What is probenecid used for?

Uses of Probenecid

Probenecid is primarily used as a uricosuric agent for the treatment of hyperuricemia associated with gout and gouty arthritis, and as an adjuvant to enhance blood levels of certain antibiotics. 1

Primary Uses

1. Treatment of Gout

• Probenecid works by inhibiting renal tubular reabsorption of urate, increasing uric acid excretion in the urine
• It is recommended as an alternative first-line urate-lowering therapy (ULT) when xanthine oxidase inhibitors (XOIs) like allopurinol or febuxostat are:
  • Contraindicated
  • Not tolerated
  • Ineffective 2

2. Antibiotic Adjuvant

• Used to elevate and prolong plasma levels of:
  • Penicillins
  • Ampicillin
  • Methicillin
  • Oxacillin
  • Cloxacillin
  • Nafcillin 1
• Functions by blocking the renal tubular secretion of these antibiotics, thereby increasing their blood concentration and duration of action 3

Clinical Considerations for Use in Gout

Patient Selection

• Best suited for patients who:
  • Cannot tolerate XOIs (allopurinol or febuxostat)
  • Have contraindications to XOIs
  • Have normal to mildly impaired renal function 2

Important Limitations

• Not recommended as first-line ULT monotherapy in patients with:
  • Creatinine clearance <50 ml/minute 2, 4
  • History of urolithiasis (kidney stones) 2
  • Elevated urine uric acid indicative of uric acid overproduction 2

Combination Therapy

• Can be effectively combined with XOIs (allopurinol or febuxostat) in patients with refractory gout 2, 5
• This combination approach is particularly useful when single-agent therapy fails to achieve target serum urate levels 2

Monitoring and Risk Management

Before Starting Probenecid

• Measure urinary uric acid levels 2
• Assess renal function (creatinine clearance) 2, 4
• Screen for history of kidney stones 2

During Treatment

• Monitor urinary uric acid levels 2
• Consider urine alkalinization (e.g., with potassium citrate) 2
• Recommend increased fluid intake to reduce risk of urolithiasis 2
• Monitor for drug interactions (probenecid affects many organic acid transporters) 3, 6

Efficacy and Response Rates

Research shows that probenecid can achieve target serum urate concentrations (<0.36 mmol/l) in approximately:

• 33% of patients when used as monotherapy
• 37% of patients when used in combination with allopurinol 5

Potential Side Effects and Concerns

• Urolithiasis (approximately 10% risk) 2
• Multiple drug interactions due to inhibition of organic anion transporters 3, 6
• Adverse events occur in approximately 13-19% of patients 5
• Requires more complex risk management compared to XOIs 2

Other Potential Effects

While not approved for these uses, probenecid has been studied for:

• Potential anti-hypertensive effects via inhibition of α-adrenergic receptors 7
• Significant alterations in metabolite levels that may affect various physiological processes 6

In summary, probenecid serves dual clinical roles as a uricosuric agent for gout management and as an adjuvant to enhance antibiotic efficacy, with specific considerations for patient selection and monitoring based on renal function and risk factors.