Allopurinol

Allopurinol is used across several conditions where uric acid levels need to be controlled. The specific conditions supported depend on the product and form used:

• Gout (adults only — tablets): Allopurinol tablets treat the signs and symptoms of primary or secondary gout, including painful attacks, tophi (lumps of uric acid crystals), joint damage, uric acid kidney disease, and uric acid kidney stones.
• Cancer-related high uric acid (adults and children — tablets and injection): Allopurinol — both the oral tablets and injectable forms (Allopurinol sodium for injection and Aloprim) — manages dangerously high uric acid levels that can occur during treatment for leukemia, lymphoma, or solid tumor cancers. The injectable forms are used specifically when patients cannot take oral medicine.
• Recurrent calcium oxalate kidney stones (adults only — tablets): Allopurinol tablets are used to reduce recurring calcium oxalate kidney stones in adults whose urinary uric acid is too high despite dietary and lifestyle changes.
• Not for asymptomatic hyperuricemia: Allopurinol tablets are not recommended when uric acid levels are high but there are no symptoms.

Allopurinol works by blocking a key enzyme called xanthine oxidase — the enzyme responsible for the final steps of uric acid production in the body. By blocking this enzyme, allopurinol reduces how much uric acid is made. The body converts allopurinol into an active compound called oxypurinol, which also inhibits xanthine oxidase and is responsible for much of the drug's ongoing effect. The result is lower uric acid in the blood and urine, which helps prevent gout attacks, kidney stone formation, and the dangerous uric acid buildup that can follow certain cancer treatments.

Allopurinol tablets are taken by mouth — usually once daily, though divided doses are sometimes used. Taking the tablet with food or milk can reduce stomach discomfort. Drinking plenty of fluids throughout the day is important to help the kidneys flush out uric acid and reduce the risk of stone formation. The injectable forms (Allopurinol sodium for injection and Aloprim) are given intravenously by a healthcare professional, typically once daily or in split infusions — they are not taken at home. Doses are adjusted based on kidney function, the condition being treated, and lab monitoring results; always follow your prescriber's specific instructions.

The most common side effects of allopurinol include:

• Skin rash — the most frequent reaction; stop immediately and call your doctor if any rash appears
• Nausea
• Diarrhea
• Elevated liver enzymes (usually seen on a blood test, not felt directly)
• Gout flares, especially in the first few months of treatment
• Drowsiness or dizziness
• Headache or general feeling of being unwell

Serious reactions — including severe skin blistering (Stevens-Johnson syndrome or toxic epidermal necrolysis), liver problems, and bone marrow suppression — are uncommon but require immediate medical attention if they occur.

• Severe skin and hypersensitivity reactions: Allopurinol has caused life-threatening skin reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), and DRESS (drug reaction with eosinophilia and systemic symptoms). Stop allopurinol at the very first sign of any rash and seek emergency care immediately. People of African, Asian (Han Chinese, Korean, Thai), or Native Hawaiian/Pacific Islander ancestry are at higher risk due to a genetic marker called HLA-B*58:01 — ask your doctor about testing before starting.
• Kidney problems: Allopurinol may cause acute kidney injury, especially in patients who already have kidney disease or kidney stones. Kidney function must be monitored regularly, and doses must be reduced in people with impaired kidney function. Staying well hydrated is important.
• Liver problems: Reversible liver toxicity has been reported. Tell your doctor if you develop loss of appetite, unexplained weight loss, or itching.
• Bone marrow suppression: Reduced blood cell counts (anemia, low white cells, low platelets) have been reported, sometimes appearing years after starting the drug. The risk is higher when used with certain chemotherapy agents.
• Gout flares early in treatment: It is common for gout attacks to occur in the first months — this doesn't mean the medicine isn't working. A separate preventive medicine (like colchicine) is typically recommended when starting allopurinol.
• Drowsiness and dizziness: Avoid driving or using heavy machinery until you know how allopurinol affects you; alcohol and other sedating drugs may worsen these effects.

