Allopurinol

Generic name: allopurinol · Brand names: Zyloprim, Lopurin

Quick facts

Drug class
Section
Highlights, Indications and Usage
Openfda pharm class epc
Xanthine Oxidase Inhibitor [EPC]
Openfda source
https://api.fda.gov/drug/label.json?search=openfda.generic_name.exact:"ALLOPURINOL"&count=openfda.pharm_class_epc.exact
Source text (exact source wording)
Allopurinol tablet is a xanthine oxidase inhibitor indicated for the management of:
Rx or otc
Rx (DailyMed: 'Product Type HUMAN PRESCRIPTION DRUG'; carton 'Rx Only')
Forms and strengths
  • 100 mg: A flat-faced raised hexagon, beveled edge, white to off-white tablet, one side engraved “ZYLOPRIM 100” with a score bar and the other side plain.
  • 200 mg: White to off-white, biconvex, round, scored tablets, imprinted “ZYLOPRIM” about the upper periphery, and 200 on the lower half, below the score and plain on the other side.
  • 300 mg: A flat-faced raised hexagon, beveled edge, peach tablet, one side engraved “ZYLOPRIM 300” with a score bar and the other side plain.
Forms note
Standard oral tablets only. Imprints shown are those of the Rising authorized-generic label and will differ for other makers.
Generic available
Value
yes
Source
DailyMed Marketing Information of the chosen label: 'NDA AUTHORIZED GENERIC NDA016084'; many ANDA allopurinol tablet labels are listed on DailyMed
Common use one line
Used for gout, for high uric acid caused by cancer treatment, and for recurrent calcium oxalate kidney stones (label section 1).

What it is used for

Allopurinol treats adults with gout. It also treats adults and children with leukemia, lymphoma or solid tumors whose cancer treatment raises uric acid, and adults with recurrent calcium oxalate stones whose daily uric acid excretion exceeds 800 mg/day in men and 750 mg/day in women despite lifestyle changes. It is not recommended for asymptomatic hyperuricemia.
Section
1 INDICATIONS & USAGE
Source text (exact source wording)
Allopurinol tablet is 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 tablet is not recommended for the treatment of asymptomatic hyperuricemia.
Medlineplus source text (exact source wording)
Allopurinol is used to treat gout (a type of arthritis in which uric acid, a naturally occurring substance in the body, builds up in the joints and causes sudden attacks of redness, swelling, pain, and heat in one or more joints). Allopurinol is also used to treat high levels of uric acid that builds up in the blood as tumors break down in people with certain types of cancer who are being treated with chemotherapy medications. It is also used to treat kidney stones that have come back in people who have high levels of uric acid in their urine. Allopurinol is in a class of medications called xanthine oxidase inhibitors. It works by reducing the production of uric acid in the body. High levels of uric acid may cause gout attacks or kidney stones. Allopurinol is used to prevent gout attacks, not to treat them once they occur.

How it works

Allopurinol blocks xanthine oxidase, the enzyme that makes uric acid. Its breakdown product, oxypurinol, also blocks this enzyme. This lowers the amount of uric acid the body makes.
Section
12.1 Mechanism of Action
Source text (exact source wording)
Allopurinol is a structural analogue of the natural purine base, hypoxanthine.
Allopurinol acts on purine catabolism, without disrupting the biosynthesis of purines. It reduces the production of uric acid by inhibiting the biochemical reactions immediately preceding its formation. It is an inhibitor of xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine and of xanthine to uric acid, the end product of purine metabolism in humans. Allopurinol is metabolized to the corresponding xanthine analogue, oxypurinol (alloxanthine), which also is an inhibitor of xanthine oxidase.

