Generic Benemid

PROBENECID
Tablets: 0.5 g (Rx) Various, Benemid (Merck), Probalan (Lannett)

Indications
Hyperuricemia: Treatment of hyperuricemia associated with gout and gouty arthritis.
Plasma levels: Adjuvant to therapy with penicillins or cephalosporins, for elevation and prolongation of plasma levels of the antibiotic.

Administration and Dosage
Gout: Do not start therapy until an acute gouty attack has subsided. However, if an acute attack is precipitated during therapy, probenecid may be continued. Give full therapeutic doses of colchicine or other appropriate therapy to control the acute attack.
Adults - 0.25 g twice/day for 1 week; 0.5 g twice/day thereafter. Gastric intolerance may indicate over-dosage, and may be reduced by decreasing dosage.
Renal impairment - Some degree of renal impairment may be present in patients with gout. A daily dosage of 1 g may be adequate. However, if necessary, the daily dosage may be increased by 0.5 g increments every 4 weeks within tolerance (usually not > 2 g/day) if symptoms of gouty arthritis are not controlled or the 24 hour urate excretion is not > 700 mg. Probenecid may not be effective in chronic renal insufficiency, particularly when the glomerular filtration rate is Urinary alkalinization - Urates tend to crystallize out of an acid urine; therefore, a liberal fluid intake is recommended, as well as sufficient sodium bicarbonate (3 to 7-5 g/day) or potassium citrate (7.5 g/day) to maintain an alkaline urine; continue alkalization until the serum uric acid level returns to normal limits and tophaceous deposits disappear. Thereafter, urinary alkalization and the restriction of purine-producing foods may be relaxed.
Maintenance therapy - Continue the dosage that maintains normal serum uric acid levels. When there have been no acute attacks for > 6 months and serum uric acid levels have remained within normal limits, decrease the daily dosage by 0.5 g every 6 months. Do not reduce the maintenance dosage to the point where serum uric acid levels increase.
Penicillin or cephalosporin therapy: The PSP excretion test may be used to determine the effectiveness of probenecid in retarding penicillin excretion and maintaining therapeutic levels. The renal clearance of PSP is reduced to about the normal rate when dosage of probenecid is adequate.
Adults - 2 g/day in divided doses. Reduce dosage in older patients in whom renal impairment may be present. Not recommended in conjunction with penicillin or a cephalosporin in the presence of known renal impairment.
Children (2 to 14 years of age) - Initial dose 25 mg/kg or 0.7 g/m2. Maintenance dose 40 mg/kg/day or 1.2 g/m2, divided into 4 doses. For children weighing > 50 kg (110 lb), use the adult dosage. Do not use in children Gonorrhea (uncomplicated) - Give probenecid as a single 1 g dose immediately before or with 4-8 million units penicillin G procaine, aqueous, divided into at least 2 doses.
Neurosyphilis - Aqueous procaine penicillin G, 2 to 4 million units/day IM plus probenecid 500 mg 4 times/day, both for 10 to 14 days.
Pelvic inflammatory disease (PID) - Cefoxitin 2 g IM plus probenecid, 1 g orally in a single dose concurrently.

Actions
Pharmacology: A uricosuric and renal tubular blocking agent, probenecid inhibits the tubular re-absorption of urate, thus increasing the urinary excretion of uric acid and decreasing serum uric acid levels.
Probenecid also inhibits the tubular secretion of most penicillins and cephalosporins and usually increases plasma levels by any route the antibiotic is given.
Pharmacokinetics: Probenecid is well absorbed after oral administration and produces peak plasma concentrations in 2 to 4 hours. It is highly protein bound (85% to 95%). Probenecid is excreted in the urine primarily as metabolites.

Contraindications
Hypersensitivity to probenecid; children

Warnings
Exacerbation of gout: Exacerbation of gout following therapy with probenecid may occur; in such cases, colchicine or other appropriate therapy is advisable.
Salicylates: Use of salicylates is contraindicated in patients on probenecid therapy.
Salicylates antagonize probenecid's uricosuric action.
Sulfa drug allergy: Probenecid is a sulfonamide; patients with a history of allergy to sulfa drugs may react to probenecid.
Hypersensitivity reactions: Rarely, severe allergic reactions and anaphylaxis have occurred.
Most of these occur within several hours after re-administration following prior use of the drug. Renal function impairment: Dosage requirements may be increased in renal impairment.
Probenecid may not be effective in chronic renal insufficiency, particularly when the glomerular filtration rate is Pregnancy: Category B.
Children: Do not use in children

Precautions
Alkalinization of urine: Hematuria, renal colic, costovertebral pain, and formation of urate stones associated with use in gouty patients may be prevented by alkalization of urine and liberal fluid intake; monitor acid-base balance.
Peptic ulcer history: Use with caution.

Drug Interactions
Drugs that may affect probenecid include salicylates.
Drugs that may be affected by probenecid include acyclovir; allopurinol; barbiturates; benzodiazepines; clofibrate; dapsone; dyphylline; methotrexate; NSAIDs; pantothenic acid; penicillamine; rifampin; sulfonamides; sulfonylureas; zidovudine; salicylates.
Drug/Lab test interactions: A reducing substance may appear in the urine during therapy. Although this disappears with discontinuation, a false diagnosis of glycosuria may be made. Confirm suspected glycosuria by using a test specific for glucose.
Falsely high determination of theophylline has occurred in vitro using the Schack and Waxier technique, when therapeutic concentrations of theophylline and probenecid were added to human plasma.
Probenecid may inhibit the renal excretion of: Phenolsulfonphthalein (PSP), 17-ketosteroids, and sulfobromophthalein (BSP).

Adverse Reactions
Adverse reactions may include headache; anorexia; nausea; vomiting; urinary frequency; hypersensitivity reactions; sore gums; flushing; dizziness; anemia; hemolytic anemia (possibly related to G-6-PD deficiency); nephrotic syndrome; hepatic necrosis; aplastic anemia; exacerbation of gout; uric acid stones with or without hematuria; renal colic or costovertebral pain.
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