ALLOPURINOL

ALLOPURINOL
(al-oh-pure'i-nole)
Alloprin A

, Alloprin, Apo-allopurinol-A

, Lopurin, Novopurinol A, Zyloprim
Classifications: antigout agent;
Therapeutic: antigout
Pregnancy Category: C

Availability

100 mg, 300 mg tablets; 500 mg vial

Action

Allopurinol reduces endogenous uric acid by selectively inhibiting action of xanthine oxidase, the enzyme responsible for converting hypoxanthine to xanthine and xanthine to uric acid (end product of purine catabolism). Has no analgesic, antiinflammatory, or uricosuric actions.

Therapeutic Effect

Thus, urate pool is decreased by the lowering of both serum and urinary uric acid levels, and hyperuricemia is prevented.

Uses

To control primary hyperuricemia that accompanies severe gout and to prevent possibility of flare-up of acute gouty attack; to prevent recurrent calcium oxalate stones; prophylactically to reduce severity of hyperuricemia associated with antineoplastic and radiation therapies, both of which greatly increase plasma uric acid levels by promoting nucleic acid degradation.

Unlabeled Uses

To reduce hyperuricemia secondary to Lesch–Nyhan syndrome, polycythemia vera, G6PD deficiency, sarcoidosis, and therapy with thiazides or ethambutol.

Contraindications

Hypersensitivity to allopurinol; as initial treatment for acute gouty attacks; idiopathic hemochromatosis (or those with family history); children (except those with hyperuricemia secondary to neoplastic disease and chemotherapy); pregnancy (category C).

Cautious Use

Impaired hepatic or renal function, history of peptic ulcer, lower GI tract disease, bone marrow depression.

Route & Dosage

Treatment of Hyperuricemia
Adult: PO 100 mg/d, may increase by 100 mg/wk (max: 800 mg/d), divide doses >300 mg/d IV 200–400 mg/m²/d (max: 600 mg/d) in 1–4 divided doses
Child: PO ≤10 y, 10 mg/kg/d in 2–3 divided doses (max: 800 mg/d) IV 200 mg/m²/d in 1–4 divided doses

Treatment of Secondary Hyperuricemia
Adult: PO 200–800 mg/d for 2–3 d or longer, divide doses >300 mg/d
Child: PO 6–10 y, 100 mg t.i.d.; <6 y, 50 mg t.i.d.

Renal Impairment
Cl_cr 10–20 mL/min: 200 mg/d; 3–10 mL/min: 100 mg qd; <3 mL/min: 100 mg with extended interval between doses (24 h or more)
Dialysis: Administer dose after dialysis or use 50% supplemental dose

Administration

Oral

Give after meals for best toleration; tablet may be crushed and taken with fluid or mixed with food.
Store at 15°–30° C (59°–86° F) in a tightly closed container.

Intravenous

PREPARE: Intermittent: ?? Reconstitute a single dose vial (500 mg) with 25 mL of sterile water for injection to yield 20 mg/mL.??Must be further diluted with NS or D5W to a concentration of ≤6 mg/mL.?? Note: Adding 2.3 mL of diluent yields 6 mg/mL.

ADMINISTER: Intermittent: Usually administered over 30–60 min.

INCOMPATIBILITIES Solution/additive: Amikacin, amphotericin B, carmustine, cefotaxime, chlorpromazine, cimetidine, clindamycin, cytarabine, dacarbazine, daunorubicin, diphenhydramine, doxorubicin, doxycycline, droperidol, floxuridine, gentamicin, haloperidol, hydroxyzine, idarubicin, imipenem-cilastatin, mechlorethamine, meperidine, methylpredinisole, metoclopramide, methylprednisolone, minocycline, nalbuphine, netilmicin, ondansetron, prochlorperazine, promethazine, sodium bicarbonate, streptozocin, tobramycin, vinorelbine.

Adverse Effects (≥1%)

CNS: Drowsiness, headache, vertigo. GI: Nausea, vomiting, diarrhea, abdominal discomfort, indigestion, malaise. Hematologic: (Rare) Agranulocytosis, aplastic anemia, bone marrow depression, thrombocytopenia. Skin: Urticaria or pruritus, pruritic maculopapular rash, toxic epidermal necrolysis. Other: Hepatotoxicity, renal insufficiency.

Diagnostic Test Interference

Possibility of elevated blood levels of alkaline phosphatase and serum transaminases (AST, ALT), and decreased blood Hct, Hgb, leukocytes.

Interactions

Drug: Alcohol may inhibit renal excretion of uric acid; ampicillin, amoxicillin increase risk of skin rash; enhances anticoagulant effect of warfarin; toxicity from azathioprine, mercaptopurine, cyclophosphamide, cyclosporin increased; increases hypoglycemic effects of chlorpropamide; thiazides increase risk of allopurinol toxicity and hypersensitivity (especially with impaired renal function); ace inhibitors increase risk of hypersensitivity; high dose vitamin C increases risk of kidney stone formation.

Pharmacokinetics

Absorption: 80–90% from GI tract. Onset: 24–48 h. Peak: 2–6 h. Metabolism: 75–80% to the active metabolite oxypurinol. Elimination: Slowly excreted in urine; excreted in breast milk. Half-Life: 1–3 h; oxypurinol, 18–30 h.

Nursing Implications

Assessment & Drug Effects

Monitor for therapeutic effectiveness which is indicated by normal serum and urinary uric acid levels usually by 1–3 wk (aim of therapy is to lower serum uric acid level gradually to about 6 mg/dL), gradual decrease in size of tophi, absence of new tophaceous deposits (after approximately 6 mo), with consequent relief of joint pain and increased joint mobility.
Monitor for S&S of an acute gouty attack which is most likely to occur during first 6 wk of therapy.
Lab tests: Monitor serum uric acid levels q1–2wk to check adequacy of dosage. Perform baseline CBC, liver and kidney function tests before therapy is initiated and then monthly, particularly during first few months. Check urinary pH at regular intervals.
Monitor patients with renal disorders more often; they tend to have a higher incidence of renal stones and drug toxicity problems.
Report onset of rash or fever immediately to physician; withdraw drug. Life-threatening toxicity syndrome can occur 2–4 wk after initiation of therapy (more common with impaired renal function) and is generally accompanied by malaise, fever, and aching, a diffuse erythematous, desquamating rash, hepatic dysfunction, eosinophilia, and worsening of renal function.

Patient & Family Education

Drink enough fluid to produce urinary output of at least 2000 mL/d (fluid intake of at least 3000 mL/d). (Note that 1000 mL is approximately equal to 1 quart.) Report diminishing urinary output, cloudy urine, unusual color or odor to urine, pain or discomfort on urination.
Report promptly the onset of itching or rash. Stop drug if a skin rash appears, even after 5 or more wk (and reportedly as long as 2 y) of therapy.
Minimize exposure of eyes to ultraviolet or sunlight which may stimulate the development of cataracts.
Do not drive or engage in potentially hazardous activities until response to drug is known.
Remain under medical supervision while taking allopurinol (generally continued indefinitely); drug can cause severe adverse reactions.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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