(al oh PURE i nole)
- Allopurinol Sodium
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, preservative free]:
Aloprim: 500 mg (1 ea)
Generic: 500 mg (1 ea [DSC])
Zyloprim: 100 mg, 300 mg [scored]
Generic: 100 mg, 300 mg
Brand Names: U.S.
- Antigout Agent
- Xanthine Oxidase Inhibitor
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.
Oral: ~80% to 90% from GI tract; Rectal: Poor and erratic
Vd: ~1.6 L/kg; Vss: 0.84 to 0.87 L/kg; enters breast milk
~75% to active metabolites, chiefly oxypurinol
Urine (76% as oxypurinol, 12% as unchanged drug); feces (20%)
Allopurinol and oxypurinol are dialyzable
Onset of Action
Gout: 2 to 3 days, peak effect: 1 to 2 weeks; Hyperuricemia associated with chemotherapy: Maximum effect: 27 hours (Coiffier, 2008)
Time to Peak
Plasma: Oral: Allopurinol: 1.54 hours; Oxipurinol: 4.5 hours
Normal renal function: Parent drug: 1 to 3 hours; Oxypurinol: 18 to 30 hours
End-stage renal disease: Prolonged
Use: Labeled Indications
Calcium oxalate calculi: Management of recurrent calcium oxalate calculi (with uric acid excretion >800 mg/day in men and >750 mg/day in women)
Gout: Management of primary or secondary gout (acute attack, tophi, joint destruction, uric acid lithiasis, and/or nephropathy)
Lesch-Nyhan syndrome: Canadian labeling: Additional use (not in U.S. labeling): Management of hyperuricemia associated with Lesch-Nyhan syndrome
Malignancies: Management of hyperuricemia associated with cancer treatment for leukemia, lymphoma, or solid tumor malignancies
IV: Malignancies: Management of hyperuricemia associated with cancer treatment for leukemia, lymphoma, or solid tumor malignancies
Severe hypersensitivity reaction to allopurinol or any component of the formulation
Canadian labeling: Additional contraindications (not in U.S. labeling): Nursing mothers and children (except those with hyperuricemia secondary to malignancy or Lesch-Nyhan syndrome)
Gout (chronic): Adults: Oral:
Manufacturer’s labeling: Initial: 100 mg once daily; increase at weekly intervals in increments of 100 mg/day as needed to achieve desired serum uric acid level. Usual dosage range: 200 to 300 mg/day in mild gout; 400 to 600 mg/day in moderate to severe tophaceous gout. Maximum daily dose: 800 mg/day.
Alternative dosing (off-label): Initial: 100 mg/day, increasing the dose gradually in increments of 100 mg/day every 2 to 5 weeks as needed to achieve desired serum uric acid level of ≤6 mg/dL (ACR guidelines [Khanna, 2012]; EULAR guidelines [Zhang, 2006]; McGill, 2010). Some patients may require therapy targeted at a serum uric acid level <5 mg/dL to control symptoms. Allopurinol may be initiated during an acute gout attack so long as antiinflammatory therapy has been initiated as well (ACR guidelines [Khanna, 2012]).
Management of hyperuricemia associated with chemotherapy and/or radiation therapy:
Oral: Note: Doses >300 mg should be given in divided doses.
Children <6 years: 150 mg daily
Children 6 to 10 years: 300 mg daily
Children >10 years and Adults: 600 to 800 mg daily in divided doses
Children 6 to 10 years: 10 mg/kg daily (do not exceed adult dosing); adjust dose as necessary after 48 hours
Adults: 600 to 800 mg daily in 2 to 3 divided doses for 2 to 3 days prior to chemotherapy/radiation therapy then adjust dose per serum uric acid level; for ongoing management, 300 to 400 mg daily is usually sufficient to control serum uric levels.
Alternative dosing (off-label; intermediate risk for tumor lysis syndrome): Children and Adults: Intermediate risk for tumor lysis syndrome: 10 mg/kg daily divided every 8 hours (maximum dose: 800 mg daily) or 50 to 100 mg/m2 every 8 hours (maximum dose: 300 mg/m2 daily), begin 12 to 24 hours (children) or 1 to 2 days (adults) before initiation of induction chemotherapy; may continue for 3 to 7 days after chemotherapy (Coiffier, 2008)
IV: Note: Intravenous daily dose can be given as a single infusion or in equally divided doses at 6-, 8-, or 12-hour intervals.
