Pharmacological properties
Pharmacodynamics. Zinacef is a bactericidal cephalosporin antibiotic with high activity against a wide range of gram-positive and gram-negative bacteria, including strains that produce β-lactamases. Zinacef is resistant to the action of β-lactamases and therefore, accordingly, is active against many ampicillin- or amoxicillin-resistant strains. The main mechanism of bactericidal action is the disruption of bacterial cell wall synthesis.
Acquired antibiotic resistance varies between regions and can change over time, and for individual strains it can vary significantly. It is advisable to consult local antibiotic susceptibility data, especially when treating severe infections.
The drug has high activity against Staphylococcus aureus (methicillin strains) and coagulase-negative staphylococci (methicillin strains), Haemophilus influenzae, Klebsiella spp., Enterobacter spp., Streptococcus pyogenes, Escherichia coli, Streptococcus mitis (viridians group), Clostridium spp., Proteus mirabilis, Proteus rettgeri , Salmonella typhi, Salmonella typhimurium and other strains of Salmonella, Shigella spp., Neisseria spp. (including strains of N. gonorrhoea that produce beta-lactamases), Bordetella pertussis. The drug shows moderate sensitivity to Proteus vulgaris, Morganella morganii (Proteus morganii) and Bacteroides fragilis.
Microorganisms insensitive to cefuroxime: Clostridium difficile, Pseudomonas spp., Campylobacter spp., Acinetobacter calcoaceticus, Legionella spp., methicillin strains of Staphylococcus aureus and coagulase-negative staphylococci.
Some strains of the following species were also found to be insensitive to Zinacef: Streptococcus faecalis, Morganella morganii, Proteus vulgaris, Enterobacter spp., Citrobacter spp., Serratia spp. and Bacteroides fragilis.
In vitro, Zinacef in combination with aminoglycoside antibiotics has at least an additive effect, sometimes with signs of synergy.
Pharmacokinetics. C max of cefuroxime in blood serum is observed 30-45 min after i / m administration. T ½ of cefuroxime with i / v and i / m administration is approximately 70 min. Simultaneous administration of probenecid slows down the elimination of cefuroxime and causes an increase in its concentration in blood plasma.
Binding to plasma proteins ranges from 33 to 50%.
Within 24 hours from the moment of administration, the drug is almost completely (85-90%) excreted unchanged in the urine, most of the drug in the first 6 hours. Cefuroxime is not metabolized and is excreted by glomerular filtration and tubular secretion.
The level of cefuroxime in blood plasma is reduced by dialysis.
Cefuroxime concentrations exceeding the minimum inhibitory concentration for most common pathogens are achieved in bone tissue, synovial and intraocular fluids. Cefuroxime penetrates the blood-brain barrier in inflammation of the meninges.
Indication
Treatment of infections caused by microorganisms sensitive to cefuroxime, or treatment of infections until the causative agent of the infectious disease is identified.
Infectious diseases of the respiratory tract: acute and chronic bronchitis, infected bronchiectasis, bacterial pneumonia, lung abscess, postoperative infections of the chest organs.
Infectious diseases of the throat and nose: sinusitis, tonsillitis, pharyngitis.
Infectious diseases of the urinary tract: acute and chronic pyelonephritis, cystitis, asymptomatic bacteriuria.
Infectious diseases of soft tissues: cellulitis, erysipeloid, wound infections.
Infectious diseases of bones and joints: osteomyelitis, septic arthritis.
Infections in obstetrics and gynecology: pelvic inflammatory diseases.
Gonorrhea, especially in cases where penicillin is contraindicated.
Other infectious diseases, including septicemia and meningitis.
Prevention of infectious complications after operations on the chest and abdominal cavity, on the pelvic organs, during vascular, cardiovascular and orthopedic surgical interventions.
In most cases, zinacef monotherapy is effective, but if necessary, the drug can be used in combination with aminoglycoside antibiotics or with metronidazole (orally, in suppositories or by injection).
In the case of an existing or expected mixed aerobic and anaerobic infection (e.g. peritonitis, aspiration pneumonia, lung, pelvic and brain abscess) and a high probability of such infection (e.g. during colon surgery and gynecological surgery), the use of Zinacef in combination with metronidazole is acceptable.
