From the Guidelines
Allopurinol can cause severe side effects, including a potentially life-threatening hypersensitivity reaction, and patients should be closely monitored, especially those with renal impairment or taking certain medications, such as thiazide diuretics, and genetic testing for HLA-B*58:01 variants is recommended prior to allopurinol therapy initiation in certain populations 1. The most common side effects of allopurinol include rash, nausea, diarrhea, and headache. However, more serious but less common side effects can occur, such as severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), liver damage, and bone marrow suppression.
- Allopurinol hypersensitivity syndrome is a rare but potentially life-threatening reaction that can occur, especially in patients with renal impairment or those taking thiazide diuretics.
- This syndrome presents with fever, rash, eosinophilia, hepatitis, and worsening kidney function.
- Patients should start allopurinol at a low dose (typically 100mg daily) and gradually increase to minimize side effects, with dosage adjustments needed for those with kidney impairment, as recommended by the EULAR evidence-based recommendations for gout management 1.
- Adequate hydration is important while taking allopurinol.
- During the first few months of treatment, allopurinol can paradoxically increase gout attacks, so colchicine or NSAIDs are often prescribed concurrently for the first 3-6 months.
- Patients should immediately report any rash, which could indicate a serious reaction requiring medication discontinuation. Key considerations for minimizing the risk of side effects include:
- Starting with a low dose and gradually increasing as needed
- Adjusting the dose for patients with kidney impairment
- Monitoring for signs of hypersensitivity reaction, such as rash, fever, and eosinophilia
- Considering genetic testing for HLA-B*58:01 variants prior to allopurinol therapy initiation in certain populations, as recommended by the 2015 updated CPIC guidelines 1.
From the FDA Drug Label
Data upon which the following estimates of incidence of adverse reactions are made are derived from experiences reported in the literature, unpublished clinical trials and voluntary reports since marketing of allopurinol tablets began The most frequent adverse reaction to allopurinol tablets is skin rash. Skin reactions can be severe and sometimes fatal Among 55 patients with gout treated with allopurinol tablets for 3 to 34 months (average greater than 1 year) and followed prospectively, Rundles observed that 3% of patients developed a type of drug reaction which was predominantly a pruritic maculopapular skin eruption, sometimes scaly or exfoliative. Most Common Reactions* Probably Causally Related: Gastrointestinal: Diarrhea, nausea, alkaline phosphatase increase, SGOT/SGPT increase. Metabolic and Nutritional: Acute attacks of gout. Skin and Appendages: Rash, maculopapular rash Incidence Less Than 1% Probably Causally Related: Body As a Whole: Ecchymosis, fever, headache. Cardiovascular: Necrotizing angiitis, vasculitis
The side effects of allopurinol include:
- Gastrointestinal: diarrhea, nausea, alkaline phosphatase increase, SGOT/SGPT increase
- Metabolic and Nutritional: acute attacks of gout
- Skin and Appendages: rash, maculopapular rash
- Body As a Whole: ecchymosis, fever, headache
- Cardiovascular: necrotizing angiitis, vasculitis The most frequent adverse reaction is skin rash, which can be severe and sometimes fatal 2. A few cases of reversible clinical hepatotoxicity have been noted in patients taking allopurinol tablets 2.
From the Research
Side Effects of Allopurinol
The side effects of allopurinol can be severe and life-threatening. Some of the known side effects include:
- Stevens-Johnson syndrome (SJS) 3, 4, 5, 6
- Toxic epidermal necrolysis (TEN) 4, 5, 6
- Erythema multiforme exudativum 6
- Acute renal failure 3, 7, 6
- Hepatic failure 6
- Exfoliative rash 7
- Allopurinol hypersensitivity syndrome 5, 7
- Skin rash 7, 6
Risk Factors
Certain factors can increase the risk of developing severe side effects from allopurinol, including:
- Impaired renal function 4, 7
- Concomitant use of ampicillin and thiazide diuretics 7
- Acute viral illness 3
Treatment and Management
If side effects occur, it is essential to discontinue allopurinol and seek medical attention immediately. Treatment may involve: