1. Clinical Overview
Probenecid is a uricosuric agent and renal tubular transport inhibitor. It is primarily used in the treatment of chronic gout and hyperuricemia by increasing the urinary excretion of uric acid. It is also used as an adjunct to penicillin and cephalosporin therapy to elevate and prolong plasma antibiotic concentrations by competitively inhibiting their renal tubular secretion.
| Onset | Duration | Bioavailability |
|---|---|---|
| Within 30 minutes to 2 hours for uricosuric effect. | Approximately 8-12 hours. | Well absorbed orally, approximately 80-100%. |
2. Mechanism of Action
Probenecid acts by competitively inhibiting the reabsorption of uric acid at the proximal convoluted tubule of the nephron via inhibition of the urate-anion exchanger (URAT1). It also potently inhibits the renal tubular secretion (via OAT1 and OAT3) of weak organic acids, including penicillins, cephalosporins, and methotrexate, thereby increasing their plasma concentrations.
3. Indications & Uses
- Chronic Gout and Hyperuricemia (as a uricosuric agent)
- Adjunct to Antibiotic Therapy (to prolong plasma levels of penicillins and some cephalosporins)
4. Dosage & Administration
Adult Dosage: Gout/Hyperuricemia: 250 mg twice daily for one week, then increase to 500 mg twice daily. May increase by 500 mg every 4 weeks to a maximum of 2-3 g/day in divided doses. Maintenance: Usually 500 mg-1 g twice daily. Antibiotic Adjuvant: 2 g/day in divided doses (e.g., 500 mg QID).
Administration: Take with food or milk to minimize GI upset. Maintain high fluid intake (at least 2-3 liters per day) to ensure a daily urine output >2L and alkalinize urine (target pH >6.5) with sodium bicarbonate or potassium citrate, especially during initial therapy, to prevent uric acid nephrolithiasis. Do not start during an acute gout attack.
5. Side Effects
Common side effects may include:
- Headache
- Anorexia, Nausea, Vomiting
- Dizziness
- Flushing
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Salicylates (Aspirin, low-dose) | Antagonizes uricosuric effect of probenecid | Major |
| Methotrexate | Increased methotrexate plasma levels and severe toxicity | Major |
| Penicillins (e.g., Amoxicillin), Cephalosporins (e.g., Cefazolin) | Increased and prolonged plasma antibiotic levels | Moderate (therapeutic use) |
| NSAIDs (e.g., Ibuprofen, Naproxen) | Increased plasma levels of NSAIDs; may also reduce uricosuric effect | Moderate |
| Acyclovir, Valacyclovir | Increased plasma levels of acyclovir; risk of CNS toxicity | Moderate |
| Sulfonylureas (e.g., Glipizide) | Enhanced hypoglycemic effect | Moderate |
| Thiazide Diuretics | May antagonize uricosuric effect and increase serum urate | Moderate |
| Rifampicin | May decrease probenecid levels | Moderate |
| Zidovudine (AZT) | Increased AZT levels and toxicity (bone marrow suppression) | Major |
7. Patient Counselling
- DO take with food or a full glass of water/milk.
- DO drink at least 8-10 glasses of water daily.
- DO inform all doctors and pharmacists you are taking probenecid.
- DO NOT take aspirin or other salicylates unless specifically advised by your doctor.
- DO NOT start this medicine during an acute gout attack.
8. Toxicology & Storage
Overdose: Nausea, vomiting, dizziness, seizures, metabolic acidosis, coma, and potential acute renal failure due to uric acid crystal deposition.
Storage: Store below 30°C in a cool, dry place, protected from light and moisture. Keep out of reach of children.