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

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.