From the Guidelines
Allopurinol can cause several side effects, with the most common being rash, and patients with the HLA-B*5801 haplotype may have an increased risk for serious adverse effects 1.
Common Side Effects
- Skin rash
- Nausea
- Diarrhea
- Headache
- Drowsiness Some patients may also experience elevated liver enzymes or mild stomach discomfort.
Serious Side Effects
More serious but less common side effects include severe skin reactions like Stevens-Johnson syndrome or toxic epidermal necrolysis, which present as painful rashes with blistering. Allopurinol can also cause bone marrow suppression resulting in reduced blood cell counts. Rarely, patients may develop hypersensitivity syndrome, particularly in those with renal impairment or taking thiazide diuretics, which includes fever, rash, eosinophilia, hepatitis, and worsening kidney function 1.
Minimizing Side Effects
To minimize side effects, allopurinol should be started at a low dose (typically 100mg daily) and gradually increased while monitoring for adverse reactions. Patients should stay well-hydrated while taking this medication and report any rash or unusual symptoms to their healthcare provider immediately, as early intervention can prevent progression of serious reactions. Side effects are more common in patients with kidney disease, so dosage adjustments are often necessary in these individuals. It is essential to consider the patient's renal function and adjust the dosage accordingly, as recommended in the guidelines 1.
From the FDA Drug Label
The most frequent adverse reaction to allopurinol tablets is skin rash. Skin reactions can be severe and sometimes fatal Therefore, treatment with allopurinol tablets should be discontinued immediately if a rash develops 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 Gastrointestinal: Hepatic necrosis, granulomatous hepatitis, hepatomegaly, hyperbilirubinemia, cholestatic jaundice, vomiting, intermittent abdominal pain, gastritis, dyspepsia. Hemic and Lymphatic: Thrombocytopenia, eosinophilia, leukocytosis, leukopenia. Musculoskeletal: Myopathy, arthralgias. Nervous: Peripheral neuropathy, neuritis, paresthesia, somnolence. Respiratory: Epistaxis
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, hepatic necrosis, granulomatous hepatitis, hepatomegaly, hyperbilirubinemia, cholestatic jaundice, vomiting, intermittent abdominal pain, gastritis, dyspepsia
- Metabolic and Nutritional: acute attacks of gout
- Body As a Whole: ecchymosis, fever, headache
- Cardiovascular: necrotizing angiitis, vasculitis
- Hemic and Lymphatic: thrombocytopenia, eosinophilia, leukocytosis, leukopenia
- Musculoskeletal: myopathy, arthralgias
- Nervous: peripheral neuropathy, neuritis, paresthesia, somnolence
- Respiratory: epistaxis 2, 2, 2
From the Research
Side Effects of Allopurinol
- Allopurinol can cause serious adverse reactions, including rash, eosinophilia, leukocytosis, fever, hepatitis, and progressive kidney failure 3
- The risk of severe adverse reactions is increased in patients with the HLA-B(*)58:01 allele, recent introduction of allopurinol, and factors that influence drug concentration 3
- Allopurinol hypersensitivity syndrome (AHS) is a severe and sometimes life-threatening adverse drug reaction that can occur within 8-9 weeks of commencing allopurinol 4
- Pretreatment testing for HLA-B*5801 and avoidance of allopurinol when positive can reduce the risk of AHS 4
- Chronic kidney disease increases the risk of AHS, but slowly increasing the allopurinol dose in chronic kidney disease has not been associated with AHS 4
Rare but Serious Side Effects
- Allopurinol can cause toxic epidermal necrolysis (TEN), a rare but potentially life-threatening condition characterized by widespread blistering of the skin and mucous membrane lesions 5
- Acute renal and hepatic failure can also occur as a result of allopurinol treatment 5
- Erythema multiforme exudativum and Steven-Johnson Syndrome (SJS) are other rare but serious hypersensitivity reactions that can occur with allopurinol use 5