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Allopurinol (Monograph)

Brand names: Aloprim, Zyloprim
Drug class: Antigout Agents
- Xanthine Oxidase Inhibitors
VA class: MS400
CAS number: 315-30-0

Medically reviewed by on Nov 8, 2023. Written by ASHP.


Xanthine oxidase inhibitor; structural isomer of hypoxanthine.

Uses for Allopurinol


Reduction of serum and urinary uric acid concentrations in primary and secondary gout. In early uncomplicated gout, preferred over uricosurics in patients with urinary uric acid excretion >900 mg daily and in those with gouty nephropathy, urinary tract stones or obstruction, or azotemia.

Management of gout when uricosuric agents cannot be used because of adverse effects, allergy, or inadequate response; when there are visible tophi or radiographic evidence of uric acid deposits and stones; or when serum urate concentrations exceed 8.5–9 mg/dL and patient has family history of tophi and low urate excretion.

Management of primary or secondary gouty nephropathy with or without secondary oliguria.

Not recommended for management of asymptomatic hyperuricemia; however, some clinicians have suggested that therapy be initiated when serum urate concentrations exceed 9 mg/dL (by colorimetric method) because these concentrations often are associated with increased joint changes and renal complications.

Of no value in the treatment of acute gout attacks (due to lack of analgesic or anti-inflammatory activity).

Chemotherapy-induced Hyperuricemia

A component of therapy (with urinary alkalinization and IV hydration) in patients with leukemia, lymphoma, and solid tumor malignancies who are undergoing cancer therapy expected to result in tumor lysis and subsequent elevations of serum and urinary uric acid concentrations.

Oral allopurinol may be slower and less effective in decreasing plasma uric acid concentrations than IV rasburicase.

Recurrent Renal Calculi

Management of recurrent calcium oxalate renal calculi in males and females whose urinary urate excretion exceeds 800 and 750 mg daily, respectively.

Prevention of uric acid renal calculi in patients with history of recurrent stone formation.

Other Uses

Has been used to reduce hyperuricemia secondary to glucose-6-phosphate dehydrogenase deficiency [off-label], Lesch-Nyhan syndrome [off-label], polycythemia vera [off-label], or sarcoidosis [off-label] or secondary to administration of thiazides [off-label] or ethambutol.

Allopurinol Dosage and Administration



Chemotherapy-induced Hyperuricemia

Pharmacogenetic Testing


Administer orally or by IV infusion.

Oral Administration

Usually administer orally once daily. If oral dose >300 mg, administer in divided doses.

Administration after meals may minimize adverse GI effects.

IV Infusion

For solution and drug compatibility information, see Stability under Compatibility.


Reconstitute vial containing allopurinol sodium equivalent to 500 mg of allopurinol with 25 mL of sterile water for injection to provide a solution containing 20 mg/mL of allopurinol. Should be diluted further before IV administration.


Dilute concentrate containing allopurinol 20 mg/mL with a compatible IV solution (see Solution Compatibility under Stability) to a final concentration of ≤6 mg/mL. Do not use diluent containing sodium bicarbonate.

Rate of Administration

Administer daily dosage by continuous infusion or in equally divided intermittent IV infusions at 6-, 8-, or 12-hour intervals. Infusion rate depends on volume of infusate.


Available as allopurinol (oral) or allopurinol sodium (for IV use); dosage is expressed in terms of allopurinol.

Pediatric Patients

Chemotherapy-induced Hyperuricemia

Children <6 years of age: Initially, 150 mg daily.

Children 6–10 years of age: Initially, 300 mg daily.

Adjust dosage after about 48 hours according to patient response.


Children ≤10 years of age: Initial dosage of 200 mg/m2 daily.

Children >10 years of age: 200–400 mg/m2 daily.



Use low initial dosage to reduce possibility of early flare-up of acute gouty attacks and because some data suggest that higher initial dosages may be associated with increased risk of severe hypersensitivity reactions. Gradually increase dosage to achieve target serum urate concentrations (<6 mg/dL) or until maximum recommended dosage is reached.