Dosage: adults

For gout, the label gives 100 mg orally daily as the initial dosage, with weekly increments of 100 mg until a serum uric acid level of 6 mg/dL or less is reached. The minimal effective dosage is 100 mg to 200 mg daily and the maximal recommended dosage is 800 mg daily. Doses in excess of 300 mg should be administered in divided doses. Baseline tests are done first, and flare prophylaxis with colchicine or an anti-inflammatory agent is recommended at the start. It is generally better tolerated if taken following meals. For hyperuricemia from cancer therapy, adults take 300 mg to 800 mg orally daily, starting 24 hours to 48 hours before chemotherapy. For recurrent calcium oxalate stones, the dosage is 200 mg to 300 mg orally daily.
Section
2 DOSAGE & ADMINISTRATION (2.1-2.5)
Source text (exact source wording)
2.1 Recommended Testing Prior to Treatment Initiation
Prior to initiating treatment with allopurinol tablets in patients with gout, assess the following baseline tests: serum uric acid level, complete blood count, chemistry panel, liver function tests (serum alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase, and total bilirubin), kidney function tests (serum creatinine and eGFR).
2.2 Recommended Prophylaxis for Gout Flares
Gout flares may occur after initiation of allopurinol tablets due to changing serum uric acid levels resulting in mobilization of urate from tissue deposits. Flare prophylaxis with colchicine or an anti-inflammatory agent according to practice guidelines is recommended upon initiation of allopurinol tablets.
2.3 Recommended Dosage for Gout
The initial recommended dosage for the management of gout is 100 mg orally daily, with weekly increments of 100 mg, until a serum uric acid level of 6 mg/dL or less is reached. Initiating treatment with lower dosages of allopurinol tablets and titrating slowly, decreases the risk of gout flares and drug induced serious adverse reactions.
The minimal effective dosage is 100 mg to 200 mg daily and the maximal recommended dosage is 800 mg daily. The appropriate dosage may be administered in divided doses or as a single equivalent dose with the 300 mg tablet. Doses in excess of 300 mg should be administered in divided doses.
In general, gout control is achieved with 200 mg to 300 mg daily in patients with mild gout, and with 400 mg to 600 mg daily in patients with moderate to severe tophaceous gout. Gout attacks usually become shorter and less severe after several months of therapy.
Allopurinol tablets is generally better tolerated if taken following meals. A fluid intake sufficient to yield a daily urinary output of at least 2 liters and the maintenance of a neutral or preferably, slightly alkaline urine are desirable.
2.4 Recommended Dosage for Hyperuricemia Associated with Cancer Therapy
Initiate therapy with allopurinol tablets 24 hours to 48 hours before the start of chemotherapy known to cause tumor cell lysis.
Adult patients – 300 mg to 800 mg orally daily
Discontinue allopurinol tablets when the risk of tumor lysis has abated (2 days to 3 days from start of chemotherapy).
2.5 Recommended Dosage for Management of Recurrent Calcium Oxalate Calculi in Hyperuricosuric Patients
The recommended dosage for the management of recurrent calcium oxalate stones in hyperuricosuric patients is 200 mg to 300 mg orally daily in divided doses or as the single equivalent.

Dosage: children

For children with cancer-therapy hyperuricemia, the label gives 100 mg/m2 orally every 8 hours to 12 hours (10 mg/kg/day, maximum 800 mg/day). Safety and effectiveness have not been established for gout or recurrent calcium oxalate stones in children.
Section
2.4 and 8.4 Pediatric Use
Source text (exact source wording)
Pediatric patients - 100 mg/m2 orally every 8 hours to 12 hours (10 mg/kg/day, maximum 800 mg/day). In patients with body surface area < 0.5 m2, consider using an alternative allopurinol formulation.
8.4 Pediatric Use: The safety and effectiveness of allopurinol for the management of pediatric patients with leukemia, lymphoma and solid tumor malignancies who are receiving cancer therapy which causes elevations of serum and urinary uric acid levels have been established in approximately 200 pediatric patients. The efficacy and safety profile observed in this patient population were similar to that observed in adults.
The safety and effectiveness of allopurinol have not been established for the treatment of signs and symptoms of primary or secondary gout in pediatric patients.
The safety and effectiveness of allopurinol have not been established for the management of pediatric patients with recurrent calcium oxalate calculi.

