How to manage hyperuricemia in a patient on Calquence (acalabrutinib)?

Management of Hyperuricemia (Uric Acid 10.5 mg/dL) in a Patient on Calquence (Acalabrutinib)

Initiate urate-lowering therapy with allopurinol, starting at 100 mg daily and titrating upward by 100 mg increments every 2-4 weeks to achieve a target serum uric acid below 6 mg/dL, while continuing Calquence without interruption. 1, 2

Rationale for Initiating Urate-Lowering Therapy

• With a serum uric acid of 10.5 mg/dL, this patient meets criteria for initiating urate-lowering therapy (ULT) even if experiencing their first gout flare, as levels >9 mg/dL warrant treatment. 1
• The 2020 ACR guidelines conditionally recommend initiating ULT for patients experiencing their first flare with serum urate >9 mg/dL. 1
• While BTK inhibitors like ibrutinib have been associated with acute gout flares even in patients on allopurinol prophylaxis, acalabrutinib (Calquence) has a different selectivity profile and this association is less established. 3

First-Line Treatment Protocol

Allopurinol is the preferred first-line agent:

• Start at 100 mg daily to minimize risk of acute flare precipitation. 1, 2
• Increase by 100 mg increments every 2-4 weeks until target serum uric acid is achieved. 1, 2
• The maximum recommended dosage is 800 mg daily. 2
• Target serum uric acid <6 mg/dL for maintenance therapy. 1, 4

Dose adjustments based on renal function:

• If creatinine clearance is 10-20 mL/min, use 200 mg daily maximum. 2
• If creatinine clearance is <10 mL/min, do not exceed 100 mg daily. 2
• In stage 4 or worse CKD, start at 50 mg daily. 1

Prophylaxis Against Acute Flares During ULT Initiation

Continue prophylactic anti-inflammatory therapy during ULT initiation:

• Low-dose colchicine (0.6 mg once or twice daily) is recommended to prevent flares when starting allopurinol. 1
• Continue prophylaxis until serum uric acid has normalized and the patient has been free from acute gouty attacks for several months. 2
• Do not discontinue ULT if an acute flare occurs; treat the flare while continuing allopurinol. 4

Addressing Medication-Related Hyperuricemia

Review and modify medications that may elevate uric acid:

• Eliminate non-essential medications that elevate serum urate, particularly thiazide and loop diuretics, niacin, and calcineurin inhibitors. 1
• Do not discontinue Calquence (acalabrutinib), as it is essential for treating the underlying hematologic malignancy. 5
• If the patient is on antihypertensives, consider switching to losartan (which has uricosuric properties) or calcium channel blockers. 1, 4

Supportive Measures

Implement lifestyle modifications:

• Increase fluid intake to achieve daily urinary output of at least 2 liters. 2
• Maintain neutral or slightly alkaline urine pH. 2
• Advise weight loss if appropriate, avoidance of alcohol (especially beer and spirits), sugar-sweetened drinks, and excessive intake of meat and seafood. 1
• Encourage low-fat dairy products and regular exercise. 1

Alternative Strategies if Target Not Achieved

If serum uric acid target is not reached with maximum appropriate allopurinol dose:

• Switch to febuxostat as an alternative xanthine oxidase inhibitor. 1, 4
• Add a uricosuric agent (probenecid, fenofibrate, or losartan) to allopurinol. 1, 4
• Probenecid is contraindicated if creatinine clearance is <50 mL/min or if there is history of urolithiasis. 1

Monitoring and Follow-Up

Regular monitoring is essential:

• Check serum uric acid levels every 2-4 weeks during dose titration to guide adjustments. 2
• Monitor for allopurinol hypersensitivity reactions, particularly in high-risk populations (though HLA-B*5801 screening is not universally recommended for Caucasians). 1
• Continue monitoring even after target is achieved to ensure maintenance of serum uric acid <6 mg/dL lifelong. 1

Common Pitfalls to Avoid

• Do not discontinue allopurinol if an acute gout flare occurs during initiation; this is expected and should be managed with anti-inflammatory therapy while continuing ULT. 4
• Do not start allopurinol at doses higher than 100 mg daily (or 50 mg in severe CKD), as this increases risk of precipitating acute flares. 1, 2
• Do not use urine alkalinization with sodium bicarbonate, as it can lead to calcium phosphate precipitation and metabolic alkalosis without clear benefit. 1
• Do not treat asymptomatic hyperuricemia alone without gout symptoms, but at 10.5 mg/dL with any gout history, treatment is warranted. 1, 4