Allopurinol

Allopurinol may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• diarrhea
• nausea (upset stomach)
• gout attacks

Some side effects can be serious. The following side effects occur less frequently, but if you experience any of them, call your doctor immediately:

• rash
• painful urination
• blood in the urine
• irritation of the eyes
• swelling of the lips or mouth
• fever, sore throat, chills, and other signs of infection
• loss of appetite
• unexpected weight loss
• itching

This is not a complete list of allopurinol drug interactions. Ask your doctor or pharmacist for more information.

Before receiving allopurinol, tell your doctor about all of your medical conditions including if you:

• have liver or kidney disease
• are pregnant or breastfeeding
• are allergic to any medications, foods, dyes or preservatives

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Allopurinol falls into category C. There are no good studies that have been done in humans with allopurinol. In animals studies, pregnant animals were given this medication and had some babies born with problems. However, this medication may sometimes still help human mothers and their babies more than it might cause harm.

Take allopurinol exactly as prescribed.

The dose your doctor recommends may be based on the following:

• the condition being treated
• other medications you are taking
• other conditions you have
• how your body responds to Aloprim
• your kidney function

Allopurinol Tablets

The adult dosage range is 100 mg to 800 mg. Your doctor will likely start you on a low dose and gradually increase the dose to avoid a flare-up of gout attacks which may occur when starting allopurinol. The recommended starting dose is 100 mg daily. The allopurinol dose is then increased by 100 mg each week based on the uric acid level in your blood.

• The maximum recommended dose is 800 mg. Doses higher than 300 mg should be divided into two or three smaller doses per day.

The adult dose for patients with cancer is allopurinol 600 mg or 800 mg daily (divided into two or three smaller doses per day) for two or three days, together with a high intake of fluids.

To prevent calcium oxalate kidney stones in adults is 200 mg or 300 mg per day, taken as a single dose or as a few (two or three) smaller doses throughout the day.

For children with cancer, ages 6 to 10, the recommended daily dose is 300 mg. Children under 6 years of age are usually given 150 mg allopurinol daily. 

Allopurinol Injection to lower high levels of uric acid in the body due to cancer treatment

• The recommended daily dose of Aloprim for adults is 200 to 400 mg/m²/day. The maximum daily dose is 600 mg.
• The recommended starting daily dose of Aloprim for children is 200 mg/m²/day.

Gout

Reduction of serum and urinary uric acid concentrations in primary and secondary gout.156 In early uncomplicated gout, preferred over uricosurics in patients with urinary uric acid excretion >900 mg daily and in those with gouty nephropathy, urinary tract stones or obstruction, or azotemia.a

Management of gout when uricosuric agents cannot be used because of adverse effects, allergy, or inadequate response; when there are visible tophi or radiographic evidence of uric acid deposits and stones; or when serum urate concentrations exceed 8.5–9 mg/dL and patient has family history of tophi and low urate excretion.a

Management of primary or secondary gouty nephropathy with or without secondary oliguria.a

Not recommended for management of asymptomatic hyperuricemia;156 however, some clinicians have suggested that therapy be initiated when serum urate concentrations exceed 9 mg/dL (by colorimetric method) because these concentrations often are associated with increased joint changes and renal complications.a

Of no value in the treatment of acute gout attacks (due to lack of analgesic or anti-inflammatory activity).a

Chemotherapy-induced Hyperuricemia

A component of therapy (with urinary alkalinization and IV hydration)160 in patients with leukemia, lymphoma, and solid tumor malignancies who are undergoing cancer therapy expected to result in tumor lysis and subsequent elevations of serum and urinary uric acid concentrations.152 153 156

Oral allopurinol may be slower and less effective in decreasing plasma uric acid concentrations than IV rasburicase.157 158 159 160 161

Recurrent Renal Calculi

Management of recurrent calcium oxalate renal calculi in males and females whose urinary urate excretion exceeds 800 and 750 mg daily, respectively.156

Prevention of uric acid renal calculi in patients with history of recurrent stone formation.a

Other Uses

Has been used to reduce hyperuricemia secondary to glucose-6-phosphate dehydrogenase deficiency†, Lesch-Nyhan syndrome†, polycythemia vera†, or sarcoidosis† or secondary to administration of thiazides† or ethambutol†.a

Does not inhibit hepatic microsomal enzymes.a

Specific Drugs

• Importance of discontinuing drug and consulting clinician at first sign of rash, painful urination, blood in urine, irritation of eyes, or swelling of lips or mouth.152 156

• Importance of maintaining fluid intake sufficient to yield daily urine output of ≥2 L.152 156

• Administering drug after meals may minimize gastric irritation.156

• Importance of continuing allopurinol therapy as prescribed for gout; optimal benefit may be delayed for 2–6 weeks.156

• Potential for drug to cause drowsiness and impair mental alertness; use caution when operating machinery or performing hazardous tasks until effects on individual are known.152 156

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.152 156

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.152 156

• Importance of informing patients of other important precautionary information.152 156 (See Cautions.)