Manufacturers recommend initial dosage of 100 mg daily. May increase dosage by 100 mg weekly to achieve target serum urate concentration or until maximum recommended dosage of 800 mg daily is reached. Manufacturers state usual dosage is 200–300 mg daily in patients with mild gout and 400–600 mg daily in those with moderately severe tophaceous gout. After serum urate concentrations are controlled, manufacturers state dosage reduction may be possible; minimum effective dosage is 100–200 mg daily.

Some experts recommend initial dosage of 100 mg or less daily; increase dosage every 2–5 weeks in increments of 100 mg daily to achieve target serum urate concentrations or until maximum dosage of 800–900 mg daily is reached.

Although a dosage of 300 mg daily is commonly used, up to one-half of patients with normal renal function will not achieve target serum urate concentrations at this dosage. In some studies utilizing dosages up to 600–800 mg daily, 75–80% of patients achieved target serum urate concentrations.

Chemotherapy-induced Hyperuricemia

600–800 mg daily for 2–3 days.


200–400 mg/m2 daily.

Recurrent Calcium Oxalate Renal Calculi

Initially, 200–300 mg daily. Titrate dosage based on 24-hour urinary urate determinations.

Prescribing Limits

Pediatric Patients


Children >10 years of age: Maximum 600 mg daily.



Maximum 800–900 mg daily.


Maximum 600 mg daily.

Special Populations

Renal Impairment


Various dosing strategies have been recommended to minimize risk of hypersensitivity reactions. Low initial dosage recommended to reduce such risk; the relationship to maintenance dosage in renal impairment is more controversial. Uncertainty is reflected in lack of consensus on dosage in renal impairment. (See Hypersensitivity Reactions under Cautions.)

Dosages, including initial dosage, should be lower than those used in patients with normal renal function.

Manufacturers state that dosages in Table 1 may be adequate.

Table 1. Manufacturer-recommended Oral Maintenance Dosage in Patients with Renal Impairment

Clcr (mL/minute)

Maintenance Dosage


200 mg daily


≤100 mg daily


Increase dosage interval (e.g., 300 mg twice weekly)

Some clinicians have recommended alternative Clcr-based maintenance dosages (see Table 2). Although widely adopted, this strategy frequently fails to reduce urate concentrations to target levels; evidence that this strategy reduces risk of hypersensitivity reactions in patients who tolerate low initial dosages of allopurinol is lacking. More recent data suggest dosage can be increased safely beyond these Clcr-based maintenance dosages, with greater reduction of serum urate concentrations.

Table 2. Clcr-based Oral Maintenance Dosage in Patients with Renal Impairment150

Clcr (mL/minute)

Maintenance Dosage


250 mg daily


200 mg daily


150 mg daily


100 mg daily


100 mg every 2 days


100 mg every 3 days

ACR and some clinicians recommend initial dosage of 50 mg daily in patients with stage 4 or worse chronic kidney disease (Clcr <30 mL/minute) based on data suggesting initial dosage is a risk factor for hypersensitivity reactions. Adjust dosage in increments of 50–100 mg every 2–5 weeks to achieve target serum urate concentration. ACR and some other clinicians state dosage may be increased to >300 mg daily, provided patients receive appropriate education and are monitored regularly for hypersensitivity reactions or other adverse effects.

Other experts and clinicians recommend even lower eGFR-based initial dosages (see Table 3), followed by gradual increase in dosage (e.g., in 50-mg increments at intervals of approximately every 4 weeks). These experts state maximum dosage should be lower than in patients without renal impairment, but target serum urate concentrations should be the same.

Table 3. GFR-based Oral Dosages for Initiation of Allopurinol Therapy in Renal Impairment

Estimated GFR (mL/minute per 1.73 m2)

Initial Dosage


50 mg weekly


50 mg twice weekly


50 mg every 2 days


50 mg daily


50 and 100 mg on alternating days


100 mg daily

Table 4. Manufacturer-recommended Maintenance IV Dosage in Patients with Renal Impairment152

Clcr (mL/minute)

Maintenance Dosage


200 mg daily


100 mg daily


100 mg at extended intervals

Cautions for Allopurinol




Hepatic Effects

Hepatotoxic reactions and elevations of serum transaminase or alkaline phosphatase concentrations reported.

