Allopurinol
Allopurinol Prescribing Information
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)
Allopurinol Tablets are not recommended for the treatment of asymptomatic hyperuricemia.
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Prior to initiating treatment with allopurinol tablets in patients with gout, assess the following baseline tests: serum uric acid level, complete blood count, chemistry panel, liver function tests (serum alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase, and total bilirubin), kidney function tests (serum creatinine and eGFR).
Gout flares may occur after initiation of allopurinol tablets due to changing serum uric acid levels resulting in mobilization of urate from tissue deposits. Flare prophylaxis with colchicine or an anti-inflammatory agent according to practice guidelines is recommended upon initiation of allopurinol tablets. While adjusting the dosage of allopurinol tablets in patients who are being treated with colchicine and/or anti-inflammatory agents, continue flare prophylaxis drugs until serum uric acid has been normalized and the patient has been free of gout flares for several months. If a gout flare occurs during allopurinol tablets treatment, allopurinol tablets need not be discontinued. Manage the gout flare concurrently, as appropriate for the individual patient
- 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). (
The initial recommended dosage for the management of gout is 100 mg orally daily, with weekly increments of 100 mg, until a serum uric acid level of 6 mg/dL or less is reached. Initiating treatment with lower dosages of allopurinol tablets and titrating slowly, decreases the risk of gout flares and drug induced serious adverse reactions.
In patients with renal impairment the initial dosage is 50 mg orally daily with lower dose increases until serum uric acid level of 6 mg/dL or less is reached. For complete dosage recommendations for patients with renal impairment see Table 1
The minimal effective dosage is 100 mg to 200 mg daily and the maximal recommended dosage is 800 mg daily. The appropriate dosage may be administered in divided doses or as a single equivalent dose with the 300 mg tablet. Doses in excess of 300 mg should be administered in divided doses. Monitor patients’ kidney function during the early stages of administration of allopurinol tablets and decrease the dosage or withdraw the drug if persistent abnormalities in kidney function occur
The dosage of allopurinol tablets to achieve control of gout varies with the severity of the disease. In general, gout control is achieved with 200 mg to 300 mg daily in patients with mild gout, and with 400 mg to 600 mg daily in patients with moderate to severe tophaceous gout. Gout attacks usually become shorter and less severe after several months of therapy.
If a dose of allopurinol tablets is missed, there is no need to double the dose at the next scheduled time. Allopurinol tablets are generally better tolerated if taken following meals. A fluid intake sufficient to yield a daily urinary output of at least 2 liters and the maintenance of a neutral or preferably, slightly alkaline urine are desirable.
Inform patients of the possibility of gout flares
Some patients, may benefit using uricosuric agents concurrently, to reduce serum uric acid to target levels.
When transferring a patient from a uricosuric agent to allopurinol tablets, reduce the dose of the uricosuric agent over a period of several weeks and increase the dose of allopurinol tablets gradually to the required dose needed to maintain target serum uric acid level.
- 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. (
The recommended initial dosages of allopurinol tablets in adult patients with renal impairment are shown in Tables 1 and 2
The recommended initial dosages in adult patients with gout with impaired kidney function are shown in Table 1
Initiate treatment with a lower dose of allopurinol tablets and increase the dose gradually in 50 mg/day increments every 2 weeks to 4 weeks in patients with renal impairment to decrease the risk of drug induced serious adverse reactions. Use the lowest dose possible to achieve the desired effect on serum and/or urine uric acid. Monitor kidney function in gout patients with chronic kidney disease closely when initiating treatment with allopurinol tablets and decrease or withdraw the drug if increased abnormalities in kidney function appear and persist.
| eGFR | Initial Dosage |
| > 60 mL/minute | No dosage modification |
| > 30 to 60 mL/minute | 50 mg daily |
| > 15 to 30 mL/minute | 50 mg every other day |
| 5 to 15 mL/minute | 50 mg twice weekly |
| < 5 mL/minute | 50 mg once weekly |
The maximum dosage that should be used in patients with various levels of renal impairment is not defined at different eGFR levels.
