allopurinol, Aloprim, Lopurin, Zyloprim

 Indications

PO: Prevention of attack of gouty arthritis and nephropathy.

PO, IV: Treatment of secondary hyperuricemia,

which may occur during treatment of tumors or leukemias.

Action

Inhibits the production of uric acid by inhibiting the action

of xanthine oxidase. Therapeutic Effects:

Lowering of serum uric acid levels.

Pharmacokinetics

Absorption: Well absorbed (80%) following oral

administration.

Distribution: Widely distributed in tissue and breast

milk.

Protein Binding: 1%.

Metabolism and Excretion: Metabolized to oxypurinol,

an active compound with a long half-life. 12%

excreted unchanged, 76% excreted as oxypurinol.

Half-life: 1–3 hr (oxypurinol 18–30 hr).

TIME/ACTION PROFILE (hypouricemic effect)

ROUTE ONSET PEAK DURATION

PO, IV 1–2 days 1–2 wk 1–3 wk†

†Duration after discontinuation of allopurinol.

Contraindications/Precautions

Contraindicated in: Hypersensitivity.

Use Cautiously in: Acute attacks of gout; Renal insufficiency

(doseprequired if CCr 20 mL/min); Dehydration (adequate hydration necessary); OB, Lactation:

Rarely used; Geri: Begin at lower end of dosage

range.

Adverse Reactions/Side Effects

CV: hypotension, flushing, hypertension, bradycardia,

and heart failure (reported with IV administration).

CNS: drowsiness. GI: diarrhea, hepatitis, nausea,

vomiting. GU: renal failure, hematuria. Derm: rash

(discontinue drug at first sign of rash), urticaria. Hemat:

bone marrow depression. Misc: hypersensitivity

reactions.

Interactions

Drug-Drug: Use with mercaptopurine and azathioprineqbone

marrow depressant properties—

doses of these drugs should bep. Use with ampicillin

or amoxicillinqrisk of rash. Use with oral hypoglycemic

agents and warfarinqeffects of these drugs.

Use with thiazide diuretics or ACE inhibitorsqrisk

of hypersensitivity reactions. Large doses of allopurinol

mayqrisk of theophylline toxicity. Mayqcyclosporine

levels.

Route/Dosage

Management of Gout

PO (Adults and Children 10 yr): Initially—100

mg/day;qat weekly intervals based on serum uric acid

(not to exceed 800 mg/day). Doses 300 mg/day

should be given in divided doses; Maintenance

dose—100–200 mg 2–3 times daily. Doses of 300

mg may be given as a single daily dose.

Management of Secondary Hyperuricemia

PO (Adults and Children 10 yr): 600–800 mg/

day in 2–3 divided doses starting 1–2 days before

chemotherapy or radiation.

PO (Children 6–10 yr): 10 mg/kg/day in 2–3 divided

doses (maximum 800 mg/day) or 300 mg daily in

2–3 divided doses.

PO (Children 6 yr): 10 mg/kg/day in 2–3 divided

doses (maximum 800 mg/day) or 150 mg daily in 3 divided

doses.

IV (Adults and Children 10 yr): 200–400 mg/m2/

day (up to 600 mg/day) as a single daily dose or in divided

doses q 8–24 hr.

IV (Children 10 yr): 200 mg/m2/day initially as a

single daily dose or in divided doses q 8–24 hr (maximum

dose 600 mg/day).

Renal Impairment

(Adults and Children): CCr 10–50 mL/min—pdose

to 50% of recommended; CCr 10 mL/min—pdosage

to 30% of recommended. Availability (generic available)

Tablets: 100 mg, 200 mg, 300 mg. Cost: Generic—

100 mg $10.83/100, 300 mg $10.83/100.

Powder for injection: 500 mg/vial.