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Allopurinol: Pediatric drug information

Allopurinol: Pediatric drug information
(For additional information see "Allopurinol: Drug information" and see "Allopurinol: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Aloprim;
  • Zyloprim
Brand Names: Canada
  • AG-Allopurinol;
  • APO-Allopurinol;
  • GEN-Allopurinol;
  • JAMP-Allopurinol;
  • Mar-Allopurinol;
  • Zyloprim
Therapeutic Category
  • Antigout Agent;
  • Uric Acid Lowering Agent
Dosing: Pediatric

Note: Dosing presenting in multiple formats (mg/m2/dose, mg/m2/day, mg/kg/day, and a fixed mg dose); take extra precautions to ensure accuracy. Before prescribing allopurinol, consider testing for the HLA-B*5801 allele in patients at elevated risk for developing severe cutaneous adverse reactions (SCAR) (including Koreans with CKD ≥ stage 3 and all patients of Han Chinese or Thai descent). A negative HLA-B*5801 genetic test, however, does not entirely rule out the possibility of allopurinol-associated SCAR, so patients should still be appropriately monitored for SCAR, as well as other forms of hypersensitivity (Ref).

Hyperuricemia associated with chemotherapy management

Hyperuricemia associated with chemotherapy management: Maintain adequate hydration; begin allopurinol 1 to 2 days before initiation of induction chemotherapy; may continue for 3 to 7 days after chemotherapy (Ref); daily doses >300 mg should be administered in divided doses:

Oral:

Manufacturer's labeling:

Children <6 years: 150 mg daily.

Children 6 to 10 years: 300 mg daily.

Children >10 years and Adolescents: 600 to 800 mg daily for 2 to 3 days in 2 to 3 divided doses.

Alternate dosing: Tumor lysis syndrome; intermediate-risk: Limited data available (Ref): Infants, Children, and Adolescents:

Weight-directed dosing: 10 mg/kg/day divided every 8 hours; maximum daily dose: 800 mg/day.

BSA-directed dosing: 50 to 100 mg/m2/dose every 8 hours; maximum daily dose: 300 mg/m2/day.

IV: For patients unable to tolerate oral therapy (BSA-directed dosing):

Manufacturer's labeling: Children and Adolescents: Initial: 200 mg/m2/day administered once daily or in equally divided doses at 6-, 8-, or 12-hour intervals.

Alternate dosing: Tumor lysis syndrome; intermediate-risk: Limited data available: Infants, Children, and Adolescents: 200 to 400 mg/m2/day in 1 to 3 divided doses; maximum daily dose: 600 mg/day (Ref).

Hyperuricemia associated with inborn errors of purine metabolism

Hyperuricemia associated with inborn errors of purine metabolism (Lesch-Nyhan syndrome): Limited data available: Oral: Infants, Children, and Adolescents: Initial: 5 to 10 mg/kg/day; adjust dose to maintain a high-normal serum uric acid concentration and a urinary uric acid/creatinine ratio <1; reported range: 3.7 to 9.7 mg/kg/day; usual maximum daily dose: 600 mg/day (Ref).

Recurrent calcium oxalate renal stones

Recurrent calcium oxalate renal stones (including glycogen storage disease): Limited data available: Oral: Children and Adolescents: 4 to 10 mg/kg/day in divided doses 3 to 4 times daily; maximum daily dose: 300 mg/day (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Allopurinol and oxypurinol are dialyzable.

Infants, Children, and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling; however, the following guidelines have been used by some clinicians:

Management of hyperuricemia associated with chemotherapy: Oral, IV:

Aronoff 2007:

GFR 30 to 50 mL/minute/1.73 m2: Administer 50% of normal dose.

GFR 10 to 29 mL/minute/1.73 m2: Administer 50% of normal dose.

GFR <10 mL/minute/1.73 m2: Administer 30% of normal dose.

Intermittent hemodialysis: Administer 30% of normal dose.

Peritoneal dialysis: Administer 30% of normal dose.

Continuous renal replacement therapy (CRRT): Administer 50% of normal dose.

Coiffier 2008: Dosage reduction of 50% is recommended in renal impairment.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Adult

(For additional information see "Allopurinol: Drug information")

Note: Before prescribing allopurinol, testing for the HLA-B*5801 allele in patients at elevated risk for developing severe cutaneous adverse reactions (SCAR) (patients of Asian descent [eg, Korean, Han Chinese, Thai] and African American patients) is recommended (Ref). A negative HLA-B*5801 genetic test, however, does not entirely rule out the possibility of allopurinol-associated SCAR, so patients should still be appropriately monitored for SCAR, as well as other forms of hypersensitivity (Ref). Use should be avoided in any patient testing positive for the allele (Ref).