Perform liver function tests (especially in patients with preexisting liver disease) before and periodically during therapy, particularly during initial months of therapy.

If anorexia, weight loss, or pruritus develops, assess liver function.

CNS Effects

Drowsiness may occur; performance of activities requiring mental alertness may be impaired.

Sensitivity Reactions

Hypersensitivity Reactions

Serious, sometimes fatal, hypersensitivity reactions reported in approximately 0.1–0.4% of patients receiving allopurinol.

Hypersensitivity reactions (also referred to as severe cutaneous adverse reactions [SCARs] ) include a spectrum of cutaneous reactions and systemic manifestations, including toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), and allopurinol hypersensitivity syndrome; systemic manifestations may include fever, leukocytosis, atypical circulating lymphocytes, eosinophilia, lymphadenopathy, vasculitis, and organ system involvement (e.g., hepatitis, acute renal failure). Onset typically occurs within weeks or months following initiation of therapy, but may occur later.

Mortality rate of severe hypersensitivity reactions is up to 20–30%. Discontinue allopurinol immediately at first appearance of rash or any sign that may indicate hypersensitivity reaction; early diagnosis and drug discontinuance may improve prognosis.

Presence of the HLA-B*5801 allelic variant is strongly associated with severe allopurinol-induced hypersensitivity reactions, particularly in certain Asian populations. (See Pharmacogenomics of Allopurinol-induced Hypersensitivity Reactions under Cautions.) However, other genetic or nongenetic factors (e.g., renal impairment, thiazide diuretic use, recent initiation of allopurinol therapy, high initial allopurinol dosage) also are associated with increased risk.

Hypersensitivity reactions may occur more frequently in patients with renal impairment receiving allopurinol and thiazide diuretics; use these drugs with caution and careful monitoring in this population. (See Specific Drugs under Interactions.)

Some data suggest that high initial dosages are associated with increased risk of hypersensitivity reactions and that initiating allopurinol at a low dosage adjusted for renal function may reduce risk.

Relationship between allopurinol maintenance dosage, particularly in patients with renal impairment, and hypersensitivity reactions is more controversial. This uncertainty is reflected in lack of consensus on allopurinol dosage in renal impairment. (See Renal Impairment under Dosage and Administration.)

Pharmacogenomics of Allopurinol-induced Hypersensitivity Reactions

Presence of HLA-B*5801, an inherited allelic variant of the HLA-B gene, is strongly associated with severe hypersensitivity reactions to allopurinol, particularly in certain Asian populations (Han Chinese, Korean, Thai).

Estimated frequency of HLA-B*5801 is up to 20%, approximately 12%, or 6–15% in individuals of Han Chinese, Korean, or Thai ancestry, respectively. Estimated frequency in Japanese and European populations is 1–2%. In the US, estimated frequency is approximately 7% in individuals of Asian ancestry, 3–6% in African-Americans, and <2% in Caucasians and Hispanics.

Strength of the association between HLA-B*5801 and hypersensitivity reactions appears to vary according to frequency of HLA-B*5801 expression. In a Taiwanese study, HLA-B*5801 was present in 100% of Han Chinese patients with allopurinol hypersensitivity syndrome, SJS, or TEN, compared with 15% of allopurinol-tolerant patients and 20% of population controls. Strong associations also reported in Thai and Korean populations. More modest associations observed in Japanese and European Caucasian populations, with HLA-B*5801 present in approximately 36–56 and 55–64%, respectively, of patients with severe hypersensitivity reactions.

Presence of HLA-B*5801 is not predictive of less severe dermatologic reactions (e.g., simple or mild rash, maculopapular eruption) to allopurinol.

