The median increase in ALT level was 2.

4 times the upper limit of normal in patients

who had acute hepatocellular injury.

Patients with AHS began receiving the drug at a significantly higher dosage than the
control patients (mean starting dose, 183.5 mg/day vs 112.2 mg/day).

Patients with AHS also were more likely to begin receiving allopurinol at doses
higher than the creatinine clearancebased dose than were control patients (OR, 16.7;
95% CI, 5.7 - 47.6; P < .001).

The percentage of patients developing AHS increased significantly as the allopurinol

dose (corrected for eGFR) increased.

There was a significant and strong dose-response relationship between the starting
dose of allopurinol (adjusted for eGFR) and the risk for AHS (overall dose effect, P
= .001).

In patients with AHS, no relationship was found between the allopurinol starting dose
and serum urate level.

79% of patients with AHS cases and 53% of control patients started at a dose of 2.0
mg or more of allopurinol per unit of eGFR (mg/mL/minute).

A starting dose based on an eGFR of 1.5 mg/mL/minute was selected as a reasonable

tradeoff between a clinically practicable dose and the absolute risk for AHS.

The authors concluded that the starting dose of allopurinol was an important risk
factor for the development of AHS and that a starting dose of 1.5 mg/unit of eGFR
was appropriate to minimize the risk for AHS.

CLINICAL IMPLICATIONS

Risk factors for AHS among patients with gout started on allopurinol include the
presence of tophi and ethnicity; clinical features include worsening renal function,
acute hepatocellular injury, fever, eosinophilia, and leukocytosis.

Starting dose of allopurinol is a risk factor for AHS; a starting dose of 1.5
mg/mL/minute of eGFR is appropriate to minimize the risk for AHS.

with severe [chronic kidney disease] probably function well as starting doses.