Xanthine Oxidase Inhibitors
Examples
Allopurinol
Indications
- Prophylaxis of Gout
- Prophylaxis of hyperuricaemia associated with cancer chemotherapy
Contraindications
Contraindications
- Not indicated for acute attacks of Gout
- Using allopurinol too quickly following an attack may precipitate a further flare up
- Ensure adequate fluid intake
- Renal insufficiency (reduce dose)
- Hepatic insufficiency (reduce dose)
Mechanism
Allopurinol and its active metabolite, alloxanthine, inhibit the enzyme Xanthine Oxidase which is involved at two stages in the conversion of hypoxanthine to uric acid, thus reducing uric acid levels in the body.
Administration
Oral
Adverse Reactions
- Rash and hypersensitivity reactions (can resemble vasculitis or Stevens Johnson syndrome)
- GI upset
Interactions
Mercaptoprine and Azathioprine - interfere with metabolism of Xanthine Oxidase Inhibitors.
Cyclophosphamide - bone marrow toxicity increased.
ACE inhibitors and angiotensin receptor blockers - risk of renal toxicity increased when co-administered with allopurinol.
Aspirin and salicylates - reduce excretion of uric acid.
Diuretics (especially thiazides) increase risk of gout.
Cyclophosphamide - bone marrow toxicity increased.
ACE inhibitors and angiotensin receptor blockers - risk of renal toxicity increased when co-administered with allopurinol.
Aspirin and salicylates - reduce excretion of uric acid.
Diuretics (especially thiazides) increase risk of gout.
Education
Explain how to avoid acute attacks of gout, include dietary information - certain foodstuffs and alcoholic drinks can increase the likelihood of acute attacks.
Ensure daily fluid intake of 2-3 litres.
Ensure daily fluid intake of 2-3 litres.
Pharmacokinetics
Orally administered allopurinol is well absorbed in the gastro-intestinal tract. Excretion is renal, hence care should be taken in renal disease.
