Properties
What is it?
ZETROXONE-SL 1500 INJECTION (Ceftriaxone and Sulbactam for Injection) Composition: One vial contains: Ceftriaxone Sodium BP equivalent to 1000 mg Ceftriaxone. Sulbactam Sodium BP equivalent to 500 mg Sulbactam. Pharmacodynamics: Mechanism of Action Ceftriaxone inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs). This interferes with the biosynthesis of the cell wall (peptidoglycan), leading to lysis and death of bacterial cells. Sulbactam is a sulfonated derivative of penicillanic acid with beta-lactamase inhibitory properties. Sulbactam binds to certain penicillin-binding proteins (PBPs) and increases the susceptibility of microbial strains to antibiotics. Due to its binding to penicillin-binding proteins, sulbactam has potent and clinically significant intrinsic antimicrobial activity against certain organisms, particularly Acinetobacter and Bacteroides species, as well as Gonococcus and Diplococcus intracellularis. Pharmacokinetics: Ceftriaxone is completely absorbed, with peak plasma concentrations reached 2-3 hours after intramuscular injection, amounting to 40 mcg/mL and 80 mcg/mL after administration of 500 mg and 1 g of ceftriaxone, respectively. Due to its high degree of plasma protein binding (80-85%), its pharmacokinetics are dose-dependent and nonlinear. The AUC is similar after intramuscular or intravenous administration of equivalent doses of ceftriaxone. It is widely distributed into tissues and body fluids, penetrates well into both inflamed and non-inflamed meninges, and reaches therapeutic concentrations in cerebrospinal fluid. Regardless of the dose, the half-life of ceftriaxone is 6 to 9 hours. In neonates, the half-life may be prolonged. Although moderate renal impairment may not affect the half-life of ceftriaxone, it is prolonged in severe renal impairment and further increased if accompanied by hepatic impairment. After administration of 1-2 g of ceftriaxone, its concentrations in the lungs, heart, biliary tract/liver, tonsils, middle ear and nasal mucosa, bones; cerebrospinal fluid, pleural, prostatic and synovial fluids exceed the minimum inhibitory concentrations for most pathogens responsible for infection even after 24 hours. It is excreted in urine by glomerular filtration at 50-60%. Intestinal flora has been shown to convert ceftriaxone into inactive metabolites. It is excreted in bile at 40-50%. In renal impairment, the primary route of excretion is via bile. In neonates and children: The elimination half-life in neonates is increased and decreases with increasing postnatal age. In infants up to 8 days old and elderly patients over 75 years of age, the mean half-life is usually 2-3 times longer than in adults. In patients with renal impairment, non-renal elimination is compensated. The half-life of sulbactam in healthy volunteers is approximately 1 hour. Serum concentrations achieved are proportional to the administered dose. It is excreted mainly unchanged by the kidneys. Indications: ZETROXONE-SL 1500 INJECTION is used for the treatment of the following infections: - Bacterial meningitis - Community-acquired pneumonia - Hospital-acquired pneumonia - Respiratory tract infections - Complicated urinary tract infections - Complicated skin and soft tissue infections - Preoperative prophylaxis of surgical site infections - A single preoperative dose can reduce the incidence of postoperative infection. Dosage and Administration: The dose depends on the severity of the disease, pathogen sensitivity, localization and type of infection, patient age, liver and kidney function. Ceftriaxone and sulbactam can be administered intravenously or intramuscularly. Adults and children over 12 years of age (≥ 50 kg) In adults with normal renal function, the recommended daily dose is equivalent to 1-2 g of ceftriaxone, administered once daily (or twice daily in equally divided doses, 12 hours apart). The dose depends on the type of infection and severity of the condition. (The total daily dose of ceftriaxone should not exceed 4 g). Neonates, infants, and children up to 12 years of age: The following dosage regimen is recommended for once-daily use: Neonates (up to 14 days): 20-50 mg/kg body weight once daily. The daily dose should not exceed 50 mg/kg body weight. Infants and children (15 days to 12 years): 20-80 mg/kg body weight once daily. Method of Administration: Ceftriaxone and sulbactam can be administered intravenously or intramuscularly. Intramuscular Administration The solution for injection of 1.5 g ceftriaxone and sulbactam should be reconstituted with 5 mL of sterile water for injection. The solution should be administered as a deep intramuscular injection. Intramuscular injections should be given into the thickness of a relatively large muscle, and not more than 1 g at one site. If lidocaine is used as a solvent, the resulting solution should not be administered intravenously. Intravenous Administration For intravenous administration, 1.5 g of injectable ceftriaxone and sulbactam is dissolved in 9.6 mL of sterile water for injection. The injection should be given over 5 minutes directly into a vein or through an intravenous infusion line. Ceftriaxone can be administered by intravenous infusion over at least 30 minutes (preferred route) or by slow intravenous injection over 5 minutes. Intravenous bolus injection should be given over 5 minutes, preferably into larger veins. Intravenous