Xanthine Oxidase Inhibitor

Allopurinol

Approved 14 Apr 2025OralTablet

The FDA lists this product in 49 strengths and forms.

Indications

Allopurinol tablets are indicated for: The management of adults with signs and symptoms of primary or secondary gout (acute attacks, tophi, joint destruction, uric acid lithiasis, and/or nephropathy) The management of adult and pediatric patients with leukemia, lymphoma and solid tumor malignancies who are receiving cancer therapy which causes elevations of serum and urinary uric acid levels The management of adult patients with recurrent calcium oxalate calculi whose daily uric acid excretion exceeds 800 mg/day in male patients and 750 mg/day in female patients, despite lifestyle changes (such as reduction of dietary sodium, non-dairy animal protein, oxylate rich foods, refined sugars and increases in oral fluids and fruits and vegetables) Limitations of Use Allopurinol tablets are not recommended for the treatment of asymptomatic hyperuricemia.

Allopurinol tablets are a xanthine oxidase inhibitor indicated for the management of: Adult patients with signs and symptoms of primary or secondary gout (acute attacks, tophi, joint destruction, uric acid lithiasis, and/or nephropathy) ( 1 ) Adult and pediatric patients with leukemia, lymphoma and solid tumor malignancies who are receiving cancer therapy which causes elevations of serum and urinary uric acid levels ( 1 ) Adult patients with recurrent calcium oxalate calculi whose daily uric acid excretion exceeds 800 mg/day in male patients and 750 mg/day in female patients, despite lifestyle changes ( 1 ) Limitations of Use Allopurinol tablets are not recommended for the treatment of asymptomatic hyperuricemia.

( 1 )

Contraindications

Allopurinol tablets are contraindicated in patients with a history of hypersensitivity reaction to allopurinol or to any of the ingredients of allopurinol tablets. Known hypersensitivity to allopurinol or to any of the ingredients of allopurinol.

Warnings and precautions

Skin Rash and Hypersensitivity: Allopurinol has been associated with serious and sometimes fatal dermatological reactions. Discontinue allopurinol at the first appearance of skin rash or other signs of hypersensitivity reaction. ( 5.1 ) Gout Flares: May occur during initiation of treatment. Concurrent prophylactic treatment with colchicine or anti-inflammatory agents is recommended. ( 5.2 ) Nephrotoxicity: Allopurinol may affect kidney function.

Indications

( 1 )

Warnings and precautions

Interactions

The following drugs may increase the risk of serious skin reactions: bendamustine, thiazide diuretics, ampicillin and amoxicillin. ( 7.1 ) Capecitabine: Avoid concomitant use. ( 7.2 ) Mercaptopurine or Azathioprine: Reduce mercaptopurine or azathioprine dose as recommended in the respective prescribing information. ( 7.2 ) Pegloticase: Discontinue and refrain from initiating treatment with allopurinol. ( 7.2 ) See FPI for complete list of significant drug interactions.

( 7.2 )

7.1Drugs Known to Affect the Occurrence of Skin Rash and Hypersensitivity

Concomitant use of the following drugs may increase the risk of skin rash, which may be severe: bendamustine, thiazide diuretics, ampicillin and amoxicillin. Renal impairment may further increase risk with concomitant use of thiazide diuretics [see Warnings and Precautions (5.1 , 5.2) and Clinical Pharmacology (12.2) ] . Monitor kidney function and reduce the dose of allopurinol in patients with concomitant thiazide diuretic use and impaired renal function [see Dosage and Administration (2.6) , Warnings and Precautions (5.1) ].

Discontinue allopurinol at the first appearance of skin rash or other signs which may indicate a hypersensitivity reaction when use concomitantly with these drugs [see Warnings and Precautions (5.1) ] .

7.2 Drugs Known to Have Clinically Important Drug Interactions with Allopurinol Table 3: Interventions for Clinically Important Drug Interactions with Allopurinol Capecitabine Clinical Impact Concomitant use with allopurinol may decrease concentration of capecitabine’s active metabolites, which may decrease capecitabine efficacy. Intervention Avoid the use of allopurinol during treatment with capecitabine Chlorpropamide Clinical Impact Allopurinol prolongs the half-life of chlorpropamide as both compete for renal tubular excretion.

