Dosage guidance:
Safety: Before use, test 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) (Ref). A negative HLA-B*5801 genetic test does not entirely rule out the possibility of allopurinol-associated SCAR or other forms of hypersensitivity (Ref). Avoid use in any patient testing positive for the allele (Ref).
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:
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: 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.
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).
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).
There are no dosage adjustments provided in the manufacturer's labeling.
Refer to adult dosing.
(For additional information see "Allopurinol: Pediatric drug information")
Dosage guidance:
Safety: Before use, consider testing for the HLA-B*5801 allele in patients at elevated risk for developing severe cutaneous adverse reactions (SCAR) (including Korean patients with CKD ≥ stage 3 and all patients of Han Chinese or Thai descent). A negative HLA-B*5801 genetic test does not entirely rule out the possibility of allopurinol-associated SCAR or other forms of hypersensitivity (Ref).
Dosing: 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.
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 (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 (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.
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.
There are no dosage adjustments provided in the manufacturer's labeling.
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)
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).
Most cases of acute hepatotoxicity with allopurinol are associated with DRESS and AHS (Ref). Hepatotoxicity may rarely occur without any features of DRESS (Ref). Liver enzyme elevations are usually hepatocellular or mixed, but may be cholestatic (Ref).
Mechanism: 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).
Hepatotoxicity: Varied; median 52 days (range 12 to 89 days) in one study (Ref).
Risk factors:
• Initial dose >100 mg/day (Ref)
• HLA alleles: HLA-B*5801 allele is strongly associated with SCARs, especially with comorbid 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)
• Comorbid kidney impairment: Correlated to delayed clearance of oxypurinol (metabolite of allopurinol) and potentially high levels of granulysin (Ref)
• Age ≥60 years, possibly due to kidney impairment (Ref)
• Female sex (Ref)
• Asymptomatic hyperuricemia, especially in patients with comorbid kidney impairment or cardiovascular disease (Ref)
• Comorbid cardiovascular disease (Ref)
• Concurrent diuretic use (conflicting data) (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)
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)
Hepatic: Cholestatic hepatitis (Fontana 2021)
Hypersensitivity: Hypersensitivity reaction (allopurinol hypersensitivity syndrome; can be severe hypersensitivity reaction) (Chen 2005)
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]).
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.
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, 200 mg, 300 mg
Yes
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): $0.13 - $0.48
200 mg (per each): $7.95
300 mg (per each): $0.25 - $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.
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
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.
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.
Oral:
Gout, treatment: Management of primary or secondary gout (acute attack, tophi, joint destruction, uric acid lithiasis, and/or nephropathy)
Guideline recommendations: EULAR guidelines: Urate-lowering therapy (ULT) (eg, allopurinol) is indicated in all patients with recurrent flares, tophi, urate arthropathy, and/or renal stones. ULT initiation is recommended close in time to first diagnosis in patients presenting at a young age (<40 years of age) or with very high serum uric acid levels (>8 mg/dL) and/or comorbidities (eg, renal impairment, hypertension, ischemic heart disease, heart failure) (EULAR [Richette 2017]).
Nephrolithiasis, prevention of recurrent calcium stones: Management in patients with hyperuricosuria (uric acid excretion >800 mg/day in men and >750 mg/day in women)
Tumor lysis syndrome, prevention: Management of hyperuricemia associated with cancer treatment for leukemia, lymphoma, and other malignancies
Limitations of use: Allopurinol is not recommended for the treatment of asymptomatic hyperuricemia. Allopurinol reduces serum and urinary uric acid concentrations; its use should be individualized for each patient and requires an understanding of its mode of action and pharmacokinetics.
IV:
Tumor lysis syndrome, prevention : Management of hyperuricemia associated with cancer treatment for leukemia, lymphoma, or solid tumor malignancies in pediatric and adult patients who cannot tolerate oral therapy.
Nephrolithiasis, prevention of recurrent uric acid stones
Allopurinol may be confused with Apresoline
Zyloprim may be confused with zolpidem, ZORprin, Zovirax
None known.
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.
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
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).
Allopurinol and the oxypurinol metabolite are present in breast milk.
Data related to the presence of allopurinol in breast milk are available from a single case report. Allopurinol 300 mg/day was initiated 1 week postpartum to a patient for the treatment of recurrent pyelonephritis. After 4 weeks of treatment, breast milk, maternal blood, and infant blood were sampled. Allopurinol concentrations in breast milk were 0.9 mcg/mL (2 hours) and 1.4 mcg/mL (4 hours) after the dose. Oxypurinol breast milk concentrations were 53.7 mcg/mL (2 hours) and 48 mcg/mL (4 hours) after the dose. Four hours after the dose, plasma concentrations of allopurinol were 1 mcg/mL (mother) and below the limit of detection in the breastfed infant; oxypurinol concentrations were 19.9 mcg/mL (mother) and 6.6 mcg/mL (infant). Authors of the study calculated the estimated daily infant dose via breast milk to be 0.14 to 0.2 mg/kg/day (allopurinol) and 7.2 to 8 mg/kg/day (oxypurinol). Adverse events were not reported in the infant (Kamilli 1993).
Due to the potential for adverse events, breastfeeding is not recommended by the manufacturer during treatment and for 1 week after the last allopurinol dose. Other sources consider allopurinol compatible or likely to have low risk with breastfeeding (Laube 2021; WHO 2002). However close monitoring for adverse events, such as hypersensitivity reactions and cytopenia, in the breastfed infant is recommended (Patel 2022).
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).
CBC; serum uric acid levels at least 2 to 4 weeks after every dose titration until desired level is achieved, then every 6 months (symptomatic patients) or every 12 months (all patients on urate-lowering therapy, regardless of symptoms) (FitzGerald 2018; Perez-Ruiz 2022), LFTs (periodically in patients with preexisting hepatic disease), renal function (BUN, serum creatinine, or creatinine clearance [prior to initiation and periodically]), prothrombin time (periodically in patients receiving warfarin). Monitor hydration status, signs/symptoms of hepatotoxicity (if occurs, evaluate LFTs), and signs/symptoms of hypersensitivity reactions, including severe cutaneous adverse reactions (SCAR). Consider HLA-B*5801 testing prior to initiation of therapy in patients at elevated risk for SCAR (eg, patients of Southeast Asian descent [eg, Korean, Han Chinese, Thai], African American patients).
Uric acid, serum:
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 |
2.3 to 5.4 mg/dL |
10 to 11 years: Female |
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 |
4 to 8.6 mg/dL |
16 to 19 years: Female |
3 to 5.9 mg/dL |
Adults:
Normal values:
Males: 3.4 to 7 mg/dL or slightly more
Females: 2.4 to 6 mg/dL or slightly more
Goal during therapy for gout: <6 mg/dL; <5 mg/dL in patients with severe gout (eg, tophi, frequent attacks, chronic arthropathy) (EULAR [Richette 2017]). Levels <3 mg/dL are not recommended long-term (EULAR [Richette 2017]).
Note: Serum uric acid values >7 mg/dL do not necessarily represent clinical gout; the American College of Rheumatology clinical practice guidelines recommend against initiating pharmacologic management of asymptomatic hyperuricemia (ACR [FitzGerald 2020]).
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.
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%).
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