Allopurinol has the following structural formula:

Allopurinol is known chemically as 1,5-dihydro-4H-pyrazolo [3,4-d]pyrimidin-4-one. It is a xanthine oxidase inhibitor which is administered orally. Each scored white tablet contains 100 mg Allopurinol and the inactive ingredients colloidal silicon dioxide, lactose monohydrate, magnesium stearate, microcrystalline cellulose and sodium starch glycolate. Each scored orange tablet contains 300 mg Allopurinol and the inactive ingredients colloidal silicon dioxide, FD&C Yellow No. 6 Lake, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. Its solubility in water at 37°C is 80 mg/dL and is greater in an alkaline solution.

THIS IS NOT AN INNOCUOUS DRUG. IT 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 (see CLINICAL PHARMACOLOGY, CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS).

Allopurinol is indicated in:

General

An increase in acute attacks of gout has been reported during the early stages of Allopurinol administration, even when normal or subnormal serum uric acid levels have been attained. Accordingly, maintenance doses of colchicine generally should be given prophylactically when Allopurinol is begun. In addition, it is recommended that the patient start with a low dose of Allopurinol (100 mg daily) and increase at weekly intervals by 100 mg until a serum uric acid level of 6 mg/dL or less is attained but without exceeding the maximum recommended dose (800 mg per day). The use of colchicine or anti-inflammatory agents may be required to suppress gouty attacks in some cases. The attacks usually become shorter and less severe after several months of therapy. The mobilization of urates from tissue deposits which cause fluctuations in the serum uric acid levels may be a possible explanation for these episodes. Even with adequate therapy with Allopurinol, it may require several months to deplete the uric acid pool sufficiently to achieve control of the acute attacks.

A fluid intake sufficient to yield a daily urinary output of at least two liters and the maintenance of a neutral or, preferably, slightly alkaline urine are desirable to (1) avoid the theoretical possibility of formation of xanthine calculi under the influence of therapy with Allopurinol and (2) help prevent renal precipitation of urates in patients receiving concomitant uricosuric agents.

Some patients with pre-existing renal disease or poor urate clearance have shown a rise in BUN during administration of Allopurinol. Although the mechanism responsible for this has not been established, patients with impaired renal function should be carefully observed during the early stages of administration of Allopurinol and the dosage decreased or the drug withdrawn if increased abnormalities in renal function appear and persist.

Renal failure in association with administration of Allopurinol has been observed among patients with hyperuricemia secondary to neoplastic diseases. Concurrent conditions such as multiple myeloma and congestive myocardial disease were present among those patients whose renal dysfunction increased after Allopurinol was begun. Renal failure is also frequently associated with gouty nephropathy and rarely with hypersensitivity reactions associated with Allopurinol. Albuminuria has been observed among patients who developed clinical gout following chronic glomerulonephritis and chronic pyelonephritis.

Patients with decreased renal function require lower doses of Allopurinol than those with normal renal function. Lower than recommended doses should be used to initiate therapy in any patients with decreased renal function and they should be observed closely during the early stages of administration of Allopurinol. In patients with severely impaired renal function or decreased urate clearance, the half-life of oxipurinol in the plasma is greatly prolonged. Therefore, a dose of 100 mg per day or 300 mg twice a week, or perhaps less, may be sufficient to maintain adequate xanthine oxidase inhibition to reduce serum urate levels.

Bone marrow depression has been reported in patients receiving Allopurinol, most of whom received concomitant drugs with the potential for causing this reaction. This has occurred as early as six weeks to as long as six years after the initiation of therapy of Allopurinol. Rarely a patient may develop varying degrees of bone marrow depression, affecting one or more cell lines, while receiving Allopurinol alone.

