Probenecid (probenecid)
Also sold as: Benemid, Probecid, Probenecid BP
Pregnancy
Cat B
Lactation
Unknown
Schedule
H
Forms
Tablets 500 mg
Indications
- Chronic gout and hyperuricaemia — urate-lowering therapy (second-line after allopurinol; used when allopurinol is inadequate or contraindicated)
- Adjunct to penicillin/ampicillin/cephalosporins — extends antibiotic action by blocking renal tubular secretion
- Gonorrhoea — adjunct to single-dose ampicillin regimen (historical use)
Adult Dosing
Chronic gout — hyperuricaemia (initiation)
250 mg orally twice daily for 1 week
Then increase to 500 mg twice daily; may increase by 500 mg/month to maximum 2 g/day (in 2–4 divided doses)
CRITICAL: Do NOT start probenecid during an acute gout attack — will worsen acute attack. Wait for full resolution. Maintain high fluid intake (at least 2 L/day) to prevent uric acid nephrolithiasis (probenecid increases urinary uric acid excretion). Add colchicine prophylaxis for 3–6 months on initiation to prevent mobilisation flares. Monitor serum uric acid; target <6 mg/dL.
Adjunct to penicillin/ampicillin/cephalosporins
500 mg orally four times daily (2 g/day)
Taken concurrently with the antibiotic course
Probenecid blocks OAT-mediated renal tubular secretion of penicillins and cephalosporins — extends antibiotic half-life and raises plasma levels. Used in penicillin-scarce settings, gonorrhoea treatment (500 mg QID + ampicillin 3.5 g stat), and to extend cefixime/ceftriaxone levels in Lyme disease.
Renal Dose Adjustment
| CrCl / eGFR | Dose Adjustment |
|---|---|
| CrCl <30 mL/min | Avoid — probenecid acts by blocking urate secretion in the renal proximal tubule; inadequate GFR means insufficient uric acid is filtered to allow effective uricosuric action. Use allopurinol or febuxostat in CKD patients. |
| CrCl ≥30 mL/min | Use with caution; probenecid is ineffective as a uricosuric when GFR is significantly reduced |
Hepatic Adjustment
No specific dose adjustment; use with caution in severe hepatic disease — limited data.
Pregnancy & Lactation
Pregnancy: Category B
Animal studies show no teratogenicity. Limited human data but widely used as an antibiotic adjunct during pregnancy without evidence of harm. Gout in pregnancy is uncommon; risks of untreated gout (dehydration, pain) should be weighed against theoretical risks. Short-term use for antibiotic augmentation is generally considered acceptable.
Lactation: Unknown
No data on breast milk excretion in humans. Use with caution during lactation; monitor infant if use is necessary.
Top Drug Interactions
| Interacting Drug | Effect | Severity |
|---|---|---|
| Penicillins, ampicillin, amoxicillin, and cephalosporins | Intentional major pharmacokinetic interaction — probenecid blocks OAT-mediated renal tubular secretion of these antibiotics, significantly increasing their plasma levels (2–3 fold) and prolonging half-life. Used clinically to extend antibiotic coverage. Monitor for antibiotic toxicity at high doses | Major |
| Methotrexate (MTX) | Probenecid blocks renal tubular secretion of methotrexate — markedly increases MTX plasma levels and risk of toxicity (bone marrow suppression, mucositis, hepatotoxicity, nephrotoxicity). Combination requires MTX dose reduction and close monitoring; generally avoid | Major |
| Salicylates (aspirin) — even low-dose aspirin | Salicylates at low doses retain uric acid (compete with urate at OAT) and antagonise the uricosuric effect of probenecid; at high doses, aspirin is weakly uricosuric. Avoid concurrent low-dose aspirin with probenecid if possible; use acetaminophen/paracetamol for analgesia instead | Moderate |
| Dapsone | Probenecid blocks renal tubular secretion of dapsone and its metabolites — increases dapsone plasma levels; risk of methaemoglobinaemia and haematological toxicity | Moderate |