Children: Starting dose: 200 mg/m2 daily beginning 1 to 2 days before chemotherapy
Adults: 200 to 400 mg/m2 daily (maximum dose: 600 mg daily) beginning 1 to 2 days before chemotherapy
Alternative dosing (off-label; intermediate risk for tumor lysis syndrome): Children and Adults: 200 to 400 mg/m2 daily (maximum dose: 600 mg daily) in 1 to 3 divided doses beginning 1 to 2 days before the start of induction chemotherapy; may continue for 3 to 7 days after chemotherapy (Coiffier, 2008)
Management of hyperuricemia associated with Lesch-Nyhan syndrome: Canadian labeling (not in U.S. labeling): Children 6 to 10 years: Oral: 10 mg/kg daily in 1 to 3 divided doses; adjust dose as necessary after 48 hours
Recurrent calcium oxalate stones: Adults: Oral: 200 to 300 mg daily in single or divided doses; may adjust dose as needed to control hyperuricosuria
Dosage adjustment in renal impairment:
Manufacturer’s labeling: Oral, IV: Lower doses are required in renal impairment due to potential for accumulation of allopurinol and metabolites.
CrCl 10 to 20 mL/minute: 200 mg daily
CrCl 3 to 10 mL/minute: ≤100 mg daily
CrCl <3 mL/minute: ≤100 mg/dose at extended intervals
Alternative dosing (off-label):
Management of hyperuricemia associated with chemotherapy: Dosage reduction of 50% is recommended in renal impairment (Coiffier, 2008)
Initiate therapy with 50 to 100 mg daily, and gradually increase to a maintenance dose to achieve a serum uric acid level of ≤6 mg/dL (with close monitoring of serum uric acid levels and for hypersensitivity) (Dalbeth, 2007; Sivera, 2013).
In patients with stage 4 CKD or worse, initiate therapy at 50 mg/day, increasing the dose every 2-5 weeks to achieve desired uric acid levels of ≤6 mg/dL; doses >300 mg/day are permitted so long as they are accompanied by appropriate patient education and monitoring for toxicity (eg, pruritus, rash, elevated hepatic transaminases). Some patients may require therapy targeted at a serum uric acid level <5 mg/dL to control symptoms (ACR guidelines; Khanna, 2012).
Hemodialysis: Initial: 100 mg alternate days given postdialysis, increase cautiously to 300 mg based on response. If dialysis is on a daily basis, an additional 50% of the dose may be required postdialysis (Dalbeth, 2007)
Dosage adjustment in hepatic impairment: There are no dosage adjustments provided in the U.S. manufacturer’s labeling. The Canadian labeling suggests that a dose reduction is necessary but does not provide specific dosing recommendations.
Reconstitute powder for injection with SWFI. Further dilution with NS or D5W (50 to 100 mL) to ≤6 mg/mL is recommended.
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 and Erickson MA 3rd, "Stability of Acetazolamide, Allopurinol, Azathioprine, Clonazepam, and Flucytosine in Extemporaneously Compounded Oral Liquids," Am J Health Syst Pharm, 1996, 53(16):1944-9.8862208Nahata MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.
Oral: Administer after meals with plenty of fluid.
IV: The rate of infusion depends on the volume of the infusion; infuse maximum single daily doses (600 mg/day) over ≥30 minutes. Whenever possible, therapy should be initiated at 24 to 48 hours before the start of chemotherapy known to cause tumor lysis (including adrenocorticosteroids). IV daily dose can be administered as a single infusion or in equally divided doses at 6-, 8-, or 12-hour interval.
Fluid intake should be administered to yield neutral or slightly alkaline urine and an output of ~2 L (in adults).
Stable in D5W, NS, SWFI.
Y-site administration: Incompatible with amikacin, amphotericin B, carmustine, cefotaxime, chlorpromazine, cimetidine, clindamycin, cytarabine, dacarbazine, daunorubicin, diphenhydramine, doxorubicin, doxycycline, droperidol, floxuridine, gentamicin, haloperidol, hydroxyzine, idarubicin, imipenem/cilastatin, mechlorethamine, meperidine, methylprednisolone sodium succinate, metoclopramide, minocycline, nalbuphine, ondansetron, prochlorperazine edisylate, promethazine, sodium bicarbonate, streptozocin, tobramycin, vinorelbine.
Compatibility in syringe: Incompatible: Ceftriaxone.
Powder for injection: Store at controlled room temperature of 20°C to 25°C (68°F to 77°F). Following preparation, intravenous solutions 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 controlled room temperature of 20°C to 25°C (68°F to 77°F). Protect from moisture and light.
