tablets concurrently. Concomitant use of the following drugs may also increase the risk of skin rash, which may be severe: bendamustine, ampicillin and amoxicillin [ see Drug Interactions (7.1) ]. Discontinue Allopurinol Tablets immediately if a skin rash develops. Instruct patients to stop taking Allopurinol Tablets immediately and seek medical attention promptly if they develop a rash. 5.2 Gout Flares Gout flares have been reported during initiation of treatment with Allopurinol Tablets, even when normal or subnormal serum uric acid levels have been attained due to the mobilization of urates from tissue deposits. Even with adequate therapy with Allopurinol Tablets, it may require several months to deplete the uric acid pool sufficiently to achieve control of the flares. The flares typically become shorter and less severe after several months of therapy. In order to prevent gout flares when treatment with Allopurinol Tablets is initiated, concurrent prophylactic treatment with colchicine or an anti-inflammatory agent is recommended [ see Dosage and Administration (2.2) ]. Advise patients to continue Allopurinol Tablets and prophylactic treatment even if gout flares occur, as it may take months to achieve control of gout flares. 5.3 Nephrotoxicity Treatment with Allopurinol Tablets may result in acute kidney injury due to formation of xanthine calculi or due to precipitation of urates in patients receiving concomitant uricosuric agents. Patients with pre-existing kidney disease, including chronic kidney disease or history of kidney stones, may be at increased risk for worsening of kidney function or acute kidney injury due to xanthine calculi while receiving treatment with Allopurinol Tablets. In patients receiving Allopurinol Tablets for the management of gout or the management of recurrent calcium oxalate calculi, monitor kidney function frequently during the early stages of allopurinol administration. Maintain fluid intake sufficient to yield a urinary output of at least 2 liters per day of neutral or, preferably, slightly alkaline urine to avoid the possibility of formation of xanthine calculi and help prevent renal precipitation of urates in patients receiving concomitant uricosuric agents. In patients receiving Allopurinol Tablets for the management of tumor lysis syndrome, monitor kidney function 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 and at least 2 liters/m 2 /day (or at least 100 mL/m 2 /hour) in pediatric patients [see Dosage and Administration ( 2.4 )]. 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. …

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 postmarketing 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. …

The following drugs may increase the risk of serious skin reactions: bendamustine, thiazide diuretics, ampicillin and amoxicillin. ( 7.1 ) Capecitabine: Avoid concomitant use. ( 7.2 ) Mercaptopurine or Azathioprine: Reduce mercaptopurine or azathioprine dose as recommended in the respective prescribing information. ( 7.2 ) Pegloticase: Discontinue and refrain from initiating treatment with Allopurinol Tablets. ( 7.2 ) See FPI for complete list of significant drug interactions. ( 7.2 ) 7.1 Drugs Known to Affect the Occurrence of Skin Rash and Hypersensitivity Concomitant use of the following drugs may increase the risk of skin rash, which may be severe: bendamustine, thiazide diuretics, ampicillin and amoxicillin. Renal impairment may further increase risk with concomitant use of thiazide diuretics [ see Warnings and Precautions ( 5.1 , 5.2 ) and Clinical Pharmacology (12.2) ]. …