Gout, treatment

Gout, treatment (chronic urate-lowering therapy): Oral: Note: Urate-lowering therapy may be initiated during a gout flare or after the flare subsides; concomitant pharmacologic prophylaxis with colchicine, NSAIDS, or a glucocorticoid is recommended for at least the first 3 to 6 months to decrease flare activity (Ref).

Initial: 100 mg once daily (Ref).

Dosage adjustments: Titrate in 100 mg increments every 2 to 4 weeks to achieve the desired serum uric acid level (Ref).

Maintenance: Doses ≥300 mg/day are usually needed to reach the desired uric acid target; doses up to 800 mg/day may be required (Ref).

Maximum: 800 mg/day

Frequency of administration: Once daily in a single dose or in 2 or 3 divided doses. Note: The manufacturer's labeling recommends doses >300 mg be given in divided doses; however, most experts prescribe a single daily dose, regardless of total dose administered, except during a brief period (eg, when initiating or titrating therapy) when divided doses may help improve GI tolerability (Ref).

Nephrolithiasis, prevention of recurrent calcium or uric acid stones

Nephrolithiasis, prevention of recurrent calcium or uric acid stones:

Due to calcium oxalate stones: Patients with hyperuricosuria (who continue to have active disease despite attempted dietary modification): Oral: 300 mg/day, usually given in a single daily dose but may be given in 2 or 3 divided doses, if needed, to improve GI tolerability (Ref).

Due to uric acid stones (off-label use): Oral: 300 mg/day, usually given in a single daily dose but may be given in 2 or 3 divided doses, if needed, to improve GI tolerability; use is reserved for patients who continue to have active disease despite urinary alkalinization therapy and increased hydration (Ref).

Tumor lysis syndrome, prevention

Tumor lysis syndrome, prevention: Patients at intermediate risk for tumor lysis syndrome (TLS) and without preexisting hyperuricemia (serum uric acid ≥8 mg/dL [476 micromol/L]):

Note: Aggressive IV hydration should always be initiated prior to cytotoxic therapy in patients at elevated risk for TLS (Ref).

Oral: 300 mg/m2/day or 10 mg/kg/day, given in 3 divided doses every 8 hours (maximum: 800 mg/day). Begin therapy 1 to 2 days before the start of induction chemotherapy and may continue for up to 3 to 7 days after chemotherapy until normalization of laboratory evidence of TLS (eg, serum uric acid, serum LDH) (Ref).

IV: 200 to 400 mg/m2/day, given in a single daily dose or in 2 or 3 divided doses (maximum: 600 mg/day). Begin therapy 1 to 2 days before the start of induction chemotherapy and may continue for 3 to 7 days after chemotherapy until normalization of laboratory evidence of TLS (eg, serum uric acid, serum LDH) (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Note: Renal impairment, particularly when a higher allopurinol starting dose and/or concomitant diuretics are used, is a risk factor for allopurinol hypersensitivity syndrome (AHS), a rare but potentially life-threatening systemic syndrome (Ref). In addition, the HLA-B*5801 allele is associated with an increased risk of allopurinol-induced severe cutaneous adverse reactions; patients of Korean, Han Chinese, or Thai descent are at increased risk for carrying this allele. Avoid allopurinol in any patient testing positive for this allele (Ref).

To minimize the risk of AHS in patients with renal impairment (in the absence of the HLA-B*5801 allele or in those not at high risk for carrying this allele), the following dosage adjustments are recommended:

Gout, treatment (chronic urate-lowering therapy): Oral:

Altered kidney function:

eGFR >60 mL/minute: No dosage adjustment necessary (Ref).

eGFR ≤60 mL/minute:

Initial: <100 mg daily (Ref); to lower the risk of AHS, some experts recommend not exceeding an initial dose of ~1.5 mg of allopurinol per mL/minute of eGFR (eg, for an eGFR of 50 mL/minute/1.73 m2, the initial dose should not exceed 75 mg daily; see table for suggested initial doses) (Ref).

Allopurinol: Suggested Initial Doses in Kidney Impairmenta

eGFR mL/minute/1.73 m2

Suggested initial dose

aACR (FitzGerald 2020); Perez-Ruiz 2022; Stamp 2012; Vargas-Santos 2017.

>30 to 60

50 mg daily

>15 to 30

50 mg every other day

5 to 15

50 mg twice weekly

<5

50 mg once weekly

Titration and maintenance: Gradually increase dose in ≤100 mg/day increments every 2 to 4 weeks; use of lower dose increments (ie, ≤50 mg/day) and longer intervals (ie, ≥4 weeks) may be preferred (Ref). Some experts delay the initial dose increase for 1 to 2 months until after peak risk for AHS has passed (Ref). Titrate to the minimum daily dose necessary to achieve goal urate-lowering effect. Doses >300 mg daily may be considered with appropriate patient education and monitoring for potential toxicity (eg, rash, pruritus, elevated transaminases) (Ref). If desired serum uric acid level cannot be achieved, conversion to an alternative agent may be considered (Ref).

