II. 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

III. 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

IV. 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

V. Precautions

  1. Maintain adequate hydration to sustain 2 to 3 liters of Urine Output per day
  2. Maintain alkaline urine

VI. 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

VII. Dosing: Gouty Arthritis (adults)

  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)

VIII. 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

IX. Safety

  1. Pregnancy Category B
  2. Unknown safety in Lactation

X. 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

XI. 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

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Related Studies

Cost: Medications

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

Ontology: Probenecid (C0033209)

Definition (NCI_NCI-GLOSS) A drug that is used to treat gout and is used together with some antibiotics to make them work better. It is being studied in the treatment of cancer. It belongs to the family of drugs called antibiotic therapy adjuncts.
Definition (NCI) A benzoic acid derivative with antihyperuricemic property. Probenecid competitively inhibits the active reabsorption of urate at the proximal tubule in the kidney thereby increasing urinary excretion of uric acid and lowering serum urate concentrations. This prevents urate deposition and promotes resolution of existing urate deposits. In addition, probenecid modulates the transport of organic acids and acidic drugs at the proximal and distal renal tubule, thereby increasing the drug serum concentration.
Definition (CSP) USP lists as a uricosuric, an agent that promotes uric acid secretion in urine.
Definition (MSH) The prototypical uricosuric agent. It inhibits the renal excretion of organic anions and reduces tubular reabsorption of urate. Probenecid has also been used to treat patients with renal impairment, and, because it reduces the renal tubular excretion of other drugs, has been used as an adjunct to antibacterial therapy.
Definition (PSY) Agent that promotes the urinary excretion of uric acid.
Definition (PDQ) A benzoic acid derivative with antihyperuricemic property. Probenecid competitively inhibits the active reabsorption of urate at the proximal tubule in the kidney thereby increasing urinary excretion of uric acid and lowering serum urate concentrations. This prevents urate deposition and promotes resolution of existing urate deposits. In addition, probenecid modulates the transport of organic acids and acidic drugs at the proximal and distal renal tubule, thereby increasing the drug serum concentration. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=40223&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=40223&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C772" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D011339
SnomedCT 387365004, 66094001
LNC LP16260-9, MTHU007603
English probenecid, Benzoic acid, 4-((dipropylamino)sulfonyl)-, Major Brand of Probenecid, Martec Brand of Probenecid, Parmed Brand of Probenecid, Probenecid Major Brand, Probenecid Martec Brand, Probenecid Parmed Brand, Probenecid Zenith Brand, Zenith Brand of Probenecid, PROB, probenecid (medication), Probenecid [Chemical/Ingredient], PROBENECID, Probenecid (product), Probenecid (substance), Probenecid
Swedish Probenecid
Czech probenecid
Finnish Probenesidi
Russian PROBENETSID, PROBETSID, ПРОБЕНЕЦИД, ПРОБЕЦИД
Japanese プロベネシッド, プロベシド, プロベネシド
Spanish Probenecid, Probenecida, probenecid (producto), probenecid (sustancia), probenecid
Polish Probenecyd
French Probénécide
German Probenecid
Italian Probenecid
Portuguese Probenecid