II. Indications
-
Gouty Arthritis
- Probenecid is rarely used due to toxicity, and lower efficacy than Allopurinol
- Allopurinol is used instead most often for gout prophylaxis
-
Penicillin Adjunct
- Increases and prolongs serum Penicillin levels via blockade of its excretion
III. Contraindications
- Age <2 years old or age >60 years old
- Nephrolithiasis
- Over-production of Uric Acid
- GFR <30 ml/min
- Probenecid is ineffective at lower Renal Function)
- Do not use in combination with Penicillin if poor Renal Function
- Acute Gouty Arthritis
- Do not start during an acute gout attack
- Wait at least 2-3 weeks, after acute gout subsides before starting
IV. Mechanism
- Benzoic acid derivative
-
Uricosuric (increases renal Uric Acid excretion)
- Competitive Inhibition of Uric Acid active reabsorption at the renal proximal convoluted tubule
- Results in increased Uric Acid urinary excretion
- Increases serum levels of organic acid and acidic drugs (e.g. Penicillin)
- Blocks their transport at the proximal and distal renal tubule
V. Precautions
- Maintain adequate hydration to sustain 2 to 3 liters of Urine Output per day
- Maintain alkaline urine
VI. Medications
- Probenecid tablets: 500 mg
-
Colchicine 0.5 mg with Probenecid 500 mg (Chronic Gouty Arthritis, initiation of prophylaxis)
- Started at 1 tab orally daily for 1 week, then 1 tab orally twice daily
- Combination helps prevent gout flares on starting Probenecid
- Alternatively, combine Probenecid with an NSAID
VII. Dosing: Gouty Arthritis (adults)
- Start: 250 mg orally twice daily 7 days
- Next: 500 mg orally twice daily
- May titrate dose in 500 mg increments every 4 weeks up to maximum
- Maximum: 2000 mg/day (1000 mg twice daily)
VIII. Dosing: Penicillin Adjunct (Increased serum levels)
- Adult: 1000 mg orally twice daily
- Child (age 2 to 14 years, Use adult dose for weight >50 kg)
- Start 25 mg/kg orally for first dose
- Next 40 mg/kg day divided four times daily
IX. Safety
- Pregnancy Category B
- Unknown safety in Lactation
X. Adverse Effects
- Anaphylaxis or severe reactions
- Nephrolithiasis
- Hepatotoxicity
- Dermatitis
- Cytopenias
- May be related to G6PD Deficiency
- Gastrointestinal upset
- Consider decreased dose
XI. Drug Interactions
-
Penicillin
- Probenecid reduces renal excretion of Penicillin
-
Salicylates (e.g. Aspirin)
- Salicylates counteract Probenecid activity
-
Methotrexate
- Probenecid increases Methotrexate levels and may cause toxicity
XII. Resources
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Related Studies
| probenecid (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
| PROBENECID 500 MG TABLET | Generic | $0.55 each |
| PROBENECID-COLCHICINE TABLET | Generic | $0.99 each |