Hemodialysis, intermittent (thrice weekly): Dialyzable (oxypurinol): ~39% to 50% (Ref).

Initial: 100 mg 3 times weekly administered post-dialysis (Ref).

Titration and maintenance: Gradually increase dose in ≤50 mg/day increments (eg, 150 mg 3 times weekly) every 2 to 5 weeks. Some experts delay the initial dose increase for 1 to 2 months until after peak risk for AHS has passed (Ref). Titrate to the minimum dose necessary to achieve goal urate-lowering effect (Ref). Doses >300 mg daily may be considered with appropriate patient education and monitoring for potential toxicity (eg, rash, pruritus, elevated transaminases) (Ref); doses up to ~400 mg daily have been reported (Ref).

Peritoneal dialysis:

Initial: 50 mg daily; gradually increase dose in ≤50 mg/day increments every 2 to 5 weeks; titrate to the minimum daily dose necessary to achieve goal urate-lowering effect (Ref). Some experts delay the initial dose increase for 1 to 2 months until after peak risk for AHS has passed (Ref). Doses >300 mg daily may be considered with appropriate patient education and monitoring for potential toxicity (eg, rash, pruritus, elevated transaminases) (Ref).

Nephrolithiasis, prevention of recurrent calcium or uric acid stones: Oral: Use a lower initial dose with gradual titration (Ref); for dosing guidance refer to gout treatment renal impairment dosing recommendations; not to exceed usual adult dose for nephrolithiasis.

Tumor lysis syndrome, prevention: IV, Oral: Dosage reduction of 50% is recommended in renal impairment (Ref).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous, as sodium [strength expressed as base]:

Generic: 500 mg (1 ea)

Solution Reconstituted, Intravenous, as sodium [strength expressed as base, preservative free]:

Aloprim: 500 mg (1 ea)

Generic: 500 mg (1 ea)

Tablet, Oral:

Zyloprim: 100 mg [scored]

Zyloprim: 300 mg [scored; contains corn starch, fd&c yellow #6(sunset yellow)alumin lake]

Generic: 100 mg, 300 mg

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Zyloprim: 100 mg, 200 mg, 300 mg

Generic: 100 mg, 200 mg, 300 mg

Administration: Pediatric

Note: Fluid intake should be sufficient to yield neutral or slightly alkaline (preferably) urine and a daily urine output of at least 2 L in adults.

Oral: Administer after meals with plenty of fluid

Parenteral: The rate of infusion is dependent upon the volume of the infusion; infuse maximum single daily doses (600 mg/day) over ≥30 minutes; whenever possible, therapy should be initiated at 12 to 24 hours (pediatric patients) or 24 to 48 hours (adults) before the start of chemotherapy known to cause tumor lysis (including adrenocorticosteroids) (Ref). Intravenous daily therapy can be administered as a single infusion or in equally divided doses at 6-, 8-, or 12-hour intervals.

Administration: Adult

Oral: Administer after meals.

IV: The rate of infusion depends on the volume of the infusion. IV daily dose can be administered as a single infusion or in equally divided doses at 6-, 8-, or 12-hour intervals (Ref).

Tumor lysis syndrome prevention: Administer aggressive fluids sufficient to maintain adequate hydration and urinary output; whenever possible, allopurinol therapy should be initiated 24 to 48 hours before the start of chemotherapy (and other treatments) known to cause tumor lysis (Ref).

Other indications: Administer fluids sufficient to yield daily urinary output of at least 2 L and to maintain a neutral or, preferably, slightly alkaline urine.

Storage/Stability

Powder for injection: Store intact vials at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Following preparation, IV solutions in NS or D5W should be stored at 20°C to 25°C (68°F to 77°F). Do not refrigerate reconstituted and/or diluted product. Must be administered within 10 hours of solution preparation.

Tablet: Store at 15°C to 25°C (59°F to 77°F). Store in a dry place. Protect from light.

Use

Oral: Management of hyperuricemia associated with cancer treatment for leukemia, lymphoma, or solid tumor malignancies (FDA approved in pediatric patients [age not specified] and adults); management of primary or secondary gout (acute attack, tophi, joint destruction, uric acid lithiasis, and/or nephropathy) (FDA approved in adults); management of recurrent calcium oxalate calculi (with uric acid excretion >800 mg/day in men and >750 mg/day in women) (FDA approved in adults); has also been used for treatment of hyperuricemia associated with inborn errors of purine metabolism (Lesch-Nyhan syndrome) and recurrent calcium oxalate calculi associated with glycogen storage disease.

