Probenecid

Probenecid tablets are indicated for the treatment of the hyperuricemia associated with gout and gouty arthritis. As an adjuvant to therapy with penicillin or with ampicillin, methicillin, oxacillin, cloxacillin, or nafcillin, for elevation and prolongation of plasma levels by whatever route the antibiotic is given.

• Gout: Therapy with probenecid should not be started until an acute gouty attack has subsided
• However, if an acute attack is precipitated during therapy, probenecid may be continued without changing the dosage, and full therapeutic dosage of colchicine, or other appropriate therapy, should be given to control the acute attack
• The recommended adult dosage is 250 mg (½ probenecid tablet), twice a day for one week, followed by 500 mg (1 tablet) twice a day thereafter
• Some degree of renal impairment may be present in patients with gout
• A daily dosage of 1000 mg may be adequate
• However, if necessary, the daily dosage may be increased by 500 mg increments every 4 weeks within tolerance (and usually not above 2000 mg per day) if symptoms of gouty arthritis are not controlled or the 24 hour uric acid excretion is not above 700 mg
• As noted, probenecid may not be effective in chronic renal insufficiency particularly when the glomerular filtration rate is 30 mg mL/minute or less
• Gastric intolerance may be indicative of over dosage, 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 high level. …

• Hypersensitivity to probenecid
• Children under 2 years of age
• Not recommended in persons with known blood dyscrasias or uric acid kidney stones
• Therapy with probenecid should not be started until an acute gouty attack has subsided

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 (see WARNINGS ). 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. …

Exacerbation of gout following therapy with probenecid may occur; in such cases colchicine or other appropriate therapy is advisable. Probenecid increases plasma concentrations of methotrexate in both animals and humans. In animal studies, increased methotrexate toxicity has been reported. If probenecid is given with methotrexate, the dosage of methotrexate should be reduced and serum levels may need to be monitored. In patients on probenecid the use of salicylates in either small or large doses is contraindicated because it antagonizes the uricosuric action of probenecid. …

The following adverse reactions have been observed and within each category are listed in order of decreasing severity. Central Nervous System : headache, dizziness. Metabolic : precipitation of acute gouty arthritis Gastrointestinal : hepatic necrosis, vomiting, nausea, anorexia, sore gums. Genitourinary : nephrotic syndrome, uric acid stones with or without hematuria, renal colic, costovertebral pain, and urinary frequency. Hypersensitivity : anaphylaxis, fever, urticaria, pruritus Hematologic : aplastic anemia, leukopenia, hemolytic anemia which in some patients could be related to genetic deficiency of glucose -6- phosphate dehydrogenase in red blood cells, anemia. …

In Pregnancy: 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 the possible hazards.

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.