Dosage adjustments

Drug interaction caps
With mercaptopurine or azathioprine, the label says the dose of those drugs needs a reduction to approximately one third to one fourth of the usual dose when taken with 300 mg to 600 mg of allopurinol per day. With a thiazide diuretic and impaired kidney function, the allopurinol dose is reduced and kidney function monitored.
Section
7.2 Table 3 (mercaptopurine, azathioprine) and 7.1
Source text (exact source wording)
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.
Monitor kidney function and reduce the dose of allopurinol tablets in patients with concomitant thiazide diuretic use and impaired renal function [see Dosage and Administration (2.6), Warnings and Precautions (5.1)].
Kidney
For adults with gout and kidney impairment the label starts at a lower dose and raises it in 50 mg/day steps every 2 weeks to 4 weeks. Table 1 gives starting doses by eGFR, from no change above 60 mL/minute to 50 mg once weekly below 5 mL/minute. The label has a separate Table 2 for cancer-therapy hyperuricemia, which is not reproduced here.
Section
2.6 Recommended Dosage in Patients with Renal Impairment (Table 1)
Source text (exact source wording)
In patients with renal impairment the initial dosage is 50 mg orally daily with lower dose increases until serum uric acid level of 6 mg/dL or less is reached.
Initiate treatment with a lower dose of allopurinol tablets and increase the dose gradually in 50 mg/day increments every 2 weeks to 4 weeks in patients with renal impairment to decrease the risk of drug induced serious adverse reactions.
Table 1. Recommended Initial Dosage in Adult Patients with Gout
eGFR Initial Dosage
> 60 mL/minute No dosage modification
> 30 to 60 mL/minute 50 mg daily
> 15 to 30 mL/minute 50 mg every other day
5 to 15 mL/minute 50 mg twice weekly
< 5 mL/minute 50 mg once weekly
The maximum dosage that should be used in patients with various levels of renal impairment is not defined at different eGFR levels.
Liver
Section
5.4 Hepatotoxicity
Source text (exact source wording)
In patients with pre-existing liver disease, monitor liver enzymes periodically.
Elderly
The label has no separate section for older adults.

Missed dose

If you miss a dose, do not double the dose at the next scheduled time.
Section
2.3 and 17 PATIENT COUNSELING INFORMATION
Source text (exact source wording)
If a dose of allopurinol tablets is missed, there is no need to double the dose at the next scheduled time.
If a single dose of allopurinol tablet is occasionally forgotten, there is no need to double the dose at the next scheduled time.
Medlineplus source text (exact source wording)
Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Overdose

There is no specific antidote for allopurinol. Allopurinol and oxipurinol can be removed by dialysis, but whether dialysis helps in an overdose is unknown. For a suspected overdose, call poison control at 1-800-222-1222.
Section
10 OVERDOSAGE
Poison control
1-800-222-1222
Source text (exact source wording)
In the management of overdosage there is no specific antidote for allopurinol. Both allopurinol and oxipurinol are dialyzable; however, the usefulness of hemodialysis or peritoneal dialysis in the management of an overdose of allopurinol is unknown.

Storage

Store at 20°C to 25°C (68°F to 77°F) in a dry place. MedlinePlus adds to keep it in the container it came in, tightly closed, out of reach of children, away from excess heat and moisture (not in the bathroom).
Section
16 HOW SUPPLIED/STORAGE AND HANDLING
Labeler specific note
Wording is from the Rising label; other labelers may word storage differently.
Source text (exact source wording)
Store at 20°C to 25°C (USP Controlled Room Temperature) (68°F to 77°F) in a dry place. Dispense in a tight container as defined in the USP.
Medlineplus source text (exact source wording)
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).

Boxed warning

The label has no boxed warning.
Value
NONE
Note
No boxed warning section appears in the chosen label.

Contraindications

Do not take allopurinol if you have had a hypersensitivity reaction to allopurinol or any of the ingredients in the tablets.
Section
4 CONTRAINDICATIONS
Source text (exact source wording)
Allopurinol tablet is contraindicated in patients with a history of hypersensitivity reaction to allopurinol or to any of the ingredients of allopurinol tablets.

