s 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-administered. 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 (see warnings ). falsely high readings for theophylline have been reported in an in vitro study, using the schack and waxler technic, when therapeutic concentrations of theophylline and probenecid were added to human plasma.

within several hours after readministration following prior usage of the drug. the appearance of hypersensitivity reactions requires cessation of therapy with probenecid. use in pregnancy probenecid crosses the placental 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.

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nute or less. gastric intolerance may be indicative of overdosage, and may be corrected by decreasing the dosage. as uric acid tends to crystallize out of an acid urine, a liberal fluid intake is recommended, as well as sufficient sodium bicarbonate (3 to 7.5 g daily), or potassium citrate (7.5 g daily) to maintain an alkaline urine (see precautions ). alkalization of the urine is recommended until the serum urate level returns to normal limits and tophaceous deposits disappear, i.e., during the period when urinary excretion of uric acid is at a high level. thereafter, alkalization of the urine and the usual restriction of purine-producing foods may be somewhat relaxed. probenecid should be continued at the dosage that will maintain normal serum urate levels. when acute attacks have been absent for 6 months or more and serum urate levels remain within normal limits, the daily dosage may be decreased by 500 mg every 6 months. the maintenance dosage should not be reduced to the point where serum urate levels tend to rise. probenecid and penicillin therapy (general) adults the recommended dosage is 2000 mg (4 tablets of probenecid) daily in divided doses. this dosage should be reduced in older patients in whom renal impairment may be present. children 2-14 years of age initial dose: 25 mg/kg body weight ( or 0.7 g/square meter body surface). maintenance dose: 40 mg/kg body weight ( or 1.2 g/square meter body surface) per day, divided into 4 doses. for children weighing more than 50 kg (110 lb) the adult dosage is recommended. probenecid is contraindicated in children under 2 years of age. 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 one-fifth the normal rate when dosage of probenecid is adequate. penicillin therapy (gonorrhea)* in uncomplicated gonococcal infections in men and women (urethral, cervical, rectal), 1 g of probenecid should be given orally with 4.8 million units of aqueous procaine penicillin g ** (given im), or 3 g of amoxicillin ** (given orally), or 3.5 g of ampicillin ** (given orally). for further guidance, see cdc recommendations for definition of regimens of choice, alternative regimens, treatment of hypersensitive patients, and other aspects of therapy. * recommended by the centers for disease control, u.s. department of health and human services, public health service (morbidity and mortality weekly report supplement, volume 34, number 4s, october 18, 1985). ** see package circulars of manufacturers for detailed information about contraindications , warnings , precautions , and adverse reactions .

s 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-administered. 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 (see warnings ). falsely high readings for theophylline have been reported in an in vitro study, using the schack and waxler technic, when therapeutic concentrations of theophylline and probenecid were added to human plasma.

r reabsorption of phosphorus is inhibited in hypoparathyroid but not in euparathyroid individuals. probenecid does not influence plasma concentrations of salicylates, nor the excretion of streptomycin, chloramphenicol, chlortetracycline, oxytetracycline, or neomycin.