From the Guidelines
Both febuxostat and allopurinol carry a risk of Stevens-Johnson syndrome (SJS), a severe cutaneous adverse reaction, though the risk is generally higher with allopurinol. When initiating these medications for gout or hyperuricemia, caution is warranted in patients with a history of severe cutaneous reactions, HLA-B5801 positive status (particularly in Han Chinese, Korean, and Thai populations), or renal impairment. Testing for HLA-B5801 is recommended before starting allopurinol in high-risk ethnic groups. For allopurinol, start at a low dose (50-100 mg daily) and gradually increase, especially in patients with renal impairment. For febuxostat, the starting dose is typically 40 mg daily. Both medications should be discontinued immediately at the first sign of a skin rash, mucosal lesions, or other hypersensitivity reactions. Most SJS reactions occur within the first 8 weeks of treatment, so patients should be monitored closely during this period. Patient education about recognizing early symptoms is crucial. The risk of SJS appears to be dose-dependent with allopurinol, so using the lowest effective dose is advisable. In patients with a history of allopurinol-induced SJS, febuxostat is not automatically safe as cross-reactivity can occur, and alternative treatments should be considered.
Key Considerations
- The risk of SJS is higher with allopurinol, especially in patients with HLA-B*5801 positive status or renal impairment 1.
- Testing for HLA-B*5801 is recommended before starting allopurinol in high-risk ethnic groups.
- Start with a low dose of allopurinol (50-100 mg daily) and gradually increase, especially in patients with renal impairment.
- The starting dose of febuxostat is typically 40 mg daily.
- Monitor patients closely for signs of SJS, especially within the first 8 weeks of treatment.
Patient Education
- Educate patients on recognizing early symptoms of SJS, such as skin rash, mucosal lesions, or other hypersensitivity reactions.
- Emphasize the importance of seeking medical attention immediately if any of these symptoms occur.
Alternative Treatments
- In patients with a history of allopurinol-induced SJS, consider alternative treatments, such as febuxostat or other urate-lowering therapies, as cross-reactivity can occur.
From the Research
Risk of Stevens-Johnson Syndrome (SJS) with Febuxostat (Uloric) versus Allopurinol (Zyloprim)
- The risk of SJS with febuxostat is highlighted in a case report where a patient developed Stevens Johnson syndrome following febuxostat administration 2.
- Another case report describes a patient who had previously developed Steven-Johnson syndrome due to allopurinol and later developed a diffuse maculopapular rash with severe itching after two years of treatment with febuxostat 3.
- In contrast, allopurinol has been reported to cause SJS in several case reports, including a case of a 95-year-old Asian female who developed SJS after starting allopurinol therapy 4, and a case of an 85-year-old Han-Chinese female who developed SJS after ingestion of allopurinol 5.
- The relative frequency of severe cutaneous disorders, including SJS, with febuxostat and allopurinol is not well documented, but it is known that allopurinol can cause severe skin reactions, including SJS, in rare instances 6.
Treatment Initiation or Avoidance
- Patients with hyperuricaemia should continue to receive allopurinol as first-line treatment, and probenecid as second-line treatment if allopurinol is ineffective 6.
- Febuxostat may be considered as an alternative treatment option for patients who are intolerant to allopurinol, but its use should be cautious due to the risk of severe cutaneous adverse reactions, including SJS 2, 3.
- A slow desensitization protocol with febuxostat may be effective in patients who have developed hypersensitivity to the drug, as reported in a case study where a patient was successfully desensitized to febuxostat using a solid preparation of diluted febuxostat given as pills 3.