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Allopurinol, renal function, and adverse effects

 

Clinical bottom line

This retrospective study shows that adverse events with allopurinol are uncommon, and not related to creatinine clearance-adjusted dose. It gives some useful recommendations about using allopurinol.


Reference


J Vázquez-Mellado et al. Relation between adverse events associated with allopurinol and renal function in patients with gout. Annals of Rheumatic Disease 2001 60: 981-983.


Study

This was a retrospective analysis of 120 consecutive patients (118 were men) with gout receiving allopurinol for at least one month before inclusion in the analysis. In all patients the initial dose of allopurinol was adjusted according to the creatinine clearance rate, as shown in Table 1.

Table 1: Initial allopurinol dose and creatinine clearance

Creatinine clearance (mL/min)

Allopurinol dose

0

100 mg every 3 days

10

100 mg every 2 days

20

100 mg daily

40

150 mg daily

60

200 mg daily

80

250 mg daily

100

300 mg daily

120

350 mg daily

140

400 mg daily

During follow up in some patients the dose of allopurinol had to be increased to achieve a sustained reduction in serum uric acid, and in these patients the dose of allopurinol was higher than that adjusted for creatinine clearance rate. Adverse events were defined as all new clinical and laboratory data appearing during follow up and not explained by gout or concomitant diseases.

Results

Fifty-two patients had allopurinol dose according to creatinine clearance, and 68 had doses higher than that recommended for their creatinine clearance. The major difference was that the latter group (higher than recommended allopurinol) had a much lower creatinine clearance (55 mL/min versus 104 mL/min). Allopurinol had been used for a mean of 3.3 years in doses from 100-450 mg daily. The distribution of allopurinol doses was not different between the two groups. The mean age was 53 years, with 13 years of gout on average.

There were five allopurinol-related adverse events, three in those with recommended doses, and two with higher than recommended doses.Four minor reactions occurred between 5 and 32 months of starting allopurinol: two cases of skin rash, mild cutaneous vasculitis, and fixed pigment drug eruption. Allopurinol rechallenge with escalating dosage did not result in any further adverse reactions.

One serious adverse event occurred in a patient using a recommended dose of allopurinol. Allopurinol hypersensitivity syndrome occurred within two weeks of starting allopurinol. After desensitisation, allopurinol was restarted.

Comment

The frequency of adverse events was low, and not related to creatinine clearance-related dosing. The paper has a useful discussion of the previous literature, which is mostly single case reports or series of patients with adverse reactions, but no information about patients without adverse reactions. The study is limited by being retrospective (though of consecutive patients), and limited in size (important for less common adverse reactions). It still has more information that other studies.

The authors make the following conclusions about allopurinol treatment:

  1. verify that there is a clear indication for allopurinol treatment
  2. start allopurinol in doses according to the creatinine clearance rate
  3. check for concomitant diseases or treatments associated with serious events in patients requiring higher doses of allopurinol
  4. in patients for whom no other urate lowering drug is available, the dose of allopurinol should be increased with caution.