What adjustments should be made to the treatment plan for a patient with hyperuricaemia, bilateral leg swelling, and medication intolerance, who is currently taking febuxostat, amlodipine, atorvastatin, Galvomet (metformin), Losec (omeprazole), and cholecalciferol, and has a history of allergic reactions to allopurinol?

Treatment Plan Adjustments for This Patient

Reduce febuxostat from 80mg to 40mg daily immediately, switch amlodipine to an alternative antihypertensive (such as an ACE inhibitor or ARB which may provide uricosuric benefit), and change Galvomet to separate metformin liquid or smaller tablets to address swallowing difficulty. 1

Hyperuricemia Management

Febuxostat Dose Reduction

• The uric acid level of 0.11 mmol/L (approximately 1.9 mg/dL) is significantly below the target of <6 mg/dL (0.36 mmol/L), indicating excessive urate-lowering therapy. 1
• Reduce febuxostat from 80mg to 40mg daily as planned, which will bring uric acid levels closer to the therapeutic target while maintaining gout control. 1
• The target serum urate should be maintained at <6 mg/dL (0.36 mmol/L) to prevent gout flares while avoiding excessive lowering. 1
• Monitor serum uric acid levels every 2-4 weeks after dose reduction to ensure levels remain in the therapeutic range of 5-6 mg/dL. 2

Important Caveat on Allopurinol

• This patient has a documented allergy to allopurinol, making febuxostat the appropriate xanthine oxidase inhibitor choice. 1
• Allopurinol hypersensitivity can be life-threatening with a 25% mortality rate, so rechallenge is absolutely contraindicated. 1

Bilateral Leg Swelling Management

Discontinue or Switch Amlodipine

• Amlodipine is a well-known cause of peripheral edema, occurring in up to 10-30% of patients, and is the most likely culprit for worsening leg swelling after bendroflumethiazide discontinuation. 1
• Switch to an alternative antihypertensive agent, preferably losartan (which the patient is already taking) at an increased dose, or add an ACE inhibitor. 1
• Losartan has uricosuric properties and may provide dual benefit for both hypertension and hyperuricemia management. 1
• If blood pressure control is inadequate with losartan alone, consider adding a non-dihydropyridine calcium channel blocker (diltiazem or verapamil) which have lower rates of peripheral edema than amlodipine. 1

Avoid Restarting Thiazide Diuretics

• While bendroflumethiazide helped with edema, thiazide diuretics can precipitate gout flares and worsen hyperuricemia. 1
• Given the patient's complex gout history and current medication regimen, alternative strategies for edema management are preferable. 1

Non-Pharmacologic Measures

• Continue leg elevation, but for longer periods (ideally legs elevated above heart level for 30 minutes, 3-4 times daily). 1
• Compression stockings (20-30 mmHg) may provide symptomatic relief if tolerated. 1

Medication Intolerance - Galvomet Tablets

Switch to Alternative Formulation

• Replace Galvomet 50/1000mg tablets with separate components: vildagliptin 50mg tablets (smaller, easier to swallow) and metformin liquid formulation 1000mg twice daily. 1
• Metformin oral solution (500mg/5mL) is available and eliminates swallowing difficulty. 1
• Alternatively, consider metformin extended-release tablets which are often smaller and may be easier to swallow, though they should not be crushed. 1

If Separation Not Feasible

• Consider switching to a different DPP-4 inhibitor/metformin combination with smaller tablet size. 1
• Evaluate for alternative diabetes medications if swallowing difficulties persist (e.g., injectable GLP-1 agonists, though this adds complexity). 1

Monitoring Plan

Short-Term (2-4 Weeks)

• Recheck serum uric acid to ensure levels are rising toward target range of 5-6 mg/dL after febuxostat dose reduction. 2
• Assess leg swelling after amlodipine discontinuation (should see improvement within 1-2 weeks). 1
• Confirm patient tolerance of new metformin formulation. 1
• Monitor blood pressure to ensure adequate control with adjusted antihypertensive regimen. 1

Medium-Term (3-6 Months)

• Continue monitoring serum uric acid every 2-3 months once stable. 2
• Assess for gout flares (patient should remain on prophylaxis if flares occur with urate level changes). 3
• Monitor kidney function given chronic lymphocytosis with neutropenia and medication adjustments. 2
• Reassess for any recurrence of itching that may be febuxostat-related. 1

Common Pitfalls to Avoid

• Do not restart amlodipine or other dihydropyridine calcium channel blockers, as peripheral edema will likely recur. 1
• Do not attempt allopurinol rechallenge given documented allergy and risk of severe hypersensitivity reactions. 1
• Do not allow uric acid to remain excessively low (<3 mg/dL), as this provides no additional benefit and wastes medication. 1
• Do not crush or split extended-release formulations if switching metformin preparations. 1
• Ensure the patient understands that leg swelling improvement may take 1-2 weeks after stopping amlodipine. 1