Allopurinol response

The dosage of allopurinol tablets to accomplish full control of gout and to lower serum uric acid to normal or near-normal levels varies with the severity of the disease. The average is 200 to 300 mg/day for individuals with mild gout and 400 to 600 mg/day for those with moderately severe tophaceous gout. The appropriate dosage may be administered in divided doses or as a single equivalent dose with the 300-mg tablet. Dosage requirements in excess of 300 mg should be administered in divided doses. The minimal effective dosage is 100 to 200 mg daily and the maximal recommended dosage is 800 mg daily. To reduce the possibility of flare-up of acute gouty attacks, it is recommended that the individual start with a low dose of allopurinol tablets (100 mg daily) and increase at weekly intervals by 100 mg until a serum uric acid level of 6 mg/dL or less is attained but without exceeding the maximal recommended dosage.

Please review the complete therapeutic recommendations that are located here (1).

Testing for the HLA–B*58:01 allele prior to starting allopurinol is conditionally recommended for individuals of Southeast Asian descent (e.g., Han Chinese, Korean, Thai) and for African American individuals, over not testing for the HLA–B*58:01 allele.

Universal testing for the HLA–B*5801 allele prior to starting allopurinol is conditionally recommended against in individuals of other ethnic or racial background over testing for the HLA–B*5801 allele. [Conditional recommendations are those “which would warrant provider-individual shared medical decision-making discussion.”]

As noted above, starting allopurinol in daily doses of ≤100 mg (and lower doses in individuals with CKD [chronic kidney disease]) is strongly recommended over starting at a higher dose.

The HLA–B*58:01 allele is associated with a markedly elevated risk for AHS. The prevalence of HLA–B*58:01 is highest among persons of Han Chinese, Korean, and Thai descent (7.4%), lower among African Americans (3.8%), and even lower among whites and Hispanics (0.7% each). Testing for this allele among Asians and African American individuals was reported to be cost-effective (incremental cost-effectiveness ratios <$109,000 per quality-adjusted life years). Asian and African American individuals taking allopurinol both have a 3-fold increased risk of AHS compared with white individuals taking allopurinol (for recommendations for ULT medications, see Table 4 and Supplementary Figure 3, available [online]).

Please review the complete therapeutic recommendations that are located here (2).

Individuals with the HLA-B*58:01 genetic variation have a strongly increased risk of developing the life-threatening cutaneous side effects Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and DRESS. The risk of an allopurinol-induced life-threatening cutaneous side effect in these individuals is 1.6-13% in the case of a normal or slightly reduced renal function and 12-100% in the case of a severely reduced renal function.

Recommendation:

• Choose an alternative, such as febuxostat.

Another option is to induce allopurinol tolerance first:

To induce allopurinol tolerance, the allopurinol dose is increased every 3 days until a dose of 100 mg/day has been achieved on Day 28. The consecutive daily doses in the induction protocol are 50 μg, 100μg, 200μg, 50 μg, 1mg, 5mg, 10mg, 25 mg, 50mg and 100mg.

Please review the complete therapeutic recommendations that are located here (5).

Given the high specificity for allopurinol-induced SCAR, allopurinol should not be prescribed to individuals who have tested positive for HLA-B*58:01. Alternative medication should be considered for these individuals to avoid the risk of developing SCAR. For individuals who have tested negative, allopurinol may be prescribed as usual. However, testing negative for HLA-B*58:01 does not totally eliminate the possibility of developing SCAR, especially in the European population.

Please review the complete therapeutic recommendations that are located here (3, 4).