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 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).
Management of hepatotoxicity, non-hepatic GI toxicity, and/or inadequate myelosuppression associated with 6-mercaptopurine maintenance therapy for acute lymphoblastic leukemia: Limited data available: Note: In clinical trials, allopurinol was administered at the same time as 6-mercaptopurine.
Fixed dosing: Infants, Children, and Adolescents:
≤30 kg: Oral: 50 mg daily (Ref).
>30 kg: Oral: 100 mg daily (Ref).
BSA-directed dosing: Infants, Children, and Adolescents: Oral: Initial: 50 mg/m2 daily; may increase dose to 100 mg/m2 daily after 4 weeks if erythrocyte levels of thioguanine nucleotides <200 nmol/mmol Hb. Maximum reported daily dose: 100 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).
Tumor lysis syndrome, prevention of hyperuricemia associated with malignancy: Maintain adequate hydration; begin allopurinol 1 to 3 days before initiation of induction chemotherapy; may continue for 3 to 7 days after chemotherapy (Ref); doses >300 mg/day should be administered in divided doses:
Oral: Infants, Children, and Adolescents:
BSA-based dosing: Oral: 50 to 100 mg/m2 every 8 to 12 hours; maximum daily dose: 800 mg/day (Ref).
Weight-directed dosing: Oral: 10 mg/kg/day divided every 8 hours; maximum daily dose: 800 mg/day (Ref).
IV: Note: For patients unable to tolerate oral therapy (BSA-directed dosing):
Infants, Children, and Adolescents: 200 to 400 mg/m2/day in 1 to 4 divided doses; maximum daily dose: 600 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.
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:
Tumor lysis syndrome, prevention of hyperuricemia associated with malignancy: Oral, IV:
Altered kidney function: There are no dosage adjustments provided in the manufacturer's labeling; some experts recommend reducing dose to 50% of normal dose in patients with kidney impairment (Ref); however, others suggest that dosage adjustment is not always utilized in patients with tumor lysis syndrome or hyperuricemia associated with malignancy (Ref).
Hemodialysis: Allopurinol and oxypurinol are dialyzable. There are no dosage adjustments provided in the manufacturer's labeling. Based on adult information, dosage adjustment may be necessary; evaluate risk versus benefits in pediatric patients (Ref).
Peritoneal dialysis: There are no dosage adjustments provided in the manufacturer's labeling. Based on adult information, dosage adjustment may be necessary; evaluate risk versus benefits in pediatric patients (Ref).
Other indications:
Altered kidney function (Ref): Oral, IV:
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.
Hemodialysis (intermittent): Allopurinol and oxypurinol are dialyzable. Administer 30% of normal dose (Ref).
Peritoneal dialysis: Administer 30% of normal dose (Ref).
Continuous renal replacement therapy (CRRT): Administer 50% of normal dose (Ref).
There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Allopurinol: Drug information")
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 [eg, Korean, Han Chinese, Thai] and African descent) (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 once daily or in 2 or 3 divided doses (Ref).
Due to uric acid stones (off-label use): Oral: 300 mg once daily or in 2 or 3 divided doses; use is reserved for patients who continue to have active disease despite urinary alkalinization therapy and increased hydration (Ref).
Tumor lysis syndrome, prevention of hyperuricemia associated with malignancy:
Note: For prevention in patients at intermediate risk for tumor lysis syndrome (TLS) with uric acid levels <8 mg/dL (476 micromole/L) (Ref). Aggressive IV hydration should always be initiated prior to cytotoxic therapy in patients at elevated risk for TLS (Ref). If HLA-B*5801 genetic testing in patients at elevated risk of developing severe cutaneous adverse reactions is not feasible (eg, urgent need for chemotherapy), consider alternative agent (eg, rasburicase) (Ref).
