Cefper

Cefoperazone, sulbactam.

In vial contains the equivalent of 500 mg Cefoperazone and Sulbactam 500 mg.
The product is available as a dry powder for reconstitution.

PHARMACODYNAMICS: Cefoperazone, a third generation cephalosporin, which acts against sensitive organisms during the active multiplication by inhibiting biosynthesis of cell wall mucopeptide. Sulbactam does not possess any useful antibacterial activity, except against Neisseriaceae and Acinetobacter. However, biochemical studies have shown its action as an irreversible inhibitor of most important beta-lactamases produced by beta-lactam antibiotic-resistant organisms. The combination of Cefoperazone and Sulbactam demonstrates, synergistic activity in a variety of organisms most markedly the following: Haemophilus influenzae, Bacteroides species, Staphylococcus species, Acinetobacter calcoaceticus, Enterobacter aerogenes, E. coli, Proteus mirabilis, Klebsiella pneumoniae, Morganella morganii, Citrobacter freundii, Enterobacter cloacae, Citrobacter diversus.
Sulbactam/Cefoperazone is active in vitro against a wide variety of clinically significant organisms: Gram-Positive Organisms: Staphylococcus aureus, penicillinase and non-penicillinase-producing strains. Streptococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyrogenes, Streptococcus agalactiae and most other strains of Beta-hemolytic streptococci.
Gram-Negative Organisms: E. coli, Klebsiella species, Enterobacter species, Citrobacter species, Haemophilus influenzae, Proteus mirabilis, Proteus vulgaris, Marganella morganii, Providencia rettgeri (formerly Proteus morganii), Providencia species, Serratia species (including S. marcescens), Salmonella and Shigella species, Pseudomonas aeroginosa and some other Pseudomonas species, Acinetobacter calcoaceticus, Neisseria gonorrhoeae and Neisseria meningitidis.
Anaerobic Organisms: Gram-negative bacilli (including Bacteroides fragilis, other Bacteroides species and Fusobacterium species).
Gram-positive and Gram-negative cocci (including Peptococcus and Peptostrepto coccus).
Gram-positive bacilli (including Clostridium and Eubacterium).
PHARMACOKINETICS: Approximately 84% of the Sulbactam dose and 25% of the Cefoperazone dose administered with Sulbactam/Cefoperazone is excreted by the kidney. Most of the remaining dose of Cefoperazone is excreted in the bile. After Sulbactam/Cefoperazone administration the mean half-life for Sulbactam is about 1 hour while that for Cefoperazone is 1.7 hours. Sulbactam and Cefoperazone exhibited longer half-life in elderly individuals with renal insufficiency and compromised hepatic function.
Both Sulbactam and Cefoperazone distribute well into a variety of tissues and fluids including bile, gall bladder, skin, ovary, uterus, and others.

CEFPER is indicated for treatment of following infection: Upper and lower respiratory tract infections; Upper and lower urinary tract infections; Peritonitis; Cholecystitis; Cholangitis; Septicemia; Skin and soft tissue infections; Bone and joint infections; Pelvic infection disease, endometritis, gonorrhea, and other genital infections.

Use in adults: Each vial contains Cefoperazone 500 mg and Sulbactam 500 mg. Daily dosage recommendation in adults is 2 - 4 g (1 - 2 g Cefoperazone activity) by intravenous administration/intramuscular administration.
Dose should be administered every 12 hours in equally divided doses. In severe or refractory infection the daily dosage of Sulbactam/Cefoperazone may be increased up to 8 g (4 g Cefoperazone activity).
Doses should be administered every 12 hours in equally divided doses.
Use in children: Daily dosage recommendation is 40 - 80 mg/kg/day (20 - 40 mg/kg/day Cefoperazone activity) by intravenous administration/intramuscular administration every 6 to 12 hours in equally divided doses. In severe or refractory infections the daily dosage of Sulbactam/Cefoperazone may be increased up to 160 mg/kg/day (80 mg/kg/day Cefoperazone activity). Doses should be administered in two to four equally divided doses.
Intravenous administration: For intermittent infusion. Each vial of Sulbactam/Cefoperazone should be reconstituted with sterile water for injection to obtain 4 ml of solution and then diluted to 20 ml with the same solution followed by administration over 15 to 60 minutes. The reconstituted solution should be kept in room temperature (23 - 29°C ) not more than 24 hours or 2 - 8°C not more than 5 days.
Intramuscular administration: Lidocaine HCl 2% is a suitable vehicle for intramuscular administration, however, not for initial reconstitution.

CEFPER is contraindicated in patients with known allergy to Penicillin, Cephalosporin, Cefoperazone or Sulbactam.