| Rifampicin | Probenecid blocks hepatic uptake and biliary excretion of rifampicin — increases rifampicin plasma levels; monitor for rifampicin-related hepatotoxicity | Moderate |
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Side Effects
Common
- Headache
- Nausea and gastrointestinal upset (take with food)
- Flushing
- Urinary frequency (increased uric acid excretion)
- Skin rash
- Dizziness
Serious / Discontinue If
- Uric acid nephrolithiasis (kidney stones) — increased urinary uric acid excretion predisposes to stone formation; high fluid intake and urinary alkalinisation mandatory
- Acute gout flare on initiation (mobilisation flare)
- Haemolytic anaemia — in patients with G6PD deficiency
- Aplastic anaemia and nephrotic syndrome (rare)
- Severe hypersensitivity including anaphylaxis
Contraindications
- Acute gout attack (do not initiate)
- Uric acid kidney stones or high uric acid excretion (>700 mg/day) — worsens stone formation
- Renal impairment (CrCl <30 mL/min) — ineffective and increases stone risk
- History of blood dyscrasias
- Children under 2 years
- Hypersensitivity to probenecid
Available Indian Brands
| Brand | Manufacturer | Price (approx) |
|---|---|---|
| Benemid 500 mg Tablets | Various manufacturers | ₹35/10 tablets |
| Probenecid BP 500 mg Tablets | Various manufacturers | ₹28/10 tablets |
Monitoring Required
- Serum uric acid — at baseline, monthly during dose titration, then every 3–6 months; target <6 mg/dL
- Urinary uric acid excretion (24-hour urine collection) — at baseline to confirm under-excretion (not over-excretion; overexcretors should not receive uricosuric therapy)
- Renal function (serum creatinine, eGFR) — probenecid is ineffective in CKD and increases stone risk
- Urinalysis — monitor for haematuria or crystals (uric acid stones)
- Fluid intake — ensure at least 2 L/day to prevent nephrolithiasis
- Urinary pH — alkalinise to pH 6.0–6.5 to improve uric acid solubility and prevent stone formation
- Gout attack frequency — to assess treatment response
Patient Counseling Points
- Do NOT take probenecid during a gout attack — it can make the attack worse. Start only after the attack has completely gone.
- Drink at least 8–10 glasses of water every day — this is essential to prevent kidney stones, as probenecid increases uric acid in the urine.
- Your doctor may prescribe sodium bicarbonate or potassium citrate to make your urine less acidic — take these as directed.
- Avoid aspirin and aspirin-containing medicines while taking probenecid — even low-dose aspirin blocks the effect of this medicine. Use paracetamol for pain instead.
- Take probenecid with food to reduce stomach upset.
- You may get a gout attack in the first few months of treatment — your doctor will give you colchicine to prevent this. Do not stop probenecid if a gout attack occurs.
- Regular blood tests (uric acid, kidney function) are needed to see if the medicine is working.
- Inform all your doctors that you are on probenecid — it interacts with several antibiotics and other medicines, and your doses may need adjusting.
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Clinically reviewed by: Dr. Sanjay Kulkarni, MD (Medicine), DM (Clinical Immunology & Rheumatology)
Last reviewed: 2026-04-15
References
- Khanna D, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 2: therapy and antiinflammatory prophylaxis of acute gouty arthritis. Arthritis Care Res (Hoboken). 2012;64(10):1447–1461.
- FitzGerald JD, et al. 2020 American College of Rheumatology Guideline for the Management of Gout. Arthritis Care Res. 2020;72(6):744–760.
- Reinders MK, et al. Efficacy and tolerability of urate-lowering drugs in gout: a randomised controlled trial of benzbromarone versus probenecid after failure of allopurinol. Ann Rheum Dis. 2009;68(1):51–56.
- Various manufacturers. Probenecid BP prescribing information. 2024.