IV: Management of hyperuricemia associated with cancer treatment for leukemia, lymphoma, or solid tumor malignancies who cannot tolerate oral therapy (FDA approved in children and adults).

Medication Safety Issues
Sound-alike/look-alike issues:

Allopurinol may be confused with Apresoline

Zyloprim may be confused with zolpidem, ZORprin, Zovirax

Adverse Reactions (Significant): Considerations
Acute gout attacks

Acute gout attacks have been reported during the early stages of allopurinol administration even when normal or optimal serum uric acid levels have been attained. Gout attacks generally decrease in duration and severity after several months of urate-lowering therapy (Ref).

Mechanism: Dose-related; related to the pharmacologic action. Decrease in serum urate leads to the dissolution of monosodium urate crystal deposits and dispersion of crystals, causing gout flares (Ref).

Onset: Varied; most likely to occur within first 6 months of treatment (Ref); risk is lower after 1 year of treatment (Ref).

Risk factors:

• Early in course of treatment (Ref)

• Initiating urate-lowering treatment without concurrent gout flare prophylaxis (Ref)

• Withdrawal of anti-inflammatory gout flare prophylaxis (Ref)

• Uric acid >6 mg/dL during treatment (Ref)

• Rapid decreases and/or greater reduction in uric acid (Ref)

• Persistence of tophi (Ref)

Hepatotoxicity

Most cases of acute hepatotoxicity with allopurinol are associated with drug reaction with eosinophilia and systemic symptoms (DRESS) and allopurinol hypersensitivity syndrome (Ref). May rarely occur without any features of DRESS (Ref). The pattern of liver enzyme elevations is usually hepatocellular or mixed, but can be cholestatic (Ref).

Mechanism: Non-dose-related; immunologic. DRESS syndrome is T-cell-mediated (Ref).

Onset: Varied; usually occur 1 to 5 weeks after initiation (Ref).

Risk factors:

• African-American race (Ref)

• Preexisting kidney disease (Ref)

Hypersensitivity reactions (delayed)

Allopurinol is associated with a variety of delayed hypersensitivity reactions (often termed allopurinol hypersensitivity syndrome [AHS]), ranging from mild maculopapular rash to severe cutaneous adverse reactions (SCAR), including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) (Ref).

Mechanism: Non-dose-related; immunologic. Delayed hypersensitivity reactions, including maculopapular eruptions and SCARs are T-cell-mediated (Ref).

Onset: Delayed hypersensitivity reactions: varied; usually occur 3 to 9 weeks after initiation (Ref), but may occur more rapidly (usually within 1 to 4 days) upon reexposure (Ref).

Risk factors:

• Presence of HLA-B*5801 allele is strongly associated with SCARs, especially with concomitant kidney impairment and in some Asian populations (Ref). HLA-A*3303 and HLA-C*0302 alleles are associated with SJS or TEN, especially in Asian populations (Ref)

• Dose (Ref)

• Kidney impairment: Correlated to delayed clearance of oxypurinol (metabolite of allopurinol) and potentially high levels of granulysin (Ref)

• Older adults (≥60 years of age), possibly due to kidney impairment (Ref)

• Females (Ref)

• Asymptomatic hyperuricemia, especially in patients with concomitant kidney or cardiovascular disease (Ref)

• Concomitant cardiovascular disease (Ref)

• Concomitant diuretic use: Although diuretic use has been associated with increased risk of allopurinol hypersensitivity reactions (Ref), some studies have not found an association between diuretic use and AHS (Ref)

• Cross-reactivity between allopurinol and febuxostat: Although there may be an increased risk of a skin reaction with febuxostat in patients with a history of reactions to allopurinol, whether this represents 2 separate reactions or cross-reactivity is not known (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

1% to 10%:

Dermatologic: Maculopapular rash (≤3%; pruritic), skin rash (≤2%)

Gastrointestinal: Nausea (1%), vomiting (≤1%)

Neuromuscular & skeletal: Gout (≤6%; acute)

Renal: Renal failure syndrome (≤1%)

<1%:

Cardiovascular: Bradycardia, edema, flushing, heart failure, hypertension, hypotension, low cardiac output, necrotizing angiitis, pericarditis, peripheral vascular disease, pulmonary embolism, septic shock, thrombophlebitis, vasculitis, vasodilation, ventricular fibrillation

Dermatologic: Alopecia, cellulitis, diaphoresis, ecchymoses, eczema, exfoliative dermatitis, furunculosis, lichen planus, onycholysis, purpuric rash, skin edema, Stevens-Johnson syndrome (Gupta 2019), toxic epidermal necrolysis (Hoyer 2021), urticaria, vesicobullous dermatitis