Warnings and precautions

Serious and sometimes fatal skin reactions (TEN, SJS, DRESS) have been reported. They occur in approximately 5 in 10,000 (0.05%) patients. Stop allopurinol permanently at the first skin rash or other sign of hypersensitivity. The HLA-B*58:01 gene raises the risk, and it is more common in people of African, Asian and Native Hawaiian/Pacific Islander ancestry. The label says to consider screening before starting in populations where this allele is common, and not to use it in HLA-B*58:01 positive patients unless the benefits clearly outweigh the risks.
Heading
5.1 Skin Rash and Hypersensitivity
Source text (exact source wording)
Serious and sometimes fatal dermatologic reactions, including toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported in patients taking allopurinol [see Adverse Reactions (6)]. These reactions occur in approximately 5 in 10,000 (0.05%) patients taking allopurinol. Other serious hypersensitivity reactions that have been reported include exfoliative, urticarial and purpuric lesions, generalized vasculitis, and irreversible hepatotoxicity. Discontinue allopurinol tablets permanently at the first appearance of skin rash or other signs which may indicate a hypersensitivity reaction.
The HLA-B*58:01 allele is a genetic marker for severe skin reactions indicative of hypersensitivity to allopurinol. Patients who carry the HLA-B*58:01 allele are at a higher risk of allopurinol hypersensitivity syndrome (AHS), but hypersensitivity reactions have been reported in patients who do not carry this allele. The frequency of this allele is higher in individuals of African, Asian (e.g., Han Chinese, Korean, Thai), and Native Hawaiian/Pacific Islander ancestry [see Clinical Pharmacology (12.5)]. The use of allopurinol tablets is not recommended in HLA- B*58:01 positive patients unless the benefits clearly outweigh the risks.
Consider screening for HLA-B*5801 before starting treatment with allopurinol tablets in patients from populations in which the prevalence of this HLA-B*5801 allele is known to be high.
Discontinue allopurinol tablets immediately if a skin rash develops. Instruct patients to stop taking allopurinol tablets immediately and seek medical attention promptly if they develop a rash.
Gout flares can happen when you start allopurinol. Colchicine or an anti-inflammatory is recommended at the start. Keep taking allopurinol and the preventive medicine even if flares occur, because it may take months to get control.
Heading
5.2 Gout Flares
Source text (exact source wording)
Gout flares have been reported during initiation of treatment with allopurinol tablets, even when normal or subnormal serum uric acid levels have been attained due to the mobilization of urates from tissue deposits. In order to prevent gout flares when treatment with allopurinol tablets is initiated, concurrent prophylactic treatment with colchicine or an anti-inflammatory agent is recommended [see Dosage and Administration (2.2)]. Advise patients to continue allopurinol tablets and prophylactic treatment even if gout flares occur, as it may take months to achieve control of gout flares.
Allopurinol may cause acute kidney injury, and people with kidney disease or a history of kidney stones may be at higher risk. Kidney function is monitored frequently early on, and fluid intake should be enough for a urinary output of at least 2 liters per day.
Heading
5.3 Nephrotoxicity
Source text (exact source wording)
Treatment with allopurinol tablets may result in acute kidney injury due to formation of xanthine calculi or due to precipitation of urates in patients receiving concomitant uricosuric agents. Patients with pre-existing kidney disease, including chronic kidney disease or history of kidney stones, may be at increased risk for worsening of kidney function or acute kidney injury due to xanthine calculi while receiving treatment with allopurinol tablets.
In patients receiving allopurinol tablets for the management of gout or the management of recurrent calcium oxalate calculi, monitor kidney function frequently during the early stages of allopurinol administration. Maintain fluid intake sufficient to yield a urinary output of at least 2 liters per day of neutral or, preferably, slightly alkaline urine.
Cases of reversible liver toxicity have occurred. If anorexia, weight loss, or pruritus develop, liver enzymes are checked. People with existing liver disease have liver enzymes monitored periodically, and the drug is stopped if liver enzymes are elevated.
Heading
5.4 Hepatotoxicity
Source text (exact source wording)
Cases of reversible clinical hepatotoxicity have occurred in patients taking allopurinol tablets, and in some patients, asymptomatic rises in serum alkaline phosphatase or serum transaminase have been observed. If anorexia, weight loss, or pruritus develop in patients on allopurinol tablets, evaluate liver enzymes. In patients with pre-existing liver disease, monitor liver enzymes periodically. Discontinue allopurinol tablets in patients with elevated liver enzymes.
Low blood counts (anemia, leukopenia, thrombocytopenia) have been reported as early as 6 weeks up to 6 years after starting. Using it with cytotoxic drugs may raise the risk, so blood counts are monitored more often.
Heading
5.5 Myelosuppression
Source text (exact source wording)
Myelosuppression, manifested by anemia, leukopenia or thrombocytopenia, has been reported in patients receiving allopurinol tablets. The cytopenias have occurred as early as 6 weeks up to 6 years after the initiation of therapy of allopurinol tablets. Concomitant use of allopurinol tablets with cytotoxic drugs associated with myelosuppression may increase the risk of myelosuppression. Monitor blood counts more frequently when cytotoxic drugs are used concomitantly [see Drug Interactions (7.2)].
Drowsiness and dizziness have been reported. Its effects on the central nervous system may add to those of alcohol and other CNS depressants. Avoid driving or dangerous machinery when starting or raising the dose until you know how it affects you.
Heading
5.6 Potential Effect on Driving and Use of Machinery
Source text (exact source wording)
Drowsiness, somnolence and dizziness have been reported in patients taking allopurinol tablets [see Adverse Reactions (6)]. Inform patients also that the central nervous system depressant effects of allopurinol tablets may be additive to those of alcohol and other CNS depressants.
Advise patients to avoid operation of automobiles or other dangerous machinery and activities made hazardous by decreased alertness when starting allopurinol tablets or increasing the dose, until they know how the drug affects them.

