Allopurinol

allopurinol

(al oh pure' i nole)

Aloprim, 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; powder for injection—500 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 < 6 mg/dL.

·        Prevention of uric acid nephropathy in certain malignancies: 600–800 mg/day PO for 2–3 days with a high fluid intake; maintenance dose should then be established as above.

·        Recurrent calcium oxalate stones: 200–300 mg/day PO; adjust dose based on 24-hr urinary urate determinations.

·        Parenteral: 200–400 mg/m²/day IV to maximum of 600 mg/day as continuous infusion or at 6, 8, 12 hr intervals.

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.

·        Parenteral: 200 mg/m²/day IV as continuous infusion or at 6, 8, 12 hr intervals.

GERIATRIC PATIENTS OR PATIENTS WITH RENAL IMPAIRMENT

For geriatric patients or patients with creatinine clearance 10–20 mL/min, 200 mg/day; for creatinine clearance < 10 mL/min, 100 mg/day; for creatinine clearance < 3 mL/min, extend intervals between doses based on patient's serum uric acid levels.

Pharmacokinetics

Route	Onset	Peak
Oral	Slow	1–2 hr
IV	10–15 min	30 min

Metabolism: Hepatic; T_1/2: 1–1.5 hr, then 23–24 hr

Distribution: Crosses placenta; may enter breast milk

Excretion: Urine

IV facts

Preparation: Dissolve contents of each vial with 25 ml of sterile water for injection. Further dilute with NSS or D₅W to final concentration of < 6 mg/ml. Administer within 10 hr of reconstitution.

Infusion: Administer as a continuous infusion or infused q 6, 8, or 12 hr with rate dependent on volume used.

Incompatibilities: Incompatible with many other drugs; do not mix with any other drug in same solution.

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, LFTs, renal function tests, urinalysis

Interventions

·        Administer drug following meals.

·        Encourage patient to drink 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.

·        WARNING: Discontinue drug at first sign of skin rash; severe to fatal skin reactions have occurred.

·        Arrange for regular medical follow-up and blood tests.

Teaching points

·        Take the drug after meals.

·        Avoid over-the-counter medications. Many of these preparations contain vitamin C or other agents that might increase the likelihood of kidney stone formation. If you need an over-the-counter preparation, check with your health care provider.

·        You may experience these side effects: Exacerbation of gouty attack or renal stones (drink plenty —2.5–3 L/day—of fluids while on this drug); nausea, vomiting, loss of appetite (take after meals or eat frequent small meals); drowsiness (use caution while driving or performing hazardous tasks).

·        Report unusual bleeding or bruising; fever, chills; gout attack; numbness or tingling; flank pain, skin rash.

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