Probenecid

Mechanism-of-action class: Organic Anion Transporter Interactions.

• Probenecid tablets are indicated for the treatment of the hyperuricemia associated with gout and gouty arthritis. As an adjuvant to therapy with penicillin or with ampicillin, methicillin, oxacillin, cloxacillin, or nafcillin, for elevation and prolongation of plasma levels by whatever route the antibiotic is given.ICD-10: M10.9

• Hypersensitivity to probenecid. Children under 2 years of age.contraindicated

Gout: Therapy with probenecid should not be started until an acute gouty attack has subsided. However, if an acute attack is precipitated during therapy, probenecid may be continued without changing the dosage, and full therapeutic dosage of colchicine, or other appropriate therapy, should be given to control the acute attack. The recommended adult dosage is 250 mg (½ probenecid tablet), twice a day for one week, followed by 500 mg (1 tablet) twice a day thereafter. Some degree of renal impairment may be present in patients with gout. A daily dosage of 1000 mg may be adequate. However, if necessary, the daily dosage may be increased by 500 mg increments every 4 weeks within tolerance (and usually not above 2000 mg per day) if symptoms of gouty arthritis are not controlled or the 24 hour uric acid excretion is not above 700 mg. As noted, probenecid may not be effective in chronic renal insufficiency particularly when the glomerular filtration rate is 30 mg mL/minute or less. Gastric intolerance may be indicative of over dosage, and may be corrected by decreasing the dosage. As uric acid tends to crystallize out of an acid urine, a liberal fluid intake is recommended, as well as sufficient sodium bicarbonate (3 to 7.5 g daily ), or potassium citrate (7.5 g daily) to maintain an alkaline urine (see PRECAUTIONS ). Alkalization of the urine is recommended until the serum urate level returns to normal limits and tophaceous deposits disappear, i.e., during the period when urinary excretion of uric acid is at high level.

Exacerbation of gout following therapy with probenecid may occur; in such cases colchicine or other appropriate therapy is advisable. Probenecid increases plasma concentrations of methotrexate in both animals and humans. In animal studies, increased methotrexate toxicity has been reported. If probenecid is given with methotrexate, the dosage of methotrexate should be reduced and serum levels may need to be monitored. In patients on probenecid the use of salicylates in either small or large doses is contraindicated because it antagonizes the uricosuric action of probenecid. The biphasic action of salicylates in the renal tubules accounts for the so-called “paradoxical effect” of uricosuric agents. In patients on probenecid who require a mild analgesic agent the use of acetaminophen rather than small doses of salicylates would be preferred. Rarely, severe allergic reactions and anaphylaxis have been reported with the use of probenecid. Most of these have been reported to occur within several hours after re-administration following prior usage of the drug. The appearance of hypersensitivity reactions requires cessation of therapy with probenecid. Use in Pregnancy: Probenecid crosses the placenta barrier and appears in cord blood. The use of any drug in women of childbearing potential requires that the anticipated benefit be weighed against the possible hazards.

The following adverse reactions have been observed and within each category are listed in order of decreasing severity. Central Nervous System : headache, dizziness. Metabolic : precipitation of acute gouty arthritis Gastrointestinal : hepatic necrosis, vomiting, nausea, anorexia, sore gums. Genitourinary : nephrotic syndrome, uric acid stones with or without hematuria, renal colic, costovertebral pain, and urinary frequency. Hypersensitivity : anaphylaxis, fever, urticaria, pruritus Hematologic : aplastic anemia, leukopenia, hemolytic anemia which in some patients could be related to genetic deficiency of glucose -6- phosphate dehydrogenase in red blood cells, anemia. Integumentary : dermatitis, alopecia, flushing.

Use in Pregnancy: Probenecid crosses the placenta barrier and appears in cord blood. The use of any drug in women of childbearing potential requires that the anticipated benefit be weighed against the possible hazards.

• Jul 29, 1976ANDAANDA080966Lannett
• Nov 23, 1976ANDAANDA084279Watson Labs
• Mar 2, 1977ANDAANDA084442Watson Labs Teva
• May 13, 2008ANDAANDA040618Ingenus Pharms Llc
• Oct 24, 2023ANDAANDA217030Rising
• Nov 20, 2023ANDAANDA217020Rising
• Oct 25, 2024NDANDA213972Iterum Therap

1. 1Diarrhoea1058.3%
2. 2Drug Ineffective665.2%
3. 3Off Label Use594.7%
4. 4Dyspnoea534.2%
5. 5Nausea504.0%
6. 6Vomiting493.9%
7. 7Asthenia483.8%
8. 8Adenovirus Infection473.7%
9. 9Fatigue473.7%
10. 10Acute Kidney Injury453.6%
11. 11Toxicity To Various Agents443.5%
12. 12Dizziness433.4%
13. 13Pain433.4%
14. 14Death403.2%
15. 15Pneumonia403.2%

