Difficult gout and new approaches for control of hyperuricemia in the allopurinol-allergic patient

Abstract

A major obstacle to the treatment of hyperuricemia in patients allergic to allopurinol is the limited availability of suitable, equally effective, alternative, urate-lowering drugs. Conventional uricosuric drugs, including probenecid and sulfinpyrazone, are recommended for allopurinol- intolerant patients with gout and "underexcretion" hyperuricemia who have normal renal function and no history of nephrolithiasis. Therapeutic options in those in whom traditional uricosuric drugs are contraindicated, ineffective, or poorly tolerated include slow oral desensitization to allopurinol and cautious administration of oxipurinol. Allopurinol desensitization is useful particularly in those who have failed other treatment modalities. If available (as in Europe, South Africa, and Japan), benzbromarone may be tried in patients with gout and mild-to-moderate renal insufficiency. Recombinant urate oxidase can be used in the short-term prophylaxis and treatment of chemotherapy- associated hyperuricemia in patients with lymphoproliferative and myeloproliferative disorders. Hyperuricemia and gout occur with increased frequency in cyclosporine-treated allograft transplant recipients. The management of gout in these patients is complicated by two main factors: cyclosporine-induced renal impairment, and interactions with medications used to preserve the allograft.

Biochemical effectiveness of allopurinol and allopurinol-probenecid in previously benzbromarone-treated gout patients

“…Uricase-based drugs are potentially very effective but also very expensive drugs, so further (pharmacoeconomic) studies on optimizing antihyperuricemic therapy with old (out of patent) drugs, like benzbromarone, are warranted. At this moment, benzbromarone seems to be the most effective antihyperuricemic drug, and from our point of view, availability of benzbromarone in other countries would make treatment of difficult gout more successful [31].…”

An effective strategy to prevent allopurinol-induced hypersensitivity by HLA typing

“…16 T-cell-mediated hypersensitivity is, however, a major mechanism in delayed hypersensitivity reaction, which requires dozens of days to increase the dose step by step for tolerance induction. 30 In the current study we used a 28-day slow tolerance induction protocol adapted from the desensitization protocol described by Fam et al, 21 which showed successful tolerance induction in 78% of hyperuricemic patients with allopurinol-induced maculopapular eruption, and borrowed the idea from the fact that allopurinol administration by a slow desensitization protocol could avoid activating already existing memory cells into effector cells. We speculated that slow, gradual escalation of the drug based on a tolerance induction protocol might help to skip the generation of effector and memory T cells, although the existence of those cells was not verified in the study.…”

Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase: A twenty‐eight–day, multicenter, phase II, randomized, double‐blind, placebo‐controlled, dose‐response clinical trial examining safety and efficacy in patients with gout

“…Allopurinol is effective in reducing sUA levels, but achieving normal sUA levels may be difficult in patients with impaired renal function or in transplant recipients (2,6,9,26). An uncommon, but significant, limitation to the use of allopurinol is the risk, more common in elderly and renally impaired individuals, of reactions that may include rashes (some severe), hematologic cytopenias, hepatitis, vasculitis, and the potentially life-threatening allopurinol hypersensitivity syndrome (1,9,26,(29)(30)(31)(32)(33)(34).…”