Active ingredient: Probenecid - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

• Uricosuric Agents

Dosage Forms

• Tablet

Brands / Synonyms

Apurina; Benecid; Benemid; Benuryl; Col-Probenecid; Colbenemid; Ethamide; Polycillin-PRB; Probalan; Probampacin; Probecid; Proben; Proben-C; Probenecid; Probenecid Acid; Probenecid and Colchicine; Probenemid; Probexin; Prolongine; Synergid R; Tubophan; Uricosid

Indications

For the treatment of gout and high levels of uric acid in the blood

Pharmacology

Probenecid is a uricosuric and renal tubular blocking agent and is used in combination with colchicine to treat chronic gouty arthritis when complicated by frequent, recurrent acute attacks of gout. It inhibits the tubular reabsorption of urate, thus increasing the urinary excretion of uric acid and decreasing serum urate levels. Effective uricosuria reduces the miscible urate pool, retards urate deposition, and promotes resorption of urate deposits.

Mechanism of Action

Probenecid inhibits the tubular reabsorption of urate, thus increasing the urinary excretion of uric acid and decreasing serum urate levels.

Absorption

Not Available

Toxicity

Not Available

Biotrnasformation / Drug Metabolism

Not Available

Contraindications

Hypersensitivity to this product or to probenecid or colchicine.

Probenecid and colchicine tablets are contraindicated in children under 2 years of age.

Not recommended in persons with known blood dyscrasias or uric acid kidney stones.

Therapy with probenecid and colchicine should not be started until an acute gouty attack has subsided.

Pregnancy

Probenecid crosses the placental barrier and appears in cord blood. Colchicine can arrest cell division in animals and plants. In certain species of animal under certain conditions, colchicine has produced teratogenic effects. The possibility of such effects in humans also has been reported. Because of the colchicine component, probenecid and colchicine is contraindicated in pregnant patients. The use of any drug in women of childbearing potential requires that the anticipated benefit be weighed against the possible hazards.

Drug Interactions

When probenecid is used to elevate plasma concentrations of penicillin, or other beta-lactams, or when such drugs are given to patients taking probenecid therapeutically, high plasma concentrations of the other drug may increase the incidence of adverse reactions associated with that drug. In the case of penicillin, or other beta-lactams, psychic disturbances have been reported.

The use of salicylates antagonizes the uricosuric action of probenecid . The uricosuric action of probenecid is also antagonized by pyrazinamide.

Probenecid produces an insignificant increase in free sulfonamide plasma concentrations but a significant increase in total sulfonamide plasma levels. Since probenecid decreases the renal excretion of conjugated sulfonamides, plasma concentrations of the latter should be determined from time to time when a sulfonamide and probenecid and colchicine are co-administered for prolonged periods. Probenecid may prolong or enhance the action of oral sulfonylureas and thereby increase the risk of hypoglycemia.

It has been reported that patients receiving probenecid require significantly less thiopental for induction of anesthesia. In addition, ketamine and thiopental anesthesia were significantly prolonged in rats receiving probenecid.

The concomitant administration of probenecid increases the mean plasma elimination half-life of a number of 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 in dosage of the drug in question should be made cautiously and in small increments when probenecid is being co-administrated. Although specific instances of toxicity due to this 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 the uricosuric action of probenecid, which probably is not significant under most circumstances.

In animals and in humans, probenecid has been reported to increase plasma concentrations of methotrexate .

Falsely high readings for theophylline have been reported in an in vitro study, using the Schack and Waxler technique, when therapeutic concentrations of theophylline and probenecid were added to human plasma.