Cefoperazone and sulbactam.
Each vial contains: Sterile blend of Cefoperazone Sodium USP equivalent to anhydrous Cefoperazone 500 mg and Sulbactam sodium USP equivalent to anhydrous Sulbactam 500 mg.
Pharmacology: Pharmacodynamics: Mechanism of action: Cefoperazone is a semi synthetic, broad-spectrum, third generation cephalosporin antibiotic. It acts by inhibiting biosynthesis of bacterial cell wall mucopeptide. Sulbactam acts as a beta-lactamase inhibitor, thus restoring Cefoperazone activity against beta-lactamase producing bacterial strains.
Pharmacokinetics: The mean serum concentration obtained at 30 min after 1 g I.V. Cefoperazone is 114 mcg/ml. The mean serum concentration obtained at 15 min after administration of 500 mg and 1000 mg IV Sulbactam are 21-40 mcg/ml and 48-88 mcg/ml respectively. The average peak plasma concentration at 5 minutes after administration of intravenous dose of 1 g is 81 mg/litre. The protein binding of Cefoperazone is 82-93% and that of Sulbactam is 38%. No significant quantity of metabolites of Cefoperazone has been found in the urine. The mean serum half-life of Cefoperazone and Sulbactam are about two hours and one hour respectively. Cefoperazone is excreted mainly in the bile. About 75-85% of Sulbactam is excreted in the urine during the first eight hours of administration. No significant changes are observed in patients with renal insufficiency compared to other patients. In patients with hepatic dysfunction, the serum half-life is prolonged and urinary excretion is increased. In patients with combined renal and hepatic insufficiency, Cefoperazone may accumulate in the serum.
The half-life of Cefoperazone in low birth weight neonates is 6-10 hours.
Microbiology: Spectrum of Antibacterial Activity: Cefoperazone is active in vitro against many Gram-negative bacteria including Pseudomonas aeruginosa, and Enterobacteriaceae (Escherichia coli, Klebsiella spp., Enterobacter spp., Citrobacter, Proteus, Morganella, Providencia, Salmonella, Shigella, and Serratia spp.). Other susceptible Gram-negative bacteria include Haemophilus influenzae, Moraxella catarrhalis, and Neisseria spp. It is slightly less active than other third-generation cephalosporins against some members of Enterobacteriaceae. It has good activity against Pseudomonas aeruginosa, but is less active than Ceftazidime. Cefoperazone is more susceptible than Cefotaxime to hydrolysis by certain beta-lactamases.
Sulbactam is a penicillanic acid sulfone with beta-lactamase inhibitory properties. It is active against Neisseriaceae and Acinetobacter baumanii, but generally has only weak antibacterial activity against other organisms. It is an irreversible inhibitor of most of the important β-lactamases and has a similar spectrum of beta-lactamase inhibition to clavulanic acid, although it is regarded as less potent. Sulbactam can therefore enhance the activity of penicillins and cephalosporins against many resistant strains of bacteria.
The combination of Cefoperazone sodium and Sulbactam sodium is indicated for the treatment of the following infections caused by susceptible organisms.
Upper and lower respiratory tract infections, urinary tract infections, peritonitis, cholecystitis, cholangitis and other intra-abdominal infections, bacterial sinusitis, meningitis, skin and soft tissue infections, bone and joint infections, pelvic inflammatory disease, endometritis, gonorrhea and other infections of the genital tract.
Adults: The usual adult dose of the combination is 2 to 4 g/day (i.e, 1-2 g/day each of Cefoperazone and Sulbactam) given IV or IM in equally divided doses every 12 hours.
In severe or refractory infections, the daily dosage may be increased to 8 g (i.e, 4 g/day each of Cefoperazone and Sulbactam) given IV in equally divided doses every 12 hours. The recommended maximum daily dosage of Sulbactam is 4 g (8 g of the combination).
Dosage regimens should be adjusted in patients with marked decrease in renal function.
Children: The usual dosage in children is 40-80mg/kg/day (20 to 40 mg/kg/day each of Cefoperazone and Sulbactam) every six to twelve hours. In serious or refractory infections, these dosages may be increased up to 160 mg/kg/day of the combination (i.e., 80 mg/kg/day each of Cefoperazone and Sulbactam) every six to twelve hours.
CERAZONE PLUS-500 is contraindicated in persons with allergy to Penicillins or Cephalosporins. As such, careful review of medical history of the patient before starting therapy is of prime importance.
CERAZONE PLUS-500 should be administered cautiously to penicillin sensitive patients due to the possibility of developing hypersensitivity reactions. Pseudomembranous colitis has been reported with the use of Cephalosporins and other broad spectrum antibiotics. This is because treatment with broad-spectrum antibiotics alters the normal flora of the colon and may permit overgrowth of Clostridia. Studies indicate that a toxin produced by Clostridium difficile is the primary cause of antibiotic-associated colitis or diarrhea. Mild cases of colitis may respond to drug discontinuance alone. Moderate to severe cases should be managed with fluid, electrolyte, and protein supplementation as indicated.
Disulfiram-like reaction has been reported in a few instances when alcohol was ingested within 72 hours of Cefoperazone administration. Patients should be advised not to take alcohol with Cefoperazone.
Hypersensitivity and related effects are found to occur very commonly.
reversible neutropenia, transient eosinophilia.
diarrhea, symptoms of pseudomembranous colitis.
transient elevations in BUN and serum creatinine concentrations.
rash, skin reactions, fever, transient pain, phlebitis.
With aminoglycosides: Concomitant administration may increase risk of nephrotoxicity.
With heparin/warfarin: Concurrent use may cause marked hypoprothrombinemia and/or prolonged bleeding time.
DIRECTIONS FOR USE: Intravenous Administration: For intermittent infusion, each vial should be reconstituted with the appropriate amount of Sterile Water for Injection and then diluted to 20 ml with the same solution followed by administration over 15 to 60 minutes.
For IV injection, each vial should be reconstituted with appropriate amount of Sterile Water for injection and administered over a minimum period of three minutes.
Intramuscular Administration: Sterile Water for Injection should be used for reconstitution. For a concentration of Cefoperazone of 250 mg/ml or larger, a two step dilution is required using Sterile Water for Injection followed by 2% Lidocaine.
Store at temperature below 30°C. Protect from light.
Reconstituted solution should be used immediately after preparation.
J01DD62 - cefoperazone and beta-lactamase inhibitor ; Belongs to the class of third-generation cephalosporins. Used in the systemic treatment of infections.
Inj (vial) 1 g (sterile, off white to yellow coloured free flowing powder, distributed in sealed containers and which, when shaken with the prescribed volume of sterile liquid, rapidly form clear and practically-free solution) x 1's.