CEFOTAXIME- cefotaxime sodium injection, powder, for solution
Wockhardt USA LLC.
Cefotaxime for injection, USP is a semisynthetic, broad spectrum cephalosporin antibiotic for parenteral administration. It is the sodium salt of 7-[2-(2-amino-4-thiazolyl) glyoxylamido]-3-(hydroxymethyl)-8-oxo-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-carboxylate 72 (Z)-(o-methyloxime), acetate (ester). Cefotaxime for injection, USP contains approximately 50.5 mg (2.2 mEq) of sodium per gram of cefotaxime activity. Solutions of cefotaxime for injection, USP range from very pale yellow to light amber depending on the concentration and the diluent used. The pH of the injectable solutions usually ranges from 5.0 to 7.5. The CAS Registry Number is 64485-93-4.
The molecular formula is C16 H16 N5 NaO7 S2 and the molecular weight is 477.45. Cefotaxime for injection, USP is supplied as a dry powder in conventional vials. Each vial contains cefotaxime sodium equivalent to 500 mg, 1 g or 2 g of cefotaxime.
Following IM administration of a single 500 mg or 1 g dose of cefotaxime for injection to normal volunteers, mean peak serum concentrations of 11.7 and 20.5 mcg/mL respectively were attained within 30 minutes and declined with an elimination half-life of approximately 1 hour. There was a dose-dependent increase in serum levels after the IV administration of 500 mg, 1 g, and 2 g of cefotaxime for injection (38.9, 101.7, and 214.4 mcg/mL respectively) without alteration in the elimination half-life. There is no evidence of accumulation following repetitive IV infusion of 1 g doses every 6 hours for 14 days as there are no alterations of serum or renal clearance. About 60% of the administered dose was recovered from urine during the first 6 hours following the start of the infusion.
Approximately 20 to 36% of an intravenously administered dose of 14 C-cefotaxime is excreted by the kidney as unchanged cefotaxime and 15 to 25% as the desacetyl derivative, the major metabolite. The desacetyl metabolite has been shown to contribute to the bactericidal activity. Two other urinary metabolites (M2 and M3 ) account for about 20 to 25%. They lack bactericidal activity.
A single 50 mg/kg dose of cefotaxime for injection was administered as an intravenous infusion over a 10- to 15-minute period to 29 newborn infants grouped according to birth weight and age. The mean half-life of cefotaxime in infants with lower birth weights (≤1500 grams), regardless of age, was longer (4.6 hours) than the mean half-life (3.4 hours) in infants whose birth weight was greater than 1500 grams. Mean serum clearance was also smaller in the lower birth weight infants. Although the differences in mean half-life values are statistically significant for weight, they are not clinically important. Therefore, dosage should be based solely on age. (See DOSAGE AND ADMINISTRATION section.)
A single intravenous dose and oral dose of probenecid (500 mg each) followed by two oral doses of probenecid 500 mg at approximately hourly intervals administered to three healthy male subjects receiving a continuous infusion of cefotaxime increased the steady-state plasma concentration of cefotaxime by approximately 80%. In another study, administration of oral probenecid 500 mg every 6 hours to six healthy male subjects with cefotaxime 1 gram infused over 5 minutes decreased the total clearance of cefotaxime by approximately 50%.
Additionally, no disulfiram-like reactions were reported in a study conducted in 22 healthy volunteers administered cefotaxime for injection and ethanol.
Cefotaxime sodium is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. Cefotaxime has activity in the presence of some beta-lactamases, both penicillinases and cephalosporinases, of Gram-negative and Gram-positive bacteria.
Mechanism of Resistance
Resistance to cefotaxime is primarily through hydrolysis by beta-lactamase, alteration of penicillin-binding proteins (PBPs), and decreased permeability.
Susceptibility to cefotaxime will vary geographically and may change over time; local susceptibility data should be consulted, if available. Cefotaxime has been shown to be active against most isolates of the following bacteria both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section:
Staphylococcus aureus (methicillin-susceptible isolates only)
Streptococcus pyogenes (Group A beta-hemolytic streptococci)
Streptococcus spp. (Viridans group streptococci)
Escherichia coli b
Klebsiella spp. (including Klebsiella pneumoniae)b
Morganella morganii b
Neisseria gonorrhoeae (including beta-lactamase-positive and negative strains)
Proteus mirabilis b
Proteus vulgaris b
Providencia rettgeri b
Providencia stuartii b
Serratia marcescens b
a Enterococcus species may be intrinsically resistant to cefotaxime.
b Most extended spectrum beta-lactamase (ESBL)-producing and carbapenemase-producing isolates are resistant to cefotaxime.
Bacteroides spp., including some isolates of Bacteroides fragilis
Clostridium spp. (most isolates of Clostridium difficile are resistant)
Fusobacterium spp. (including Fusobacterium nucleatum).
The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following microorganisms exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for cefotaxime. However, the efficacy of cefotaxime in treating clinical infections due to these microorganisms has not been established in adequate and well-controlled clinical trials.
