Sulperazon 1 g vial
Sulperazon 1 g vial
QUALITATIVE AND QUANTITATIVE COMPOSITION
Sulbactam sodium / cefoperazone sodium dry powder for injection, which is available as a mixture of sulbactam and cefoperazone in the ratio 1:1 (SBT / CPZ).
Sulbactam is a penicillin derivative of the main core. It is an irreversible beta-lactamase inhibitor for parenteral administration only. Chemical nature is sodium penicillanate sulfone. Each gram contains 92 mg sodium (4 mEq). Sulbactam is an off-white crystalline powder with high water solubility. The molecular weight is 255.22.
Cefoperazone sodium is a semisynthetic broad-spectrum cephalosporin antibiotic for parenteral administration. Each gram contains 34 mg of sodium (1.5 mEq). Cefoperazone is a white crystalline powder that is readily soluble in water. The molecular weight is 667.65.
3. PHARMACEUTICAL FORM
The vials contained equivalent amounts of sulbactam and cefoperazone 1000 mg + 1000 mg.
4. CLINICAL DATA
Sulbactam / cefoperazone is indicated for the treatment of severe infections requiring parenteral treatment for sensitive combination microorganisms:
- Respiratory tract infections (upper and lower);
- Urinary tract infections (upper and lower);
- Peritonitis, cholecystitis, cholangitis and other intra-abdominal infections;
- Skin infections and infections of the soft tissues;
- Bone and joint infections;
- Pelvic inflammatory disease, endometritis, gonorrhea and other infections of the reproductive system.
Due to the wide spectrum of sulbactam / cefoperazone most infections can be treated adequately with this antibiotic monotherapy. However, sulbactam / cefoperazone may be used concomitantly with other antibiotics if such combinations are shown.
If an aminoglycoside (see section 6.2. Incompatibilities - Aminoglycosides), renal function should be monitored during treatment (see section 4.2. Dosage and Administration - Use in renal failure).
4.2. Dosage and method of administration
Use in adults
The daily dose is administered, divided into two equal portions over 12 hours.
In severe or refractory infections, the daily dose of sulbactam / cefoperazone may be increased to 8 g of a 1:1 ratio (i.e., activity of cefoperazone - 4 g). You may need additional cefoperazone administered separately in some patients receiving the 1:1 ratio. The daily dose should be administered 12 hours, divided into equal parts.
The recommended maximum dose of sulbactam is 4 g.
Use in hepatic impairment
Cf. Section 4.4. Special warnings and precautions for use.
Use in renal failure
In patients with significantly impaired renal function (creatinine clearance <30 ml / min) is necessary to adjust the dosage regimen to compensate for the reduced clearance of sulbactam. In patients with creatinine clearance between 15 and 30 ml / min should be a maximum of 1 g sulbactam in 12 hours (maximum daily dose - 2 g sulbactam), while in patients with creatinine clearance below 15 ml / min should be a maximum of 500 mg sulbactam for 12 hours (maximum daily dose -1 g sulbactam). In severe infections may require additional application of cefoperazone.
The pharmacokinetic profile of sulbactam significantly altered by hemodialysis. The serum half-life of cefoperazone is reduced slightly during hemodialysis. Therefore, the drug should be administered after dialysis.
Use in the elderly
Cf. Section 5.2. Pharmacokinetics.
Use in children
The daily dose should be administered every 6 to 12 hours, divided into equal parts.
In severe or refractory infections these doses may be increased to 160 mg / kg per day from the 1:1 ratio (ie the activity of cefoperazone - 160 mg / kg per day). The daily dose should be npi 2 to 4 equal parts (see Section 4.4. Special warnings and precautions for use - Use in children and Section 5.3. Preclinical Safety - Use in children).
Use in infants
In neonates the first week of life, the drug should be administered 12 hours. The maximum daily dose of sulbactam in children should not exceed 80 mg / kg daily (see section 4.4. Special warnings and precautions for use - Use in infancy).
For intermittent infusion, each vial sulbactam / cefoperazone must be reconstituted with the appropriate quantity (see Section 6.6. Instructions for use - dilution) 5% aqueous solution of glucose, 0.9% sodium chloride for injection or sterile water for injection, and then diluted to 20 ml with the same solution, and then applied for 15 to 60 minutes.
Ringer lactate is a suitable vehicle for intravenous infusion, but not for initial reconstitution (see section 6.2. Incompatibilities - Ringer lactate and Section 6.6. Application Instructions - Ringer lactate).
For intravenous injection, each vial is to be reconstituted, as mentioned above, and can be applied for at least 3 minutes.
Lidocain NS12% is a suitable vehicle for intramuscular use, but not for initial reconstitution (see section 6.2. Incompatibilities - Lidocain and Section 6.6. Application Instructions - Lidocain).
Sulbactam / cefoperazone is contraindicated in patients with known hypersensitivity to penicillins, sulbactam, cefoperazone or other cephalosporin antibiotic.
