Probenecid

Urinary tract

Membranous nephropathy has been attributed to probenecid in a 79-year-old man who had taken probenecid 500 mg bd for 1 year, but in whom the dosage had been increased to 1500 mg bd; probenecid was withdrawn and he recovered fully within 6 weeks [ ]. Other cases have been reported [ ].

Immunologic

A hypersensitivity reaction has been attributed to probenecid in a patient with AIDS [ ].

In a patient with a class III hypersensitivity reaction there was cross-reactivity with other drugs with structures related to sulphonamides [ ].

Lactation

Probenecid can enter breast milk [ ].

• A breast-fed infant of a 30-year-old woman taking oral probenecid and cefalexin for a breast infection developed severe diarrhea. The average concentrations of probenecid and cefalexin in the milk were 964 and 745 μg/l respectively, corresponding to infant doses of 145 micrograms/kg/day of probenecid and 112 micrograms/kg/day of cefalexin.

The infant’s adverse reactions were rated as possible for probenecid and probable for cefalexin based on the Naranjo probability scale.

Acetylsalicylic acid (aspirin)

In low dosages (up to 2 g/day), aspirin reduces urate excretion and blocks the effects of probenecid and other uricosuric agents [ , ]. However, in 11 patients with gout, aspirin 325 mg/day had no effect on the uricosuric action of probenecid [ ]. In higher dosages (over 5 g/day), salicylates increase urate excretion and inhibit the effects of spironolactone, but it is not clear whether these phenomena are of importance.

Beta-lactam antibiotics

Probenecid inhibits the renal excretion of most beta-lactam antibiotics [ , ]. It inhibits the renal tubular secretion of various penicillins [ ] and many cephalosporins [ ]. In a non-randomized, non-blinded study in 26 patients who were given intravenous cefazolin 2000 mg every 8 hours or 2000 mg once daily plus oral probenecid 500 mg qds, in those who took probenecid the average serum peak concentrations on days 1 and 5 were 147 and 148 mg/l and trough concentrations were 2.0 and 2.7 mg/l [ ]. In those who received cefazolin every 8 hours, peak concentrations were 122 and 137 mg/l and trough concentrations were 19 and 17 mg/l. The authors concluded that probenecid maintained therapeutic serum concentrations of low-dose cefazolin at steady-state. In another study ceforanide was not affected by probenecid [ ].