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Australian Journal of Pharmacy : May 2008
education pharmacy practice research aJPcPd continuinG professional development snapshot of people’s characteristics and what may be the influential factors in their management. In this study the appropriateness of each person’s allopurinol dosing regimen was assessed using the Hande et al4 dosing guidelines which are based on renal function. The effectiveness of allopurinol was based on the number of acute attacks in past years and the plasma urate concentration achieved by each person. Allopurinol dosing The doses of allopurinol in this study ranged from 50mg to 300mg daily. However, only 26% of patients received the recommended allopurinol dose, according to the renal function (and the Hande guidelines4 ). Interestingly, plasma oxypurinol concentrations were variable and tended to be higher than recommended levels from other studies.1 Of most importance, it was clear that plasma urate concentrations often remain above target levels despite receiving higher than recommended doses of allopurinol (Table One). Response to therapy These data indicated that patients newly diagnosed with gout and/or recently commenced on allopurinol had more acute attacks per year. A number of patients in the study cohort were also taking diuretics which are known to decrease the efficacy of allopurinol and increase the risk acute attacks. Furthermore, a number of patients were also taking low- dose aspirin which has also been suggested to affect gout control (yet the significance of this is not well understood).1 Parameter Age (yrs) Allopurinol dose (mg/day) Oxypurinol Concentration (mg/L) Estimated creatinine clearance (mL/min) Disease duration < 10 years Duration of allopurinol therapy < 5 years Tophi present Taking aspirin Taking diuretics Cardiovascular disease Type 2 diabetes Chronic renal failure = One acute attack in the past two years = Two acute attack/yr Patient knowledge, adherence and beliefs In this study 50% of patients did not know how allopurinol works and 5% thought allopurinol ‘treats acute attacks’. Interestingly, 45% of patients self-reported missing doses of allopurinol. Compared with their other prescribed medications, patients thought allopurinol therapy was less necessary and less likely to cause side-effects and dependency. The preliminary analysis of the data found no correlation between patient adherence and beliefs and number of acute attacks per year and plasma urate concentration. Many patients were unaware of the possible precipitation of acute gout when treatment of allopurinol is commenced. The reason for this problem is not known, but can be largely overcome by initial concomitant treatment with non- steroidal anti-inflammatory or low daily doses of colchicines. The impact of concomitant medication on the efficacy and safety of allopurinol therapy in people with gout is an active area of research. 88 Unwanted effects Allied to this project is an investigation to understand why some people are more sensitive to allopurinol adverse effects. Rash occurs in about 2% of treated patients and intolerance in up to 10% of patients (which includes the australian journal of pharmacy vol.89 may 2008 urate = 0.36 mmol/L n = 59 68 ± 13 249 ± 84 14.8 ± 10.4 78.8 ± 35.8 32 (54%) 20 (38%) 5 (10%) 19 (32%) 24 (41%) 34 (58%) 11 (19%) 8 (14%) 19 (32%) 7 (14%) sTable ONe: cross-sectional data on people receiving allopurinol who are below or above the target urate concentration.3 urate > 0.36 mmol/L n = 37 73 ± 10 161 ± 92 16.2 ± 9.8 52.0 ± 27.4 19 (51%) 12 (38%) 2 (6%) 15 (41%) 23 (62%) 31 (84%) 15 (41%) 11 (30%) 11 (37%) 4 (13%) hepatic enzyme, gastrointestinal, and central nervous system effects). Allopurinol hypersensitivity syndrome is rare (<1/1000 treated patients) and potentially very serious (20% fatality rate).5 Allopurinol dosing is also difficult in patients receiving azathioprine or 6-mercaptopurine, both of which are commonly used for the management of inflammatory bowel syndrome in the community setting. The dose of azathioprine or mercaptopurine must be reduced by about 75%. The next steps The next major study in the project will explore the possible impact of a person’s URAT1, OAT1, OAT2, OAT3 and OAT4 genes on the control of their gout, and particularly the pharmacokinetics and pharmacodynamics of oxypurinol. This work will be done in collaboration with researchers from the School of Pharmacy at the University of California, San Francisco. References available on request. , The articles in this series are authored by academics at the University of Sydney’s Faculty of Pharmacy, on behalf of the Pharmacy Practice Foundation. *Professor McLachlan can be contacted on email@example.com