Drugs for Gout
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Direct answer
Gout treatment divides into the acute attack and long-term urate lowering. An acute attack is treated with a non-steroidal anti-inflammatory drug (indomethacin classically, naproxen, diclofenac), colchicine (low-dose regimen 1 mg then 500 microgram every eight hours — microtubule inhibition stops neutrophil migration), or corticosteroids when both are contraindicated, especially in renal impairment. Urate lowering starts after the attack settles: allopurinol is first-line (titrated to serum urate below 6 mg/dL, HLA-B*5801 screening in high-risk Asians), febuxostat is the alternative, and probenecil the uricosuric for under-excretors; never start or stop urate-lowering therapy during a flare without continuation strategy.
What you must remember
- Colchicine binds tubulin, preventing microtubule assembly and neutrophil chemotaxis into the inflamed joint; it has no urate-lowering action and no analgesic action in other pains.
- Low-dose colchicine (1 mg, then 500 microgram eight-hourly) matches efficacy of the old high-dose regimen with far less diarrhoea — the modern standard.
- Colchicine toxicity rises with CYP3A4 and P-glycoprotein inhibitors (clarithromycin, statins, ciclosporin) and in renal impairment — neuromyopathy is the chronic form.
- NSAIDs are first-line for the attack in patients with intact kidneys; steroids (oral prednisolone or intra-articular for monoarticular disease) are the safe choice in renal failure and diabetes-prone polypharmacy.
- Allopurinol: xanthine oxidase inhibitor, start 100 mg daily (lower in renal impairment) and titrate monthly to urate below 6 mg/dL — under 5 for tophi.
- HLA-B*5801 carriage (high frequency in Han Chinese, Thai and Korean populations) predicts severe allopurinol hypersensitivity syndrome (Stevens-Johnson/toxic epidermal necrolysis) — screen where prevalent.
- Allopurinol with azathioprine or 6-mercaptopurine is potentially lethal — xanthine oxidase blockade piles up the active antimetabolite; reduce the immunosuppressant by 65–75 per cent or avoid.
- Febuxostat is the non-purine xanthine oxidase inhibitor for allopurinol intolerance or renal impairment, with a boxed cardiovascular mortality warning (CARES trial).
- Probenecid is uricosuric (blocks tubular urate reabsorption), useless when creatinine clearance is below about 50 mL/min, and requires high fluid intake to avoid uric acid stones.
- When starting urate-lowering therapy, cover the first three to six months with low-dose colchicine to prevent flares; continue allopurinol through any later attack.
- Asymptomatic hyperuricaemia is not treated with drugs; lifestyle (purine restriction, alcohol and fructose reduction, diuretic review) suffices.
How to work through a first attack
A 42-year-old man wakes with an exquisitely painful, red, swollen first metatarsophalangeal joint. Step one, confirm and treat simultaneously: the clinical picture is gout until proven otherwise, and aspiration showing needle-negative birefringent crystals settles it when available. Step two, choose the attack drug by his comorbidities — normal renal function and no bleeding history allow naproxen with a proton pump inhibitor; if he were on dialysis, intra-articular or oral steroid would be the answer; colchicine suits early, mild attacks within 36 hours of onset. Step three, do not start allopurinol mid-flare as a reflex — classic teaching delays it until the attack has settled for two to four weeks, then begins at 100 mg with three to six months of colchicine cover, because early urate lowering provokes flares. Step four, titrate allopurinol monthly to a urate target under 6 mg/dL — undertitration, not drug choice, is the commonest real-world failure. Step five, hunt the contributors: beer, organ meats, fructose drinks, thiazide or low-dose aspirin, and rising body weight. The chapter is a two-phase algorithm, and confusing the phases is the cardinal error.
Where students slip
The penalised slips are precise. Quoting high-dose colchicine (hourly until diarrhoea) — abandoned; the low-dose regimen is the answer. Prescribing allopurinol to lower urate during the acute attack without cover, or stopping it during a subsequent attack — both are marked wrong. Missing the azathioprine-allopurinol interaction in a transplant patient stem costs the mark. Forgetting febuxostat's cardiovascular boxed warning dates the answer. And the HLA-B*5801 question is the modern pharmacogenomics favourite in Asian-population exams.
Frequently asked questions
What is colchicine's mechanism and why does it not lower urate?
It binds tubulin and blocks microtubule-dependent neutrophil migration and phagocytosis of crystals in the joint — purely anti-inflammatory, with no effect on urate production or excretion.
When are corticosteroids preferred for an acute gout attack?
In renal impairment, peptic ulcer disease, anticoagulation or diabetes-prone polypharmacy where NSAIDs and colchicine are unsafe — intra-articular for confirmed monoarthritis, oral for polyarticular flares.
Why is HLA-B*5801 testing relevant before allopurinol?
The allele, common in Han Chinese, Thai and Korean populations, strongly predicts allopurinol hypersensitivity syndrome with Stevens-Johnson syndrome and toxic epidermal necrolysis — screening high-risk groups prevents a lethal reaction.
How does allopurinol interact with azathioprine?
Xanthine oxidase converts azathioprine's active metabolite onward; blocking it raises 6-mercaptopurine levels several-fold, causing myelosuppression — reduce the azathioprine dose by 65–75 per cent or avoid the combination.
What is the target serum urate on urate-lowering therapy and why?
Below 6 mg/dL (below 5 mg/dL with tophi) — below the saturation point of monosodium urate, allowing crystal dissolution and preventing recurrent attacks over months.