EDOXIM

Cefpodoxime proxetil is an oral prodrug for the extended-spectrum, semi-synthetic cephalosporin antibiotic cefpodoxime. The spectrum of cefpodoxime is similar to third-generation cephalosporins and has mainly gram-negative coverage, but also covers some gram-positive organisms. The drug is highly stable in the presence of beta-lactamase enzymes, as a result, many organisms resistant to penicillins and some cephalosporins (due to beta-lactamases) may be susceptible to cefpodoxime. Cefpodoxime is indicated for the treatment of upper and lower respiratory tract infections, urinary tract infections, sexually transmitted diseases, and skin and skin structure infections. Cefpodoxime has a long half-life, allowing twice-daily administration.

Cefpodoxime proxetil is administered orally either as tablets or as a suspension. Following oral administration, approximately 50% of the administered dose of cefpodoxime proxetil is absorbed systemically. Over the recommended dosing range (100 to 400 mg) for the tablets, the rate and extent of cefpodoxime absorption exhibited dose-dependency; dose-normalized Cmax and AUC decreased by up to 32% with increasing dose. Peak plasma concentrations after single doses of 100, 200, or 400 mg cefpodoxime Tablets were 1.4 mcg/ml, 2.2 mcg/ml, and 3.8 mcg/ml, respectively. The Tmax was approximately 2 to 3 hours. Average Cmax, Tmax, and AUC for the oral suspension were similar to those in patients receiving equivalent doses of the tablets. In the systemic circulation, cefpodoxime proxetil is de-esterified to its active metabolite, cefpodoxime. Protein binding of cefpodoxime ranges from 22 to 33% in serum and from 21 to 29% in plasma. Adequate concentrations of the active drug are achieved in lung tissue, skin blister fluid, and tonsil tissue. Food administered concomitantly with film-coated tablets increases the extent of absorption (mean AUC) and the mean peak plasma concentration. Following a 200 mg tablet dose taken with food, the AUC was 21 to 33% higher than under fasting conditions. Time to peak concentration was not significantly different between fed and fasted subjects. When a 200 mg dose of the suspension was taken with food, the extent of absorption (mean AUC) and mean peak plasma concentration in fed subjects were not significantly different from fasted subjects, but the rate of absorption was slower with food (48% increase in Tmax). There is minimal metabolism of cefpodoxime in vivo. Over the recommended dose range (100 to 400 mg), approximately 29 to 33% of the administered dose was excreted unchanged in the urine in 12 hours. The elimination half-life is approximately 3 hours.

Cefpodoxime, like other beta-lactam antibiotics (e.g., penicillins), is mainly bactericidal. It inhibits the third and final stage of bacterial cell wall synthesis by preferentially binding to specific penicillin-binding proteins (PBPs) that are located inside the bacterial cell wall. Penicillin-binding proteins are responsible for several steps in the synthesis of the cell wall and are found in quantities of several hundred to several thousand molecules per bacterial cell. Penicillin-binding proteins vary among different bacterial species. Thus, the intrinsic activity of cefpodoxime as well as the other cephalosporins and penicillins against a particular organism depends on its ability to gain access to and bind with the necessary PBP. Like all beta-lactam antibiotics, the ability of cefpodoxime to interfere with PBP-mediated cell wall synthesis ultimately leads to cell lysis. Lysis is mediated by bacterial cell wall autolytic enzymes (i.e., autolysins). The relationship between PBPs and autolysins is unclear, but it is possible that the beta-lactam antibiotic interferes with an autolysin inhibitor. In general, third-generation cephalosporins are more active and have a broader spectrum against gram-negative species than do the earlier generations of cephalosporins. They are less active, however, against the gram-positive species than are their first-generation counterparts. In vitro and clinical data suggest cefpodoxime is effective against infections caused by the following organisms: Escherichia coli, Haemophilus influenzae (beta-lactamase negative), Haemophilus influenzae (beta-lactamase positive), Klebsiella pneumoniae, Moraxella (Branhamella) catarrhalis, Neisseria gonorrhoeae (including penicillinase-producing strains), Proteus mirabilis, Staphylococcus aureus (methicillin-resistant strains are resistant), Streptococcus pneumoniae, and Streptococcus pyogenes. Although no clinical data are available, cefpodoxime has exhibited in vitro activity against other organisms including: Citrobacter diversus, Haemophilus parainfluenzae, Klebsiella oxytoca, Peptostreptococcus magnus, Proteus vulgaris, Providencia rettgeri, Streptococcus agalactiae (group B streptococci), and Streptococcus sp. (Groups, C, F, G). Enterobacter, Enterococcus, and Pseudomonas are resistant to cefpodoxime.

No dosage adjustment is recommended for patients with hepatic insufficiency.

Dosage of cefpodoxime should be modified according to the degree of renal impairment for patients with creatinine clearance of less than 30 ml/minute.

Edoxim is contraindicated in individuals who show hypersensitivity to cefpodoxime proxetil, to cephalosportins or other beta-lactamas.

Cefpodoxime may be administered to pregnant women only if clearly indicated.

Cefpodoxime is excreted in human milk. A decision should be made whether to discontinue nursing or to discontinue the drug.

No dose adjustment is recommended in elderly patients with normal renal function.

Cefpodoxime proxetil is not recommended for infants under five months of age.

Adverse effects reported in clinical trials are mild and transient and include diarrhoea, nausea, vomiting, abdominal pain, colitis and headache. Rarely hypersensitivity reactions, rash, pruritus, dizziness, thrombocytopenia, leucopenia or eosinophilia may occur.