Recent PubMed references pinned to Probenecid as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• A refined chronic MPTP/probenecid model of Parkinson's disease in mature adult mice.
  Experimental neurology · 2026 · Shen Z, Garland B, Mellick GD, et al.
  PMID 41941954DOI 10.1016/j.expneurol.2026.115759
• Evaluation of Probenecid Against Filovirus Replication in Vero E6 Cells.
  Viruses · 2025 · Alfson K, Carrion R Jr, Tripp RA, et al.
  PMID 41600808DOI 10.3390/v18010043
• Probenecid Suppresses Migration, invasion and angiogenesis in hepatocellular carcinoma by modulating purinergic signaling and p38 MAPK pathway.
  Biochemical pharmacology · 2026 · Matera I, Pistone A, Castiglione Morelli MA, et al.
  PMID 41453525DOI 10.1016/j.bcp.2025.117665
• Probenecid Treatment Inhibits Replication of the Edmonston Measles Virus Strain in Vero Cells.
  Viruses · 2025 · Murray J, Martin DE, Tripp RA, et al.
  PMID 41305497DOI 10.3390/v17111475
• Probenecid relieves LPS-induced neuroinflammation by modulating the NLRP1 inflammasome pathway in BV2 cells.
  Scientific reports · 2025 · Wang X, Tian H, Chen S, et al.
  PMID 41062518DOI 10.1038/s41598-025-19015-5
• Serum, urinary and fecal concentrations of perfluoroalkyl substances after interventions with cholestyramine/colesevelam and probenecid - cross-over trials in Ronneby, Sweden.
  Environment international · 2025 · Andersson AG, Xu Y, Kärrman A, et al.
  PMID 40974835DOI 10.1016/j.envint.2025.109794
• Evaluation of the Safety and Pharmacokinetics of Single-Dose Oral Probenecid Administration in Healthy Dogs.
  Journal of veterinary internal medicine · 2025 · Cook M, Gustafson DL, Kroeker K, et al.
  PMID 40884532DOI 10.1111/jvim.70221
• Cryo-EM structures of human OAT1 reveal drug binding and inhibition mechanisms.
  Structure (London, England : 1993) · 2025 · Jeon HM, Eun J, Kim KH, et al.
  PMID 40845848DOI 10.1016/j.str.2025.07.019

The 10 most recently updated of 68 ClinicalTrials.gov registrations naming Probenecid as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Novel Use of Probenecid to Alleviate Symptoms of Opioid Withdrawal
  Recruiting · Phase 2 · Interventional · 40 enrolled · University of Calgary
  NCT04939623updated 2026-05-01
• Therapeutics for Moderate and Severe Dengue
  Not yet recruiting · Phase 3 · Interventional · 8,800 enrolled · Oxford University Clinical Research Unit, Vietnam
  NCT07543458updated 2026-04-21
• Oral Moxifloxacin Versus Cefazolin and Oral Probenecid in the Management of Skin and Soft Tissue Infections in the Emergency Department
  Completed · Phase 3 · Interventional · 390 enrolled · University of British Columbia
  NCT00323219updated 2026-04-13
• A Study to Learn About How the Study Medicines Called Itraconazole and Probenecid Change How the Body Processes PF-07220060
  Completed · Phase 1 · Interventional · 25 enrolled · Pfizer
  NCT07160738updated 2026-04-03
• Pharmacokinetics of Sulopenem Etzadroxil Plus Probenecid in Adolescents
  Recruiting · Phase 1 · Interventional · 12 enrolled · Iterum Therapeutics, International Limited
  NCT07092813updated 2026-03-27
• Probenecid Administration for Alcohol Craving and Consumption
  Recruiting · Phase 2 · Interventional · 120 enrolled · Brown University
  NCT07118618updated 2026-03-17
• Improvement of Reproductive Function in Men With Spinal Cord Injury (SCI)
  Recruiting · Phase 3 · Interventional · 90 enrolled · University of Miami
  NCT05903859updated 2026-03-02
• Data Analysis for Drug Repurposing for Effective Alzheimer's Medicines - (DREAM) Probenecid vs Allopurinol
  Completed · Observational · 294,878 enrolled · Brigham and Women's Hospital
  NCT04746989updated 2026-02-27
• Probenecid (PB) to Treat Hereditary Nephrogenic Diabetes Insipidus (NDI), ADPKD Treated With Tolvaptan, and Severely Polyuric Patients With Previous Lithium Administration
  Completed · Phase 2 · Interventional · 36 enrolled · Mayo Clinic
  NCT05190744updated 2026-01-27
• The Re-Prosper HF Study
  Completed · Phase 2 · Phase 3 · Interventional · 99 enrolled · VA Office of Research and Development
  NCT04551222updated 2026-01-07

CPIC-curated drug–gene pairs for Probenecid. Levels describe the strength of curated evidence and guideline status — never a recommendation to test or to adjust therapy.

• G6PDCPIC CFDA label: Informative PGx
  G6PD

Frequently asked questions

How does Probenecid work?

Mechanism-of-action class: Organic Anion Transporter Interactions.

What is Probenecid used for?

According to FDA labeling, Probenecid carries indications including: Probenecid tablets are indicated for the treatment of the hyperuricemia associated with gout and gouty arthritis. As an adjuvant to therapy with penicillin or with ampicillin, methicillin, oxacillin, cloxacillin, or nafcillin, for elevation and prolongation of plasma levels by whatever route the antibiotic is given.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Probenecid?

Probenecid is classified as Preparations increasing uric acid excretion, Organic Anion Transporter Interactions, Decreased Renal Organic Ion Excretion, Uricosuric Activity.

What are the brand names for Probenecid?

Probenecid is marketed under brand names including Orlynvah.

What are the contraindications for Probenecid?

Probenecid labeling lists contraindications including: Hypersensitivity to probenecid. Children under 2 years of age.. Always consult the full prescribing information and a clinician.