doses of 50 mg/kg or more in neonates and children up to 12 years of age should be administered by infusion. Intravenous doses in neonates should be administered over 60 minutes to reduce the potential risk of bilirubin encephalopathy. Intramuscular administration should be considered when the intravenous route is not possible or less feasible for the patient. Doses greater than 2 g should be administered intravenously. For preoperative prophylaxis of surgical site infections, ceftriaxone should be administered 30-90 minutes before surgery. Contraindications: ZETROXONE-SL 1500 INJECTION is contraindicated in patients with known hypersensitivity to penicillins and cephalosporins. Warnings and Special Precautions: Nonsusceptible microorganisms may lead to the development of superinfections. There is evidence of the development of pseudomembranous colitis with the use of ceftriaxone, making it important to consider this diagnosis in patients who develop diarrhea following the use of ceftriaxone and sulbactam for injection. With doses higher than standard, ceftriaxone precipitation and accumulation of its calcium salts in the gallbladder may occur, which may be mistaken for gallstones. At the same time, symptoms are absent, and shadows disappear upon completion of therapy or shortly after. Caution is advised when using ceftriaxone and sulbactam for injection in neonates with hyperbilirubinemia. To avoid the risk of developing bilirubin encephalopathy, the use of ceftriaxone and sulbactam for injection should generally be avoided in neonates, especially premature infants. Special caution is required when used in patients sensitive to penicillin. In case of serious hypersensitivity reactions, subcutaneous administration of epinephrine and other emergency measures are recommended. Allergic reaction is an indication for discontinuation of the use of ceftriaxone and sulbactam for injection. Ceftriaxone and sulbactam for injection should not be administered to neonates in general, especially those with hyperbilirubinemia and premature infants. Interactions with Other Medicinal Products and Other Forms of Interaction: Calcium-containing solutions, such as Ringer's solution or Hartmann's solution, should not be used to reconstitute ceftriaxone or for further dilution of the reconstituted vial's contents for intravenous administration, as precipitation may occur. Ceftriaxone calcium precipitate may also form if ceftriaxone is administered in the same system as intravenous calcium-containing solutions. Concomitant use of oral anticoagulants may enhance the vitamin K-antagonistic effect and increase the risk of bleeding. Frequent monitoring of the International Normalized Ratio (INR) and dose adjustment of drugs affecting vitamin K are recommended during and after ceftriaxone treatment. Pregnancy and Lactation: Pregnancy Ceftriaxone crosses the placental barrier. Data on the use of ceftriaxone in pregnant women are limited. During pregnancy, and especially in the first trimester, ceftriaxone should be administered only if the expected benefit to the mother outweighs the expected risk to the fetus. Lactation Ceftriaxone is excreted in breast milk in low concentrations, however, effects on breastfed infants are not expected during treatment with therapeutic doses of ceftriaxone. At the same time, the risk of developing diarrhea and fungal infections of the mucous membranes cannot be excluded. The possibility of sensitization should be considered. Sulbactam is excreted in breast milk in small amounts; no side effects have been observed in breastfed infants. Effects on Ability to Drive and Use Machines: Adverse effects (e.g., dizziness) may occur during treatment with ceftriaxone, which may affect the ability to drive and operate machinery. Caution is required when driving or operating machinery. Adverse Effects: When the combination is used, side effects observed during ceftriaxone therapy may occur. Gastrointestinal: Diarrhea, nausea and vomiting (less frequent), stomatitis and glossitis. Hepatic: Increased levels of serum glutamic oxaloacetic transaminase (SGOT) and glutamic pyruvic transaminase (SGPT). Hematological: Eosinophilia, thrombocytopenia, leukopenia, granulocytopenia, hematoma or bleeding. Hemolytic anemia is less frequently reported. Agranulocytosis (< 500/mm³) has been observed occasionally with total cumulative doses exceeding 20 g. Skin Reactions: Exanthema, allergic dermatitis, pruritus, urticaria, edema, erythema multiforme. Other adverse effects such as headache, dizziness, increased serum creatinine, genital tract mycosis, oliguria, fever, and chills have been reported. Anaphylactic shock may develop, requiring emergency measures. Local Reactions: A small number of patients may experience pain, induration, and tenderness. Inflammation of the vein wall may develop with intravenous administration. This can be reduced by slow injection over 2-5 minutes. Overdosage: Nausea, vomiting, and diarrhea may occur in case of overdosage. Ceftriaxone concentration cannot be reduced by hemodialysis or peritoneal dialysis. There is no specific antidote. Treatment is symptomatic. Storage Conditions: Store in a dark, dry place at a temperature not exceeding 25°C. Keep out of reach of children. Shelf Life: 3 years Dispensing Rule: Pharmaceutical Product Group - II, dispensed with prescription form №3 Packaging: 1 vial of 20 ml in a cardboard box.