OBJECTIVE: Approved dosage regimens for prescription drug products are developed with a view to obtaining a favourable therapeutic index in the overall exposed population. The purpose of this study was to examine differences between the approved dosage regimen and the clinically prescribed doses of allopurinol in major hospitals in Japan. METHODS: The prescribing records for allopurinol were scrutinized at five national hospitals in Japan. Prescription information, including mean dose and the distribution of doses, was extracted for each hospital and the data compared with the dosage recommended in the approved labelling for the product. In addition, therapeutic drug monitoring (TDM) data were examined to evaluate relationships between dose administered, serum concentration of oxypurinol, and clinical efficacy. RESULTS: The mean dose of allopurinol prescribed in the five institutions, 131.7 mg/day, was lower than the approved dosage of 200-300 mg/day. There were no differences in the mean dose between the hospitals, and similar dose distributions were seen among the hospitals. Approximately 60-70% of patients were treated with 100 mg/day and 20-30% with 200 mg/day of allopurinol. The most frequent dosage of allopurinol used in clinical practice was 100 mg/day. In the TDM study, the mean trough serum concentrations of oxypurinol were 9.5+/-3.6 microg/mL (50 mg/day), 13.0+/-6.8 microg/mL (100 mg/day), 19.8+/-12.9 microg/mL (200 mg/day) and 15.7+/-7.3 microg/mL (300 mg/day). The mean values of creatinine clearance were 17.0+/-16.4 mL/min (50 mg/day), 33.5+/-32.8 mL/min (100 mg/day), 57.8+/-33.8 mL/min (200 mg/day) and 94.3+/-35.8 mL/min (300 mg/day, in patients with normal renal function), and showed a downward trend together with a reduction of dosage of allopurinol. Allopurinol was given to 91% (91/100) of patients at a daily dose of 100-200 mg, and the oxypurinol trough serum concentration attained (>4.6 microg/mL) was sufficient to maintain a therapeutic effect in 92.3% (84/91) of these patients. A daily dose of 100-200 mg may be enough to obtain therapeutic serum oxypurinol concentrations in most Japanese patients. CONCLUSIONS: Dose of 100-300 mg/day was an effective and commonly used dosing regimen for allopurinol in Japanese patients. The approved dosage range (200-300 mg/day) may be too high for patients with renal dysfunction, suggesting the recommended dosing regimen for allopurinol should be revised to include the lower doses.
OBJECTIVE: Approved dosage regimens for prescription drug products are developed with a view to obtaining a favourable therapeutic index in the overall exposed population. The purpose of this study was to examine differences between the approved dosage regimen and the clinically prescribed doses of allopurinol in major hospitals in Japan. METHODS: The prescribing records for allopurinol were scrutinized at five national hospitals in Japan. Prescription information, including mean dose and the distribution of doses, was extracted for each hospital and the data compared with the dosage recommended in the approved labelling for the product. In addition, therapeutic drug monitoring (TDM) data were examined to evaluate relationships between dose administered, serum concentration of oxypurinol, and clinical efficacy. RESULTS: The mean dose of allopurinol prescribed in the five institutions, 131.7 mg/day, was lower than the approved dosage of 200-300 mg/day. There were no differences in the mean dose between the hospitals, and similar dose distributions were seen among the hospitals. Approximately 60-70% of patients were treated with 100 mg/day and 20-30% with 200 mg/day of allopurinol. The most frequent dosage of allopurinol used in clinical practice was 100 mg/day. In the TDM study, the mean trough serum concentrations of oxypurinol were 9.5+/-3.6 microg/mL (50 mg/day), 13.0+/-6.8 microg/mL (100 mg/day), 19.8+/-12.9 microg/mL (200 mg/day) and 15.7+/-7.3 microg/mL (300 mg/day). The mean values of creatinine clearance were 17.0+/-16.4 mL/min (50 mg/day), 33.5+/-32.8 mL/min (100 mg/day), 57.8+/-33.8 mL/min (200 mg/day) and 94.3+/-35.8 mL/min (300 mg/day, in patients with normal renal function), and showed a downward trend together with a reduction of dosage of allopurinol. Allopurinol was given to 91% (91/100) of patients at a daily dose of 100-200 mg, and the oxypurinol trough serum concentration attained (>4.6 microg/mL) was sufficient to maintain a therapeutic effect in 92.3% (84/91) of these patients. A daily dose of 100-200 mg may be enough to obtain therapeutic serum oxypurinol concentrations in most Japanese patients. CONCLUSIONS: Dose of 100-300 mg/day was an effective and commonly used dosing regimen for allopurinol in Japanese patients. The approved dosage range (200-300 mg/day) may be too high for patients with renal dysfunction, suggesting the recommended dosing regimen for allopurinol should be revised to include the lower doses.