For the use of a Registered Medical Practitioner or a Hospital or a Laboratory only.

Cefoperazone with Sulbactam for Injection

CEFOZEN FORTE
FOR IM & IV USE ONLY

DESCRIPTION
Cefoperazone is a third generation cephalosporin antimicrobial agent. It has increased activity gainst
Gram negative organisms. Chemically it is {(ethyl-4 dioxo-2,3 piperazine carboxamido)-2 (hydroxy-4
phenyl) -2 acetamido-(r)} -7 {(methyl-1 htetrazoly1-5)thiomethyl} -3 oxo-8thia-5 aza-1 bicyclo
{4.2.0.}octene-2 carboxylatec-Z-(Br, 7cr) of sodium. Sulbactam is a beta lactamase inhibitor.
Sulbactam sodium is a derivative of the basic penicillin nucleus. Chemically it is sodium penicillinate
sulfone and is an off-white crystalline powder highly soluble in water.

COMPOSITION :
Each vial contains:
Cefoperazone Sodium (Sterile) IP
Eq. to Anhydrous Cefoperazone 1.00 gm
Sulbactam Sodium (Sterile) USP
Eq. to Anhydrous Sulbactam 0.50 gm
Sterile water for Injections IP 10 ml
Supplied with 1 pack of 10 ml Sterile Water for Injections IP.

CLINICAL PHARMACOLOGY
Pharmacodynamics
The antibacterial component of CEFOZEN FORTE is cefoperazone, a third generation cephalosporin,
which acts against sensitive organisms during the stage of active multiplication by inhibiting the
biosynthesis of cell wall mucopeptide.

Pharmacokinetics
Approximately 84% of the sulbactam dose and 25% of the cefoperazone dose administered with
CEFOZEN FORTE is excreted by the kidney. Most of the remaining dose of cefoperazone is excreted
in the bile. After CEFOZEN FORTE administration the mean half-life for sulbactam is about one hour
while that for cefoperazone is 1.7 hours. Serum concentrations have been shown to be proportional
to the dose administered. These values are consistent with previously published values forthe agents
when given alone.

Mean peak sulbactam, and cefoperazone concentrations after administration of 2 gms of CEFOZEN
FORTE (1 gm Sulbactam, 1 gm Cefoperazone) intravenously over 5 minutes were 130.2 and 236.8
mcg/ml, respectively. This reflects the larger volume of distribution for sulbactam (Vd=18.0-27.6L)
compared to cefoperazone (Vd =10.2-1 1 .3L).

After multiple dosing no significant changes in the pharmacokinetics of either component of

CEFOZEN FORTE have been reported and no accumulation has been observed when administered
every 8 to 12 hours.

The pharmacokinetics of CEFOZEN FORTE have been studied in elderly individuals with renal
insufficiency and compromised hepatic function. Both sulbactam and cefoperazone exhibited longer
half-life, lower clearance, and larger volume of distribution when compared to data from normal
volunteers. The pharmacokinetics of sulbactam correlated well with the degree of renal dysfunction
while for cefoperazone there was a good correlation with the degree of hepatic dysfunction.