Endocrine & metabolic: Albuminuria, decreased libido, gynecomastia, hypercalcemia, hyperglycemia, hyperkalemia, hyperlipidemia, hypernatremia, hyperphosphatemia, hyperuricemia, hypervolemia, hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia, lactic acidosis, metabolic acidosis, water intoxication

Gastrointestinal: Abdominal pain, ageusia, anorexia, constipation, dysgeusia, dyspepsia, enlargement of abdomen, enlargement of salivary glands, flatulence, gastritis, gastrointestinal hemorrhage, hemorrhagic pancreatitis, intestinal obstruction, proctitis, stomatitis

Genitourinary: Glycosuria, hematuria, impotence, male infertility, oliguria, uremia, urinary tract infection

Hematologic & oncologic: Agranulocytosis, anemia, aplastic anemia, bone marrow aplasia, bone marrow depression, chronic myelocytic leukemia, disseminated intravascular coagulation, eosinophilia, eosinophilic fibrohistiocytic bone marrow lesion, hemolytic anemia, hemorrhage, hypoprothrombinemia, leukocytosis, leukopenia, lymphadenopathy, lymphocytosis, neutropenia, pancytopenia, reticulocytosis, splenomegaly, thrombocytopenia, tumor lysis syndrome

Hepatic: Cholestatic jaundice, granulomatous hepatitis, hepatic failure, hepatic necrosis, hepatomegaly (Childs 2012), hepatotoxicity (Chalasani 2021), hyperbilirubinemia, jaundice

Hypersensitivity: Drug reaction with eosinophilia and systemic symptoms (Chung 2015), facial edema, hypersensitivity angiitis, tongue edema

Infection: Infection, sepsis

Local: Injection-site reaction

Nervous system: Agitation, amnesia, asthenia, cerebral infarction, cerebrovascular accident, chills, coma, confusion, depression, dizziness, drowsiness, dystonia, headache, hypotonia, insomnia, malaise, mental status changes, myoclonus, neuritis, pain, paralysis, paresthesia, peripheral neuropathy, seizure, status epilepticus, tremor, twitching, vertigo

Neuromuscular & skeletal: Arthralgia, foot-drop, myalgia, myopathy

Ophthalmic: Amblyopia, cataract, conjunctivitis, iritis, macular retinitis, optic neuritis

Otic: Tinnitus

Renal: Nephritis (including interstitial nephritis) (Gelbart 1977)

Respiratory: Acute respiratory distress syndrome, apnea, asthma, bronchospasm, epistaxis, pharyngitis, respiratory failure, rhinitis, tachypnea

Miscellaneous: Fever

Frequency not defined:

Gastrointestinal: Diarrhea

Hepatic: Increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferase

Postmarketing:

Dermatologic: Sweet syndrome (Polimeni 2016)

Hematologic & oncologic: Pure red cell aplasia (Shankar 2003)

Hypersensitivity: Hypersensitivity reaction (allopurinol hypersensitivity syndrome; can be severe hypersensitivity reaction) (Chen 2005)

Contraindications

Severe hypersensitivity reaction to allopurinol or any component of the formulation.

Canadian labeling: Additional contraindications (not in the US labeling): Breastfeeding mothers and children (except those with cancer therapy-induced hyperuricemia or Lesch-Nyhan syndrome).

Note: To avoid the risk of severe cutaneous adverse reactions (SCAR), HLA-B*5801-positive patients should avoid allopurinol (Perez-Ruiz 2022; Saito 2016). The American College of Rheumatology recommends HLA-B*5801 screening in patients at elevated risk of SCAR, including patients of Asian descent (eg, Korean, Han Chinese, Thai) and African American patients (ACR [FitzGerald 2020]).

Warnings/Precautions

Concerns related to adverse effects:

• CNS effects: May occasionally cause drowsiness; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).

Disease-related concerns:

• Renal impairment: Dose reductions are recommended in patients with renal impairment; monitor closely. Some patients with preexisting renal disease or poor urate clearance have shown a rise in BUN with allopurinol. Patients with renal impairment should be carefully monitored during the early stages of allopurinol treatment; reduce the dose or withdraw therapy if increased renal function abnormalities appear and persist. Renal failure associated with allopurinol has been observed in patients with hyperuricemia secondary to neoplastic diseases. Concurrent conditions including multiple myeloma and congestive myocardial disease were present among patients whose renal dysfunction increased after allopurinol was begun. Renal failure is also frequently associated with gouty nephropathy. Albuminuria has been observed among patients who developed clinical gout following chronic glomerulonephritis and chronic pyelonephritis.