Pregnancy and breastfeeding

Based on animal findings, allopurinol may cause fetal harm, and it crosses the placenta. Limited published data among approximately 50 pregnancies reported 2 infants with major congenital malformations. Pregnant women are advised of the potential risk to a fetus. Allopurinol and oxypurinol are present in human milk, so the label advises women not to breastfeed during treatment and for one week after the last dose. MedlinePlus says to tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding.
Section
8.1 Pregnancy; 8.2 Lactation
Source text (exact source wording)
8.1 Pregnancy: 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.
8.2 Lactation: Allopurinol and oxypurinol are present in human milk. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatments with allopurinol and for one week after the last dose.
Medlineplus source text (exact source wording)
tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking allopurinol, call your doctor.

Side effects

Common
The label says the most frequent side effect is skin rash. Reactions in 1% or more of people are diarrhea, nausea, increases in alkaline phosphatase and AST/ALT, acute attacks of gout, rash and maculopapular rash.
Section
6 ADVERSE REACTIONS - Most Common Adverse Reactions (≥ 1%); Highlights
Threshold
≥ 1% (section 6 heading). Highlights say 'incidence > 1%'.
Source text (exact source wording)
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.
Highlights source text (exact source wording)
Most common adverse reactions (incidence > 1%) are nausea, diarrhea, and increase in liver function tests. (6)
Less common
The label lists less common reactions (below 1%) such as fever, headache, vomiting, dizziness, drowsiness, muscle pain, hair loss, itching, hives, and changes in taste. See the full list in the source text.
Section
6 ADVERSE REACTIONS - Less Common Adverse Reactions (< 1%)
Note
The label gives no placebo-controlled table; this is its '< 1%' list, with no per-reaction percentages.
Source text (exact source wording)
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).
Serious
The label warns of serious and sometimes fatal skin reactions (TEN, SJS, DRESS), other serious hypersensitivity reactions, acute kidney injury, reversible liver toxicity and low blood counts. MedlinePlus says to stop taking allopurinol and call your doctor immediately or get emergency treatment for rash, itching or hives; peeling, blistering or shedding skin; red or purple spots; painful urination; blood in the urine; eye irritation; swelling of the lips or mouth; fever or flu-like symptoms; swollen glands; or yellowing of the skin or eyes.
Label section
5 WARNINGS AND PRECAUTIONS; 6 ADVERSE REACTIONS
Label source text (exact source wording)
Serious and sometimes fatal dermatologic reactions, including toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported in patients taking allopurinol. Other serious hypersensitivity reactions that have been reported include exfoliative, urticarial and purpuric lesions, generalized vasculitis, and irreversible hepatotoxicity. (5.1)
Treatment with allopurinol tablets may result in acute kidney injury (5.3).
Cases of reversible clinical hepatotoxicity have occurred (5.4).
Myelosuppression, manifested by anemia, leukopenia or thrombocytopenia, has been reported (5.5).
Medlineplus source text (exact source wording)
Some side effects can be serious. The following symptoms are uncommon, but if you experience any of them, stop taking allopurinol and call your doctor immediately or get emergency treatment:
rash, itching, or hives
peeling, blistering, or shedding skin
red or purple spots on skin
painful urination
blood in the urine
irritation of the eyes
swelling of the lips or mouth
fever or flu-like symptoms
swollen glands
yellowing of the skin or eyes, pain in the upper right part of the stomach, nausea, vomiting, itching, or extreme tiredness
Source text (exact source wording)
see label_source_text and medlineplus_source_text
Led to discontinuation
The label does not give how many people stopped treatment because of side effects.
Medwatch
To report SUSPECTED ADVERSE REACTIONS, Rising Pharma Holdings, Inc. at 1-844-874-7464 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Medlineplus less serious source text (exact source wording)
Allopurinol may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
nausea
diarrhea
drowsiness

