What are the monitoring parameters for initiating allopurinol (xanthine oxidase inhibitor) therapy?

From the Guidelines

Before starting allopurinol, it is essential to monitor several key parameters to minimize the risk of adverse reactions and ensure effective treatment, including baseline renal function, liver function tests, serum uric acid levels, and screening for hypersensitivity reactions, particularly in high-risk populations, as recommended by the 2017 EULAR evidence-based recommendations for the management of gout 1.

Key Monitoring Parameters

• Baseline renal function with serum creatinine and estimated glomerular filtration rate (eGFR) to adjust allopurinol dosing in renal impairment, as allopurinol dosing requires adjustment in renal impairment, with a starting dose of no greater than 100 mg/day for any patient, and 50 mg/day in stage 4 or worse CKD 1.
• Baseline liver function tests, including ALT and AST, since allopurinol can rarely cause hepatotoxicity, and dose can be raised above 300 mg daily, even with renal impairment, as long as this is accompanied by adequate patient education and monitoring for drug toxicity 1.
• Baseline serum uric acid levels to establish a reference point for treatment effectiveness, with a target typically below 6 mg/dL, and a lower SUA target (<5 mg/dL) to facilitate faster dissolution of crystals is recommended for patients with severe gout, until total crystal dissolution and resolution of gout 1.
• Screen for a history of hypersensitivity reactions, particularly in patients of Han Chinese, Korean, or Thai descent who should undergo HLA-B*5801 testing due to increased risk of severe cutaneous adverse reactions, as recommended by the 2012 American College of Rheumatology guidelines for management of gout 1.
• Document baseline complete blood count, as allopurinol can occasionally cause bone marrow suppression.

Post-Initiation Monitoring

• Monitor renal and liver function and complete blood count every 2-4 weeks for the first 3 months, then periodically thereafter, to minimize the risk of adverse reactions and ensure effective treatment.
• Check serum uric acid levels 2-4 weeks after starting therapy and after each dose adjustment, to ensure that the target serum uric acid level is achieved and maintained.
• Patients should be educated about potential hypersensitivity reactions, including rash, fever, and eosinophilia, which typically occur within the first 8 weeks of treatment and require immediate discontinuation of the medication, as recommended by the 2017 EULAR evidence-based recommendations for the management of gout 1.

From the FDA Drug Label

In patients with decreased renal function or who have concurrent illnesses which can affect renal function such as hypertension and diabetes mellitus, periodic laboratory parameters of renal function, particularly BUN and serum creatinine or creatinine clearance, should be performed and the patient’s dosage of allopurinol tablets reassessed The correct dosage and schedule for maintaining the serum uric acid within the normal range is best determined by using the serum uric acid as an index. In patients with pre-existing liver disease, periodic liver function tests are recommended during the early stages of therapy

The monitoring parameters for starting allopurinol include:

• Serum uric acid levels to determine the correct dosage and schedule
• Renal function tests, such as BUN and serum creatinine or creatinine clearance, in patients with decreased renal function or concurrent illnesses that can affect renal function
• Liver function tests in patients with pre-existing liver disease 2 2

From the Research

Monitoring Parameters for Starting Allopurinol

When considering the initiation of allopurinol, a medication commonly used to treat gout and high levels of uric acid, monitoring of liver function is crucial due to the potential for hepatotoxicity. The key parameters to monitor include:

• Liver function tests (LFTs) such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), and bilirubin 3
• Albumin, INR, and platelet count, which are often overlooked but provide valuable information about liver health 4
• It is essential to interpret these tests correctly, as normal values do not rule out advanced chronic liver disease, and high levels do not automatically indicate liver failure 4

Interpretation of Liver Function Tests

The interpretation of LFTs is critical in assessing liver health.

• Hepatocellular injury is defined as disproportionate elevation of AST and ALT levels compared with alkaline phosphatase levels 5
• Cholestatic injury is defined as disproportionate elevation of alkaline phosphatase level as compared with AST and ALT levels 5
• Elevated conjugated bilirubin implies hepatocellular disease or cholestasis 5
• A true healthy normal ALT level ranges from 29 to 33 IU/l for males, 19 to 25 IU/l for females, and levels above this should be assessed 5

Evaluation of Abnormal Liver Chemistries

When abnormal liver chemistries are detected, a comprehensive evaluation should be undertaken, including:

• Testing for viral hepatitis A, B, and C 5
• Assessment for nonalcoholic fatty liver disease and alcoholic liver disease 5
• Screening for hereditary hemochromatosis, autoimmune hepatitis, Wilson's disease, and alpha-1 antitrypsin deficiency 5
• A history of prescribed and over-the-counter medicines should be sought 5
• A liver biopsy may be considered when serologic testing and imaging fails to elucidate a diagnosis, to stage a condition, or when multiple diagnoses are possible 5