Probenecid

Probenecid is a prescription medication used to prevent gout and gouty arthritis.

• Probenecid is available under the following different brand names: Benemid

Adult and pediatric dosage

Tablet

• 500mg

Gout

Adult dosage

• 250 mg orally twice daily for 1 week; increase to 500 mg orally twice daily to 2 g/day maximum with dosage increases of 500 mg every 4 weeks
• If gout attacks do not occur for 4 months and uric acid levels are within normal may reduce the dose by 500 mg every 6 months

Prolong Penicillin Serum Levels

Adult dosage

• 500 mg orally four times daily

Pediatric dosage

• Children below 2 years: Contraindicated
• Children above 2 years: 
  • Less than 50 kg: 25 mg/kg body weight (or 700mg/m2) orally once with PCN; for maintenance, increase to 40 mg/kg body weight (or 1.2 g/m2) per day orally divided every 6 hours; not to exceed 500 mg/dose  
  • More than 50 kg: 500 mg orally four times daily

Pelvic Inflammatory Disease

Adult dosage

• 1 g orally with 2 g cefoxitin IM as a single dose

Gonorrhea

Adult dosage

• 1 g orally with 2 g cefoxitin IM as a single dose

Pediatric dosage

• Children less than 45 kg: Safety and efficacy not established
• Children more than 45 kg: 1 g orally with 2 g cefoxitin IM as a single dose

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of Probenecid include:

• nausea, 
• loss of appetite, 
• dizziness, 
• vomiting, 
• headache, 
• sore gums, and
• frequent urination.

Serious side effects of Probenecid include:

• lower back pain, 
• difficult/painful urination, 
• change in amount/color of urine,
• easy bruising/bleeding, 
• signs of infection such as fever, sore throat,
• severe abdominal pain, 
• pale stools,
• unusual tiredness,
• dark urine, 
• yellowing eyes/skin
• allergic reaction: rash, itching/swelling (especially of the face/tongue/throat), 
• severe dizziness, and
• trouble breathing.

Rare side effects of Probenecid include:

• nephrotic syndrome, and
• hepatic necrosis.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Probenecid has severe interactions with no other drugs.
• Probenecid has serious interactions with the following drugs:
  • aspirin
  • aspirin rectal
  • aspirin/citric acid/sodium bicarbonate
  • baricitinib
  • imipenem/cilastatin
  • imipenem/cilastatin/relebactam
  • ketorolac
  • ketorolac intranasal
  • meropenem/vaborbactam
  • methotrexate
  • nafcillin
  • pivmecillinam
  • temocillin
  • ticarcillin
• Probenecid has moderate interactions with at least 96 other drugs
• Probenecid has minor interactions with at least 22 other drugs. 

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns.

Contraindications

• Children less than 2 years
• Uric acid kidney stones, acute gouty arthritis
• Hypersensitivity
• Blood dyscrasias
• Administration during a gouty attack
• Small or large dose aspirin therapy

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Probenecid?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Probenecid?”

Cautions

• Use caution in patients with G6PD deficiency; may increase the risk for hemolytic anemia
• Use caution in patients with peptic ulcer disease
• Salicylates may reduce the therapeutic effects of probenecid (effect may be pronounced with high chronic doses
• May cause exacerbation of acute gouty attack; in such cases colchicine or other appropriate therapy is advisable
• May increase the serum concentration of methotrexate; if probenecid is given with methotrexate, reduce the dosage of methotrexate and monitor serum levels
• Hematuria, renal colic, costovertebral pain, and formation of uric acid stones associated with the use of probenecid in gouty patients may be prevented by alkalization of the urine and a liberal fluid intake; in these cases when alkali is administered, the acid-base balance of the patient should be watched
• 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 administration following prior usage of the drug; the appearance of hypersensitivity reactions requires cessation of therapy with probenecid; discontinue drug if allergic reaction occurs
• Probenecid has been used in patients with some renal impairment, but dosage requirements may be increased; probenecid may not be effective in chronic renal insufficiency particularly when the glomerular filtration rate is less than or equal to 30 mL/minute because of its mechanism of action, probenecid is not recommended in conjunction with penicillin in the presence of known renal impairment

Drug interaction overview

• In patients on Probenecid, the use of salicylates in either small or large doses is contraindicated because 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
• Concomitant administration of probenecid increases the mean plasma elimination half-life of several drugs which can lead to increased plasma concentrations; these include agents such as indomethacin, acetaminophen, naproxen, ketoprofen, meclofenamate, lorazepam, and rifampin
• Although the clinical significance of this observation has not been established, a lower dosage of the drug may be required to produce a therapeutic effect, and increases a dosage of the drug in question should be made cautiously and in small increments when probenecid is being coadministered
• Although specific instances of toxicity due to potential interaction have not been observed to date, physicians should be alert to this possibility
• Probenecid given concomitantly with sulindac had only a slight effect on plasma sulfide levels, while plasma levels of sulindac and sulfone were increased; sulindac was shown to produce a modest reduction in uricosuric action of probenecid, which probably is not significant under most circumstances

Pregnancy and Lactation

• 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 possible hazards

Lactation

• Not known if distributed into breast milk, use with caution