Cefobactam injection 1 gm and 2 gm
Cefoperazone (as sodium) IM /IV
Sulbactam (as sodium) 1:1
QUALITATIVE AND QUANTATIVE COMPOSITION;
Sulbactam sodium /cefaperazone sodium combination is available as a dry powder for reconstitution in a 1:1 ratio in term of free SBT/CPT. Sulbactam sodium is a derivative of the basic penicillin nucleus. It is an irreversible beta-lactamase inhibiters for Paranteral use only.
Chemically it is sodium penicillinate sulfone. It contains 92mg sodium (94 mEq) per gram. Subactam is an off-white crystalline powder which is highly soluble in water. The molecular weight is 255.22.
Cefaparazone sodium semisynthetic broad-spectrum cephalosporin antibiotic for parenteral use only it contains 34mg sodium (5.1mEq) per gram cefoperazone is a white crystalline powder which is freely soluble in water. The molecular weight is 667 . 65.
Pharmaceutical form
Vials of the 1:1 product contain the equivalent of 500mg+500mg+1000mg+1000mg of sulbactam and cefoperazone, respectively.
Clinical particulars
Therapeutic indications
Mono-therapy
Sulbactam /Cefoperazone are indicated for the treatment of the following infections when caused by susceptible organism;
Respiratory tract infections (upper and lower), urinary peritonitis cholecysitic , cholangits, and other intra-abdominals infections septicemia, meningitis, skin and soft tissue infections bone and joint infections, pelvic inflammatory diseases, endometritis gonorrhea, and other infections of the genital tract.
Combination therapy
Because of the broad spectrum of activity of sulbactam/cefoperazone most infection can be treated adequate with these antibiotic alone. However sulbactam /cefoperazone may be used concomitantly with others antibiotic if such combination is indicated. If aminoglycoside is used (see section 6.2 incompatibilities animoglyside), renal function should be monitored during the course the therapy (posology and method of administration Use in renal dysfunction).
Posology and method of administration use in adults
Daily dosage recommendation for sulbactam/cefoperazone in adults is as follow:
Sulbactam Cefoperazone
Ratio SBT/CPZ (g) Activity (g) Activity (g)
………………………………………………………………………………………………………
1:1 2.0 – 4.0 1.0 – 2.0 1.0 – 2.0
Doses should be administrated every 12 hour in equally divided doses.
In sever or refractory infections the daily dosage of sulbactam/cefoperazone may be in creased up to 8g of the 1:1 ratio (I .e., 4gcefoperazone activity).
Patient receiving the 1:1 ratio may require additional cefoperazone administrated separately. Dose should be administrated every 12 hour in equally divided dose.
The recommended maximum daily dosage of sulbactam is 4g.
Use in hepatic dysfunction
Special warnings and special precautions for use
Use in renal dysfunction
Dosage regimens of sulbactam/cefoperazone should be adjusted in patients with marked decreased in renal function (creatinine clearance of less than 20ml/min) to compensate for the reduced clearance of sulbatam. patients with creatinine clearance between 15 and 30ml/min) should received a maximum of 1g of sulbactam administrated every 12 hours
(Maximum daily dosage of 2g sulbactam), while patients with creatinine clearance of less than 15m/min should receive a maximum of 500mg of sulbactam every 12 hour. (Maximum daily dosage 1m of sulbactam). In sever infections it may be necessary to administrator additional cefoperazone.
Athe pharmacokinetic profile of sulbactam is significantly altered by hemodialysis.
The serum half-life of cefoperazone is reduced slightly during hemodialysis thus
Dosing should be scheduled to follow a dialysis period
Use in elderly
Pharmacokinetic properties
Use in children
Daily dosage recommendation for sulbactam/Cefoperazone in children is follows;
Sulbactam Cefoperazone
Ratio SBT/CPZ(g)
Mg/kg/day Activity Mg/kg/day Activity Mg/kg/day
………………………………………………………………………………………………………
1:1 40 – 80 20 – 40 20 – 40
............................................................................................................................................
Doses should be administrated every 6 hour in equally divided doses.
In serious or refractory infections , these dosages may be increased up to 160mg/kg/day. Doses should be administrated in tow to four equally divided doses (special warning and especial precautions for use in infancy and preclinical safely data use in pediatrics).
Use in neonates
For neonates in the first week of life the drugs should be given every 12 hour. The maximum daily doses of sulbactam in pediatrics should not exceed 80mg /kg/day.
If more than 80mh/kg/day of cefoperazone cactivity are necessary, additional cefoperazone should be administrated separately (especial warning and especial precaution for use infancy).