Other warnings/precautions:

• Hydration: For tumor lysis syndrome prevention, administer aggressive fluids sufficient to maintain adequate hydration and urinary output (Coiffier 2008). For other indications, fluid intake sufficient to yield a daily urinary output of at least 2 L and maintenance of a neutral or (preferably) a slightly alkaline urine are desirable in order to avoid possible formation of xanthine calculi due to allopurinol therapy and to help prevent renal urate precipitation in patients receiving concomitant uricosuric agents.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program

Aluminum Hydroxide: May decrease the serum concentration of Allopurinol. Management: Consider administering allopurinol 3 hours prior to aluminum hydroxide. Risk D: Consider therapy modification

Amoxicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Amoxicillin. Risk C: Monitor therapy

Ampicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Ampicillin. Risk C: Monitor therapy

Angiotensin-Converting Enzyme Inhibitors: May enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Risk C: Monitor therapy

AzaTHIOprine: Allopurinol may increase serum concentrations of the active metabolite(s) of AzaTHIOprine. More specifically, allopurinol may increase mercaptopurine serum concentrations and promote formation of active thioguanine nucleotides. Management: Reduce azathioprine dose to one third to one quarter of the usual dose if used with allopurinol, and monitor closely for systemic toxicity. Further dose reduction or alternative therapies should be considered for patients with low or absent TPMT activity. Risk D: Consider therapy modification

Bacampicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Bacampicillin. Risk C: Monitor therapy

Bendamustine: Allopurinol may enhance the adverse/toxic effect of Bendamustine. Specifically, the risk of severe skin reactions may be enhanced. Risk C: Monitor therapy

CarBAMazepine: Allopurinol may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy

Cyclophosphamide: Allopurinol may increase the serum concentration of Cyclophosphamide. Risk C: Monitor therapy

CycloSPORINE (Systemic): Allopurinol may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy

Didanosine: Allopurinol may increase the serum concentration of Didanosine. Risk X: Avoid combination

Doxofylline: Allopurinol may increase the serum concentration of Doxofylline. Risk C: Monitor therapy

Fluorouracil Products: Allopurinol may decrease serum concentrations of the active metabolite(s) of Fluorouracil Products. Risk X: Avoid combination

Loop Diuretics: May enhance the adverse/toxic effect of Allopurinol. Loop Diuretics may increase the serum concentration of Allopurinol. Specifically, Loop Diuretics may increase the concentration of Oxypurinol, an active metabolite of Allopurinol. Risk C: Monitor therapy

Mercaptopurine: Allopurinol may increase the serum concentration of Mercaptopurine. Allopurinol may also promote formation of active thioguanine nucleotides. Management: Reduce the mercaptopurine dose to one third to one quarter of the usual dose if used with allopurinol, and monitor closely for systemic toxicity. Risk D: Consider therapy modification

Pegloticase: Allopurinol may enhance the adverse/toxic effect of Pegloticase. Specifically, Allopurinol may blunt increases in serum urate that would signal an increased risk of anaphylaxis and infusion reactions. Risk X: Avoid combination

Riluzole: Allopurinol may enhance the adverse/toxic effect of Riluzole. Specifically, the risk of hepatotoxicity may be increased. Management: Consider alternatives to allopurinol in patients receiving treatment with riluzole due to the potential for additive hepatotoxicity. Risk D: Consider therapy modification

Theophylline Derivatives: Allopurinol may increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy

Thiazide and Thiazide-Like Diuretics: May enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Allopurinol may enhance the anticoagulant effect of Vitamin K Antagonists. Management: Monitor for increased prothrombin times (PT)/therapeutic effects of oral anticoagulants if allopurinol is initiated/dose increased, or decreased effects if allopurinol is discontinued/dose decreased. Reductions in coumarin dosage will likely be needed. Risk D: Consider therapy modification

Dietary Considerations

For tumor lysis syndrome prevention, administer aggressive fluids sufficient to maintain adequate hydration and urinary output (Coiffier 2008). For other indications, fluid intake should be administered to yield neutral or slightly alkaline urine and an output of ~2 L (in adults).

Pregnancy Considerations

Allopurinol crosses the placenta.

Following a single dose of allopurinol 500 mg IV immediately prior to delivery, allopurinol and the oxypurinol metabolite were present in cord blood (Kaandorp 2014; Torrance 2009).

Outcome data following maternal use of allopurinol in pregnancy are limited. Based on similar adverse outcomes from 2 case reports, use during the first trimester is generally avoided until additional data are available. Close maternal and fetal monitoring is recommended when treatment with allopurinol is needed (El-Sonbaty 2001; Hoeltzenbein 2013; Jones 2021; Laube 2021; Patel 2022; Serikawa 2011; Sheikh 2015; Simsek 2018; van Veen 2015).