Interactions

Drugs
These drugs may increase the risk of skin rash, which may be severe. Kidney problems may raise the risk further with thiazide diuretics.
Name
Bendamustine, thiazide diuretics, ampicillin and amoxicillin
Section
7.1
Source text (exact source wording)
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.
Monitor kidney function and reduce the dose of allopurinol tablets in patients with concomitant thiazide diuretic use and impaired renal function.
Allopurinol may lower capecitabine's active metabolites and its effect. Avoid using them together.
Name
Capecitabine
Section
7.2 Table 3
Source text (exact source wording)
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 tablets during treatment with capecitabine
Allopurinol lengthens the half-life of chlorpropamide. With kidney problems, low blood sugar risk may rise, so these patients are monitored.
Name
Chlorpropamide
Section
7.2 Table 3
Source text (exact source wording)
Clinical Impact Allopurinol tablets 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 tablets concomitantly.
Allopurinol raises cyclosporine levels, so levels are monitored more often and the cyclosporine dose adjusted as appropriate.
Name
Cyclosporine
Section
7.2 Table 3
Source text (exact source wording)
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 tablets.
This combination increases bone marrow suppression in patients with neoplastic disease, except leukemia. Blood counts and regular follow-up are recommended.
Name
Cyclophosphamide and other cytotoxic agents (doxorubicin, bleomycin, procarbazine, mechloroethamine)
Section
7.2 Table 3
Source text (exact source wording)
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.
Allopurinol lengthens the half-life of dicumarol. Prothrombin time is monitored and the dicumarol dose adjusted.
Name
Dicumarol
Section
7.2 Table 3
Source text (exact source wording)
Clinical Impact Allopurinol tablets prolongs the half-life of the anticoagulant, dicumarol. The mechanism of this drug interaction has not been established but should be noted when allopurinol tablet is given to patients already on dicumarol therapy.
Intervention Monitor prothrombin time. Adjust the dosage of dicumarol accordingly when allopurinol tablet is added to anticoagulant therapy.
Allopurinol may reduce the anti-tumor activity of fluorouracil. Avoid using them together.
Name
Fluorouracil
Section
7.2 Table 3
Source text (exact source wording)
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.
Allopurinol raises exposure to mercaptopurine or azathioprine and their risk of myelosuppression. Their doses need to be reduced to approximately one third to one fourth of the usual dose when taken with 300 mg to 600 mg of allopurinol per day.
Name
Mercaptopurine or azathioprine
Section
7.2 Table 3
Source text (exact source wording)
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.
Allopurinol may blunt the rise in uric acid and raise the risk of pegloticase-related anaphylaxis. Stop and do not start allopurinol during pegloticase treatment.
Name
Pegloticase
Section
7.2 Table 3
Source text (exact source wording)
Clinical Impact Concomitant use of allopurinol tablets 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.
Allopurinol doses of 600 mg/day or more may lower theophylline clearance, so theophylline doses are monitored and adjusted.
Name
Theophylline
Section
7.2 Table 3
Source text (exact source wording)
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 lower oxypurinol exposure and increase uric acid in the urine. Uric acid levels are monitored.
Name
Uricosuric drugs
Section
7.2 Table 3
Source text (exact source wording)
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.
Intervention Monitor uric acid levels due to the increased chance of hypouricemic effects.
Allopurinol may increase warfarin's blood-thinning effect. INR is checked frequently and the warfarin dose adjusted.
Name
Warfarin
Section
7.2 Table 3
Source text (exact source wording)
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.
Food and alcohol
Take it after meals to lessen stomach irritation.
Name
Food
Section
2.3; 17
Source text (exact source wording)
Allopurinol tablets is generally better tolerated if taken following meals.
Advise patients to take allopurinol tablets after meals to minimize gastric irritation.
Its central nervous system effects may add to those of alcohol and other CNS depressants.
Name
Alcohol
Section
5.6
Source text (exact source wording)
Inform patients also that the central nervous system depressant effects of allopurinol tablets may be additive to those of alcohol and other CNS depressants.
Adults should drink at least 2 liters of liquids per day to stay hydrated and help prevent kidney stones.
Name
Fluids
Section
17
Source text (exact source wording)
Advise them to increase fluid intake during therapy (i.e., for adults, at least 2 liters of liquids per day) and to stay well hydrated to prevent kidney stones [see Warnings and Precautions (5.3)].
The sources do not mention grapefruit.
Name
Grapefruit
Section
none
Other
The label tells patients about risks when allopurinol is used with dicumarol, warfarin, sulfinpyrazone, mercaptopurine, azathioprine, ampicillin, amoxicillin, pegloticase, theophylline and thiazide diuretics.
Name
Patient counseling list of interacting drugs
Section
17
Source text (exact source wording)
Inform patients that there are risks of adverse effects when allopurinol tablets are used with the following drugs: dicumarol, warfarin, sulfinpyrazone, mercaptopurine, azathioprine, ampicillin, amoxicillin, pegloticase, theophylline, and thiazide diuretics.
The label lists no antiviral interactions.
Name
Antiviral interactions
Section
7
Source text (exact source wording)
not applicable: the label lists no antiviral drug interactions, so the Liverpool HIV and HEP checkers were not used (not checked).

