Zyloric

Zyloric is a brand of allopurinol, a xanthine oxidase inhibitor used to lower uric acid levels in the blood. It is available in tablet strengths of 100mg and 300mg and is the most widely prescribed long-term treatment for gout, recurrent gout attacks, uric acid nephrolithiasis (uric acid kidney stones), and hyperuricaemia associated with malignancy or its treatment.

Mechanism of Action

Uric acid is the end product of purine metabolism in humans. The enzyme xanthine oxidase catalyses the conversion of hypoxanthine and xanthine into uric acid. Allopurinol and its active metabolite oxipurinol are competitive inhibitors of xanthine oxidase, blocking this final step in uric acid production. By reducing uric acid synthesis, allopurinol lowers serum urate levels, preventing the deposition of monosodium urate crystals in joints, tendons, and soft tissues (tophi), the underlying cause of gout, and reducing the formation of uric acid stones in the kidneys.

When Zyloric Is Used

Zyloric is indicated for the long-term management of gout in patients who experience recurrent attacks (two or more per year), patients with tophi or gouty joint damage, and patients with hyperuricaemia associated with renal disease, haematological malignancies, or cytotoxic chemotherapy. It is not used for the acute treatment of gout attacks; rather, it is a disease-modifying therapy that reduces urate levels over time to prevent future attacks and organ damage.

A critical principle in gout management is that Zyloric should not be started during an acute gout attack. Initiating urate-lowering therapy during an acute attack can mobilise urate crystals and prolong or worsen inflammation. Treatment should begin only once an acute attack has fully resolved, typically at least two to four weeks after the last episode. Anti-inflammatory prophylaxis with colchicine or an NSAID should be co-prescribed for the first three to six months of Zyloric therapy, as the initial reduction in urate levels can paradoxically trigger gout flares.

Zyloric is taken orally, once daily, preferably after food to minimise gastrointestinal side effects. Tablets should be swallowed whole with a full glass of water. Adequate hydration (at least 2 litres of fluid daily) is important during treatment to reduce the risk of kidney stone formation and to assist with renal urate clearance.

Starting Treatment

Do not start Zyloric until any current gout attack has completely resolved. Begin at the lowest dose (100mg once daily) and titrate upward at monthly intervals until the target serum urate level is achieved. This gradual titration reduces the risk of precipitating a flare during dose initiation. A gout flare prophylaxis agent (colchicine 500mcg once or twice daily, or a low-dose NSAID) should be prescribed concurrently for at least the first six months.

Monitoring and Target Urate Level

The therapeutic goal with Zyloric is to reduce serum uric acid to below 360 micromol/L (6mg/dL). In patients with severe gout, tophi, or gout-related joint damage, a target of below 300 micromol/L may be appropriate. Serum urate should be checked every 4 weeks during dose titration and every 6-12 months once stable. Do not discontinue Zyloric when a gout attack occurs, continue treatment and manage the acute episode separately with colchicine, NSAIDs, or corticosteroids.

Zyloric (allopurinol) tablets: 100mg and 300mg strengths.

Usual starting dose: 100mg once daily, taken after food.

Usual maintenance dose: 200-600mg daily (in divided doses if above 300mg/day).

Maximum dose: 900mg daily.

In renal impairment, dose reduction is essential as oxipurinol is renally excreted. For GFR 30-60mL/min, 100-200mg daily is typically appropriate. For GFR 10-30mL/min, 100mg daily or less. For dialysis patients, a single dose of 100mg after each dialysis session is often used.

In hepatic impairment, a reduced dose and close monitoring of liver function are recommended. In elderly patients, use the lowest effective dose and monitor renal function closely.

Common Side Effects

• Skin rash (common; if mild, may resolve; if progressive or blistering, stop immediately)
• Nausea or vomiting
• Diarrhoea
• Elevated liver enzymes (typically transient)
• Gout flares in the first months of treatment (due to crystal mobilisation)
• Drowsiness or headache

Serious Side Effects

• Severe cutaneous adverse reactions (SCARs): Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), stop Zyloric immediately if any blistering, skin peeling, or mucosal ulceration develops
• DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms): fever, diffuse rash, lymphadenopathy, organ involvement, medical emergency; stop immediately
• Allopurinol hypersensitivity syndrome: rare but potentially fatal; includes fever, rash, vasculitis, renal and hepatic failure
• Bone marrow suppression: agranulocytosis, thrombocytopenia (rare, particularly with renal impairment)

Zyloric carries a risk of severe and potentially life-threatening skin reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and DRESS syndrome. Any skin rash, blistering, or mucosal ulceration developing during Zyloric treatment should prompt immediate discontinuation of the medicine and urgent medical review. Do not restart Zyloric after a serious skin reaction.

HLA-B*5801 Genetic Testing

The risk of severe cutaneous adverse reactions to allopurinol is significantly higher in individuals carrying the HLA-B*5801 allele. This genetic variant is present in approximately 6-8% of Han Chinese, 6-9% of Thai, and 12% of Korean individuals. Current guidelines recommend that **Han Chinese, Thai, and Korean patients should be tested for HLA-B*5801 before starting Zyloric, and should not receive it if positive**. The prevalence of this allele is much lower in European populations, for whom routine pre-treatment testing is not currently mandated.

Drug Interactions

Allopurinol significantly increases plasma levels of azathioprine and mercaptopurine by inhibiting their metabolism. Concurrent use requires a dose reduction of azathioprine or mercaptopurine to approximately 25% of the usual dose with close monitoring. It also interacts with ciclosporin (increased levels), warfarin (increased anticoagulant effect), and ampicillin or amoxicillin (increased risk of skin rash).

• Acute gout attack (do not initiate or increase dose during an attack)
• Known hypersensitivity to allopurinol or any excipient
• Positive HLA-B*5801 status in Han Chinese, Thai, or Korean patients
• Previous severe cutaneous adverse reaction to allopurinol (SJS, TEN, DRESS)
• Concomitant use with azathioprine or mercaptopurine without dose reduction (standard doses are contraindicated)
• Children (except in specific clinical scenarios such as enzyme disorders or malignancy -- specialist use only)
• Severe hepatic failure without dose adjustment and specialist supervision