When to avoid allopurinol (Zyloprim) in patients with impaired renal function or other contraindications?

From the Guidelines

Allopurinol should be avoided in patients with a history of severe hypersensitivity reactions, renal impairment, and those with the HLA-B*5801 genotype, particularly of Han Chinese, Thai, or Korean descent, due to the increased risk of severe cutaneous adverse reactions, as supported by the 2017 EULAR evidence-based recommendations for the management of gout 1. When considering the use of allopurinol, it is essential to weigh the potential benefits against the risks, particularly in patients with certain comorbidities or genetic predispositions.

• Patients with a history of severe hypersensitivity reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, or drug rash with eosinophilia and systemic symptoms (DRESS), should avoid allopurinol due to the high risk of recurrence.
• Renal impairment is another critical consideration, as allopurinol is primarily excreted by the kidneys, and dosage adjustments are necessary to prevent toxicity, as recommended by the 2012 American College of Rheumatology guidelines for management of gout 1.
• The HLA-B*5801 genotype, particularly in patients of Han Chinese, Thai, or Korean descent, is associated with a significantly higher risk of severe cutaneous adverse reactions, and these patients should avoid allopurinol if possible, as suggested by the 2017 EULAR recommendations 1.
• Additionally, allopurinol should be used cautiously in patients with certain medications, including azathioprine and mercaptopurine, as it inhibits their metabolism, potentially leading to toxicity.
• Pregnant women should avoid allopurinol unless the benefits clearly outweigh the risks, and patients should undergo baseline renal function tests before starting the medication, which should be initiated at a low dose (typically 100mg daily) and gradually increased to minimize the risk of hypersensitivity reactions and gout flares.
• The 2017 EULAR recommendations also suggest a "start low, go slow" approach to minimize the risk of acute gout attacks during treatment initiation, and to consider alternative treatments, such as febuxostat or pegloticase, in patients with severe gout or those who cannot tolerate allopurinol 1.

From the FDA Drug Label

Patients with decreased renal function require lower doses of allopurinol tablets than those with normal renal function. Renal failure in association with administration of allopurinol tablets has been observed among patients with hyperuricemia secondary to neoplastic diseases. Bone marrow depression has been reported in patients receiving allopurinol tablets, most of whom received concomitant drugs with the potential for causing this reaction.

Allopurinol should be avoided or used with caution in the following situations:

• Renal impairment: Patients with decreased renal function or pre-existing renal disease should be carefully observed during the early stages of administration, and the dosage decreased or the drug withdrawn if increased abnormalities in renal function appear and persist 2.
• Bone marrow depression: Patients who have experienced bone marrow depression or are at risk of developing it should be monitored closely while receiving allopurinol tablets 2.
• Hypersensitivity reactions: Patients who have experienced hypersensitivity reactions to allopurinol tablets should avoid using the medication 2.
• Concomitant use of certain medications: Patients taking dicumarol, sulfinpyrazone, mercaptopurine, azathioprine, ampicillin, amoxicillin, and thiazide diuretics should be cautious when using allopurinol tablets, as there may be certain risks associated with concomitant use 2.

From the Research

When to Avoid Allopurinol

Allopurinol is a commonly used medication for the treatment of gout and hyperuricemia, but it can cause severe adverse reactions in some patients. The following are situations when allopurinol should be avoided or used with caution:

• Renal Impairment: Patients with renal impairment are at increased risk of developing allopurinol hypersensitivity syndrome (AHS) due to elevated oxypurinol concentrations 3, 4, 5, 6.
• Hypersensitivity Reactions: Patients who have experienced hypersensitivity reactions to allopurinol in the past should avoid the medication 4, 7, 5, 6.
• Old Age: Elderly patients are at increased risk of developing AHS, and allopurinol should be used with caution in this population 4, 5.
• Concomitant Thiazide Diuretic Intake: Patients taking thiazide diuretics may be at increased risk of developing AHS, and allopurinol should be used with caution in this population 5.
• Asymptomatic Hyperuricemia: Allopurinol should only be used for accepted indications, and asymptomatic hyperuricemia may not be a sufficient reason to initiate therapy 6.
• Previous History of Skin Rash or Allergic Reactions: Patients with a history of skin rash or allergic reactions should be monitored closely while taking allopurinol, as they may be at increased risk of developing AHS 4, 7, 5, 6.