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Probenecid

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Probenecid

  • See Also
  1. Uricosuric
  2. Gouty Arthritis
  • Indications
  1. Gouty Arthritis
    1. Probenecid is rarely used due to toxicity, and lower efficacy than Allopurinol
    2. Allopurinol is used instead most often for gout prophylaxis
  2. Penicillin Adjunct
    1. Increases and prolongs serum Penicillin levels via blockade of its excretion
  • Contraindications
  1. Age <2 years old or age >60 years old
  2. Nephrolithiasis
  3. Over-production of Uric Acid
  4. GFR <30 ml/min
    1. Probenecid is ineffective at lower Renal Function)
    2. Do not use in combination with Penicillin if poor Renal Function
  5. Acute Gouty Arthritis
    1. Do not start during an acute gout attack
    2. Wait at least 2-3 weeks, after acute gout subsides before starting
  • Mechanism
  1. Benzoic acid derivative
  2. Uricosuric (increases renal Uric Acid excretion)
    1. Competitive Inhibition of Uric Acid active reabsorption at the renal proximal convoluted tubule
    2. Results in increased Uric Acid urinary excretion
  3. Increases serum levels of organic acid and acidic drugs (e.g. Penicillin)
    1. Blocks their transport at the proximal and distal renal tubule
  • Precautions
  1. Maintain adequate hydration to sustain 2 to 3 liters of Urine Output per day
  2. Maintain alkaline urine
  • Medications
  1. Probenecid tablets: 500 mg
  2. Colchicine 0.5 mg with Probenecid 500 mg (Chronic Gouty Arthritis, initiation of prophylaxis)
    1. Started at 1 tab orally daily for 1 week, then 1 tab orally twice daily
    2. Combination helps prevent gout flares on starting Probenecid
    3. Alternatively, combine Probenecid with an NSAID
  1. Start: 250 mg orally twice daily 7 days
  2. Next: 500 mg orally twice daily
  3. May titrate dose in 500 mg increments every 4 weeks up to maximum
  4. Maximum: 2000 mg/day (1000 mg twice daily)
  • Dosing
  • Penicillin Adjunct (Increased serum levels)
  1. Adult: 1000 mg orally twice daily
  2. Child (age 2 to 14 years, Use adult dose for weight >50 kg)
    1. Start 25 mg/kg orally for first dose
    2. Next 40 mg/kg day divided four times daily
  • Safety
  1. Pregnancy Category B
  2. Unknown safety in Lactation
  • Adverse Effects
  1. Anaphylaxis or severe reactions
  2. Nephrolithiasis
  3. Hepatotoxicity
  4. Dermatitis
  5. Cytopenias
    1. May be related to G6PD Deficiency
  6. Gastrointestinal upset
    1. Consider decreased dose
  • Drug Interactions
  1. Penicillin
    1. Probenecid reduces renal excretion of Penicillin
  2. Salicylates (e.g. Aspirin)
    1. Salicylates counteract Probenecid activity
  3. Methotrexate
    1. Probenecid increases Methotrexate levels and may cause toxicity
  • Resources
  1. Probenecid (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ab497fd8-00c3-4364-b003-b39d21fbdf38