4.4. Special warnings and precautions for use
Observed serious and often fatal hypersensitivity (anaphylaxis) in patients who are administered therapy with beta-lactam or cephalosporin. The occurrence of these reactions are more likely in patients with a history of sensitivity to multiple allergens. If an allergic reaction occurs, the drug should be discontinued and appropriate therapy instituted.
Serious anaphylactic reactions require immediate emergency administration of epinephrine. If indicated, should be administered oxygen, intravenous corticosteroids and maintain airway, including intubation.
Use in hepatic impairment
Cefoperazone is excreted exclusively via the bile. In patients with liver disease and / or biliary obstruction serum half-life of the drug is usually prolonged and urinary excretion increases. Even with severe hepatic insufficiency cefoperazone achieves therapeutic concentrations in bile and only a 2-4-fold increase in half-life.
Modification of dosage is necessary in cases of severe biliary obstruction, severe liver disease, or in cases of both renal impairment and any of the above.
In patients with liver failure and concomitant renal impairment should be monitored serum cefoperazone and thereafter, if required, the doses can be adjusted. In case you do not provide a close monitoring of the serum concentrations, the dose of cefoperazone should not exceed 2 g daily.
As in treatment with other antibiotics, and in a few patients treated with cefoperazone, failure was observed to vit. The mechanism is probably related to the suppression of the intestinal flora which normally synthesize this vitamin. Patients at highest risk are those with a poor diet, a malabsorption syndrome (e.g., cystic fibrosis) and patients on long-term intravenous feeding. In these patients and in patients on anticoagulant therapy should be monitored for prothrombin time and introduces exogenous vit. K depending on the indication.
As with other antibiotics during prolonged treatment with sulbactam / cefoperazone may result in overgrowth of resistant organisms. Patients should be monitored closely during treatment. It is recommended that, as with all powerful operating system antibiotics, prolonged therapy periodically to monitor organ system dysfunction, which includes renal, hepatic and hematopoietic systems. This is especially important in newborns, especially in premature and infants.
Use in infants
Sulbactam / cefoperazone has been used successfully in infants. Not been extensively studied in premature infants or neonates. Therefore, before initiating therapy in premature and newborn infants should be weighed against the potential benefits / possible risks (see section 5.3. Preclinical safety data - Use in children).
Cefoperazone not displace bilirubin from its binding sites to plasma proteins.
4.5. Drug interactions and other forms of interaction
Ingestion of alcohol during treatment with cefoperazone and the fifth day after the interruption was observed reaction characterized by flushing, sweating, headache, and tachycardia. A similar response was also observed in other cephalosporins and patients should be advised not to drink alcohol during treatment with sulbactam / cefoperazone. For patients requiring oral or parenteral artificial nutrition, is to be avoided solutions containing ethanol.
Interactions with laboratory tests
False positive reaction for glucose in the urine may occur with tests using Benedict's or Fleming.
4.6. Pregnancy and lactation
Use in Pregnancy
Were made reproduction studies in rats at doses up to 10 times higher than human and have revealed no evidence of impaired fertility or teratogenic effects. Sulbactam and cefoperazone cross the placental barrier. However, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human reproduction, this drug may be used during pregnancy only if clearly needed.
Use in nursing
Only small amounts of sulbactam and cefoperazone is excreted in human milk. Although poorly excreted into the milk in lactating women, sulbactam / cefoperazone should be used with caution in them.
4.7. Effects on ability to drive and use machines
Clinical experience indicates that it is unlikely sulbactam / cefoperazone impair the patient's ability to drive or use machines.
4. 8. Undesirable effects
Sulbactam / cefoperazone is generally well tolerated. The majority of adverse reactions were mild to moderate and resolved during treatment. In pooled data from comparative and non-comparative clinical trials involving 2500 patients were observed following side effects:
Gastrointestinal: As with antibiotics, the most common adverse reactions were gastrointestinal. The most frequently observed: diarrhea / loose stools - 3.9%, followed by nausea and vomiting - 0.6%.
Dermatological reactions: As with all penicillins and cephalosporins, hypersensitivity manifested by maculopapular rash and urticaria -0.6% - 0.08%. These reactions often occur in patients with a history of allergies, particularly to penicillin.
Hematology: Slight decreases in neutrophils - 0.4% (5/1131). As with other beta-lactam antibiotics, prolonged use may cause reversible neutropenia - 0.5% (9/1696). In some patients, there was a positive test of the direct Coombs - 5,5% (15/296) during treatment. Considered is a decrease in hemoglobin and -0.9% (13/1416) or the hematocrit - 0.9% (13/1409), which is consistent with the published literature for the cephalosporins. Observed transient eosinophilia -3.5% (40/1130), and thrombocytopenia - 0.8% (11/1414), as well as hypoprothrombinemia - 3.8% (10/262).
• Miscellaneous: Headache - 0.04%, temperature - 0.5%, pain at the injection site - 0.08%, chills - 0.04%.
Laboratory changes: observed transient increases in liver function tests: AST-5.7% (94/1638) ALT - 6.2% (95/1529), alkaline phosphatase-2, 4% (37/1518) and bilirubin levels, 1.2% (12/1040).
