Side effects of Pefloxacin

Pefloxacin (perfloxacine) is an older-generation fluoroquinolone that was developed by Rhoˆne-Poulenc and has the chemical formula l-ethyl- 6-fluoro-1,4-dihydro-4-oxo-7(4-methyl-1-piperazinyl)-quinoline-3-carboxylic acid. Overall, the antibacterial spectrum of pefloxacin is similar to that of norfloxacin and enoxacin, but is narrower than that of ciprofloxacin. Although pefloxacin has little clinical advantage over these other fluoroquinolones, its good penetration of the central nervous system (CNS) is notable, but there are only limited clinical data available to support its use for treatment of infections of the CNS. Hence, there are now few clinical situations in which pefloxacin would be considered the fluoroquinolone of choice.

Pefloxacin is available in some European, Asian, and Latin American countries, but is not available in the USA or Australia.

Bioavailability 

Pefloxacin is rapidly absorbed from the gastrointestinal tract, with over 80% bioavailability. The elimination half-life of pefloxacin after a single dose is 10.5 hours (7.2–12.3 hours), but increases to 14.8–15.4 hours with repeated dosing, suggesting saturation of the clearance pathway. In serum, pefloxacin is 20–30% protein bound.

Excretion 

The minor difference in structure between pefloxacin and norfloxacin alters the half-life and renal handling of pefloxacin such that, unlike norfloxacin, which is secreted by the renal tubule, there is a net renal tubular reabsorption of pefloxacin. Renal clearance of pefloxacin is low, and urinary excretion of pefloxacin and its active metabolite (norfloxacin) accounts for only 34% of the pefloxacin dose. However, it is notable that pefloxacin, like other fluoroquinolones, including ciprofloxacin, ofloxacin, and enoxacin, is less active in urine, with MICs being increased 8- to 64-fold compared with results on standard culture media, possibly as a result of the presence of higher concentrations of magnesium ions or lower pH. Biliary excretion of pefloxacin and its metabolites accounts for 20– 30% of an oral dose. 

Biliary concentrations after an 800-mg i.v. dose are 2- to 3-fold greater than the serum concentrations, with the peak biliary concentrations reached about 4 hours post-dose. After a 400- mg oral dose, gallbladder bile concentrations of 83 mg/ml can be expected 12 hours post dose if there is no biliary obstruction. Fecal concentrations of pefloxacin after repeated oral dosing of 400 mg twice daily are high – approximately 171–187 mg/g.

Nonrenal clearance is the main elimination pathway for pefloxacin, with the liver being the predominant organ of metabolism. Five metabolites have been identified, of which four are measurable in human urine – N-desmethylpefloxacin (norfloxacin), pefloxacin-N-oxide, oxo-norfloxacin and oxo-pefloxacin. Both pefloxacin N-oxide and N-desmethylpefloxacin (norfloxacin) have been found in human serum; the former has very little antibacterial activity, but norfloxacin is very active. Most of the activity (84%) in serum is due to unchanged pefloxacin.

Side effects

Toxicities associated with pefloxacin are similar to those reported for other fluoroquinolones. In a review of spontaneous notifications to the manufacturer of potential pefloxacin toxicity from 1985 to 1990, skin and musculoskeletal toxicities were most commonly reported.

Gastrointestinal symptoms such as nausea and indigestion have been reported in about 7% patients in clinical trials – a higher rate than for ciprofloxacin, moxifloxacin, or levofloxacin. C. difficile diarrhea has occurred, as with most antibiotics. Reversible thrombocytopenia and, less frequently, neutropenia have been reported, as have reductions in renal function.