Patient tips

Take it after meals. Stop and get medical help at the first sign of a skin rash, blisters, fever, painful urination, blood in the urine, eye irritation, or swelling of the lips or mouth. Gout flares may happen at first, so keep taking allopurinol and the preventive medicine. Report signs of liver or blood problems such as jaundice, bleeding, bruising, infection, fever, or significant fatigue. MedlinePlus adds: take it at the same time every day, it may take several months or longer to feel the full benefit, continue even if you feel well, do not stop without talking to your doctor, drink at least eight 8-ounce (240-milliter) cups of liquids a day unless told otherwise, and do not drive until you know how it affects you.
Label source
Section 17 PATIENT COUNSELING INFORMATION (no separate Patient Information leaflet in the chosen label)
Label source text (exact source wording)
Advise patients to take allopurinol tablets after meals to minimize gastric irritation.
Inform patients that allopurinol tablets may increase the risk of serious and sometimes fatal dermatologic reactions. Instruct patients to discontinue allopurinol tablets and to seek medical attention immediately, at the first sign of a skin rash, blisters, fever, painful urination, blood in the urine, irritation of the eyes, swelling of the lips or mouth, or other signs and symptoms of hypersensitivity reactions.
Inform patients that gout flares may occur during initiation of treatment with allopurinol tablets, even when their serum uric acid is normal. Advise patients to continue treatment with both, allopurinol tablets and the prophylactic therapy as prescribed, even if gout flares occur.
Inform patients of the risk of hepatotoxicity and to report to their healthcare provider any signs and symptoms of liver failure, including jaundice, pruritus, bleeding, bruising, or anorexia.
Advise patients of the risk of myelosuppression and to report any signs and symptoms of infection, fever, bleeding, shortness of breath, or significant fatigue to their healthcare provider.
Medlineplus source text (exact source wording)
It is usually taken once or twice a day, preferably after a meal. To help you remember to take allopurinol, take it around the same time every day. Take allopurinol exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
It may take several months or longer before you feel the full benefit of allopurinol. Continue to take allopurinol even if you feel well. Do not stop taking allopurinol without talking to your doctor.
Drink at least eight 8-ounce (240-milliter) cups of water or other liquids each day while taking allopurinol unless directed to do otherwise by your doctor.
you should know that allopurinol may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.

