Cefiximee

IT IS THIRD GENERATION ORAL CEPHALOSPORIN, EFFECTIVE AGAINST A WIDE SPECTRUM OF SENSITIVE GRAM POSITIVE, GRAM NEGATIVE & ANAEROBIC BACTERIAL PATHOGENS INCLUDING BETALACTAMASE PRODUCING STRAINS. IT HAS HIGH AFFINITY FOR PENICILLIN-BINDING PROTEINS WITH VARYING SITE OF ACTIVITY. IT ACTS BY INHIBITION OF BACTERIAL CELL-WALL SYNTHESIS. THE ELIMINATION HALF-LIFE IS ABOUT 3 HOURS, WITH LITTLE VARIATION OVER THE USUAL THERAPEUTIE DOSAGE RANGE.

Dose:

ADULT :- 200-400 MG DAILY AS SINGLE OR 2 DIVIDED DOSES FOR 7-14 DAYS. CHILDREN :- 8 MG/KG BODY-WT. DAILY AS A SINGLE OR 2 DIVIDED DOSES. NOT RECOMMENDED FOR CHILDREN BELOW 6 MONTHS.

Monograph

CEFIXIME TRIHYDRATE DESCRIPTION: TAXIM-O (cefixime) is a semisynthetic, cephalosporin antibiotic for oral administration. Chemically, it is (6R,7R)-7-(2-(2-Amino- 4- thiazolyl) glyoxylamido)-8-oxo-3-vinyl-5-thia- 1-azabicyclo(4.2.0)oct-2-ene-2- carboxylic acid, 7(square)-(Z)-(O-(carboxymethyl)oxime)trihydrate. Molecular weight = 507.50 as the trihydrate. ACTIONS/CLINICAL PHARMACOLOGY: TAXIM-O, given orally, is about 40% to 50% absorbed whether administered with or without food; however, time to maximal absorption is increased approximately 0.8 hours when administered with food. A single 200 mg tablet of TAXIM-O produces an average peak serum concentration of approximately 2 mcg/mL (range 1 to 4 mcg/mL); a single 400 mg tablet produces an average peak concentration of approximately 3.7 mcg/mL (range 1.3 to 7.7 mcg/mL). The oral suspension produces average peak concentrations approximately 25%-50% higher than the tablets, when tested in normal Adult volunteers. Two hundred and 400 mg doses of oral suspension produce average peak concentrations of 3 mcg/mL (range 1 to 4.5 mcg/mL) and 4.6 mcg/mL (range 1.9 to 7.7 mcg/mL), respectively, when tested in normal Adult volunteers. The area under the time versus concentration curve is greater by approximately 10%-25% with the oral suspension than with the tablet after doses of 100 to 400 mg, when tested in normal Adult volunteers. This increased absorption should be taken into consideration if the oral suspension is to be substituted for the tablet. Because of the lack of bioequivalence, tablets should not be substituted for oral suspension in the treatment of otitis media. (See DOSAGE AND ADMINISTRATION.) Cross-over studies of tablet versus suspension have not been performed in children. Peak serum concentrations occur between 2 and 6 hours following oral administration of a single 200 mg tablet, a single 400 mg tablet, or 400 mg of suspension of TAXIM-O. Peak serum concentrations occur between 2 and 5 hours following a single administration of 200 mg of suspension. ------------------------------------------------------------------------------ TABLE Serum Levels of Cefixime After Administration of Tablets (mcg/mL) ------------------------------------------------------------------------------ DOSE 1h 2h 4h 6h 8h 12h 24h ------------------------------------------------------------------------------ 100 mg 0.3 0.8 1.0 0.7 0.4 0.2 0.02 200 mg 0.7 1.4 2.0 1.5 1.0 0.4 0.03 400 mg 1.2 2.5 3.5 2.7 1.7 0.6 0.04 ------------------------------------------------------------------------------ Serum Levels of Cefixime After Administration of Oral Suspension (mcg/mL) ------------------------------------------------------------------------------ DOSE 1h 2h 4h 6h 8h 12h 24h ------------------------------------------------------------------------------ 100 mg 0.7 1.1 1.3 0.9 0.6 0.2 0.02 200 mg 1.2 2.1 2.8 2.0 1.3 0.5 0.07 400 mg 1.8 3.3 4.4 3.3 2.2 0.8 0.07 ------------------------------------------------------------------------------ Approximately 50% of the absorbed dose is excreted unchanged in the urine in 24 hours. In animal studies, it was noted that cefixime is also excreted in the bile in excess of 10% of the administered dose. Serum protein binding is concentration independent with a bound fraction of approximately 65%. In a multiple dose study conducted with a research formulation which is less bioavailable than the tablet or suspension, there was little accumulation of drug in serum or urine after dosing for 14 days. The serum half-life of cefixime in healthy subjects is independent of dosage form and averages 3.0-4.0 hours but may range up to 9 hours in some normal volunteers. Average AUCs at steady state in elderly patients are approximately 40% higher than average AUCs in other healthy adults. In subjects with moderate impairment of renal function (20 to 40 mL/min creatinine clearance), the average serum half-life of cefixime is prolonged to 6.4 hours. In severe renal impairment (5 to 20 mL/min creatinine clearance), the half-life increased to an average of 11.5 hours. The drug is not cleared significantly from the blood by hemodialysis or peritoneal dialysis. However, a study indicated that with doses of 400mg, patients undergoing