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Uricosuric Agent — OAT Inhibitor Pregnancy: Avoid — insufficient safety data

Probenecid

Brand names: Benemid (discontinued UK — obtained via MHRA specials)

Adult dose

Dose: 250 mg twice daily for 1 week, then 500 mg twice daily
Route: Oral
Frequency: Twice daily
Max: 2000 mg/day (titrate based on serum urate target <360 µmol/L)
Not first-line gout management in UK (allopurinol preferred). Used when allopurinol and febuxostat are contraindicated or ineffective. Ensure urine output >2 L/day — alkalinise urine with sodium bicarbonate or potassium citrate to prevent uric acid renal stone formation. Do not use in acute gout attack — initiate after flare subsides.

Paediatric dose

Route:
Not routinely used in paediatric gout — seek specialist opinion

Dose adjustments

Renal

Avoid if eGFR <30 mL/min — uricosuric efficacy lost and urate stone formation risk increases

Hepatic

Use with caution in severe hepatic impairment

Clinical pearls

  • Mechanism: inhibits OAT1 and OAT3 (organic anion transporters) in renal proximal tubule — blocks reabsorption of urate, increases urinary uric acid excretion
  • Aspirin critical interaction: even low-dose aspirin (75 mg) completely blocks probenecid's uricosuric effect — patients on antiplatelet aspirin should not use probenecid; use febuxostat instead
  • Creatinine rise: probenecid also blocks OAT3-mediated creatinine secretion — serum creatinine rises without true GFR reduction (same mechanism as trimethoprim); this is an artefact, not renal deterioration
  • 24-hour urinary uric acid: check before starting — if >3.5 mmol/24h (high excretor), probenecid is contraindicated (further increasing urinary uric acid = stone risk)
  • Urine alkalinisation (pH >6.5) with potassium citrate or sodium bicarbonate is MANDATORY — uric acid stones form in acidic urine; at pH >6.5, uric acid converts to soluble urate

Contraindications

  • Uric acid urolithiasis
  • Blood dyscrasias
  • eGFR <30 mL/min
  • Acute gout attack
  • Hypersensitivity to probenecid

Side effects

  • Renal urate stone formation — prevent with high fluid intake and urine alkalinisation
  • GI effects — nausea, vomiting, gastric irritation
  • Flushing
  • Hypersensitivity reactions — rash, rarely anaphylaxis
  • Initial gout flare precipitation (start low, titrate slowly)

Interactions

  • Aspirin — low-dose aspirin blocks uricosuric effect; avoid concurrent use; paracetamol preferred for analgesia
  • Methotrexate — probenecid reduces renal tubular secretion of MTX; MTX toxicity risk — avoid combination
  • Penicillins and cephalosporins — probenecid reduces renal clearance (historically used therapeutically to extend penicillin effect)
  • Indomethacin — probenecid reduces indomethacin renal clearance; increased NSAID toxicity

Monitoring

  • Serum urate — target <360 µmol/L (<300 µmol/L in tophaceous gout)
  • 24-hour urinary uric acid before starting
  • Renal function (eGFR and creatinine — note artefactual rise)
  • Signs of gout flare (especially first 3–6 months)

Reference: BNFc; BNF 90; BSR Gout Guidelines 2017; NICE NG219 (Gout 2022); SPC Benemid. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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