Alternatives

Class
Xanthine Oxidase Inhibitor [EPC]
Class source
Label: 'Allopurinol tablet is a xanthine oxidase inhibitor'; openFDA openfda.pharm_class_epc for allopurinol
Candidates
Name
febuxostat
Source
openFDA count query on openfda.pharm_class_epc.exact 'Xanthine Oxidase Inhibitor [EPC]' returned ALLOPURINOL and FEBUXOSTAT
Note
Candidate only; no recommendation of one over another.

Frequently asked questions

Question
What is allopurinol used for?
Answer
It is used for adults with signs and symptoms of primary or secondary gout, for adults and children with leukemia, lymphoma or solid tumors whose cancer therapy raises uric acid, and for adults with recurrent calcium oxalate stones. It is not recommended for asymptomatic hyperuricemia.
Source section
1 INDICATIONS & USAGE
Source
DailyMed Rising allopurinol label
Question
Should I take allopurinol with food?
Answer
The label says it is generally better tolerated if taken following meals, and advises taking it after meals to minimize gastric irritation.
Source section
2.3; 17
Source
DailyMed Rising allopurinol label
Question
What if I miss a dose?
Answer
There is no need to double the dose at the next scheduled time. MedlinePlus says to take it as soon as you remember, skip it if it is almost time for the next dose, and not take a double dose.
Source section
2.3; 17; MedlinePlus
Source
DailyMed Rising allopurinol label; MedlinePlus
Question
Can I drink alcohol or drive on allopurinol?
Answer
Its central nervous system depressant effects may be additive to those of alcohol and other CNS depressants. Drowsiness, somnolence and dizziness have been reported, so avoid driving or dangerous machinery when starting or raising the dose until you know how it affects you.
Source section
5.6
Source
DailyMed Rising allopurinol label
Question
What are the common side effects?
Answer
The most frequent side effect is skin rash. In 1% or more of people, the label lists diarrhea, nausea, increased alkaline phosphatase, increased AST/ALT, acute attacks of gout, rash and maculopapular rash.
Source section
6 ADVERSE REACTIONS
Source
DailyMed Rising allopurinol label
Question
Why did my gout flare after I started allopurinol?
Answer
Gout flares have been reported during initiation of treatment, even when uric acid levels are normal or subnormal. Colchicine or an anti-inflammatory is recommended at the start. Keep taking allopurinol, since it may take months to get control of flares.
Source section
5.2; 17
Source
DailyMed Rising allopurinol label
Question
Can I take allopurinol while pregnant or breastfeeding?
Answer
Based on animal findings, allopurinol may cause fetal harm and crosses the placenta, so pregnant women are advised of the potential risk to a fetus. Allopurinol and oxypurinol are present in human milk, and the label advises women not to breastfeed during treatment and for one week after the last dose.
Source section
8.1; 8.2
Source
DailyMed Rising allopurinol label
Question
What should I not combine with allopurinol?
Answer
Avoid it with capecitabine and fluorouracil, and do not start it during pegloticase treatment. Mercaptopurine and azathioprine doses need reducing. Warfarin, cyclosporine, theophylline at 600 mg/day or more, chlorpropamide, dicumarol, uricosuric drugs, and thiazide diuretics, ampicillin, amoxicillin and bendamustine also interact.
Source section
7.1; 7.2
Source
DailyMed Rising allopurinol label

Sources

Information is taken from the cited sources and is for general reference only. It is not medical advice. Report side effects to FDA MedWatch at 1-800-FDA-1088. For a poison emergency call 1-800-222-1222. See prices for this drug