Allopurinol
Indications
Allopurinol is used for:
Hyperuricaemia, Uric acid nephropathy, Cancer therapy-induced hyperuricaemia, Gout, Recurrent renal stones
Adult Dose
Adult: PO Gout; Hyperuricaemia
Mild: 100 mg/day PO initially; increased weekly to 200-300 mg/day
Moderate to severe: 100 mg/day PO initially; increased weekly to 400-600 mg/day
Prevention of hyperuricaemia associated w/ chemotherapy treatment or enzyme disorders 600-800 mg/day, starting 2-3 days before cancer treatment.
Hepatic impairment: Dose reduction may be needed. Monitor liver function regularly.
Child Dose
Renal Dose
Renal impairment: Haemodialysis: Administer dose after session or administer 50% supplemental dose.
CrCl (ml/min)
10-20 200 mg daily.
<3 100 mg daily at extended intervals.
3-10 100 mg daily.
Administration
Administration Should be taken with food. Take immediately after meals.
Contra Indications
Hypersensitivity; acute attack of gout.
Precautions
Ensure adequate fluid intake. Prophylactically with an anti-inflammatory or colchicine for at least 1 mth. Withdraw immediately when sensitivity (skin rash, etc) appears. Pregnancy, lactation. Hepatic and renal impairment.
Lactation: Agent is distributed into breast milk; use with caution.
Pregnancy-Lactation
Pregnancy
Experience with human pregnancy limited partly because women of reproductive age rarely require treatment with drug;
There are, however, no adequate or well controlled studies in pregnant women; because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed
Lactation
Allopurinol and oxipurinol have been found in milk of mother who was receiving drug; since effect of allopurinol on nursing infant is unknown, exercise caution when therapy is administered to nursing woman
Interactions
May inhibit the metabolism of mercaptopurine and azathioprine; reduce dose of mercaptopurine and azathioprine when given w/ allopurinol. May increase effect of warfarin and other coumarin anticoagulants. Increased excretion of the oxipurinol (metabolite) w/ salicylates or uricosuric agents. Increased toxicity w/ thiazide diuretics, some antibacterials, other antineoplastics, ciclosporin, some sulfonylurea antidiabetics, theophylline and vidarabine.
Adverse Effects
Side effects of Allopurinol :
1-10%
Rash (1.5%), Nausea (1.3%), Renal failure (1.2%), Vomiting (1.2%)
Frequency Not Defined
Amblyopia, Arthralgias, Blood dyscrasias, Bronchospasm, Cardiovascular abnormalities, Cataracts, Confusion, Decrease in libido, Dizziness, Ecchymosis, Electrolyte abnormalities, Epistaxis, Foot drop, Hematuria, Hepatotoxicity, Hypotonia, Iritis, Kidney function abnormality, Macular retinitis, Malaise, Neuritis, Pharyngitis, Pruritus, Skin edema, Stevens-Johnson syndrome, Sweating, Tinnitus
Potentially Fatal: Stevens-Jonhson and/or Lyell's Syndrome (urticaria, fever, lymphadenopathy, arthralgia). Occasionally, thrombocytopaenia, agranulocytosis and aplastic anaemia.
Mechanism of Action
Allopurinol is an inhibitor of the enzyme xanthine oxidase which converts hypoxanthine to xanthine then uric acid. The reduced production of uric acid relieves all symptoms associated with hyperuricaemia and gout. Inhibition of xanthine oxidase leads to accumulation of its substrates hypoxanthine and xanthine but since their renal clearance is more than 10 times that of uric acid, there is no risk of nephrolithiasis.