In the treatment of pneumonia and exacerbation of chronic bronchitis, Zinacef can be administered before oral cefuroxime axetil (Zinnat), when necessary.
Application
Susceptibility to zinacef varies between regions and may change over time. Local antibiotic susceptibility data should be consulted if necessary.
Zinacef injections are intended for intravenous or intramuscular administration only.
Since cefuroxime is also available as oral cefuroxime axetil (Zinnat), it is possible to switch from parenteral Zinacef therapy to oral Zinnat therapy sequentially when clinically appropriate.
general recommendations
Children (including newborns). 30-100 mg/kg/day, divided into 3-4 injections. For most infections, the optimal dose is 60 mg/kg/day. In newborns, 30-100 mg/kg/day is used, divided into 2-3 injections. It should be noted that T ½ of cefuroxime in the first weeks of life may be 3-5 times longer than in adults.
gonorrhea
1.5 g by 1 injection or 750 mg by 2 injections i / m in both buttocks.
meningitis
Zinacef is used as monotherapy for bacterial meningitis if it is caused by sensitive strains.
Adults: 3 g IV every 8 hours.
Children (including neonates): 200-240 mg/kg/day IV in 3 or 4 divided doses. This dosage may be reduced to 100 mg/kg/day IV after 3 days of use or if clinical improvement occurs. In neonates, the initial dose should be 100 mg/kg/day IV. The dose may be reduced to 50 mg/kg/day if clinical improvement occurs.
prevention
The usual dose is 1.5 g IV during induction of anesthesia for abdominal, pelvic, and orthopedic surgery. This dose may be supplemented by 750 mg IM at 8 and 16 hours.
For operations on the heart, lungs, esophagus, and blood vessels, the usual dose is 1.5 g IV, administered at the induction stage of anesthesia and then supplemented with 750 mg IM 3 times a day for the next 24-48 hours.
For total joint replacement, 1.5 g of cefuroxime powder is mixed with one packet of methyl methacrylate polymer cement before adding the liquid monomer.
The drug is also available in the form of cefuroxime axetil (Zinnat) for oral administration, which allows for the sequential administration of oral forms of the drug after parenteral administration, if clinically appropriate.
sequential therapy
Pneumonia: 1.5 g of Zinacef 2-3 times a day (in / m or in / in) for 48-72 hours, then you should switch to oral administration of 500 mg of Zinnat 2 times a day for 7-10 days.
Exacerbation of chronic bronchitis: 750 mg of Zinacef 2-3 times a day (in / m or in / in) for 48-72 hours, then you should switch to oral administration of 500 mg of Zinnat 2 times a day for 7 days.
The duration of both parenteral and oral therapy is determined by the severity of the infection and the clinical condition of the patient.
Renal impairment. Cefuroxime is excreted by the kidneys. Therefore, as with other similar antibiotics, patients with impaired renal function are recommended to reduce the dose of cefuroxime to compensate for the slower excretion of the drug. There is no need to reduce the standard dose (750 mg-1.5 g 3 times a day) if the creatinine clearance level is more than 20 ml/min. Adults with severe renal impairment (creatinine clearance 10-20 ml/min) are recommended a dose of 750 mg 2 times a day, in more severe cases (creatinine clearance less than 10 ml/min) - 750 mg 1 time a day.
In hemodialysis, 750 mg should be administered intravenously or intramuscularly at the end of each dialysis session. In addition to parenteral administration, cefuroxime can be added to the peritoneal dialysis fluid (usually 250 mg for every 2 liters of dialysis fluid). For patients undergoing programmed hemodialysis or high-flux hemofiltration in intensive care units, the recommended dose is 750 mg 2 times a day. Patients undergoing low-flux hemofiltration should follow the dosing regimen for treatment of impaired renal function.
Features of drug administration. For i/m administration, add 3 ml of water for injection to 750 mg of Zinacef. Shake gently until an opaque suspension is formed.
For intravenous administration, dissolve 750 mg of Zinacef in at least 6 ml of water for injection, 1.5 g in 15 ml. For infusions lasting no more than 30 minutes, 1.5 g of cefuroxime can be dissolved in 50-100 ml of water for injection. The resulting solutions can be administered directly into a vein or into a drip tube during infusion therapy.