Data are insufficient to provide dosage recommendations for the treatment of recurrent calcium oxalate calculi in patients with renal impairment. Allopurinol and its metabolites are excreted by the kidney, and accumulation of the drug can occur in renal failure
The recommended dosage of allopurinol tablets for the management of hyperuricemia associated with cancer therapy in adult patients with renal impairment is shown in Table 2
| eGFR | Recommended Dosage |
| > 20 mL/min to 60 mL/min | No dosage modification |
| 10 mL/min to 20 mL/min | 200 mg/day |
| < 10 mL/min | 100 mg/day |
| On dialysis | 50 mg every 12 hours, or 100 mg every 24 hours |
Treatment with allopurinol tablets has not been studied in pediatric patients with severe renal impairment (eGFR < 20 mL/min) or on dialysis. There is insufficient information to establish dosing for allopurinol tablets in pediatric patients with renal impairment. In these patients, consider the risks and potential benefits before initiating treatment with allopurinol tablets
- See complete information in the Full Prescribing Information (FPI).
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- Adults: 300 mg to 800 mg orally daily.
- Pediatric patients: 100 mg/m2 orally every 8 hours to 12 hours (10 mg/kg/day, maximum 800 mg/day)
- See complete information in the FPI. (
Initiate therapy with allopurinol tablets 24 hours to 48 hours before the start of chemotherapy known to cause tumor cell lysis. Administer fluids sufficient to yield a daily urinary output of at least 2 liters in adults (at least 100 mL/m2/hour in pediatric patients) with a neutral or, preferably, slightly alkaline urine.
The recommended dosage of allopurinol tablets are:
• Adult patients – 300 mg to 800 mg orally daily
• Pediatric patients - 100 mg/m2orally every 8 hours to 12 hours (10 mg/kg/day, maximum 800 mg/day). In patients with body surface area < 0.5 m2, consider using an alternative allopurinol formulation.
The dosage of allopurinol tablets to maintain normal or near-normal serum uric acid varies with the severity of the disease. Monitor serum uric acid levels at least daily and administer allopurinol tablets at a dose and frequency to maintain the serum uric acid within the normal range. Discontinue allopurinol tablets when the risk of tumor lysis has abated (2 days to 3 days from start of chemotherapy). For complete dosage recommendations for patients with renal impairment, see Table 2
The recommended initial dosages of allopurinol tablets in adult patients with renal impairment are shown in Tables 1 and 2
The recommended initial dosages in adult patients with gout with impaired kidney function are shown in Table 1
Initiate treatment with a lower dose of allopurinol tablets and increase the dose gradually in 50 mg/day increments every 2 weeks to 4 weeks in patients with renal impairment to decrease the risk of drug induced serious adverse reactions. Use the lowest dose possible to achieve the desired effect on serum and/or urine uric acid. Monitor kidney function in gout patients with chronic kidney disease closely when initiating treatment with allopurinol tablets and decrease or withdraw the drug if increased abnormalities in kidney function appear and persist.
| eGFR | Initial Dosage |
| > 60 mL/minute | No dosage modification |
| > 30 to 60 mL/minute | 50 mg daily |
| > 15 to 30 mL/minute | 50 mg every other day |
| 5 to 15 mL/minute | 50 mg twice weekly |
| < 5 mL/minute | 50 mg once weekly |
The maximum dosage that should be used in patients with various levels of renal impairment is not defined at different eGFR levels.
Data are insufficient to provide dosage recommendations for the treatment of recurrent calcium oxalate calculi in patients with renal impairment. Allopurinol and its metabolites are excreted by the kidney, and accumulation of the drug can occur in renal failure
The recommended dosage of allopurinol tablets for the management of hyperuricemia associated with cancer therapy in adult patients with renal impairment is shown in Table 2
| eGFR | Recommended Dosage |
| > 20 mL/min to 60 mL/min | No dosage modification |
| 10 mL/min to 20 mL/min | 200 mg/day |
| < 10 mL/min | 100 mg/day |
| On dialysis | 50 mg every 12 hours, or 100 mg every 24 hours |
Treatment with allopurinol tablets has not been studied in pediatric patients with severe renal impairment (eGFR < 20 mL/min) or on dialysis. There is insufficient information to establish dosing for allopurinol tablets in pediatric patients with renal impairment. In these patients, consider the risks and potential benefits before initiating treatment with allopurinol tablets
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The recommended dosage for the management of recurrent calcium oxalate stones in hyperuricosuric patients is 200 mg to 300 mg orally daily in divided doses or as the single equivalent. This dose may be adjusted depending upon the resultant control of the hyperuricosuria based upon subsequent 24-hour urinary urate determinations.