Information for Patients

Patients should be informed of the following:
(1) They should be cautioned to discontinue Allopurinol and to consult their physician immediately at the first sign of a skin rash, painful urination, blood in the urine, irritation of the eyes, or swelling of the lips or mouth. (2) They should be reminded to continue drug therapy prescribed for gouty attacks since optimal benefit of Allopurinol may be delayed for two to six weeks. (3) They should be encouraged to increase fluid intake during therapy to prevent renal stones. (4) If a single dose of Allopurinol is occasionally forgotten, there is no need to double the dose at the next scheduled time. (5) There may be certain risks associated with the concomitant use of Allopurinol and dicumarol, sulfinpyrazone, mercaptopurine, azathioprine, ampicillin, amoxicillin, and thiazide diuretics, and they should follow the instructions of their physician. (6) Due to the occasional occurrence of drowsiness, patients should take precautions when engaging in activities where alertness is mandatory. (7) Patients may wish to take Allopurinol after meals to minimize gastric irritation.

Laboratory Tests

The correct dosage and schedule for maintaining the serum uric acid within the normal range is best determined by using the serum uric acid as an index.

In patients with pre-existing liver disease, periodic liver function tests are recommended during the early stages of therapy (see WARNINGS).

Allopurinol and its primary active metabolite, oxipurinol, are eliminated by the kidneys; therefore, changes in renal function have a profound effect on dosage. In patients with decreased renal function or who have concurrent illnesses which can affect renal function such as hypertension and diabetes mellitus, periodic laboratory parameters of renal function, particularly BUN and serum creatinine or creatinine clearance, should be performed and the patient's dosage of Allopurinol reassessed.

The prothrombin time should be reassessed periodically in the patients receiving dicumarol who are given Allopurinol.

Drug Interactions

In patients receiving mercaptopurine or IMURAN (azathioprine), the concomitant administration of 300 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 (see CLINICAL PHARMACOLOGY).

It has been reported that Allopurinol prolongs the half-life of the anticoagulant, dicumarol. The clinical basis of this drug interaction has not been established but should be noted when Allopurinol is given to patients already on dicumarol therapy.

Since the excretion of oxipurinol is similar to that of urate, uricosuric agents, which increase the excretion of urate, are also likely to increase the excretion of oxipurinol and thus lower the degree of inhibition of xanthine oxidase. The concomitant administration of uricosuric agents and Allopurinol has been associated with a decrease in the excretion of oxypurines (hypoxanthine and xanthine) and an increase in urinary uric acid excretion compared with that observed with Allopurinol alone. Although clinical evidence to date has not demonstrated renal precipitation of oxypurines in patients either on Allopurinol alone or in combination with uricosuric agents, the possibility should be kept in mind.

The reports that the concomitant use of Allopurinol and thiazide diuretics may contribute to the enhancement of Allopurinol toxicity in some patients have been reviewed in an attempt to establish a cause-and-effect relationship, and a mechanism of causation. Review of these case reports indicates that the patients were mainly receiving thiazide diuretics for hypertension and that tests to rule out decreased renal function secondary to hypertensive nephropathy were not often performed. In those patients in whom renal insufficiency was documented, however, the recommendation to lower the dose of Allopurinol was not followed. Although a causal mechanism and a cause-and-effect relationship have not been established, current evidence suggests that renal function should be monitored in patients on thiazide diuretics and Allopurinol even in the absence of renal failure, and dosage levels should be even more conservatively adjusted in those patients on such combined therapy if diminished renal function is detected.

An increase in the frequency of skin rash has been reported among patients receiving ampicillin or amoxicillin concurrently with Allopurinol compared to patients who are not receiving both drugs. The cause of the reported association has not been established.

Enhanced bone marrow suppression by cyclophosphamide and other cytotoxic agents has been reported among patients with neoplastic disease, except leukemia, in the presence of Allopurinol. However, in a well-controlled study of patients with lymphoma on combination therapy, Allopurinol did not increase the marrow toxicity of patients treated with cyclophosphamide, doxorubicin, bleomycin, procarbazine, and/or mechlorethamine.

Tolbutamide's conversion to inactive metabolites has been shown to be catalyzed by xanthine oxidase from rat liver. The clinical significance, if any, of these observations is unknown.

Chlorpropamide's plasma half-life may be prolonged by Allopurinol, since Allopurinol and chlorpropamide may compete for excretion in the renal tubule. The risk of hypoglycemia secondary to this mechanism may be increased if Allopurinol and chlorpropamide are given concomitantly in the presence of renal insufficiency.

Rare reports indicate that cyclosporine levels may be increased during concomitant treatment with Allopurinol. Monitoring of cyclosporine levels and possible adjustment of cyclosporine dosage should be considered when these drugs are coadministered.

Drug/Laboratory Test Interactions

Allopurinol is not known to alter the accuracy of laboratory tests.