In patients with renal insufficiency, the risk of hypoglycemia may be increased due to this mechanism. Intervention Monitor patients with renal insufficiency for hypoglycemia when administering chlorpropamide and allopurinol concomitantly. Cyclosporine Clinical Impact Concomitant use of allopurinol increases cyclosporine concentrations, which may increase the risk of adverse reactions. Intervention Increase frequency of monitoring cyclosporine concentrations as reflected in its prescribing information and modify the dosage of cyclosporine as appropriate when used concomitantly with allopurinol.

Cyclophosphamide and Other Cytotoxic Agents Clinical Impact Concomitant use of allopurinol with cyclophosphamide and other cytotoxic agents (doxorubicin, bleomycin, procarbazine, mechloroethamine) increases bone marrow suppression among patients with neoplastic disease, except leukemia. Intervention Blood count monitoring and regular physician follow-up are recommended. Dicumarol Clinical Impact Allopurinol prolongs the half-life of the anticoagulant, dicumarol.

The mechanism of this drug interaction has not been established but should be noted when allopurinol is given to patients already on dicumarol therapy. Intervention Monitor prothrombin time. Adjust the dosage of dicumarol accordingly when allopurinol is added to anticoagulant therapy. Fluorouracil Clinical Impact Based on non-clinical data, allopurinol may decrease anti-tumor activity due to suppression of phosphorylation of 5-fluorouracil.

Intervention Concomitant administration with fluorouracil should be avoided. Mercaptopurine or Azathioprine Clinical Impact Allopurinol inhibits xanthine oxidase mediated metabolism of mercaptopurine and azathioprine. Concomitant use of allopurinol increases the exposure of either mercaptopurine or azathioprine which may increase the risk of their adverse reactions, including myelosuppression [see Warnings and Precautions 5.5 ].

Intervention In patients receiving mercaptopurine or azathioprine, the concomitant administration of 300 mg to 600 mg of allopurinol per day will require a reduction in dose to approximately one third to one fourth of the usual dose of mercaptopurine or azathioprine. Subsequent adjustment of doses of mercaptopurine or azathioprine should be made on the basis of therapeutic response and the appearance of toxic effects.

Pegloticase Clinical Impact Concomitant use of allopurinol and pegloticase may potentially blunt the rise of serum uric acid levels and increase the risk of pegloticase related anaphylaxis in patients whose uric acid level increase to above 6 mg/dL. Intervention Discontinue and do not institute allopurinol therapy during treatment with pegloticase. Theophylline Clinical Impact Concomitant use of allopurinol doses greater than or equal to 600 mg/day may decrease the clearance of theophylline Intervention Monitor and adjust theophylline doses as reflected in the prescribing information.

Uricosuric Drugs Clinical Impact Uricosuric agents increase the excretion of the active allopurinol metabolite oxypurinol. Concomitant use with uricosuric agents decreases oxypurinol exposure which may reduce the inhibition of xanthine oxidase by oxypurinol and increases the urinary excretion of uric acid. The net effect of such combined therapy may be useful in some patients in achieving minimum serum uric acid levels provided the total urinary uric acid load does not exceed the competence of the patient's kidney function.

Intervention Monitor uric acid levels due to the increased chance of hypouricemic effects. Warfarin Clinical Impact Allopurinol may inhibit the metabolism of warfarin, possibly enhancing its anticoagulant effect. Intervention Monitor patients on concomitant therapy for excessive anticoagulation. Assess INR frequently and adjust warfarin dosage accordingly when allopurinol is added to warfarin therapy.

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary Based

on findings in animals, allopurinol may cause fetal harm when administered to a pregnant woman. Adverse developmental outcomes have been described in exposed animals (see Data). Allopurinol and its metabolite oxypurinol have been shown to cross the placenta following administration of maternal allopurinol. Available limited published data on allopurinol use in pregnant women do not demonstrate a clear pattern or increase in frequency of adverse developmental outcomes.

Among approximately 50 pregnancies described in published literature, 2 infants with major congenital malformations have been reported with following maternal allopurinol exposure. Advise pregnant women of the potential risk to a fetus. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The background risk of major birth defects and miscarriage for the indicated population is unknown.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Human Data Experience with allopurinol during human pregnancy has been limited partly because women of reproductive age rarely require treatment with allopurinol. A case report published in 2011 described the outcome of a full-term pregnancy in a 35-year-old woman who had recurrent kidney stones since age 18 who took allopurinol throughout the pregnancy.

The child had multiple complex birth defects and died at 8 days of life. A second report in 2013 provided data on 31 prospectively ascertained pregnancies involving mothers exposed to allopurinol for varying durations during the first trimester. The overall rate of major fetal malformations and spontaneous abortions was reported to be within the normal expected range; however, one child had severe malformations similar to those described in the cited earlier case report.

