allopurinol
(al oh pure' i nole)
Apo-Allopurinol (CAN), Purinol (CAN), Zyloprim

Pregnancy Category C

Drug class
Antigout drug

Therapeutic actions
Inhibits the enzyme responsible for the conversion of purines to uric acid, thus reducing the production of uric acid with a decrease in serum and sometimes in urinary uric acid levels, relieving the signs and symptoms of gout

Indications
· Management of the signs and symptoms of primary and secondary gout
· Management of patients with malignancies that result in elevations of serum and urinary uric acid
· Management of patients with recurrent calcium oxalate calculi whose daily uric acid excretion exceeds 800 mg/day (males) or 750 mg/day (females)
· Orphan drug use: treatment of Chagas' disease; cutaneous and visceral leishmaniasis
· Unlabeled uses: amelioration of granulocyte suppression with fluorouracil; as a mouthwash to prevent fluorouracil-induced stomatitis

Contraindications and cautions
· Contraindicated with allergy to allopurinol, blood dyscrasias.
· Use cautiously with liver disease, renal failure, lactation, pregnancy.

Available forms
Tablets--100, 300 mg

Dosages
ADULTS
· Gout and hyperuricemia: 100–800 mg/day PO in divided doses, depending on the severity of the disease (200–300 mg/day is usual dose).
· Maintenance: Establish dose that maintains serum uric acid levels within normal limits.
· Prevention of acute gouty attacks: 100 mg/day PO; increase the dose by 100 mg at weekly intervals until uric acid levels are within normal limits.
· Prevention of uric acid nephropathy in certain malignancies: 600–800 mg/day PO for 2–3 days; maintenance dose should then be established as above.
· Recurrent calcium oxalate stones: 200–300 mg/day PO; adjust dose up or down based on 24-hr urinary urate determinations.
PEDIATRIC PATIENTS
· Secondary hyperuricemia associated with various malignancies:
6–10 yr: 300 mg/day PO.
< 6 yr: 150 mg/day; adjust dosage after 48 hr of treatment based on serum uric acid levels.
GERIATRIC PATIENTS OR PATIENTS WITH RENAL IMPAIRMENT
Creatinine clearance 10–20 mL/min--200 mg/day; creatinine clearance < 10 mL/min--100 mg/day; creatinine clearance < 3 mL/min--intervals between doses will need to be extended, based on patient's serum uric acid levels.

Adverse effects
CNS: Headache, drowsiness, peripheral neuropathy, neuritis, paresthesias
Dermatologic: Rashes--maculopapular, scaly or exfoliative--sometimes fatal
GI: Nausea, vomiting, diarrhea, abdominal pain, gastritis, hepatomegaly, hyperbilirubinemia, cholestatic jaundice
GU: Exacerbation of gout and renal calculi, renal failure
Hematologic: Anemia, leukopenia, agranulocytosis, thrombocytopenia, aplastic anemia, bone marrow depression

Interactions
Drug-drug
· Increased risk of hypersensitivity reaction with ACE inhibitors
· Increased toxicity with thiazide diuretics
· Increased risk of rash with ampicillin
· Increased risk of bone marrow suppression with cyclophosphamide, other cytotoxic agents
· Increased half-life of oral anticoagulants
· Increased serum levels of theophylline
· Increased risk of toxic effects with thiopurines, 6-MP (azathioprine dose and dose of 6-MP should be reduced to one-third to one-fourth the usual dose)

Nursing considerations
Assessment
· History: Allergy to allopurinol, blood dyscrasias, liver disease, renal failure, lactation
· Physical: Skin lesions, color; orientation, reflexes; liver evaluation, normal urinary output; normal output; CBC, renal and liver function tests, urinalysis

Interventions
· Administer drug following meals.
· Force fluids--2.5 to 3 L/day to decrease the risk of renal stone development.
· Check urine alkalinity--urates crystallize in acid urine; sodium bicarbonate or potassium citrate may be ordered to alkalinize urine.
· Arrange for regular medical follow-up and blood tests.

Teaching points
· Take the drug following meals.
· These side effects may occur: exacerbation of gouty attack or renal stones (drink plenty of fluids while on this drug, 2.5–3 L/day); nausea, vomiting, loss of appetite (take after meals or eat small, frequent meals); drowsiness (use caution while driving or performing hazardous tasks).
· Avoid OTC medications. Many of these preparations contain vitamin C or other agents that might increase the likelihood of kidney stone formation. If you need an OTC preparation, check with your health care provider.
· Report rash; unusual bleeding or bruising; fever, chills; gout attack; numbness or tingling; flank pain.

Adverse effects in Italic are most common; those in Bold are life-threatening.