Probenecid inhibits the reabsorption of uric acid in the proximal convoluted tubules of the kidneys resulting in the excess excretion of uric acid.

Probenecid Uses:

• It is indicated for the management of hyperuricemia due to gout, gouty arthritis, prolongation and elevation of beta-lactam plasma levels.

Guideline recommendations:

• Gout:

  • Probenecid is a uricosuric drug that is prescribed alone or concurrently with allopurinol in patients without proper control with allopurinol alone.

• Off Label Use of Probenecid in Adults:

  • Neurosyphilis including ocular syphilis
  • Pelvic inflammatory disease

Probenecid dosage in adults:

Probenecid Dose for the treatment of Hyperuricemia with gout:

• 250 mg twice daily per oral for 7 days.
• It can be increased to 500 mg twice daily.
• If needed it can be increased to a maximum of 2 g/day (increase dosage in 500 mg increments every one month).
• If serum uric acid levels become normal and there are no gout attacks for 6 months, daily dosage may be reduced by 500 mg every 6 months.

Probenecid Dosage for prolonging serum penicillin levels:

• 500 mg per oral 4 times a day.

Probenecid dose for the treatment of Neurosyphilis, including ocular syphilis, as an alternative to the preferred therapy:

• 500 mg per oral 4 times/day in combination with procaine penicillin intramuscular for 10 to 14 days.

Probenecid dose for the treatment of Pelvic inflammatory disease:

• 1 g as a single dose per oral in addition to cefoxitin intramuscular as a single dose plus oral doxycycline (with/ without oral metronidazole) for 2 weeks.

Probenicid dosage in children:

Probenecid dose to prolong serum penicillin levels:

• Children ≥2 years and Adolescents:

Note: Dosing for some indication-specific dosing may vary.

• Patient weight ≤50 kg:

  • Initial dose of 25 mg/kg per oral  or 700 mg/m  as a single dose
  • maintenance: 40 mg/kg per oral per day or 1,200 mg /m /day in 4 divided doses
  • maximum dose: 500 mg.

• Patient weight >50 kg:

  • 500 mg per oral 4 times daily.

Probenecid dose for the treatment of Gonorrhea and uncomplicated infections of cervix, urethra, and rectum:

• Adolescents >45 kg:

  • 1,000 mg as a single dose per oral in addition with cefoxitin
  • Note: A combination of ceftriaxone plus azithromycin is preferred.

Probenecid dose for the treatment of Pelvic inflammatory disease in Adolescents:

• 1,000 mg per oral as a single dose with cefoxitin and doxycycline with/without metronidazole.

Probenecid dose for the treatment of Neurosyphilis in Adolescents:

• 500 mg per oral 4 times daily with procaine penicillin for 10 to 14 days as an alternative therapy to aqueous penicillin G therapy.

Probenecid Dose in the prevention of Cidofovir nephrotoxicity:

Note: The manufacturer's labeling considers use in patients <2 years of age is contraindicated, however, clinical studies have included younger ages including infants for this indication.

• Weight-based dosing:

  • 25 to 40 mg/kg/dose per oral (maximum dose: 2,000 mg) administered 3 hours before cidofovir infusion and 10 to 20 mg/kg/dose (maximum dose: 1,000 mg) at 2 to 3 hours and 8 to 9 hours after cidofovir infusion.

• BSA-based dosing:

  • 1,000 or 1,250 mg/m²/dose per oral given 3 hours prior to cidofovir, followed by 500 to 1,250 mg/m² /dose 1 to 2 hours and 8 hours after completion.

Probenecid Pregnancy Risk Category: B

• Probenecid can cross the placenta.
• According to available data, there is no evidence of an increase in the risk of adverse fetal outcomes.
• Breastmilk may contain small amounts of the drug.

Probenicid dose adjustment in renal disease:

• Glomerular filtration rate <30 mL/minute:

  • It should not be prescribed(reduced efficacy with renal impairment)

Note: Probenecid is not prescibed as first-line urate-lowering single agent in patients with renal impairment (CrCl <50 mL/minute).

Probenecid dose adjustment in liver disease:

There are no dosage adjustments provided in the manufacturer’s labeling.

Side effects of Probenecid:

• Cardiovascular:

  • Flushing

• Central Nervous System:

  • Dizziness
  • Headache
  • Pain (Costovertebral)

• Dermatologic:

  • Alopecia
  • Dermatitis
  • Pruritus
  • Skin Rash

• Endocrine & Metabolic:

  • Acute Gouty Arthritis

• Gastrointestinal:

  • Anorexia
  • Dyspepsia
  • Gastroesophageal Reflux Disease
  • Gingival Pain
  • Nausea
  • Vomiting

• Genitourinary:

  • Hematuria
  • Nephrotic Syndrome

• Hematologic & Oncologic:

  • Anemia
  • Aplastic Anemia
  • Hemolytic Anemia (In G6PD Deficiency)
  • Leukopenia

• Hepatic:

  • Hepatic Necrosis

• Hypersensitivity:

  • Anaphylaxis
  • Hypersensitivity Reaction

• Renal:

  • Polyuria
  • Renal Colic

• Miscellaneous:

  • Fever

Contraindication to Probenecid:

• Hypersensitivity reactions to the drug, or any component thereof, are contraindications.
• Aspirin therapy
• blood dyscrasias
• Urin acid renal calculus
• Children under 2 years old
• Gout attacks that are severe

Warnings and precautions

• Allergy reaction:

  • Although severe hypersensitivity reactions, including anaphylaxis, are rare, it is important to discontinue therapy if they occur.

• Gout

  • Could cause acute gout inflammation.

• G6PD deficiency:

  • Patients with G6PD deficiency should be cautious as this can increase the risk of hemolytic anemia.

• Peptic ulcer disease:

  • Patients with peptic ulcer disease should be cautious.

• Renal impairment

  • A creatinine clearance of 30mL/minute is ineffective for single-agent.
  • According to the American College of Rheumatology Guidelines for Hyperuricemia Treatment, probenecid is not recommended as a first-line or alternative therapy for patients with creatinine clearances below 50 mL/minute.

Probenecid: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

Different parameters including serum and urine uric acid, renal function, complete blood count, and frequency of gout attacks should be monitored.

How to administer Probenecid?

It should be administered with food to avoid gastrointestinal effects.

Mechanism of action of Probenecid:

• It causes competitive inhibition of the reabsorption uric acids at the proximal convoluted tubeule, leading to an increase in excretion and a decrease in serum uric Acid level.
• This causes an increase in plasma levels of weak organic acids, such as penicillins and cephalosporins or other beta-lactam antibiotics, by competitively inhibiting the secretion of renal tubules

The onset of action:

• Effect on penicillin levels: 120 minutes;
• Uric acid renal clearance: 30 minutes

Absorption:

• Rapid and complete

Protein binding:

• 85% to 95%

Metabolism:

• Occurs in liver

Half-life elimination (dose-dependent):

• Normal renal function: 6 to 12 hours

The time to reach peak serum concentration:

• 2 to 4 hours

Excretion:

• occurs in urine

Probenecid Brand Names (International): 

• Benuryl
• Benacid
• Bencid
• Benecid Valdecasas
• Benemid
• Benemide
• Benuryl
• Brocid
• Gonocilin
• Pro-Cid
• Probecid
• Probecilin
• Probenecid Weimer
• Probenecid ”Dak”
• Probenecid ”Medic”
• Procid
• Pronid
• Santuril
• Uri-Forte

Probenecid Brand Names in Pakistan:

No Brands Available in Pakistan.