ALLOPURINOL tablet ALLOPURINOL tablet

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

ALLOPURINOL (UNII: 63CZ7GJN5I) (ALLOPURINOL - UNII:63CZ7GJN5I)

Available from:

Accord Healthcare Inc.

INN (International Name):

ALLOPURINOL

Composition:

ALLOPURINOL 100 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Allopurinol tablets are 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 are not recommended for the treatment of asymptomatic hyperuricemia. Allopurinol tablets are contraindicated in patients with a history of hypersensitivity reaction to allopurinol or to any of the ingredients of allopurinol tablets. Risk Summary Based on findings in animals, allopurinol may cause fetal harm when administered to a pregnant woman. Adverse developmental outcomes have been described in exposed animals ( see Data ). Allopurinol and its metabolite oxypurinol have been shown to cross the placenta following administration of maternal allopurinol. Available limited published data on allopurinol use in pregnant women do not demonstrate a clear pattern or increase in frequency of adverse developmental outcomes. Among approximately 50 pregnancies described in published literature, 2 infants with major congenital malformations have been reported with following maternal allopurinol exposure. Advise pregnant women of the potential risk to a fetus. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Human Data Experience with allopurinol during human pregnancy has been limited partly because women of reproductive age rarely require treatment with allopurinol. A case report published in 2011 described the outcome of a full-term pregnancy in a 35-year-old woman who had recurrent kidney stones since age 18 who took allopurinol throughout the pregnancy. The child had multiple complex birth defects and died at 8 days of life. A second report in 2013 provided data on 31 prospectively ascertained pregnancies involving mothers exposed to allopurinol for varying durations during the first trimester. The overall rate of major fetal malformations and spontaneous abortions was reported to be within the normal expected range; however, one child had severe malformations similar to those described in the cited earlier case report. Animal Data There was no evidence of fetotoxicity or teratogenicity in rats or rabbits treated during the period of organogenesis with oral allopurinol at doses up to 200 mg/kg/day and up to 100 mg/kg/day, respectively (about 2.4 times the human dose on a mg/m 2 basis). However, there is a published report in pregnant mice that single intraperitoneal doses of 50 mg/kg or 100 mg/kg (about 0.3 or 0.6 times the human dose on a mg/m 2 basis) of allopurinol on gestation days 10 or 13 produced significant increases in fetal deaths and teratogenic effects (cleft palate, harelip, and digital defects). It is uncertain whether these findings represented a fetal effect or an effect secondary to maternal toxicity. Risk Summary Allopurinol and oxypurinol are present in human milk. Based on information from a single case report, allopurinol and its active metabolite, oxypurinol, were detected in the milk of a mother receiving 300 mg of allopurinol daily at 5 weeks postpartum. The estimated relative infant dose were 0.14 mg/kg and 0.2 mg/kg of allopurinol and between 7.2 mg/kg to 8 mg/kg of oxypurinol daily. There was no report of effects of allopurinol on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatments with allopurinol and for one week after the last dose. Hyperuricemia Associated with Cancer Therapy The safety and effectiveness of allopurinol for the management of pediatric patients with leukemia, lymphoma and solid tumor malignancies who are receiving cancer therapy which causes elevations of serum and urinary uric acid levels have been established in approximately 200 pediatric patients. The efficacy and safety profile observed in this patient population were similar to that observed in adults. Primary or Secondary Gout The safety and effectiveness of allopurinol have not been established for the treatment of signs and symptoms of primary or secondary gout in pediatric patients. Recurrent Calcium Oxalate Calculi The safety and effectiveness of allopurinol have not been established for the management of pediatric patients with recurrent calcium oxalate calculi. Inborn Errors of Metabolism The safety and effectiveness of allopurinol have not been established in pediatric patients with rare inborn errors of purine metabolism. Allopurinol and its primary active metabolite, oxipurinol, are eliminated by the kidneys; therefore, changes in renal function have a profound effect on exposure. In patients with decreased renal function or who have concurrent illnesses which can affect renal function, perform periodic laboratory parameters of renal function and reassess the patient's dosage of allopurinol [ see Dosage and Administration (2.6), Warnings and Precautions (5.3) ].

Product summary:

How Supplied Allopurinol tablets, USP are available in multiple tablet strengths with functional scoring and package sizes (bottles) as listed in Table 4. Storage and Handling Store at 20°C to 25°C (USP Controlled Room Temperature) (68°F to 77°F) in a dry place. Dispense in a tight container as defined in the USP.

Authorization status:

Abbreviated New Drug Application

Summary of Product characteristics

ALLOPURINOL- ALLOPURINOL TABLET
ACCORD HEALTHCARE INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
ALLOPURINOL TABLETS
SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
ALLOPURINOL TABLETS.
ALLOPURINOL TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL:1966
INDICATIONS AND USAGE
Allopurinol 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 are not recommended for the treatment of
asymptomatic hyperuricemia. ( 1)
DOSAGE AND ADMINISTRATION
Gout: Prior to initiating treatment assess serum uric acid level,
complete blood count, chemistry panel,
liver and kidney function tests. Prophylactic treatment for gout
flares is recommended. ( 2.1, 2.2)
Patients with normal kidney function: Initial dosage is 100 mg orally
daily. Increase by 100 mg weekly
increments until serum uric acid of 6 mg/dl or less is reached
(maximum 800 mg daily). ( 2.3)
Patients with impaired kidney function: The initial dosage is 50 mg
orally daily. Follow
recommendations for titration in patients with renal impairment until
target serum uric acid level is
reached. ( 2.6)
See complete information in the Full Prescribing Information (FPI).
Hyperuricemia Associated with Cancer Therapy: The recommended dosage
is:
Adults: 300 mg to 800 mg orally daily.
Pediatric patients: 100 mg/m
orally every 8 hours to 12 hours (10 mg/kg/day, maximum 800
mg/day)
See complete information in the FPI. ( 2.4, 2.6)
Recurrent Calciu