probenecid

Available forms
Available by prescription only
Tablets: 500 mg

Indications and dosages
 Adjunct to penicillin therapy. Adults and children older than age 14 or weighing over 50 kg (110 lb): 500 mg P.O. q.i.d.
Children ages 2 to 14 or weighing under 50 kg: Initially, 25 mg/kg or 700 mg/m² daily; then 40 mg/kg or 1.2 g/m² divided q.i.d.
 Single-dose penicillin treatment of gonorrhea. Adults: 1 g P.O. given together with penicillin treatment, or 1 g P.O. 30 minutes before I.M. dose of penicillin.
 Hyperuricemia related to gout. Adults: 250 mg P.O. b.i.d. for first week, then 500 mg b.i.d., to maximum of 2 to 3 g daily.
 To diagnose parkinsonian syndrome or mental depression ◇. Adults: 500 mg P.O. q 12 hours for five doses.

Pharmacodynamics
Uricosuric action: Competitively inhibits the active reabsorption of uric acid at the proximal convoluted tubule, thereby increasing urinary excretion of uric acid.
Adjunctive action in antibiotic therapy: Competitively inhibits secretion of weak organic acids, such as penicillins, cephalosporins, and other beta-lactam antibiotics, thereby increasing serum levels of these drugs.

Pharmacokinetics
Absorption: Completely absorbed after oral administration.
Distribution: Distributed throughout body; about 75% protein-bound. CSF levels about 2% of serum levels.
Metabolism: Metabolized in liver to active metabolites, with some uricosuric effect.
Excretion: Drug and metabolites excreted in urine; drug (but not metabolites) actively reabsorbed.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug, in those with uric acid kidney stones or blood dyscrasias; in acute gout attack; and in children younger than age 2. Use cautiously in patients with impaired renal function or peptic ulcer.

Interactions
Drug-drug. Aminosalicylic acid, dapsone, methotrexate, nitrofurantoin: Increases serum levels; increases risk of toxicity of these drugs. Monitor patient for toxicity.
Bumetanide, ethacrynic acid, furosemide: Impairs natriuretic effects of these drugs. Adjust dosages as needed.
Cephalosporins, ketamine (possibly), penicillins, sulfonamides, thiopental (possibly), other beta-lactam antibiotics: Significantly increases or prolongs effects of these drugs. Monitor patient closely.
Chlorpropamide, other oral sulfonylureas: Enhances hypoglycemic effects. Adjust dosages as needed.
Diuretics, pyrazinamide: Increases uric acid levels. Increased doses of probenecid may be needed.
Indomethacin, naproxen: Decreases excretion of these drugs. Use lower dosages.
Salicylates: Inhibits uricosuric effect of probenecid only in doses that achieve levels of 50 mcg/ml or more; occasional use of low-dose aspirin doesn’t interfere. Monitor patient closely.
Weak organic acids: Inhibits urinary excretion of these drugs. Monitor patient.
Zidovudine: Increases bioavailability of zidovudine; may cause cutaneous eruptions accompanied by systemic symptoms (including malaise, myalgia, or fever). Monitor patient for toxicity.
Drug-lifestyle. Alcohol use: Decreases uric acid levels of probenecid. Discourage alcohol use. Increased doses of probenecid may be needed with alcohol use.

Adverse reactions
CNS: headache, dizziness, fever.
GI: anorexia, nausea, vomiting, sore gums.
GU: urinary frequency, renal colic, nephrotic syndrome.
Hematologic: hemolytic anemia, aplastic anemia, anemia.
Hepatic: hepatic necrosis.
Skin: dermatitis, pruritus, flushing.
Other: exacerbation of gout, hypersensitivity reactions (including anaphylaxis).

Effects on lab test results
• May decrease uric acid levels.
• May decrease hemoglobin and hematocrit.

Overdose and treatment
Toxicity may cause nausea, copious vomiting, stupor, coma, and tonic-clonic seizures.
 Treat supportively, using mechanical ventilation, if needed; induce emesis or use gastric lavage, as appropriate. Control seizures with I.V. phenobarbital and phenytoin.

Special considerations
• When used for hyperuricemia related to gout, probenecid has no analgesic or anti-inflammatory actions and no effect on acute attacks; start therapy after attack subsides. Because drug may increase frequency of acute attacks during first 6 to 12 months of therapy, prophylactic doses of colchicine or an NSAID should be given during first 3 to 6 months of probenecid therapy.
• Give with food, milk, or prescribed antacids to lessen GI upset.
• Maintain adequate hydration with high fluid intake to prevent formation of uric acid stones. Also maintain alkalinization of urine.
• Monitor BUN and serum creatinine levels closely; drug is ineffective in severe renal insufficiency.
• Monitor uric acid levels and adjust dosage to lowest dose that maintains normal uric acid levels.
• Drug has been used in the diagnosis of parkinsonian syndrome and mental depression.
• Probenecid causes false-positive test results for urinary glucose with tests using cupric sulfate reagent (Benedict’s reagent, Clinitest, and Fehling’s test); perform tests with glucose oxidase reagent (Diastix, Chemstrip uG, or glucose enzymatic test strip) instead.
Breast-feeding patients
• It isn’t known if drug appears in breast milk. An alternative to breast-feeding is recommended during therapy.
Pediatric patients
• Drug is contraindicated in infants younger than age 2.
Geriatric patients
• Lower dosages are indicated in elderly patients.

Patient education
• Instruct patient not to stop drug without medical approval.
• Warn patient not to use drug for pain or inflammation and not to increase dose during gouty attack.
• Tell patient to drink 8 to 10 glasses of fluid daily and to take drug with food to minimize GI upset.
• Warn patient to avoid aspirin and other salicylates, which may antagonize probenecid’s uricosuric effect.
• Caution diabetic patients to use glucose enzymatic test strip, Diastix, or Chemstrip uG for urine glucose testing.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use