Intravenous administration
For intermittent infusion each vial of sulbactam /cefoperazone should be reconstitute
The appropriate amount (instructions for use/handing reconstitution)of 5% dextrose in water ,0.9% sodium chloride injection or sterile water for injection and then diluted to 20ml with the same solution followed by administration over to 15 to 60 minutes.
Located ranger solution is a suitable vehicle for intravenous infusion, however not for initial reconstitution (incompatibilities located rangers solution and instruction for use/handing located rangers solution).
For intravenous injection each vial should be reconstitute as above and administrated over minimum of 3 minutes.
Intra muscular administration
Lidocaine HCI2% is a suitable vehicle for intra muscular administration, how ever not for initial reconstitution (incompatibilities lidocain and instructions for use/handing lidocain)
Contraindication
Sulbacam/cefoperazon is contraindication in patients with know allergy to penicillin,sulbactam,cefoperazone, or any of the cephalosporin.
Special warning and special precaution use.
Hypersensitivity
Serious and occasionally fatal hypersensitivity (anaphylactic reaction has been reported in patients receiving beta-lactamase or cephalosporin therapy). These reactions occur, the drugs in individual with the history of hypersensitivity reaction to multiple allergens. If an allergic reaction occur, the drug should be discontinuous and the appropriate therapy institute. Serious anaphylactic reaction required immediate emergency treatment epinephrine. Oxygen, intravenous steroid, and airway management, including incubation, should be administrated as indicated.
Use in hepatic dysfunction
Cefoperazone is extensively excreted in bile. The serum half-life of cefoperazone is usually prolonged and urinary excretion of the drug increased in patients with hepatic disease and/or biliary obstruction. Even with sever hepatic dysfunction, therapeutic concentration of cefoperazone are obtain in bile and only a 2- to -4 fold increased in half-life is seen. Dose modification may be that condition. In patients with hepatic dysfunction and concomitant renal impairment, cefoperazone serum concentrations should be monitoring of serum concentrations.
Use in fancy
Sulbactam/cefoperazone has been actively used in infant. It has been extensively studied in premature. Instituting therapy (preclinical safety data use in in pediatric).
Cefoperazone does not displace bilirubin from plasma protein binding site.
Interaction with others medicaments and others form of interaction.
Pregnancy and lactation
Usage during pregnancy
Reproduction studies have been performed in rats at doses up to 10 times the human dose and have revealed no evidence of impaired fertility and no teratological findings. Sulbactam and cefoperazone cross the placental barrier. There are how ever, no adequate and well-controlled studies in pregnant woman because animal reproduction studies are not always predictive of human response; this drug should be used during pregnancy only if clearly needed.
Usage in nursing mothers
Only small quantities of sulbactam and cefoperazone are excreted in human milk. Although both drugs pass poorly onto breast milk of nursing mothers, caution should be exercised when sulbactam and Cefoperazone is administrated to a nursing mother.
Pharmacological properties
Pharamcodynamic properties
The antibacterial component of sulbactam and Cefoperazone is Cefoperazone a third generation cephapolosorin, which act against sensitive organism during the stage of active multiplication by inhibiting biosynthesis of cell wall mucopeptide. Sulbactam dose not possesses any usual antibacterial activity, except against Neissiareae. And Antibacterial
However biochemical studies with cell-free bacterial system have shown it to be and irreversible inhibitors of most important beta lactmases produced by beta-lactamase antibiotic resistant organism.
The potential for sulbactam’s preventing the destruction of penicillin’s and cephalosporin by resistant organism was confirmed in whole-organism studies using resistant strains in which sulbactam exhibited marks synergy with pencilins and cephalosporin’s.
As sulbactams also bind with some pencilins binding with patients, sensitive strains are also often rendered more susceptible to sulbactam/sefoperazone than to sefoperazone alone.
The combination of sulbactam and sefoperazone is active against all organisms sensitive to sefoperazone. In addition demonstrates synergistic activity (up to fourfold reduction and minimum inhibitory concentrations for the combination versus those for each component)
And a verity of organism, most markedly the following: homophiles influenza, Bactericides species, staphylococcus species, and a cinetobector calcobaceticus, introbacter aerogenenes, Escherichia coli, proteus, mirabilis, klebsiella, pneumonia, morganella morgganii, citrobacter freundii, entrobacter cloacae, citrobacter devises.