Oral: 100 mg/m2/dose every 8 hours (maximum: 800 mg/day). Begin therapy 1 to 2 days before the start of induction chemotherapy and may continue until normalization of laboratory evidence of TLS (eg, serum uric acid, serum LDH) or resolution of TLS risk (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 until normalization of laboratory evidence of TLS (eg, serum uric acid, serum LDH) or resolution of TLS risk (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 2020a); 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).
The liver dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Matt Harris, PharmD, MHS, BCPS, FAST, FCCP; Jeong Park, PharmD, MS, BCTXP, FCCP, FAST; Arun Jesudian, MD; Sasan Sakiani, MD.
Note: Allopurinol is primarily metabolized by the liver through oxidation into the active metabolite, oxypurinol; parent drug and oxypurinol are excreted in the urine (Ref). 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 (Ref). Avoid allopurinol in any patient testing positive for this allele (Ref).
Liver impairment prior to treatment initiation:
Initial or dose titration in patients with preexisting liver cirrhosis :
Child-Turcotte-Pugh Class A to C: IV, Oral: No dosage adjustment necessary (Ref).
Liver impairment developing in patients already receiving allopurinol :
Acute worsening of hepatic function (eg, requiring hospitalization):
Child-Turcotte-Pugh Class A to C: IV, Oral: No dosage adjustment necessary; however, if allopurinol-induced liver injury is confirmed or suspected, permanently discontinue allopurinol therapy secondary to high risk of mortality (Ref).
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-B*5801 allele is strongly associated with SCARs, especially with comorbid kidney impairment and in some 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 (≥1%), skin rash (2%)
Gastrointestinal: Diarrhea (≥1%), nausea (1%), vomiting (≤1%)
Hepatic: Increased serum alanine aminotransferase (≥1%), increased serum alkaline phosphatase (≥1%), increased serum aspartate aminotransferase (≥1%)
Neuromuscular & skeletal: Gout (≥1%; acute)
Renal: Kidney failure (≤1%)
<1%:
Cardiovascular: Bradycardia, edema, flushing, heart failure, hypertension, hypotension, low cardiac output, necrotizing angiitis, pericarditis, peripheral vascular disease, pulmonary embolism, thrombophlebitis, vasculitis, vasodilation, ventricular fibrillation
Dermatologic: Alopecia, cellulitis, diaphoresis, ecchymoses, eczema, exfoliative dermatitis, furunculosis, lichen planus, onycholysis, purpuric rash, skin edema, Stevens-Johnson syndrome, toxic epidermal necrolysis, 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: Erectile dysfunction, glycosuria, hematuria, 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, hepatotoxicity, hyperbilirubinemia, jaundice
Hypersensitivity: Drug reaction with eosinophilia and systemic symptoms, facial edema, hypersensitivity angiitis, tongue edema
Infection: Infection, sepsis, septic shock
Local: Injection-site reaction
Nervous system: Agitation, amnesia, asthenia, cerebral infarction, cerebrovascular accident, chills, coma, confusion, depression, dizziness, drowsiness, headache, hypotonia, insomnia, malaise, mental status changes, myoclonus, neuritis, pain, paralysis, paresthesia, peripheral neuropathy, seizure, status epilepticus, tremor, twitching, vertigo
Neuromuscular & skeletal: Arthralgia, dystonia, foot-drop, myalgia, myopathy
Ophthalmic: Amblyopia, cataract, conjunctivitis, iritis, macular retinitis, optic neuritis
Otic: Tinnitus
Renal: Nephritis (including interstitial nephritis)
Respiratory: Acute respiratory distress syndrome, apnea, asthma, bronchospasm, epistaxis, pharyngitis, respiratory failure, rhinitis, tachypnea
Miscellaneous: Fever
Postmarketing:
Dermatologic: Sweet syndrome (Ref)
Hematologic & oncologic: Pure red cell aplasia (Ref)
Hepatic: Cholestatic hepatitis (Ref)
Hypersensitivity: Hypersensitivity reaction (allopurinol hypersensitivity syndrome; can be severe hypersensitivity reaction) (Ref)
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 (eg, Korean, Han Chinese, Thai) and African descent (ACR [FitzGerald 2020a]).
