COMPOSITION :
Cefoperazone sodium – Sulbactam sodium Powder for injection 1 g, each vial contains : Cefoperazone sodium equivalent to Cefoperazone 500 mg and Sulbactam sodium equivalent to Sulbactam 500 mg.
DESCRIPTIONS :
Cefoperazone sodium – Sulbactam sodium with active ingredient Cefoperazone sodium (equivalent to Cefoperazone) and Sulbactam sodium (equivalent to Sulbactam) are available in 1 g of sterile powder for injection in vial pack.
INDICATIONS :
- Monotherapy : For the treatment of the following infections when caused by sensitive organisms : Respiratory tract infections (upper and lower), urinary tract infections (upper and lower), peritonitis, cholecystitis, cholangitis and other intra-abdominal infections, skin and soft tissue infections.
- Combination therapy : Because of the broad spectrum of activity of Cefoperazone sodium – Sulbactam sodium, most infections can be treated adequately with antibiotic alone. However, Cefoperazone sodium – Sulbactam sodium may be used concomitantly with other antibiotics if such combination are indicated. If an Aminoglycoside is used, renal function should be monitored during the course of therapy.
DOSAGE AND ADMINISTRATIONS :
- Adults
Daily dosage recommendation for Cefoperazone sodium – Sulbactam sodium in adults are as follows :
| Ratio | Cefoperazone sodium – Sulbactam sodium (g) | Sulbactam activity (g) | Cefoperazone activity (g) |
| 1 : 1 | 2 – 4 | 1 – 2 | 1 – 2 |
Dose should be administered every 12 hours in equally divided doses. In severe or refractory infections the daily dosage of Cefoperazone sodium – Sulbactam sodium may be increased up to 8 g of the 1 : 1 (i.e., 4 g Cefoperazone activity). Patients receiving the 1 : 1 ratio may require additional Cefoperazone administered separately. Doses should be administered every 12 hours in equally divided doses.
The recommended maximum daily dosage of Sulbactam is 4 g.
- Hepatic dysfunction
See section WARNINGS AND PRECAUTIONS.
- Renal dysfunction
Dosage regimens of Cefoperazone sodium – Sulbactam sodium should be adjusted in patients with marked decrease in renal function (creatinine clearance < 30 ml/minute) to compensate for the reduced clearance of Sulbactam. Patients with creatinine clearance of 15 – 30 ml/minute should received a maximum of 1 g of Sulbactam administered every 12 hours (maximum daily dosage of 2 g Sulbactam), while patients with creatinine clearance < 15 ml/minute should receive a maximum of 500 mg of Sulbactam every 12 hours (maximum daily dosage of 1 g Sulbactam). In severe infections it may be necessary to administer additional Cefoperazone.
The 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.
- Children
| Ratio | Cefoperazone sodium – Sulbactam sodium (mg/kg/day) | Sulbactam activity (mg/kg/day) | Cefoperazone activity (mg/kg/day) |
| 1 : 1 | 40 – 80 | 20 – 40 | 20 – 40 |
Doses should be administered every 6 – 12 hours in equally divided doses. In serious or refractory infections, these dosages may be increased up to 160 mg/kg/day of the 1 : 1 ratio. Doses should be administered in 2 – 4 equally divided doses.
- Neonates
For neonates in the first week of life, Cefoperazone sodium – Sulbactam sodium should be given every 12 hours. The maximum daily dosage of Sulbactam in pediatrics should not exceed 80 mg/kg/day. For doses of Cefoperazone sodium – Sulbactam sodium requiring > 80 mg/kg/day Cefoperazone activity, additional Cefoperazone should be administered separately.
Instruction for use/handling :
Reconstitution Cefoperazone sodium – Sulbactam sodium is available in 1 g strength vial.
| Total dosage (g) | Equivalent dosage of Sulbactam + Cefoperazone (g) | Volume of diluent | Maximum final concentration (mg/ml) |
| 1 | 0.5 + 0.5 | 3.4 | 125 + 125 |
The solvent used for reconstitution is water for injection that has been proven to be compatible with Cefoperazone sodium – Sulbactam sodium at concentrations of 10 mg Cefoperazone and 5 mg Sulbactam per ml and up to 250 mg Cefoperazone and 125 mg Sulbactam per ml.