Sulbactam/sefoperazone active in vitro against wide variety of clinically significant organisms:
Staphyloccosus aurous Penicillin’s and non-pencilinase producing strains, staphylococcus epidermindis, streptococcus pneumoniae (formally diplococcic pneumonia) streptococcus pyogenes (group a beta-hemolytic streptococci), streptococcus agalactiai (Group B beta-hemolytic streptococci)
Most others strains of beta-hemolytic streptococci
Money strains of streptococcus faecalis (enterococcus)
Gram-negative organism:
Escherichia coli, klebsiella morganii species, enterobacter species, haemophilus influenzae, proteus mirabilis, proteus vulgaris morganella morganii (formerly proteus morganii), providencia retteri (formerly proteus retteri), providencia species, serratia species (including S. marcescens), salmonella and shigella species, pseudomonas aeruginosa and some other pseudomonas species, Acinetobacter calcoaceticus, neiseria gonorrhea, neisseria meningitis, borddetella pertussis, yersinia enterrocolitica.
Anaerobic organisms:
Gram negative bacilli (including bactericides, other bactericide species, and fusobacteium species)
Gram positive and gram-negative cocci (including peptococcus and veilonella species)
Gram positive bacilli (including clostridium and lactobacillus species)
Use in hepatic dysfunction
Special warning and special precaution for use
Use in renal dysfunction
In patient with deferent degree of renal function administrated sulcabtam/sefoperazonw the total body clearance of sulbatam was highly correlated estimated creatinine clearance,
Patients who are functionally anaphric showed a significant logger half-life of sulbatam (mean 6.9 and 9.7 hour in separate studies). Homedailysis significantly altered the half-life today body clearance and volume of distribution of sulbactam. No significant deferent have been observed in the pharmacokinetics of cefaperzone in renal failure patients.
Use in elderly
The pharmacokinetics of selbatam/sefaperzone has been situated in elderly individually with renal insuffiency and compromised hepatic function. Both sulbatam and cefoperazone inxhibited longer half-life lower cleanse and larger volume of distribution when compared to data from normal volunteers the pharmacokinetic of sulbactam correlated well with the degree of renal dysfunction whittle for sefoperazonw there way a good correlation with the degree of hepatic dysfunction.
Use in children
Studies conducted in pediatric have shown no significant change in the pharmacokinetic of the components of sulbactam/sefoperazone compared to adult values.
The mean half-life in children has ranged from from 0.90 to 1.42 hour for sulbactam and from 1.44 to 1.88 hour for cefoperazone
Preclinical safety data
Use in pediatric
Cefoperazone has adverse effect on the tested of prepurats at all dose tested
Subcutaneous administration of 1,000mg kg per day (approximately 16 times the average adult of human dose)
Resulted in reduced testicular weight, arrested spermatogenesis, and reduced germinal cell population and vacoulation of sertoil. Cell cytoplasm
The severity of lesion was dose dependent in the 100 to 1,000/kg/day range; the low dose caused a minor decree in spermatocytes. This effect has not been observed in adult rats.
Histological the lesions were reversible at all but the highest dosage levels. How ever these studies did not evaluate subsequent development of reproductive function in the rats.
The relationship of these finding to human is unknown.
When sulbactam cefoperazone (1:1) was given subcutaneously to neonatal rats for 1 month reduced testicular weights and immature tubules were seen in group given 300+300mg/kg/day. Because there is a great individual variation in t his degree of testicular maturation in rat pups and because immature tests were found in control any relation to study drug is uncertain. No such findings were seen in infant dogs at doses over 10 times the average adult’s dose.
Pharmaceutical particulars
Instruction of use/handing
Reconstitution
Sulbactam/sefoperazone is available in 2.0g strength vials.
……………………………………………………………………………………………………
Total equivalent dosage of volume of maximum final
Dosage (g) sulb + cefoperazone (g) diluent conc. (Mg/ml)
1.0 0.5 +0.5 3.4 125+125
2.0 1.0 +1.0 6.7 125+125
………………………………………………………………………………………………………
Sulbactam/cefoperazone has been shown to be compatible with water injection 5% dextrose in 0.225% saline, 5% dextrose in normal saline at concentration of 10mg cefoperazone and 5mg sulbactam per ml and up to 250mg cefoperazone and 125mg sulbactam per ml
Lactated ringers solution
Sterile water for injection should be used for reconstitution (see section 5.1 incompatibilities lactate ed ringers solution) a toe step dilution is required using sterile water for injection (shown in table above) further diluted with lactated ringers solution) to a sulbactam concentration of 5mm/ml (use 2ml initial dilution in 50 ml or 4ml initial dilution in 100ml located ringers solution.
Lidocaine
Sterile water for injection should be used for reconstitution (see section 5.1 incompatibilities lidicaine) for a concentration of cefoperazone of 250mg/ml or larger a tow step dilution required using sterile water for injection (shown in table above) further dilution with 2% lidocaine to yield solution containing up to 250mg cefoperazone and 125mg sulbactam per ml in approximately a 0.5% lidocaine HCI solution.
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