hemodialysis have similar blood profiles as subjects with creatinine clearances of 21-60 mL/min. There is no evidence of metabolism of cefixime In Vivo. Adequate data on CSF levels of cefixime are not available. MICROBIOLOGY: As with other cephalosporins, bactericidal action of TAXIM-O results from inhibition of cell-wall synthesis. TAXIM-O is highly stable in the presence of beta-lactamase enzymes. As a result, many organisms resistant to penicillins and some cephalosporins due to the presence of beta- lactamases, may be susceptible to cefixime. TAXIM-O has been shown to be active against most strains of the following organisms both In Vitro and in clinical infections (see INDICATIONS AND USAGE): Gram-Positive Organisms. Streptococcus Pneumoniae, Streptococcus Pyogenes. Gram-Negative Organisms. Haemophilus Influenzae (beta-lactamase positive and negative strains), Moraxella (Branhamella) Catarrhalis (most of which are beta-lactamase positive), Escherichia Coli, Proteus Mirabilis, Neisseria Gonorrhoeae (including penicillinase- and non-penicillinase- producing strains). TAXIM-O has been shown to be active In Vitro against most strains of the following organisms; however, clinical efficacy has not been established. Gram-Positive Organisms. Streptococcus Agalactiae. Gram-Negative Organisms. Haemophilus Parainfluenzae (beta-lactamase positive and negative strains), Proteus Vulgaris, Klebsiella Pneumoniae, Klebsiella Oxytoca, Pasteurella Multocida, Providencia species, Salmonella species, Shigella species, Citrobacter Amalonaticus, Citrobacter Diversus, Serratia Marcescens. Note: Pseudomonas species, strains of group D streptococci (including enterococci), Listeria Monocytogenes, most strains of staphylococci (including methicillin-resistant strains) and most strains of Enterobacter are resistant to TAXIM-O. In addition, most strains of Bacteroides Fragilis and Clostridia are resistant to TAXIM-O. SUSCEPTIBILITY TESTING SUSCEPTIBILITY TESTS: DIFFUSION TECHNIQUE Quantitative methods that require measurement of zone diameters give an estimate of antibiotic susceptibility. One such procedure (REF. 1-3) has been recommended for use with disks to test susceptibility to cefixime. Interpretation involves correlation of the diameters obtained in the disk test with minimum inhibitory concentration (MIC) for cefixime. Reports from the laboratory giving results of the standard single-disk susceptibility test with a 5-mcg cefixime disk should be interpreted according to the following criteria: ------------------------------------------------------------------------------------------------------------------------ Recommended Susceptibility Ranges: Agar Disk Diffusion ------------------------------------------------------------------------------------------------------------------------ Moderately- Organisms Resistant Susceptible S usceptible ----------------------------------------------------------------------------------------------------------------------- Neisseria Gonorrhoeae(a) -- -- >/= 31 mm All other organisms /= 19 mm ---------------------------------------------------------------------------------------------------------------------- (a) Using GC Agar Base with a defined 1% supplement without cysteine. A report of "Susceptible" indicates that the pathogen is likely to be inhibited by generally achievable blood levels. A report of "Moderately Susceptible" indicates that inhibitory concentrations of the antibiotic may well be achieved if high dosage is used or if the infection is confined to tissues and fluids (eg, urine) in which high antibiotic levels are attained. A report of "Resistant" indicates that achievable concentrations of the antibiotic are unlikely to be inhibitory and other therapy should be selected. Standardized procedures require the use of laboratory control organisms. The 5- mcg disk should give the following zone diameter: ORGANISM ZONE DIAMETER (MM) E. Coli ATCC 25922 23-27 N. Gonorrhoeae ATCC 49226(a) 37-45 ---------- (a) Using GC Agar Base with a defined 1% supplement without cysteine. ---------- The class disk for cephalosporin susceptibility testing (the cephalothin disk) is not appropriate because of spectrum differences with cefixime. The 5-mcg cefixime disk should be used for all In Vitro testing of isolates. Dilution Techniques: Broth or agar dilution methods can be used to determine the minimum inhibitory concentration (MIC) value for susceptibility of bacterial isolates to cefixime. The recommended susceptibility break points are as follows: MIC Interpretive Standards (mcgm/mL) -------------------------------------------------------------------------------------------------------------------- Moderately Organisms Resistant Susceptible Susceptible -------------------------------------------------------------------------------------------------------------------- Neisseria Gonorrhea(a) --- --- /=4 2