Intravenous administration :
- Intermittent infusion : 1 vial of Cefoperazone sodium – Sulbactam sodium should be reconstituted with the appropriate amount (see section instruction for use/handling) with sterile water for injection and then diluted to 20 ml with the same solution followed by administration over 15 – 60 minutes.
- Intravenous injection : 1 vial Cefoperazone sodium – Sulbactam sodium should be reconstituted with the appropriate amount (see section instruction for use/handling) with sterile water for injection and then diluted to 20 ml with the same solution followed by administration over a minimum of 3 minutes.
OVERDOSAGE :
Limited information is available on the acute toxicity of Cefoperazone sodium and Sulbactam sodium in humans. Overdosage of the drug would be expected to produce manifestations that are principally extensions of the adverse reactions reported with the drug. The fact that high CSF concentration of β-lactam antibiotics may cause neurologic effects, including seizures, should be considered. Because Cefoperazone and Sulbactam are both removed from the circulation by hemodialysis, these procedures may enhance elimination of the drug from the body if overdosage occurs in patients with impaired renal function.
CONTRAINDICATIONS :
Patients with known allergy to Penicillins, Sulbactam, Cefoperazone or any of the Cephalosporins.
WARNINGS AND PRECAUTIONS :
- Hypersensitivity : Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving β-lactam or Cephalosporins therapy. These reactions are more apt to occur in individuals with a history of hypersensitivity reactions to multiple allergens. 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 as indicated.
- Use in hepatic dysfunction : Cefoperazone is extensively excreted in bile. The serum half-life of Cefoperazone is usually prolonged and urinary prolonged and urinary excretion of the drug increased in patients with hepatic diseases and/or biliary obstruction. Even with severe hepatic dysfunction, therapeutic concentrations of Cefoperazone are obtained in bile and only a 2- to 4-fold increase in half-life seen.
Dose modification 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, Cefoperazone serum concentrations should be monitored and dosage adjusted as necessary. In these cases dosages should not exceed 2 g/day of Cefoperazone.
- General :
- As with other antibiotics, vitamin K deficiency has occurred in a few patients treated with Cefoperazone. The mechanism is most probably related to the suppression of gut flora which normally synthesize this vitamin. Those at risk include patients with poor diet, malabsorption states (e.g. cystic fibrosis) and patients on prolonged intravenous alimentation regimens. Prothrombin time should be monitored in these patients, and patients receiving anticoagulant therapy, and exogenous vitamin K administered as indicated.
- As with other antibiotics, overgrowth of nonsusceptible organisms may occur during prolonged use of Cefoperazone sodium – Sulbactam sodium. Patients should be observed carefully during treatment. As with any potent systemic agent, 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 children.
- Use in children : Cefoperazone sodium – Sulbactam sodium has been effectively used in children. It has not been extensively studied in premature children or neonates. Therefore, in treating premature children and neonates potential benefits and possible risks involved should be considered before instituting therapy.
Cefoperazone does not displace bilirubin from plasma protein binding sites.
- 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 teratogenical findings. Sulbactam and Cefoperazone cross the placental barrier. There are, however, no adequate and well-controlled studies in pregnant women. 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 mother : Only small quantities of Sulbactam and Cefoperazone are excreted in human milk. Although both drugs pass poorly into breast milk of nursing mothers, caution should be exercised when Cefoperazone sodium – Sulbactam sodium is administered to a nursing mother.
- Effects on ability to drive and use machines : Clinical experience with Sulbactam/Cefoperazone indicates that is unlikely to impair a patient’s ability to drive or use machines.
