Allopurinol
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Dosing and administration[2]
Oral, once daily after food for doses up to 300 mg; divide larger total daily doses (no single dose above 300 mg). Start low and titrate to a serum urate target with adequate hydration. Co-prescribe flare prophylaxis (colchicine or an NSAID) on initiation and for the first months. Consider HLA-B*5801 screening in higher-risk ancestries (Han Chinese, Thai, Korean) given the risk of severe cutaneous adverse reactions.
| Indication | Starting dose | Titration and maximum |
|---|---|---|
| Gout (urate lowering) | Start 100 mg once daily (100 to 200 mg), increasing by about 100 mg at weekly intervals. | Titrate against serum urate to below 360 micromol/L (6 mg/dL), or below 300 micromol/L (5 mg/dL) in tophaceous or severe gout. Usual maintenance 200 to 300 mg/day (mild) up to 400 to 600 mg/day (moderate to severe); maximum 800 mg/day. Start 50 to 100 mg/day or lower in renal impairment. |
Onset. Serum urate normalises within about 1 to 3 weeks; adjust to target.
Renal adjustment. Reduce the dose in renal impairment (allopurinol and its active metabolite oxypurinol accumulate): with creatinine clearance about 10 to 20 mL/min use around 200 mg/day; below 10 mL/min do not exceed 100 mg/day; with severe impairment extend the dosing interval. Start low (50 to 100 mg/day or lower) and up-titrate slowly.
Hepatic. Use reduced doses and monitor liver function periodically in hepatic impairment.
Monitoring
- Serum urate to guide titration to target.
- Periodic liver function, renal function, and complete blood count.
- Vigilance for allopurinol hypersensitivity syndrome and severe cutaneous adverse reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), highest in the first weeks and in HLA-B*5801 carriers; stop immediately for any rash.
Contraindications
- Previous severe hypersensitivity to allopurinol.
- Do not initiate during an acute flare; start after it settles, under flare prophylaxis.
Key interactions
- Azathioprine and mercaptopurine: allopurinol markedly increases their toxicity through xanthine oxidase inhibition; substantially reduce their dose or avoid the combination.
- Increased risk of rash with ampicillin or amoxicillin.
- Caution with warfarin and theophylline (levels may rise).
- Aluminium-containing antacids can reduce allopurinol absorption; separate the doses.
Clinical notes
How it is used in gout
Xanthine oxidase inhibitor, strongly recommended as preferred first-line ULT for all patients including CKD stage 3 or worse, over all other agents. A xanthine oxidase inhibitor is also strongly preferred over probenecid in CKD stage 3 or worse.[1]
Before starting
HLA-B*5801 testing before starting allopurinol is conditionally recommended for patients of Southeast Asian descent (for example Han Chinese, Korean, Thai) and African American patients, who have a higher allele prevalence, and conditionally recommended against in others. The allele is strongly associated with allopurinol hypersensitivity syndrome.[1]
Monitoring
Serial serum urate guides dose titration to and maintenance of the target below 6 mg/dL (treat-to-target, strongly recommended). Specific on-treatment laboratory intervals are not set by the gout guideline; follow the product monograph and reconcile.[1]
Common effects
Background clinical knowledge (not from the guideline): rash, gastrointestinal upset, and transaminase elevation can occur; ULT initiation transiently increases flare risk, mitigated by anti-inflammatory prophylaxis.
Important cautions
Background clinical knowledge and monograph, not from the gout guideline: allopurinol hypersensitivity syndrome (including SJS/TEN and DRESS) is the key severe risk, higher early, with higher starting dose, and in renal impairment, which is why a low start is used. Allopurinol inhibits xanthine oxidase and markedly raises levels of azathioprine and 6-mercaptopurine, risking severe myelosuppression; avoid the combination or reduce the thiopurine substantially with close monitoring. Reconcile dosing and interactions with the product monograph.
References
- FitzGerald JD, Dalbeth N, Mikuls T, et al. 2020 American College of Rheumatology Guideline for the Management of Gout. Arthritis Care Res (Hoboken). 2020;72(6):744-760. doi:10.1002/acr.24180 https://doi.org/10.1002/acr.24180
- ALLOPURINOL (allopurinol tablets) Product Monograph. Health Canada authorized product monograph (Apotex), 2024. https://pdf.hres.ca/dpd_pm/00076177.PDF