Can allopurinol cause urethritis?

Allopurinol and Urethritis

Allopurinol is not known to cause urethritis as a documented adverse effect, though it can cause severe hypersensitivity reactions that may include mucosal manifestations.

Documented Adverse Effects of Allopurinol

Allopurinol is associated with several well-documented adverse effects, but urethritis is not specifically listed among them:

• Allopurinol hypersensitivity syndrome (AHS) is the most serious adverse reaction, consisting of erythematous desquamating rash, fever, hepatitis, eosinophilia, and worsening renal function 1
• Skin reactions ranging from mild rash to severe cutaneous adverse reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis 2
• Potential impact on renal function, particularly in hypertensive patients with glomerular filtration rates above 80 ml/min 1
• Fixed pigmented drug eruption and leucocytoclastic vasculitis have been reported 1
• Increased risk of cataract extraction in elderly patients has been observed in case-control studies 1

Risk Factors for Allopurinol Adverse Reactions

Several factors increase the risk of developing adverse reactions to allopurinol:

• Ethnicity: Han-Chinese, Korean, and Thai populations have higher risk of severe hypersensitivity reactions 3
• HLA-B*5801 genotype: Strongly associated with severe cutaneous reactions 3, 4
• Renal impairment: Increases risk of toxicity due to accumulation of oxypurinol (active metabolite) 3
• Higher starting doses: Beginning with doses >100mg daily increases risk 3, 4
• Concomitant diuretic use 4

Management Considerations

When prescribing allopurinol, the following precautions should be taken to minimize adverse effects:

• Start with low doses (100 mg daily, or 50 mg in renal impairment) and titrate gradually 3
• Consider HLA-B*5801 testing before initiating therapy in high-risk ethnic groups 3
• Reduce dose by at least 50% in patients with renal insufficiency 3
• Monitor for early signs of hypersensitivity reactions 4
• Educate patients about signs and symptoms of severe adverse reactions 4
• Use caution with diuretics, which may aggravate hyperuricemia 1

Alternative Treatments

If allopurinol toxicity occurs, alternative treatments include:

• Other xanthine oxidase inhibitors like febuxostat (may have less cross-reactivity) 1
• Uricosuric agents such as probenecid or sulphinpyrazone 1
• Non-pharmacological approaches including education, weight loss, reducing alcohol consumption, and dietary modification 1

Conclusion on Urethritis

While urethritis is not specifically documented as an adverse effect of allopurinol in the available guidelines and research, patients experiencing urinary symptoms while on allopurinol should be evaluated for:

• Possible manifestation of a broader hypersensitivity reaction 1
• Alternative causes of urethritis unrelated to allopurinol
• Potential interaction with other medications being taken concurrently

If urethritis symptoms develop during allopurinol treatment and no other cause is identified, consider monitoring symptoms closely and potentially discontinuing the medication if symptoms persist or worsen, especially if accompanied by other signs of hypersensitivity 4.