DRUG INTERACTIONS :
- Alcohol : A reaction characterized by flushing, sweating, headache and tachycardia has been reported when alcohol was ingested during and as late as fifth day after Cefoperazone administration. A similar reaction has been reported with certain other Cephalosporins and patients should be cautioned concerning ingestion of alcoholic beverages in conjunction with administration of Cefoperazone sodium – Sulbactam sodium. For patients requiring artificial feeding orally or parenterally, solutions containing ethanol should be avoided.
- Drug laboratory test interactions : A false positive reaction for glucose in the urine may occur with Benedict’s or Fehling’s solution.
- Incompatibilities :
- Aminoglycosides : Solutions of Cefoperazone sodium – Sulbactam sodium and Aminoglycosides should not be directly mixed, since there is a physical incompatibility between them. If combination therapy with Cefoperazone sodium – Sulbactam sodium and an Aminoglycoside is contemplated (see section INDICATIONS) this can be accomplished by sequential intermittent intravenous infusion provided that separate secondary intravenous tubing is used and that the primary intravenous tubing is adequately irrigated with an approved diluent between doses. It is also suggested that doses of Cefoperazone sodium – Sulbactam sodium be administered throughout the day at times as far removed from administration of the Aminoglycosides as possible.
- Lactated Ringer’s solution : Initial reconstitution with Lactated Ringer’s solution should be avoided since these mixtures have been shown to be incompatible. However, a two step dilution process involving initial reconstitution in water for injection will result in a compatible mixture when further diluted with Lactated Ringer’s solution.
- Lidocaine : Initial reconstitution with 2% Lidocaine HCl solution should be avoided since these mixtures have been shown to be incompatible. However, a two step dilution process involving initial reconstitution in water for injection will result in a compatible mixture when further diluted with 2% Lidocaine HCl solution.
- As most beta-lactams, Aminoglycosides combination with Cefoperazone sodium is not recommended because it will cause both drugs potentially become inactive. Also reports of incompatibilities with other drugs including Diltiazem, Pentamidine, Perfenazin, Pethidine and Promethazine.
ADVERSE REACTIONS :
- Gastrointestinal : Diarrhea most frequently followed by nausea and vomiting.
- Dermatologic reactions : Maculopapular rash, urticaria, eosinophilia and drug fever.
- Hematology : Neutrophils, reversible neutropenia, positive direct Coombs, decreased hemoglobin or hematocrit, transient eosinophilia, thrombocytopenia, hypoprothrombinemia, hemolytic anemia.
- Miscellaneous : Headache, fever, injection pain, chills.
- Laboratory abnormalities : Transient elevations of SGOT, SGPT, alkaline phosphate and bilirubin levels.
- Local reactions : As with other Cephalosporins and Penicillins, when Cefoperazone sodium – Sulbactam sodium is administered by an intravenous catheter some patients may develop phlebitis at the infusion site.
- Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving β-lactam or Cephalosporins therapy. These reactions are more apt to occur in individuals with a history of hypersensitivity reactions to multiple allergens. If an allergic reaction occur, 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 as indicated.
- A reaction characterized by flushing, sweating, headache and tachycardia has been reported when alcohol was ingested during and as late as the fifth day after Cefoperazone administration. A similar reaction has been reported with certain other Cephalosporins and patients should be cautioned as to the possible adverse events following ingestion of alcoholic beverages in conjunction with administration of Cefoperazone sodium – Sulbactam sodium. For patients requiring artificial feeding orally or parenterally, solutions containing ethanol should be avoided.
PRESENTATION :
Cefoperazone sodium – Sulbactam sodium Powder for Injection 1 g Box, 1 vial @ 1 g
Reg. No. GKL0802340444A1
STORAGE :
STORE BELOW 30ºC, PROTECT FROM LIGHT
The reconstituted solution is stable for 7 days at temperature 2 – 8°C and for 24 hours at below 25°C.
ON MEDICAL PRESCRIPTION ONLY
Manufactured by :
BERNOFARM
Sidoarjo – Indonesia