Allopurinol has several clinically important drug interactions that can affect safety or treatment effectiveness:

• Mercaptopurine or azathioprine: Allopurinol dramatically raises levels of these drugs in the body — their doses must be significantly reduced to avoid serious bone marrow suppression.
• Warfarin: Allopurinol may increase warfarin's blood-thinning effect; INR (a measure of clotting) should be monitored closely and warfarin dose adjusted if needed.
• Capecitabine: Avoid combining — allopurinol may reduce capecitabine's cancer-fighting effectiveness.
• Fluorouracil (5-FU): Avoid combining — allopurinol may reduce its anti-cancer activity.
• Pegloticase: Do not use allopurinol at the same time — it can interfere with safe monitoring of pegloticase and increase the risk of serious allergic reactions.
• Cyclosporine: Allopurinol raises cyclosporine blood levels, increasing the risk of its side effects; monitoring is required.
• Thiazide diuretics (water pills): Increase the risk of severe skin/hypersensitivity reactions, particularly if kidney function is reduced.
• Ampicillin, amoxicillin, or bendamustine: Increase the risk of skin rash when used with allopurinol.
• Chlorpropamide (diabetes medicine): Allopurinol competes with chlorpropamide for kidney excretion, which may raise the risk of low blood sugar in patients with kidney problems.
• Theophylline (breathing medicine): High doses of allopurinol may reduce theophylline clearance, potentially raising theophylline levels.

This is not a complete list of interactions. Always talk with your doctor or pharmacist before starting, stopping, or changing any medication.

• Allergy to allopurinol: Do not take allopurinol if you have ever had a hypersensitivity reaction to it or any of its ingredients.
• Kidney disease: Allopurinol and its active metabolite are cleared by the kidneys — lower doses are required, and kidney function must be monitored frequently.
• Liver disease: Patients with pre-existing liver disease need periodic liver enzyme monitoring.
• Genetic risk for skin reactions: People of African, Asian (Han Chinese, Korean, Thai), or Native Hawaiian/Pacific Islander ancestry may carry the HLA-B*58:01 gene variant that raises the risk of life-threatening skin reactions — discuss genetic screening with your doctor before starting.
• Pregnancy: Allopurinol may cause fetal harm — animal studies showed harmful effects, and isolated case reports of major birth defects in humans exist. Tell your doctor if you are pregnant or planning to become pregnant.
• Breastfeeding: Allopurinol and oxypurinol pass into breast milk. Women should not breastfeed while taking allopurinol tablets or for one week after the last dose.
• Children: The cancer-related use (managing high uric acid from chemotherapy) is established in children for both tablets and injectable forms. Allopurinol tablets have not been established as safe or effective for gout or kidney stones in children.
• Drowsiness risk: Allopurinol can cause drowsiness and dizziness — alcohol and other sedating medications can worsen this effect.

There is no specific antidote if someone takes too much allopurinol. Both allopurinol and its active metabolite oxypurinol can be removed by dialysis, though whether dialysis is useful in managing an overdose is not known. If an overdose is suspected, contact a poison control center or emergency services right away.

Allopurinol lowers the body's production of uric acid in a dose-dependent way — meaning higher doses produce a larger reduction. Its main effect is carried out by its active metabolite, oxypurinol. By blocking xanthine oxidase, allopurinol causes the body to retain more of the precursor compounds hypoxanthine and xanthine, which get reused for other purposes rather than being converted into uric acid. The levels of these compounds in the blood remain well below the point at which they would form crystals, so the tradeoff is considered safe.

When taken by mouth, allopurinol tablets are about 90% absorbed from the digestive tract. Blood levels of allopurinol peak within about 1.5 hours, while levels of its active form, oxypurinol, peak around 4.5 hours after a dose. Allopurinol itself clears the body in 1 to 2 hours, but oxypurinol has a much longer half-life of about 15 hours — this is why allopurinol's effects last throughout the day with once-daily dosing. Both allopurinol and oxypurinol are eliminated primarily by the kidneys, which is why kidney function directly affects how the drug is processed and why dose adjustments are necessary in people with reduced kidney function. About 20% of an oral dose is excreted in the stool.

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.