Allopurinol (Adverse effects)

Allopurinol is a medication primarily used to reduce uric acid levels in certain clinical conditions. Some people may have a greater genetic predisposition to developing serious adverse reactions associated with this treatment. The HLA-B*58:01 allele has been linked to an increased risk of severe skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis.

Allopurinol is a xanthine oxidase inhibitor widely used for the treatment of hyperuricemia and gout. By reducing uric acid production, it helps prevent the deposition of urate crystals and the development of gout attacks.

Although generally well-tolerated, allopurinol can be associated with adverse reactions ranging from mild skin rashes to potentially severe hypersensitivity syndromes. One of the main pharmacogenetic factors related to the risk of severe toxicity is the presence of the HLA-B*58:01 allele.

Although the incidence of severe adverse reactions is relatively low, their high morbidity and mortality have driven intense research into predictive risk factors, especially pharmacogenetic markers. Among these, HLA-B*58:01 has established itself as the most relevant genetic determinant associated with severe cutaneous adverse reactions (SCAR) induced by allopurinol.

Mechanism of Action

Allopurinol is a structural analog of hypoxanthine that inhibits xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine and xanthine to uric acid. Its active metabolite, oxypurinol, significantly contributes to its therapeutic effect through prolonged inhibition of xanthine oxidase activity. Consequently, serum and urinary uric acid concentrations decrease, reducing the risk of urate crystal formation and promoting the dissolution of existing deposits.

Contraindications

Allopurinol is contraindicated in patients with known hypersensitivity to the active substance or any of its excipients.

Special caution is recommended in patients with renal impairment, as oxypurinol accumulation may increase the risk of adverse reactions.

Likewise, concomitant administration with azathioprine, mercaptopurine, or other drugs metabolized by xanthine oxidase requires dose adjustment and close monitoring due to the risk of severe toxicity.

In individuals carrying the HLA-B*58:01 allele, treatment with allopurinol should be avoided whenever suitable therapeutic alternatives exist, due to the significant increase in the risk of developing severe cutaneous hypersensitivity reactions.

Adverse Reactions

Allopurinol generally has good tolerability, and most adverse reactions are mild, including gastrointestinal upset, nausea, vomiting, diarrhea, headache, skin rash, and transient elevations in liver enzymes. However, in rare cases, it can induce severe cutaneous adverse reactions (SCAR), a group of potentially life-threatening immune-mediated hypersensitivity syndromes including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS).

Brand Names

Allopurinol is marketed under various names, including:

• Aloprim®
• Urosin®
• Zyloric®
• Zyloprim®