Based on the ministry of public health announcement: 1. Do not use in hypersensitive patients.
2. This drug may cause allergic reaction and could be fatal. Penicillin-sensitive patients may be allergic to this drug.
3. If skin rash, irritation or edema occurs, the drug should be discontinued and consult the doctor.
Hypersensitivity: If an allergic reaction occurs, the drug should be discontinued and the appropriate therapy instituted. Serious anaphylactic reactions require immediate emergency treatment with epinephrine, oxygen, intravenous steroids and airway management including intubation should be administered.

General: Vitamin K deficiency has occurred in a few patients treated with Cefoperazone. Those at risk include patients with poor diet, malabsorption states (e.g. cystic fibrosis), patients on prolonged intravenous alimentation regimens and patients receiving anticoagulant. The prothrombin time should be monitored and exogenous vitamin K should be administered. Prolonged using may cause overgrowth of non-susceptible organisms. It is advisable to check periodically for organ system dysfunction during extended therapy; this includes renal, hepatic, and hematopoietic systems. This is particularly important in neonates, especially when premature, and other infants.
Use in hepatic dysfunction: Cefoperazone is extensively excreted in bile. Dosage adjustment may be necessary in cases of severe biliary obstruction, severe hepatic disease or in cases of renal dysfunction coexistent with either of those conditions. In patients with hepatic dysfunction and concomitant renal impairment, dosage should not exceed 2 g of Cefoperazone activity/day, Cefoperazone serum concentrations should be monitored and dosage adjustment as necessary.
Use in renal dysfunction: Patients with creatinine clearances between 15 - 30 ml/min the maximum dose of Sulbactam should not exceed 1 g every 12 hours, while patients with creatinine clearances less than 15 ml/min the maximum dose of Sulbactam should not exceed 500 mg every 12 hours.
In severe case, the additional dose of Cefoperazone alone may be given. Patients with hemodialysis, half-life of serum Cefoperazone is reduced slightly during hemodialysis. Thus, dosing should be scheduled after dialysis period.
Use in pregnancy: No adequate and well-controlled studies in pregnant women. This drugs should be used during pregnancy only if clearly needed.
Use in lactation: Only small quantities of CEFPER are excreted in human milk. Caution should be exercised when the drug was administered in nursing mother.
Use in children: It has not been extensively studied in premature infants or neonates. Therefore, the potential benefit and possible risk must be considered before starting this medication. Cefoperazone does not replace bilirubin from plasma protein binding sites.

General: Anaphylactoid Reaction, Shock.
Gastrointestinal: Nausea and Vomiting, Loose Stools, Pseudomembranous Colitis.
Dermatologic reactions: Maculopapular Rash, Urticaria.
Cardiovascular: Hypotension, Vasculitis.
Hematopoietic: Slight Decrease in Neutrophils, Reversible Neutropenia, Positive Direct Coombs Test, Decreased Hemoglobin or Hematocrit, Transient Eosinophilia and Thrombocytopenia Hypo-Prothrombinemia, Leucopenia.
Skin/appendages: Pruritus, Stevens-Johnson Syndrome.
Urinary: Hematuria.
Miscellaneous: Headache, Fever, Pain at injection site and Chills.
Laboratory abnormalities: Transient Elevations of SGOT, SGPT, Alkaline Phosphatase and Bilirubin.
Local reactions: Transient Pain, Phlebitis.

Alcohol: Patients should be cautioned concerning ingestion of alcoholic beverages in conjunction with administration of CEFPER. For patients requiring artificial oral feeding or parenterally, solutions containing ethanol should be avoided.
Drug Laboratory Test Interactions: A false-positive reaction for glucose test in urine may occur with benedict's or fehling's solution.

INCOMPATIBILITIES: Aminoglycosides: Solution of CEFPER and aminoglycosides should not be directly mixed, since there is a physical incompatibility between them. The combination therapy can be accomplished by sequential intermittent intravenous infusion provided that separate secondary intravenous tubing is used, and the primary intravenous tubing is adequately irrigated with an appropriate diluent between doses. It is also suggested that each dose of CEFPER should be administered as far as the dose of aminoglycosides infusion as possible.
Lactated Ringer's solution: Lactated Ringer's solution should not be used for initial reconstituted solution. Sterile water for injection should be used for initial reconstitution then further diluted with Lactated Ringer's solution to obtained Sulbactam concentration of 5 mg/ml.
Lidocaine: 2% lidocaine should not be used for initial reconstituted solution since the mixture has been shown to be incompatible. However, initial reconstitution in sterile water for injection and further dilution with 2% lidocaine to obtain solutions of 0.5% lidocaine will result in a compatible mixture.

Store below 25°C.

Cephalosporins

J01DD62 - cefoperazone and beta-lactamase inhibitor ; Belongs to the class of third-generation cephalosporins. Used in the systemic treatment of infections.

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