From the Guidelines
Allopurinol commonly causes side effects including rash, nausea, diarrhea, and headache, with more serious but less common side effects including severe skin reactions like Stevens-Johnson syndrome, liver damage, and bone marrow suppression. Patients may experience elevated liver enzymes, kidney problems, or drowsiness 1. A potentially life-threatening hypersensitivity reaction called DRESS syndrome can occur, especially in the first few months of treatment. Allopurinol can also trigger acute gout attacks when first starting the medication, which is why it's often prescribed with colchicine or an anti-inflammatory drug for the first few months. People with kidney disease need dose adjustments as they're at higher risk for side effects. Patients should start at a low dose (typically 100mg daily) and gradually increase to minimize side effects. Anyone experiencing severe rash, yellowing of skin/eyes, unusual bleeding/bruising, or difficulty breathing should seek immediate medical attention.
Some key points to consider when prescribing allopurinol include:
- The most common adverse event with allopurinol is rash 1
- Persons with the HLA-B*5801 haplotype may have an increased risk for serious adverse effects with allopurinol 1
- Allopurinol can cause fatal hypersensitivity reactions, although these are rare 1
- Patients with kidney disease should have their dose adjusted to minimize the risk of side effects 1
- The starting dose of allopurinol should be no greater than 100 mg per day, with gradual upward titration of the maintenance dose every 2–5 weeks to an appropriate maximum dose for gout 1
It's essential to weigh the benefits and risks of allopurinol therapy and to monitor patients closely for potential side effects, especially in the first few months of treatment. By doing so, healthcare providers can help minimize the risk of adverse reactions and ensure the safe and effective use of allopurinol for the management of gout.
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following estimates of incidence of adverse reactions are made are derived from experiences reported in the literature, unpublished clinical trials and voluntary reports since marketing of allopurinol tablets began The most frequent adverse reaction to allopurinol tablets is skin rash.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 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:
- Skin reactions: rash, maculopapular rash, which can be severe and sometimes fatal
- Gastrointestinal: diarrhea, nausea, alkaline phosphatase increase, SGOT/SGPT increase
- Metabolic and Nutritional: acute attacks of gout
- Body As a Whole: ecchymosis, fever, headache
- Cardiovascular: necrotizing angiitis, vasculitis These side effects are based on data from the literature, unpublished clinical trials, and voluntary reports since the marketing of allopurinol tablets began 2. Additionally, other side effects have been reported, such as hepatotoxicity, and Stevens-Johnson syndrome (erythema multiforme exudativum) 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) and Toxic Epidermal Necrolysis (TEN), which are life-threatening delayed hypersensitivity reactions 3, 4
- Severe cutaneous adverse reactions, which can be categorized based on the area of skin involvement 3
- Acute renal failure and hemodynamic compromise, especially in patients with concomitant acute viral illness 3
- Gastrointestinal symptoms, although not explicitly mentioned in the provided studies, are commonly associated with allopurinol therapy
Comparison with Febuxostat
Allopurinol and febuxostat are both used to prevent flare-ups in gout patients. However, febuxostat is associated with an increase in all-cause and cardiovascular mortality and is therefore not routinely recommended 5. A comparative study found that allopurinol was noninferior to febuxostat in controlling flares, with similar outcomes in patients with stage 3 chronic kidney disease 6.
Renal Outcomes
A systematic review found that febuxostat may be more renoprotective than allopurinol in patients with both hyperuricemia and chronic kidney disease, although the evidence is based on small long-term retrospective studies with serious risk of bias 7.
Patient-Specific Factors
Certain patient populations, such as Asian and African American patients, may be more susceptible to severe hypersensitivity reactions like SJS and TEN 4. Additionally, patients with chronic kidney disease may require closer monitoring and dose adjustments when taking allopurinol 7.