Monitoring Parameters

CBC, serum uric acid levels every 2 to 5 weeks during dose titration until desired level is achieved and every 6 months thereafter (ACR guidelines [Khanna 2012]), liver function tests (periodically in patients with preexisting hepatic disease), renal function (BUN, serum creatinine or creatinine clearance (periodically), prothrombin time [periodically in patients receiving warfarin]); consider HLA-B*5801 testing prior to initiation of therapy in patients at a higher risk for allopurinol hypersensitivity syndrome (ACR guidelines [Khanna 2012]). Monitor hydration status, for signs and symptoms of hypersensitivity, hepatotoxicity

Reference Range

Children and Adolescents:

Uric Acid Normal Values

Age

Normal Serum Concentration

1 to 3 years

1.8 to 5 mg/dL

4 to 6 years

2.2 to 4.7 mg/dL

7 to 9 years

2 to 5 mg/dL

10 to 11 years

Male

Female

2.3 to 5.4 mg/dL

3 to 4.7 mg/dL

12 to 13 years: Male

2.7 to 6.7 mg/dL

14 to 15 years: Male

2.4 to 7.8 mg/dL

12 to 15 years: Female

3 to 5.8 mg/dL

16 to 19 years

Male

Female

4 to 8.6 mg/dL

3 to 5.9 mg/dL

Adult:

Males: 3.4 to 7 mg/dL or slightly more

Females: 2.4 to 6 mg/dL or slightly more

Target: ≤6 mg/dL

In adults, values >7 mg/dL are sometimes arbitrarily regarded as hyperuricemia, but there is no sharp line between normals on the one hand, and the serum uric acid of those with clinical gout. Normal ranges cannot be adjusted for purine ingestion, but high purine diet increases uric acid. Uric acid may be increased with body size, exercise, and stress.

Mechanism of Action

Allopurinol inhibits xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine to uric acid. Allopurinol is metabolized to oxypurinol which is also an inhibitor of xanthine oxidase; allopurinol acts on purine catabolism, reducing the production of uric acid without disrupting the biosynthesis of vital purines.

Pharmacokinetics (Adult data unless noted)

Onset of action:

Gout: Decrease in serum and urine uric acid: 2 to 3 days; peak effect: 1 week or longer; normal serum urate levels achieved typically within 1 to 3 weeks.

Cancer therapy-induced hyperuricemia: Median time to plasma uric acid control: 27 hours (Cortes 2010).

Absorption: Oral: 90% from GI tract.

Distribution: Vss: ~0.87 ± 0.13 L/kg.

Metabolism: Rapidly oxidized to active metabolites, primarily oxypurinol.

Bioavailability: ~49% to 53%.

Half-life elimination:

Oral: Parent drug: ~1 to 2 hours; Oxypurinol: ~15 hours.

IV: Parent drug: 1.21 ± 0.33 hours; Oxypurinol: 23.5 ± 4.5 hours.

Time to peak, plasma: Oral: Allopurinol: 1.5 hours; Oxypurinol: 4.5 hours.

Excretion: Urine (76% as oxypurinol, 12% as unchanged drug); feces (~20%).

Extemporaneous Preparations

20 mg/mL Oral Suspension:

A 20 mg/mL oral suspension may be made with tablets and either a 1:1 mixture of Ora-Sweet and Ora-Plus or a 1:1 mixture of Ora-Sweet SF and Ora-Plus or a 1:4 mixture of cherry syrup concentrate and simple syrup, NF. Crush eight 300 mg tablets in a mortar and reduce to a fine powder. Add small portions of chosen vehicle and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 120 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 120 mL. Label “shake well.” Stable for 60 days refrigerated or at room temperature (Allen 1996; Nahata 2004).

Allen LV Jr, Erickson MA 3rd. Stability of acetazolamide, allopurinol, azathioprine, clonazepam, and flucytosine in extemporaneously compounded oral liquids. Am J Health Syst Pharm. 1996;53(16):1944-1949.8862208
Nahata MC, Pai VB, Hipple TF. Pediatric Drug Formulations. 5th ed. Cincinnati, OH: Harvey Whitney Books Co; 2004.
Pricing: US

Solution (reconstituted) (Allopurinol Sodium Intravenous)

500 mg (per each): $3,480.00 - $4,680.00

Solution (reconstituted) (Aloprim Intravenous)

500 mg (per each): $4,784.47

Tablets (Allopurinol Oral)

100 mg (per each): $0.24 - $0.48

300 mg (per each): $0.61 - $0.92

Tablets (Zyloprim Oral)