Animal Data There was no evidence of fetotoxicity or teratogenicity in rats or rabbits treated during the period of organogenesis with oral allopurinol at doses up to 200 mg/kg/day and up to 100 mg/kg/day, respectively (about 2.4 times the human dose on a mg/m 2 basis). However, there is a published report in pregnant mice that single intraperitoneal doses of 50 mg/kg or 100 mg/kg (about 0.3 or 0.6 times the human dose on a mg/m 2 basis) of allopurinol on gestation days 10 or 13 produced significant increases in fetal deaths and teratogenic effects (cleft palate, harelip, and digital defects).

It is uncertain whether these findings represented a fetal effect or an effect secondary to maternal toxicity.

Adverse reactions

The following clinically significant adverse reactions are described elsewhere in the labeling: Skin Rash and Hypersensitivity [see Warnings and Precautions (5.1) ] Nephrotoxicity [see Warnings and Precautions (5.3) ] Hepatoxicity [see Warnings and Precautions (5.4) ] Myelosuppression [see Warnings and Precautions (5.5) ] Potential Effect on Driving and Use of Machinery [see Warnings and Precautions (5.6) ] The following adverse reactions associated with the use of allopurinol were identified in literature, unpublished clinical trials or postmarketing reports.

Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The most frequent adverse reaction to allopurinol is skin rash. Most Common Adverse Reactions (≥ 1%) Gastrointestinal : Diarrhea, nausea, alkaline phosphatase increase, AST/ALT increase. Metabolic and Nutritional : Acute attacks of gout.

Skin and Appendages : Rash, maculopapular rash. Less Common Adverse Reactions (< 1%) Body As a Whole : Ecchymosis, fever, headache, malaise. Cardiovascular : Necrotizing angiitis, vasculitis, pericarditis, peripheral vascular disease, thrombophlebitis, bradycardia, vasodilation. Gastrointestinal : Hepatic necrosis, granulomatous hepatitis, hepatomegaly, hyperbilirubinemia, cholestatic jaundice, vomiting, intermittent abdominal pain, gastritis, dyspepsia, hemorrhagic pancreatitis, gastrointestinal bleeding, stomatitis, salivary gland swelling, hyperlipidemia, tongue edema, anorexia.

Hemic and Lymphatic: Thrombocytopenia, eosinophilia, leukocytosis, leukopenia, aplastic anemia, agranulocytosis, eosinophilic fibrohistiocytic lesion of bone marrow, pancytopenia, prothrombin decrease, anemia, hemolytic anemia, reticulocytosis, lymphadenopathy, lymphocytosis. Musculoskeletal: Myopathy, arthralgias, myalgia. Nervous: Peripheral neuropathy, neuritis, paresthesia, somnolence, optic neuritis, confusion, dizziness, vertigo, foot drop, decrease in libido, depression, amnesia, tinnitus, asthenia, insomnia.

Respiratory: Epistaxis, bronchospasm, asthma, pharyngitis, rhinitis. Skin and Appendages : Erythema multiforme exudativum (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), hypersensitivity vasculitis, purpura, vesicular bullous dermatitis, exfoliative dermatitis, eczematoid dermatitis, pruritus, urticaria, alopecia, onycholysis, lichen planus, furunculosis, facial edema, sweating, skin edema.

Special Senses : Taste loss/perversion, cataracts, macular retinitis, iritis, conjunctivitis, amblyopia. Urogenital: Renal failure, uremia, nephritis, impotence, primary hematuria, albuminuria. Endocrine: Infertility (male), hypercalcemia, gynecomastia (male). Most common adverse reactions (incidence > 1%) are nausea, diarrhea, and increase in liver function tests. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Allopurinol

Indications

Contraindications

Warnings and precautions

Two medicines in one question?

Allopurinol

Indications

Contraindications

Warnings and precautions

Two medicines in one question?

5.1Skin Rash and Hypersensitivity Serious

5.2Gout Flares

5.3Nephrotoxicity Treatment

5.4Hepatotoxicity Cases

5.5Myelosuppression

5.6Potential Effect on Driving and Use of Machinery

Interactions

7.1Drugs Known to Affect the Occurrence of Skin Rash and Hypersensitivity

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary Based

Adverse reactions

Composition

Strengths and forms

Official product information

At a glance