Allopurinol
From Ganfyd
A xanthine oxidase inhibitor used widely in prophylaxis of gout. It has also been used in leishmaniasis. Its ability to reduce myocardial oxygen consumption at high dose raises the potential to use it to control symptoms of angina on exercise and in improving outcome after surgery for valvular heart disease[1]. There is some evidence suggesting this might not work at the doses usually used in gout[2]. It has also been suggested as adjuvant treatment for schizophrenia[3]. There are reasons to evaluate its potential in hypoxic-ischaemic encephalopathy[4] and stroke[5] as it reduces free radical formation. It also has been tried in sarcoid[6]
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Dose
Usual dose 100-300mg daily, occasionally up to 900mg.
- There is a tendency to underdose in those with gout
- The initial dose should be below 1.5 mg per unit of estimated GFR (mg/ml/minute) to minimise risk of allopurinol hypersensitivity syndrome[7].
Effect and use
Gout involves the formation of crystals from high concentrations of urate. In most species urate is metabolised onward to Allantoin, more soluble and thus more easily excretable via the kidneys. Humans are an exception. The precursor substances to urate are more soluble than it, allopurinol blocks that metabolic step leaving the xanthine and proto-xanthine to be excreted. Existing urate in crystals in the joints slowly redissolves and is excreted, this takes years rather than months.
Induction
Start at 100mg, increase to produce a serum urate below 300 micromols.
Side-effects
- Skin rash (common (say 5%) and can be severe, including potentially fatal toxic epidermal necrolysis)
- Granulomatous hepatitis
Interactions
- Mercaptopurine or azathioprine require a significant dose reduction if administered at the same time.
Place in therapy
It should be the first line preventive agent in gout. It is interesting that the clinical trials of febuxostat used for comparison lower typical doses of allopurinol and accordingly with normal renal function it is reasonable to go up to 600-800mg a day of allopurinol before assuming treatment failure.
References
- ↑ Talwar S, Sandeep JA, Choudhary SK, Velayoudham D, Lakshmy R, Kasthuri JM, Kumar AS. Effect of preoperative administration of allopurinol in patients undergoing surgery for valvular heart diseases. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. 2010 Feb 24.(Epub ahead of print) (Link to article – subscription may be required.)
- ↑ Gavin AD, Struthers AD. Allopurinol reduces B-type natriuretic peptide concentrations and haemoglobin but does not alter exercise capacity in chronic heart failure. Heart (British Cardiac Society). 2005 Jun; 91(6):749-53.(Link to article – subscription may be required.)
- ↑ Buie LW, Oertel MD, Cala SO. Allopurinol as adjuvant therapy in poorly responsive or treatment refractory schizophrenia. The Annals of pharmacotherapy. 2006 Dec; 40(12):2200-4.(Link to article – subscription may be required.)
- ↑ Chaudhari T, McGuire W. Allopurinol for preventing mortality and morbidity in newborn infants with suspected hypoxic-ischaemic encephalopathy. Cochrane database of systematic reviews (Online). 2008; (2):CD006817.(Epub) (Link to article – subscription may be required.)
- ↑ Muir SW, Harrow C, Dawson J, Lees KR, Weir CJ, Sattar N, Walters MR. Allopurinol use yields potentially beneficial effects on inflammatory indices in those with recent ischemic stroke: a randomized, double-blind, placebo-controlled trial. Stroke; a journal of cerebral circulation. 2008 Dec; 39(12):3303-7.(Link to article – subscription may be required.)
- ↑ Doherty CB, Rosen T. Evidence-based therapy for cutaneous sarcoidosis. Drugs. 2008; 68(10):1361-83.
- ↑ [Arthritis & Rheumatism, 64: 2529–2536. doi: 10.1002/art.34488 Stamp1 LK, Taylor WJ, Jones PB, Dockerty JL, Drake J, Frampton C, Dalbeth N. Starting dose is a risk factor for allopurinol hypersensitivity syndrome: A proposed safe starting dose of allopurinol Arthritis & Rheumatism 2012, 64: 2529–2536. doi: 10.1002/art.34488]