100 mg (per each): $3.98

300 mg (per each): $11.19

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Acepurin (NL);
  • Adenock (JP);
  • AL (PH);
  • Alinol (TH);
  • Allnol (HK);
  • Allo (CO);
  • Allo-Puren (DE);
  • Allogut (TR);
  • Allonol (LK);
  • Allopin (TH);
  • Allopur (CH, NO);
  • Allopurinol-ratiopharm (LU);
  • Alloric (TH);
  • Alloril (IL);
  • Allosig (AU);
  • Allozym (JP);
  • Allpargin (LU);
  • Allurase (PH);
  • Alluric (EG);
  • Allurit (IT);
  • Alopron (BM, BS, GY, JM, MT, SR, TR, TT);
  • Alopur (IE);
  • Alopurinol (HR);
  • Aloric (BD);
  • Alorinol (EG);
  • Alositol (JP);
  • Alpurase (PH);
  • Alpuric (LU);
  • Alpurin (PH);
  • Alunlan (TW);
  • Aluric (LB);
  • Aluron (VE);
  • Anoprolin (JP);
  • Anzief (JP);
  • Ao Mai Bi Li (CN);
  • Aprinol (JP);
  • Apronal (TH);
  • Apurin (FI, GR);
  • Apurol (SA);
  • Atisuril (CR, DO, GT, HN, MX, NI, PA, SV);
  • Aurinol (PH);
  • Benoxuric (ID);
  • Bleminal (DE);
  • Caplenal (GB);
  • Cellidrin (DE);
  • Clint (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZM, ZW);
  • Dertrifort (CR, DO, GT, HN, NI, PA, SV);
  • Etindrax (MX);
  • Foligan (DE);
  • Genozyl (MX);
  • Gichtex (AT);
  • Goutex (BD);
  • Goutilex (TW);
  • Hamarin (GB);
  • Huma-Purol (HU);
  • Isoric (ID);
  • Ketanrift (JP);
  • Ketobun-A (JP);
  • Lessuric (EG);
  • Litinol (VE);
  • Llanol (VN);
  • Logout (LK);
  • Loric (SA);
  • Loric-100 (BH, PH, QA);
  • Loric-300 (BH, PH);
  • Masaton (JP);
  • Mensil (PY);
  • Mephanol (AE, BF, BJ, CH, CI, CY, ET, GH, GM, GN, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, MY, NE, NG, OM, QA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZM, ZW);
  • Milurit (BG, CZ, HU, SK);
  • Miniplanor (JP);
  • Neufan (JP);
  • Nilapur (ID);
  • Nipurol (VE);
  • No-Uric (AE, BH, CY, ET, IQ, IR, JO, KW, LB, LY, OM, QA, SY, YE);
  • Pritanol (ID);
  • Progout (AU, SG);
  • Puribel 300 (MX);
  • Puricemia (ID);
  • Puricos (ZA);
  • Purinol (AE, BD, CZ, IE, JO, MY, QA, RU, SA, ZW);
  • Remid (DE, PY);
  • Riball (JP);
  • Ridonra (TW);
  • Rinolic (ID);
  • Ripunin (TW);
  • Sadapron (VN);
  • Salterprim (ZA);
  • Sinoric (ID);
  • Takanarumin (JP);
  • Tipuric (IE);
  • Tonsaric (TW);
  • Trianol (PH);
  • Tylonic (ID);
  • Unizuric (CR, DO, GT, HN, NI, PA, SV);
  • Unizuric 300 (MX);
  • Uranid (TW);
  • Uric (JP);
  • Uricad (TH);
  • Uriconorm (CH);
  • Urinol (MY);
  • Urocuad (CO);
  • Urogquad (AR);
  • Uroquad (AE, BF, BJ, BM, BS, CI, ET, GH, GM, GN, GY, JM, KE, LR, MA, ML, MR, MU, MW, NE, NG, SA, SC, SD, SL, SN, SR, TN, TT, TZ, UG, ZM, ZW);
  • Urosin (AT, DE, EC, LU);
  • Valeric (CN);
  • Xandase (TH);
  • Xanol (TH);
  • Xanurace (PH);
  • Xoric (BD);
  • Xylonol (TW);
  • Yi Da Tong (CN);
  • Zanuric (JO);
  • Zylapour (GR);
  • Zyloprim (AU, BB, BM, BS, CR, DO, GT, GY, HN, JM, MX, NI, PA, PH, PR, PY, SR, SV, TT);
  • Zyloric (AE, BE, BF, BH, BJ, BR, CH, CI, CL, CY, DE, EE, EG, ES, ET, FI, FR, GB, GH, GM, GN, HK, ID, IE, IN, IQ, IR, IT, JO, KE, KR, KW, LB, LR, LU, LY, MA, ML, MR, MT, MU, MW, MY, NE, NG, NL, NO, OM, PK, PL, PT, QA, RU, SA, SC, SD, SE, SG, SK, SL, SN, SY, TH, TN, TR, TZ, UG, UY, VE, VN, YE, ZM, ZW);
  • Zyngot (PE);
  • Zyroric (KR)


For country code abbreviations (show table)
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