• Dosage in Patients with Renal Impairment: See FPI for dosage modifications in patients with renal impairment. (
The recommended initial dosages of allopurinol tablets in adult patients with renal impairment are shown in Tables 1 and 2
The recommended initial dosages in adult patients with gout with impaired kidney function are shown in Table 1
Initiate treatment with a lower dose of allopurinol tablets and increase the dose gradually in 50 mg/day increments every 2 weeks to 4 weeks in patients with renal impairment to decrease the risk of drug induced serious adverse reactions. Use the lowest dose possible to achieve the desired effect on serum and/or urine uric acid. Monitor kidney function in gout patients with chronic kidney disease closely when initiating treatment with allopurinol tablets and decrease or withdraw the drug if increased abnormalities in kidney function appear and persist.
| eGFR | Initial Dosage |
| > 60 mL/minute | No dosage modification |
| > 30 to 60 mL/minute | 50 mg daily |
| > 15 to 30 mL/minute | 50 mg every other day |
| 5 to 15 mL/minute | 50 mg twice weekly |
| < 5 mL/minute | 50 mg once weekly |
The maximum dosage that should be used in patients with various levels of renal impairment is not defined at different eGFR levels.
Data are insufficient to provide dosage recommendations for the treatment of recurrent calcium oxalate calculi in patients with renal impairment. Allopurinol and its metabolites are excreted by the kidney, and accumulation of the drug can occur in renal failure
The recommended dosage of allopurinol tablets for the management of hyperuricemia associated with cancer therapy in adult patients with renal impairment is shown in Table 2
| eGFR | Recommended Dosage |
| > 20 mL/min to 60 mL/min | No dosage modification |
| 10 mL/min to 20 mL/min | 200 mg/day |
| < 10 mL/min | 100 mg/day |
| On dialysis | 50 mg every 12 hours, or 100 mg every 24 hours |
Treatment with allopurinol tablets has not been studied in pediatric patients with severe renal impairment (eGFR < 20 mL/min) or on dialysis. There is insufficient information to establish dosing for allopurinol tablets in pediatric patients with renal impairment. In these patients, consider the risks and potential benefits before initiating treatment with allopurinol tablets
Allopurinol Tablets have functional scoring and are available in the following strengths:
- 100 mg: White to off white scored, flat cylindrical tablet with "I" and '135' on either side of the break line on one side and plain on other side.
- 300 mg: Peach, scored, flat cylindrical tablet with "I" and '136' on either side of the break line on one side and plain on other side.
• Pregnancy: May cause fetal harm. (
Based on findings in animals, allopurinol tablets may cause fetal harm when administered to a pregnant woman. Adverse developmental outcomes have been described in exposed animals
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.
Experience with allopurinol tablets during human pregnancy has been limited partly because women of reproductive age rarely require treatment with allopurinol tablets. 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.
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/m2basis). 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/m2basis) 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.
• Lactation: Advise not to breastfeed. (
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 tablets and for one week after the last dose.
Allopurinol Tablets are contraindicated in patients with a history of hypersensitivity reaction 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. (
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
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
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
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.
• Gout Flares: May occur during initiation of treatment. Concurrent prophylactic treatment with colchicine or anti-inflammatory agents is recommended. (
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
• Nephrotoxicity: Allopurinol may affect kidney function. Patients with decreased kidney function require lower doses of allopurinol tablets. (
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/m2/day (or at least 100 mL/m2/hour) in pediatric patients
• Hepatoxicity: Cases of reversible hepatotoxicity have occurred. If signs and symptoms of hepatotoxicity develop, evaluate liver function. (
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.
• Myelosuppression: Bone marrow suppression has been reported with allopurinol. (
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
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
• Potential Effect on Driving and Use of Machinery: Drowsiness, somnolence and dizziness have been reported in patients taking allopurinol tablets. (
Drowsiness, somnolence and dizziness have been reported in patients taking allopurinol tablets
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.