Consider pharmacogenetic testing for HLA-B*5801 prior to initiation of allopurinol therapy in certain high-risk populations in which this allele is known to be highly prevalent. (See Pharmacogenetic Testing under Dosage and Administration.)

Experts recommend avoiding allopurinol in patients who have tested positive for HLA-B*5801. If allopurinol use cannot be avoided and the benefits are considered to outweigh the risks, more intensive monitoring is required.

Cost-effectiveness analyses conducted mostly in Asia suggest screening for HLA-B*5801 prior to initiating allopurinol would be cost-effective in certain populations (e.g., Taiwanese and Thai populations, Korean patients with chronic renal insufficiency). Prospective studies suggest that screening of Taiwanese patients of Han Chinese ancestry and Korean patients with chronic renal insufficiency reduces incidence of allopurinol-induced severe adverse cutaneous reactions below historically predicted rates. Additional studies needed to assess role of screening in other populations with lower or ill-defined frequencies of the allele. Some clinicians suggest screening of African-Americans may be cost-effective.

Regardless of genotyping results, closely monitor patients receiving allopurinol.

General Precautions

Acute Gout

Allopurinol is of no value in the treatment of acute gout attacks; will prolong and exacerbate inflammation during the acute phase.

May increase frequency of acute attacks during the first 6–12 months of therapy; therefore, administer prophylactic doses of colchicine concurrently during the first 3–6 months of therapy.


Maintain sufficient fluid intake and a neutral or slightly alkaline urine to avoid possible formation of xanthine calculi and to prevent renal precipitation of urates in patients receiving concomitant uricosuric agents.

Adequate Laboratory Monitoring

Perform liver and renal function tests and complete blood cell counts before and periodically during therapy (particularly during initial months of therapy).

Specific Populations


Category C.


Allopurinol and oxypurinol distribute into milk; use with caution in nursing women.

Pediatric Use

Rarely indicated in children except in those with hyperuricemia secondary to neoplastic disease, cancer chemotherapy, or genetic disorders of purine metabolism.

Safety and efficacy profile for allopurinol sodium for injection in children is similar to that in adults.

Geriatric Use

Select dosage carefully due to age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy. Elimination may be prolonged due to age-related changes in renal function.

Numbers of geriatric patients in clinical studies of IV allopurinol sodium insufficient to determine whether they respond differently than younger adults; other clinical experience identified no difference in response.

Renal Impairment

Increased half-life. Reduce dosage. (See Renal Impairment under Dosage and Administration.)

Monitor closely; if deterioration in renal function occurs and persists, reduce dosage or discontinue drug.

Possible increased risk of rash.

Increased risk of severe hypersensitivity reactions. (See Hypersensitivity Reactions under Cautions.) Concomitant therapy with a thiazide diuretic in patients with renal impairment may increase risk of allopurinol-induced hypersensitivity reactions; use with caution in such patients and observe closely. (See Specific Drugs under Interactions.)

Common Adverse Effects

Oral therapy: Pruritic maculopapular rash.

IV therapy: Rash, renal failure/impairment, nausea, vomiting.

Drug Interactions

Does not inhibit hepatic microsomal enzymes.

Specific Drugs





Potential for increased serum urate concentrations

May need to increase allopurinol dosage

Ampicillin and amoxicillin

Increased incidence of rash in patients with hyperuricemia

Clinical importance not determined; avoid concomitant use, if possible

Anticoagulants (e.g., dicumarol, warfarin)

Inhibition of dicumarol metabolism; not shown to substantially potentiate anticoagulant effect of warfarin

In patients receiving dicumarol and allopurinol, monitor PT and observe patient for increased anticoagulant effects


Inhibition of azathioprine metabolism; possible increase in toxic effects (including bone marrow depression)

Decrease azathioprine dosage initially by 66–75%; base subsequent dosage adjustments on patient response and toxic effects


Potential for adverse hepatorenal reactions; competition with chlorpropamide for renal tubular secretion

Observe for signs of excessive hypoglycemia, especially in patients with renal impairment