Local reactions: Sulbactam / cefoperazone is well tolerated following intramuscular administration. Sometimes such an application may follow transient pain. As with other penicillins and cephalosporins, as sulbactam / cefoperazone is administered by an intravenous catheter, it is possible in some patients (0.1%) to achieve phlebitis at the infusion site.
After leaving the drug on the market, the following additional adverse reactions:
General: anaphylactic reaction (including shock);
Gastrointestinal: pseudomembranous colitis; Hemopoietic: leukopenia;
Skin / Appendages: pruritus syndrome, Stevens-Johnson;
Urinary: hematuria; Vascular: vasculitis.
There is limited information on the acute toxicity of cefoperazone sodium and sulbactam sodium in humans. Overdose are expected to lead to reactions that are more severe adverse reactions reported for medicinal products. You have to pay attention to the fact that high concentrations of beta-lactam antibiotics in the CNS can cause neurological effects, including seizures. Since cefoperazone, and sulbactam are removed from circulation by hemodialysis, these procedures may accelerate the elimination of the drug from the body if an overdose in patients with impaired renal function.
5. Pharmacological Properties
5.1. Pharmacodynamic properties
The antibacterial component of sulbactam / cefoperazone is cefoperazone, a third-generation cephalosporin, which acts on sensitive active multiplication of microorganisms by inhibiting biosynthesis of cell wall mukopeptid. Sulbactam has no useful antibacterial activity except against Neisseriaceae and Acinetobacter. However, biochemical studies with cell-free bacterial systems have proved to be an irreversible inhibitor of beta-lactamases produced by resistant to beta-lactam antibiotics of microorganisms.
Ability of sulbactam to prevent the destruction of penicillins and cephalosporins by resistant organisms was confirmed in studies using whole bacterial cells resistant strains where sulbactam showed marked synergy with penicillins and cephalosporins. Since sulbactam is also associated with some of the penicillin-binding proteins susceptible strains also are often more susceptible to sulbactam / cefoperazone, than just cefoperazone. The combination of sulbactam and cefoperazone is active against all organisms sensitive to cefoperazone. In addition it demonstrates synergistic activity (up to fourfold reduction of the minimum inhibitory concentrations of the combination in comparison with that of each component) in a variety of organisms, it is the most remarkable in:
Sulbactam / cefoperazone is active in-vitro against a variety of clinically relevant microorganisms.
Staphylococcus aureus - penitsilinazoprodutsirashti and penitsilinazoneprodutsirashti strains
Streptococcus pneumoniae (before Diplococcus pneumoniae) Streptococcus pyogenes (group A beta-hemolytic streptococci) Streptococcus agalactiae (group B beta-hemolytic streptococci)
Most strains of beta-hemolytic streptococci Most strains of Streptococcus faecalis (enterococci)
Gram-negative microorganisms: Escherichia coli Klebsiella spp. Enterobacter spp. Citrobacter spp. Haemophilus influenzae Proteus mirabilis Proteus vulgaris Morganella morganii (before Proteus morganii) Providencia rettgeri (before Proteus rettgeri) Providencia spp.
Serratia spp. (including S. marcescens) Salmonella and Shigella spp.
Pseudomonas aeruginosa and other Pseudomonas spp.
Gram-negative bacilli (including Bacteroides fragilis, other Bacteroides spp. And Fusobacterium spp.)
Gram-positive and Gram-negative cocci (including Peptococcus, Peptostreptococcus and Veillonella spp.)
Gram-positive bacilli (including Clostridium, Eubacterium and Lactobacillus species)
For the determination of the IPC can be used serial dilutions of sulbactam / cefoperazone 1:1 by plating on agar or broth. It is recommended that the use of test discs antibakterilna sensitivity containing 30 mcg sulbactam and 75 mcg cefoperazone in the drive. Laboratory results "sensitive" indicates that the causative agent of the infection would be responded to therapy with sulbactam / cefoperazone, and laboratory results "resistant" indicates that the creator would not be affected. Laboratory results "moderately sensitive" implies that the creator would be sensitive to sulbactam / cefoperazone, if using a higher dose of the medicinal product or if the infection is confined to tissues or fluids, which reached high antibiotic concentrations.
Recommended following control strains for quality control of antibacterial sensitivity discs - 30 mcg/75 mcg sulbactam / cefoperazone:
Control strain radius area
Acinetobacter spp. ATCC 43498 26-32
Pseudomonas aeruginosa ATCC 27853 22-28
Escherichia coli ATCC 25922 27-33
Staphylococcus aureus ATCC 25923 23-30
About 84% of the dose of sulbactam and 25% of the dose of cefoperazone, attached as sulbactam / cefoperazone, is excreted by the kidneys. The majority of the remaining dose cefoperazone excreted in the bile. After administration of sulbactam / cefoperazone sulbactam average half-life of about 1 hour, while that of cefoperazone is approximately 1.7 hours. It was found that serum concentrations are proportional to the administered dose. These values are comparable to the previously published values for each one of the substances administered separately.