PROBENECID-AFT Film coated tablet Ref.[8255] Active ingredients: Probenecid

Use with caution in patients with a history of peptic ulcer.

The appearance of hypersensitivity reactions requires cessation of probenecid therapy.

If probenecid is given with methotrexate, the dosage of methotrexate should be reduced and serum levels may need to be monitored.

Haematuria, renal colic, costovertebral pain, and formation of urate stones associated with the use of probenecid in gouty patients may be prevented by alkalisation of the urine and a liberal fluid intake. Sufficient sodium bicarbonate (3g to 7.5g daily) or potassium citrate (7.5g daily) is recommended to maintain alkaline urine. With such quantities of alkali, the acid-base balance of the patient should be watched.

Alkalisation of the urine is recommended until the serum acid level returns to normal (upper normal limit in males is about 6mg/100ml and in females, about 5mg/100ml) and tophaceous deposits disappear, i.e. during the period when urinary excretion of urates is at a high level. After the miscible pool of uric acid decreases to normal (about 1g) and deposited urates are re-sorbed and eliminated, alkalisation of the urine probably is unnecessary, since the urinary urate concentration is lower and less likely to cause crystallisation.

Exacerbation of gout during therapy with probenecid may occur; in such cases, a therapeutic dosage of indomethacin, colchicine or other appropriate therapy should be added.

In patients on probenecid the use of acetylsalicylic acid in either small or large doses is contraindicated because it antagonises the uricosuric action of probenecid. In patients on probenecid who require a mild analgesic agent the use of paracetamol rather than small doses of salicylates would be preferred.

Caution should be used if probenecid is administered simultaneously with methotrexate. Probenecid has been reported to decrease the tubular secretion of methotrexate and to potentiate toxicity.

Probenecid increases the mean plasma elimination half-life of a number of other medicines which can lead to increased peak plasma concentrations. These medicines include acetaminophen, naproxen, indomethacin, ketoprofen, meclofenamate, lorazepam, rifampin, acyclovir, ganciclovir and zidovudine. The clinical significance of this effect on plasma elimination half-life is not known; however, adjustment in the usual dosage of these medicines may be required.

Since probenecid decreases the renal excretion of conjugated sulfonamides, plasma concentrations of the latter should be determined from time to time when a sulfa medicine and probenecid are co-administered for prolonged periods. Probenecid may prolong or enhance the action of oral sulfonylureas and thereby increase the risk of hypoglycaemia. The uricosuric action of probenecid is antagonised by pyrazinamide. In animals, the renal tubular re-absorption of erythromycin is inhibited by probenecid and the renal excretion of sodium acetrizoate is decreased.

Because of its mechanism of action, probenecid is not recommended in conjunction with a β-lactam antibiotic in the presence of known renal impairment. In addition to its effect on the excretion of uric acid, the β-lactam antibiotics (other than cephaloridine) probenecid decreases the urinary excretion of p-aminosalicylic acid (PAS), p-aminohippuric acid (PAH), phenolsulfonphthalein (PSP), pantothenic acid, 17-ketosteroids, sodium iodomethamate and related iodinated organic acids, probenecid decreases both hepatic and renal excretion of sulfobromophthalein (BSP). The renal tubular re-absorption of phosphorus is inhibited in hypoparathyroid but not in euparathyroid individuals.

A reducing substance may appear in the urine of patients receiving probenecid which may produce a false-positive Benedict’s test leading to the possibility of a false diagnosis of glycosuria. However, this disappears with discontinuance of therapy. 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.

Category B2.

Probenecid crosses the placental barrier and appears in cord blood. The use of any medicine in women of childbearing potential requires that the anticipated benefit be weighed against possible hazards.

Reproduction studies in the rabbit and the rat at doses up to 10 times the recommended human dose have shown no evidence of teratogenic effects to the foetus due to probenecid. Because animal reproduction studies are not always predictive of human response, probenecid should be used during pregnancy only if clearly needed.

It is not known whether the medicine is excreted in human milk. Because many medicines are excreted in human milk, caution should be exercised when probenecid is administered to a nursing mother.

Although this medicine is unlikely to affect your ability to drive or operate machinery, a few people may be impaired and care should be taken.

Central Nervous System: Headache, dizziness

Gastrointestinal: Nausea, anorexia, vomiting

Genitourinary: Urinary frequency, in gouty patients exacerbation of gout, and uric acid stones with or without haematuria, renal colic, or costovertebral pain, have been observed, nephrotic syndrome occurs rarely

Hypersensitivity reactions: Anaphylaxis, dermatitis, pruritus, urticaria, fever and Stevens-Johnson syndrome.

Haematological: Anaemia, haemolytic anaemia which in some instances could be related to genetic deficiency of glucose-6-phosphate dehydrogenase in red blood cells, leucopoenia and aplastic anaemia occur rarely.

Other: Exacerbation of gout, sore gums, flushing, alopecia, with toxic epidermal necrolysis reported rarely after combination therapy of colchicine and probenecid.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions https://nzphvc.otago.ac.nz/reporting/.

Not applicable.