Potential for bone marrow depression; mechanism not known


Increased blood concentrations of cyclosporine

Monitor blood concentration and consider dosage adjustments of cyclosporine


Potential for increased serum urate concentrations

May need to increase allopurinol dosage


Increased didanosine peak plasma concentration and AUC, particularly in patients with renal impairment; possible increased didanosine toxicity

Concomitant use contraindicated

Diuretics (e.g., thiazides, furosemide, ethacrynic acid)

Potential for increased serum urate concentrations; potential for increased serum oxypurinol concentrations and increased risk of allopurinol toxicity, including hypersensitivity reactions, particularly in patients with renal impairment

Depending on indication for diuretic, consider use of alternative agents (e.g., other antihypertensives)

If concomitant use necessary, increase intensity of monitoring for hypersensitivity reactions, particularly with thiazide use in patients with chronic renal impairment

Monitor renal function; adjust dosage of allopurinol if necessary


Inhibition of mercaptopurine metabolism; possible increase in toxic effects (including bone marrow depression)

Decrease mercaptopurine dosage initially by 66–75%; base subsequent dosage adjustments on patient response and toxic effects


Potential for increased serum urate concentrations

May need to increase allopurinol dosage


Increased uric acid excretion; possible reduction in inhibition of xanthine oxidase by oxypurinol; possible renal precipitation of oxypurines

May use smaller doses of each drug

Allopurinol Pharmacokinetics



About 80–90% absorbed following oral administration; peak plasma concentrations of allopurinol and oxypurinol are reached in 1.5 and 4.5 hours, respectively.

Following IV infusion over 30 minutes, peak plasma concentrations of allopurinol and oxypurinol are reached in about 30 minutes and 4 hours, respectively.


In patients with gout, serum urate concentrations begin to decrease slowly within 24–48 hours; minimum concentrations may not be reached for about 1–3 weeks. Because of continued mobilization of urate deposits, substantial reduction of uric acid may be delayed 6–12 months or may not occur in some patients.


After discontinuance of therapy, serum urate concentrations return to pretreatment levels within 1–2 weeks.

Special Populations

In geriatric patients (71–93 years of age), peak plasma concentrations and AUC of oxypurinol following oral allopurinol dose are 50–60% higher than in younger adults (24–35 years of age); apparently related to changes in renal function in older population.



Uniformly distributed in total tissue water, except in the brain where concentrations are approximately 50% of those in other tissues. Allopurinol and oxypurinol are distributed into milk.

Plasma Protein Binding

Allopurinol and oxypurinol are not bound to plasma proteins.



Rapidly metabolized by xanthine oxidase; metabolized principally to an active metabolite, oxypurinol.

Elimination Route

Excreted in urine as oxypurinol (about 70%) and in feces as unchanged drug (about 20%) within 48–72 hours.

Allopurinol and oxypurinol are dialyzable.


1–3 and 18–30 hours for allopurinol and oxypurinol, respectively.

Special Populations

In patients with severe renal impairment or decreased urate clearance, plasma half-life of oxypurinol is greatly prolonged.

Patients genetically deficient in xanthine oxidase are unable to convert allopurinol to oxypurinol.





15–25°C in dry place; protect from light.


Powder for Injection


Store diluted allopurinol sodium solutions containing ≤6 mg/mL of allopurinol at 20–25°C; use within 10 hours of reconstitution. Do not refrigerate reconstituted and/or diluted solutions.



Solution Compatibility152


Dextrose 5% in water

Sodium chloride 0.9%

Drug Compatibility
Y-Site CompatibilityHID


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Advice to Patients


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name



Dosage Forms


Brand Names




100 mg*

Allopurinol Tablets

Zyloprim (scored)


300 mg*

Allopurinol Tablets

Zyloprim (scored)


* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Allopurinol Sodium


Dosage Forms


Brand Names



For injection, for IV infusion only

500 mg (of allopurinol)*

Allopurinol Sodium for Injection



AHFS DI Essentials™. © Copyright 2024, Selected Revisions November 18, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

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