ACE Inhibitors: May enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Consider therapy modification
Amoxicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Amoxicillin. Monitor therapy
Ampicillin: Allopurinol may enhance the potential for allergic or hypersensitivity reactions to Ampicillin. Monitor therapy
Antacids: May decrease the absorption of Allopurinol. Exceptions: Sodium Bicarbonate. Consider therapy modification
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 the azathioprine dose to one third to one quarter of the usual dose if used concomitantly with allopurinol, and monitor closely for systemic toxicity (particularly hematologic toxicity, nausea, and vomiting). Consider therapy modification
Bendamustine: Allopurinol may enhance the adverse/toxic effect of Bendamustine. Specifically, the risk of severe skin reactions may be enhanced. Monitor therapy
CarBAMazepine: Allopurinol may increase the serum concentration of CarBAMazepine. Monitor therapy
ChlorproPAMIDE: Allopurinol may increase the serum concentration of ChlorproPAMIDE. Monitor therapy
Cyclophosphamide: Allopurinol may enhance the adverse/toxic effect of Cyclophosphamide. Specifically, bone marrow suppression. Monitor therapy
Didanosine: Allopurinol may increase the serum concentration of Didanosine. Avoid combination
Doxofylline: Allopurinol may increase the serum concentration of Doxofylline. Monitor therapy
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. 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. US labeling for mercaptopurine oral suspension (Purixan brand) recommends avoiding allopurinol. 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. Avoid combination
Tegafur: Allopurinol may diminish the therapeutic effect of Tegafur. Avoid combination
Theophylline Derivatives: Allopurinol may increase the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Monitor therapy
Thiazide Diuretics: May enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Thiazide Diuretics may increase the serum concentration of Allopurinol. Specifically, Thiazide Diuretics may increase the concentration of Oxypurinol, an active metabolite of Allopurinol. Monitor therapy
Vitamin K Antagonists (eg, warfarin): Allopurinol may enhance the anticoagulant effect of Vitamin K Antagonists. Consider therapy modification
Most commonly reported:
Dermatologic: Skin rash
Endocrine & metabolic: Gout (acute)
Gastrointestinal: Diarrhea, nausea
Hepatic: Increased liver enzymes, increased serum alkaline phosphatase
<1% (Limited to important or life-threatening): Ageusia, agranulocytosis, alopecia, angioedema, aplastic anemia, cataract, cholestatic jaundice, ecchymoses, eczematoid dermatitis, eosinophilia, exfoliative dermatitis, hepatic necrosis, hepatitis, hepatomegaly, hepatotoxicity (idiosyncratic) (Chalasani, 2014), hyperbilirubinemia, hypersensitivity reaction, leukocytosis, leukopenia, lichen planus, macular retinitis, myopathy, necrotizing angiitis, nephritis, neuritis, neuropathy, onycholysis, pancreatitis, purpura, renal failure, skin granuloma (annulare), Stevens-Johnson syndrome, thrombocytopenia, toxic epidermal necrolysis, toxic pustuloderma, uremia, vasculitis, vesicobullous dermatitis
Concerns related to adverse effects:
• Allergic reaction: Has been associated with a number of hypersensitivity reactions, including severe reactions (vasculitis and Stevens-Johnson syndrome); discontinue at first sign of rash. Consider HLA-B*5801 testing in patients at a higher risk for allopurinol hypersensitivity syndrome (eg, Koreans with stage 3 or worse CKD and Han Chinese and Thai descent regardless of renal function) prior to initiation of therapy (ACR guidelines [Khanna, 2012]).
• Bone marrow suppression: Has been reported; use caution with other drugs causing myelosuppression.
• Hepatotoxicity: Reversible hepatotoxicity has been reported; use with caution in patients with preexisting hepatic impairment.
• Asymptomatic hyperuricemia: Do not use to treat asymptomatic hyperuricemia.
• Renal impairment: Use with caution in patients with renal impairment; may be at increased risk for hypersensitivity reactions. Dosage adjustments needed.
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant drug interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
• Appropriate use: Full effect on serum uric acid levels in chronic gout may take several weeks to become evident; gradual titration is recommended.
CBC, serum uric acid levels every 2 to 5 weeks during dose titration until desired level is achieved; every 6 months thereafter (ACR guidelines [Khanna, 2012]), I & O, hepatic and renal function, especially at start of therapy; signs and symptoms of hypersensitivity
Pregnancy Risk Factor
Adverse events were observed in some animal reproduction studies. Allopurinol crosses the placenta (Torrance, 2009). An increased risk of adverse fetal events has not been observed (limited data) (Hoeltzenbein, 2013).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience diarrhea, dyspepsia, or injection site irritation. Have patient report immediately to prescriber signs of hepatic impairment, dysuria, hematuria, paresthesia, urinary retention, oliguria, chills, pharyngitis, eye irritation, severe arthralgia, ecchymosis, hemorrhaging, myalgia, significant asthenia, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.