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. [DSC] = Discontinued product
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 [DSC] [scored]
Zyloprim: 300 mg [DSC] [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): $5.55 - $7.95
300 mg (per each): $0.25 - $0.92
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:
Generic: 100 mg, 200 mg, 300 mg
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).
Note: Fluid intake should be sufficient to yield neutral or slightly alkaline (preferably) urine and urine output of at least 100 mL/m2/hour. For tumor lysis syndrome prevention, administer aggressive fluids sufficient to maintain adequate hydration and urinary output; whenever possible, allopurinol therapy should be initiated at least 24 to 48 hours before the start of chemotherapy (and other treatments) known to cause tumor lysis (Ref).
Oral: Administer after meals.
Parenteral: The rate of infusion is dependent upon the volume of the infusion; infuse maximum single daily doses (600 mg/day) over ≥30 minutes.
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.
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.
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 management of hepatotoxicity, non-hepatic GI toxicity, and inadequate myelosuppression associated with 6-mercaptopurine maintenance therapy for acute lymphoblastic leukemia; 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).
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 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 drug interactions program
Aluminum Hydroxide: May decrease serum concentration of Allopurinol. Management: Consider administering allopurinol 3 hours prior to aluminum hydroxide. Risk D: Consider Therapy Modification
Amoxicillin: Allopurinol may increase hypersensitivity effects of Amoxicillin. Risk C: Monitor
Ampicillin: Allopurinol may increase hypersensitivity effects of Ampicillin. Risk C: Monitor
Angiotensin-Converting Enzyme Inhibitors: May increase hypersensitivity effects of Allopurinol. Risk C: Monitor
AzaTHIOprine: Allopurinol may increase active metabolite exposure 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 increase hypersensitivity effects of Bacampicillin. Risk C: Monitor
Bendamustine: Allopurinol may increase adverse/toxic effects of Bendamustine. Specifically, the risk of severe skin reactions may be enhanced. Risk C: Monitor
CycloPHOSphamide: Allopurinol may increase serum concentration of CycloPHOSphamide. Risk C: Monitor
CycloSPORINE (Systemic): Allopurinol may increase serum concentration of CycloSPORINE (Systemic). Risk C: Monitor
Didanosine: Allopurinol may increase serum concentration of Didanosine. Risk X: Avoid
Doxofylline: Allopurinol may increase serum concentration of Doxofylline. Risk C: Monitor
Fluorouracil Products: Allopurinol may decrease active metabolite exposure of Fluorouracil Products. Risk X: Avoid
Loop Diuretics: May increase adverse/toxic effects of Allopurinol. Loop Diuretics may increase serum concentration of Allopurinol. Specifically, Loop Diuretics may increase the concentration of Oxypurinol, an active metabolite of Allopurinol. Risk C: Monitor
Mercaptopurine: Allopurinol may increase 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 increase adverse/toxic effects of Pegloticase. Specifically, Allopurinol may blunt increases in serum urate that would signal an increased risk of anaphylaxis and infusion reactions. Risk X: Avoid
Riluzole: Allopurinol may increase adverse/toxic effects 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 serum concentration of Theophylline Derivatives. Risk C: Monitor
Thiazide and Thiazide-Like Diuretics: May increase hypersensitivity effects of Allopurinol. Risk C: Monitor
Vitamin K Antagonists: Allopurinol may increase anticoagulant effects 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
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).
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).
CBC, serum uric acid levels, liver function tests, kidney function (hydration status, BUN, serum creatinine), signs and symptoms of cutaneous hypersensitivity; consider HLA-B*5801 testing prior to initiation of therapy in patients at a higher risk for allopurinol hypersensitivity syndrome (ACR [Khanna 2012]).
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 via the liver 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%).