Pregnancy

Teratogenic Effects:

Reproductive studies have been performed in rats and rabbits at doses up to twenty times the usual human dose (5 mg/kg/day), and it was concluded that there was no impaired fertility or harm to the fetus due to Allopurinol. There is a published report of a study in pregnant mice given 50 or 100 mg/kg Allopurinol intraperitoneally on gestation days 10 or 13. There were increased numbers of dead fetuses in dams given 100 mg/kg Allopurinol but not in those given 50 mg/kg. There were increased numbers of external malformations in fetuses at both doses of Allopurinol on gestation day 10 and increased numbers of skeletal malformations in fetuses at both doses on gestation day 13. It cannot be determined whether this represented a fetal effect or an effect secondary to maternal toxicity. There are, however, no adequate or well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Experience with Allopurinol during human pregnancy has been limited partly because women of reproductive age rarely require treatment with Allopurinol. There are two unpublished reports and one published paper of women giving birth to normal offspring after receiving Allopurinol during pregnancy.

Nursing Mothers

Allopurinol and oxipurinol have been found in the milk of a mother who was receiving Allopurinol. Since the effect of Allopurinol on the nursing infant is unknown, caution should be exercised when Allopurinol is administered to a nursing woman.

Pediatric Use

Allopurinol is rarely indicated for use in children with the exception of those with hyperuricemia secondary to malignancy or to certain rare inborn errors of purine metabolism (see INDICATIONS AND USAGE, and DOSAGE AND ADMINISTRATION).

(al oh PURE i nole)

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)

Time to Peak

Plasma: Oral: Allopurinol: 1.5 hours; Oxypurinol: 4.5 hours

Half-Life Elimination

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

Oral:

Calcium oxalate calculi (recurrent): Management of recurrent calcium oxalate calculi (with uric acid excretion >800 mg/day in men and >750 mg/day in women)

Cancer therapy-induced hyperuricemia: Management of hyperuricemia associated with cancer treatment for leukemia, lymphoma, and other malignancies

Gout: Management of primary or secondary gout (acute attack, tophi, joint destruction, uric acid lithiasis, and/or nephropathy)

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: Cancer therapy-induced hyperuricemia: Management of hyperuricemia associated with cancer treatment for leukemia, lymphoma, or solid tumor malignancies in patients who cannot tolerate oral therapy.

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

• 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, nausea, or injection site irritation. Have patient report immediately to prescriber signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), painful urination, hematuria, chills, pharyngitis, eye irritation, joint pain, bruising, bleeding, severe loss of strength and energy, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (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.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

• Gout (Gouty Arthritis)
• Kidney Stones

More frequently reported side effects include: acute gout attack. See below for a comprehensive list of adverse effects.

• Allopurinol may be used to decrease levels of uric acid in people with gout, kidney stones, or who are receiving certain types of chemotherapy.
• Allopurinol reduces the production of uric acid (a compound produced by the body associated with gout and kidney stones), by inhibiting an enzyme called xanthine oxidase. Allopurinol reduces levels of uric acid in the blood and the urine.
• Allopurinol belongs to the class of medicines called xanthine oxidase inhibitors.

• May be used to prevent acute attacks of gout and to reduce ongoing complications of gout such as tophi (deposits of crystalline uric acid that form painful nodules), joint destruction, uric acid lithiasis (the formation of kidney or bladder stones), and kidney disease. Note that allopurinol does not treat acute attacks of gout, although once started, it should be continued throughout an acute attack.
• May be used temporarily to reduce elevated uric acid levels caused by certain cancer treatments in people with leukemia, lymphoma, and other malignancies.
• May also be used to treat recurrent kidney stones (calcium oxalate calculi) in males with a urinary uric acid level of more than 800 mg/day, or in females with levels greater than 750 mg/day. The need for continued treatment should be reassessed periodically.
• Available as an oral tablet and as an injection.
• Can be taken once a day.
• Generic allopurinol is available.

Allopurinol is used in the treatment of high uric acid levels associated with gout, kidney stones, and cancer treatment. If a rash occurs while taking allopurinol, immediate discontinuation of allopurinol is required and urgent medical advice should be sought.

Substance Name

Allopurinol

CAS Registry Number

315-30-0

Drug Class

Antigout Agents

Enzyme Inhibitors

Gout Suppressants

LactMed Record Number

334

Last Revision Date

20170411

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Information presented in this database is not meant as a substitute for professional judgment. You should consult your healthcare provider for breastfeeding advice related to your particular situation. The U.S. government does not warrant or assume any liability or responsibility for the accuracy or completeness of the information on this Site.