Allopurinol

Action

Inhibits conversion of xanthine to uric acid and increases reutilization of hypoxanthine and xanthine for nucleic acid synthesis, thereby decreasing uric acid levels in both serum and urine

Availability

Powder for injection: 500-mg vial

Tablets: 100 mg, 300 mg

Indications and dosages

➣ Gout in patients with frequent disabling attacks; gout resulting from hyperuricemia, acute or chronic leukemia, psoriasis, or multiple myeloma

Adults: 200 to 300 mg P.O. daily in mild cases or 400 to 600 mg P.O. daily in severe cases, to a maximum dosage of 800 mg/day; or 200 to 400 mg/m²/day I.V. as a single infusion or in equally divided doses q 6, 8, or 12 hours to a maximum dosage of 600 mg/day

Children ages 6 to 10: 300 mg P.O. daily

Children younger than age 6: 150 mg P.O. daily

➣ To prevent acute gout attacks Adults: 100 mg P.O. daily; increase by 100 mg at weekly intervals without exceeding maximum dosage of 800 mg, until uric acid level falls to 6 mg/dl or less

➣ Recurrent calcium oxalate calculi

Adults: 200 to 300 mg P.O. daily in single dose or divided doses

➣ To prevent uric acid nephropathy during cancer chemotherapy

Adults: 600 to 800 mg P.O. daily for 2 to 3 days, accompanied by high fluid intake

Dosage adjustment

• Renal impairment

Off-label uses

• Hematemesis caused by gastritis induced by nonsteroidal anti-inflammatory drugs

• Pain from acute pancreatitis

• Seizures refractory to standard therapy

Contraindications

• Hypersensitivity to drug

Precautions

Use cautiously in:

• acute gout attack, renal insufficiency, dehydration

• pregnant or breastfeeding patients.

Administration

• Reconstitute single-dose vial with 25 ml sterile water for injection. Further dilute with normal saline solution or D₅W to a concentration of 6 mg/ml or less.

• Infuse over 30 to 60 minutes.

• Don't mix I.V. form with other drugs or give through same I.V. port as drugs that may be incompatible.

• Divide oral doses larger than 300 mg.

• Give oral form with or right after meals.

• Don't give oral form with mineral water, orange juice, or caffeinated beverages.

Adverse reactions

CNS: drowsiness, dizziness, headache, peripheral neuropathy, neuritis, paresthesia

CV: hypersensitivity vasculitis, necrotizing vasculitis

EENT: retinopathy, cataract, epistaxis

GI: nausea, vomiting, diarrhea, abdominal pain, dyspepsia, gastritis

GU: exacerbation of gout and renal calculi, uremia, renal failure

Hematologic: eosinophilia, anemia, thrombocytopenia, bone marrow depression, agranulocytosis, leukocytosis, aplastic anemia, leukopenia

Hepatic: cholestatic jaundice, hepatomegaly, hepatitis, hepatic necrosis

Musculoskeletal: myopathy, joint pain

Skin: rash; alopecia; maculopapular, urticarial, or purpuric lesions; severe furunculosis of nose; ichthyosis; bruising; scaly or exfoliative erythema multiforme; toxic epidermal necrolysis

Other: abnormal taste, loss of taste, fever, chills

Interactions

Drug-drug. Amoxicillin, ampicillin, bacampicillin: increased risk of rash

Anticoagulants (except warfarin): increased anticoagulant effect

Antineoplastics: increased risk of myelosuppression

Azathioprine, mercaptopurine: inhibition of allopurinol metabolism

Chlorpropamide: increased hypoglycemic effects

Diazoxide, diuretics, mecamylamine, pyrazinamide: increased uric acid levels

Ethacrynic acid, thiazide diuretics: increased risk of allopurinol toxicity

Uricosurics: increased uric acid excretion

Urine-acidifying drugs (ammonium chloride, ascorbic acid, potassium or sodium phosphate): increased risk of renal calculi

Xanthines: increased theophylline levels

Drug-diagnostic tests. Alanine aminotransferase, alanine phosphatase, aspartate aminotransferase, bilirubin, eosinophils: increased levels

Granulocytes, hemoglobin, platelets, white blood cells: decreased levels

Drug-food. Caffeine-containing beverages and foods, mineral water, orange juice: decreased drug absorption, increased uric acid level

Drug-behaviors. Alcohol use: increased uric acid level

Patient monitoring

• Assess fluid intake and output. Intake should be sufficient to yield daily output of at least 2 L of slightly alkaline urine.

• Monitor uric acid level to help evaluate drug efficacy.

Patient teaching

☞ Instruct patient to promptly report painful urination, bloody urine, rash, eye irritation, or swelling of lips and mouth.

• Tell patient to take drug with food or milk, exactly as prescribed.

• Explain that gout attacks may not ease significantly until 2 to 6 weeks of therapy.

• Caution patient to avoid driving and other hazardous tasks until he knows how drug affects concentration and alertness.

• Advise patient to avoid alcohol, caffeine-containing beverages and foods, mineral water, and orange juice during therapy.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, and behaviors mentioned above.