Salmonella spp. (including Salmonella typhi)
Susceptibility Test Methods
For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.
Cefotaxime for injection, USP is indicated for the treatment of patients with serious infections caused by susceptible strains of the designated microorganisms in the diseases listed below.
(1) Lower respiratory tract infections , including pneumonia, caused by Streptococcus pneumoniae (formerly Diplococcus pneumoniae), Streptococcus pyogenes * (Group A streptococci) and other streptococci (excluding enterococci, e.g., Enterococcus faecalis), Staphylococcus aureus (penicillinase and non-penicillinase producing), Escherichia coli , Klebsiella species, Haemophilus influenzae (including ampicillin resistant strains), Haemophilus parainfluenzae , Proteus mirabilis , Serratia marcescens *, Enterobacter species, indole positive Proteus and Pseudomonas species (including P. aeruginosa).
(2) Genitourinary infections. Urinary tract infections caused by Enterococcus species, Staphylococcus epidermidis , Staphylococcus aureus *, (penicillinase and non-penicillinase producing), Citrobacter species, Enterobacter species, Escherichia coli , Klebsiella species, Proteus mirabilis , Proteus vulgaris *, Providencia stuartii , Morganella morganii *, Providencia rettgeri *, Serratia marcescens and Pseudomonas species (including P. aeruginosa). Also, uncomplicated gonorrhea (cervical/urethral and rectal) caused by Neisseria gonorrhoeae , including penicillinase producing strains.
(3) Gynecologic infections , including pelvic inflammatory disease, endometritis and pelvic cellulitis caused by Staphylococcus epidermidis , Streptococcus species, Enterococcus species, Enterobacter species*, Klebsiella species*, Escherichia coli , Proteus mirabilis , Bacteroides species (including Bacteroides fragilis *), Clostridium species, and anaerobic cocci (including Peptostreptococcus species and Peptococcus species) and Fusobacterium species (including F. nucleatum *). Cefotaxime for injection, USP, like other cephalosporins, has no activity against Chlamydia trachomatis. Therefore, when cephalosporins are used in the treatment of patients with pelvic inflammatory disease and C. trachomatis is one of the suspected pathogens, appropriate anti-chlamydial coverage should be added.
(4) Bacteremia/Septicemia caused by Escherichia coli , Klebsiella species, and Serratia marcescens , Staphylococcus aureus and Streptococcus species (including S. pneumonia).
(5) Skin and skin structure infections caused by Staphylococcus aureus (penicillinase and non-penicillinase producing), Staphylococcus epidermidis , Streptococcus pyogenes (Group A streptococci) and other streptococci, Enterococcus species, Acinetobacter species*, Escherichia coli , Citrobacter species (including C. freundii *), Enterobacter species, Klebsiella species, Proteus mirabilis , Proteus vulgaris *, Morganella morganii , Providencia rettgeri *, Pseudomonas species, Serratia marcescens , Bacteroides species, and anaerobic cocci (including Peptostreptococcus * species and Peptococcus species).
(6) Intra-abdominal infections including peritonitis caused by Streptococcus species*, Escherichia coli , Klebsiella species, Bacteroides species, and anaerobic cocci (including Peptostreptococcus * species and Peptococcus * species) Proteus mirabilis *, and Clostridium species*.
(7) Bone and/or joint infections caused by Staphylococcus aureus (penicillinase and non-penicillinase producing strains), Streptococcus species (including S. pyogenes *), Pseudomonas species (including P. aeruginosa *), and Proteus mirabilis *.
(8) Central nervous system infections , e.g., meningitis and ventriculitis, caused by Neisseria meningitidis , Haemophilus influenzae , Streptococcus pneumoniae , Klebsiella pneumoniae * and Escherichia coli *.
(*) Efficacy for this organism, in this organ system, has been studied in fewer than 10 infections.
Although many strains of enterococci (e.g., S. faecalis) and Pseudomonas species are resistant to cefotaxime sodium in vitro , cefotaxime for injection, USP has been used successfully in treating patients with infections caused by susceptible organisms.
Specimens for bacteriologic culture should be obtained prior to therapy in order to isolate and identify causative organisms and to determine their susceptibilities to cefotaxime for injection, USP. Therapy may be instituted before results of susceptibility studies are known; however, once these results become available, the antibiotic treatment should be adjusted accordingly.
In certain cases of confirmed or suspected gram-positive or gram-negative sepsis or in patients with other serious infections in which the causative organism has not been identified, cefotaxime for injection, USP may be used concomitantly with an aminoglycoside. The dosage recommended in the labeling of both antibiotics may be given and depends on the severity of the infection and the patient’s condition. Renal function should be carefully monitored, especially if higher dosages of the aminoglycosides are to be administered or if therapy is prolonged, because of the potential nephrotoxicity and ototoxicity of aminoglycoside antibiotics. It is possible that nephrotoxicity may be potentiated if cefotaxime for injection, USP is used concomitantly with an aminoglycoside.
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