When storing already diluted solutions, changes in their color saturation may occur.
Children. Used in children from the first days of life.
Contraindication
Hypersensitivity to cefuroxime or any of the excipients. Hypersensitivity to cephalosporin antibiotics. History of severe hypersensitivity (e.g. anaphylactic reactions) to other β-lactam antibiotics (penicillins, monobactams and carbapenems).
Side effects
Side effects are rare (1/10,000) and are mild and reversible. The frequency of their occurrence given below is approximate, since for most reactions there is insufficient data to make a detailed calculation. In addition, the frequency of side effects varies depending on the indications.
Clinical trial data were used to classify adverse reactions from very common to rare. The frequency of other adverse reactions (e.g. 1/10,000) is based on marketing data and reflects the frequency of adverse reactions rather than their occurrence.
Criteria for assessing the frequency of side effects: very common (≥1/10); common (≥1/100 and 1/10); uncommon (≥1/1000 and 1/100); rare (≥1/10,000 and 1/1000); very rare (1/10,000).
Infections and infestations: rarely - overgrowth of non-susceptible microorganisms, e.g. Candida.
Cephalosporins have the property of being absorbed on the surface of the erythrocyte membrane and interacting with antibodies there, causing a positive Coombs test, which can affect blood group determination and very rarely lead to the development of hemolytic anemia.
On the part of the immune system: hypersensitivity reactions, including: infrequently - skin rash, urticaria and itching; rarely - drug fever; very rarely - interstitial nephritis, anaphylaxis, cutaneous vasculitis.
On the part of the gastrointestinal tract: infrequently - discomfort in the gastrointestinal tract; very rarely - pseudomembranous colitis (see Features of use).
Hepatobiliary reactions: often - transient increase in liver enzymes; infrequently - temporary increase in bilirubin levels.
Transient elevations of liver enzymes or bilirubin occurred mainly in patients with pre-existing liver disease, but there is no evidence of hepatotoxicity.
Skin and subcutaneous tissue disorders: very rarely - erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis.
From the urinary system: very rarely - increased plasma creatinine levels, blood urea nitrogen and decreased creatinine clearance.
General disorders and administration site conditions: Common: Injection site reactions including pain and thrombophlebitis.
The occurrence of pain at the site of intramuscular injection is more likely when using the drug in higher doses, but this should not be a reason for discontinuation of treatment.
Special instructions
As with other β-lactam antibiotics, severe and sometimes fatal hypersensitivity reactions have been reported. If severe hypersensitivity reactions occur, treatment with cefuroxime should be discontinued immediately and appropriate emergency measures should be taken.
Before initiating treatment, the patient should be evaluated for a history of severe hypersensitivity reactions to cefuroxime, cephalosporin antibiotics, or other β-lactam antibiotics. Use with caution in patients who have had hypersensitivity reactions to other β-lactam antibiotics.
High doses of cephalosporin antibiotics should be administered with caution to patients receiving treatment with potent diuretics such as furosemide or aminoglycoside antibiotics, as adverse effects on renal function have been reported with this combination. Renal function should be monitored in these patients, as in the elderly and in patients with renal insufficiency (see Dosage and Administration).
As with other meningitis regimens, moderate to severe hearing loss has been reported in a few pediatric patients treated with cefuroxime.
As with other antibiotics, cultures of Haemophilus influenzae have been detected in the cerebrospinal fluid 18-36 hours after cefuroxime injection. However, the clinical significance of this finding is unknown.
As with other antibiotics, prolonged use of cefuroxime may result in overgrowth of non-susceptible organisms (such as Candida, Enterococci, Clostridium difficile), which may necessitate discontinuation of treatment.
Pseudomembranous colitis has been reported with antibiotic use and can range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who develop diarrhea during or after antibiotic use. In the event of prolonged and severe diarrhea or if the patient develops abdominal cramps, treatment should be discontinued immediately and further evaluation should be performed.
When using Zinacef in the sequential therapy regimen, the time of transition to oral administration of Zinnat is determined by the severity of the infection, the clinical condition of the patient and the sensitivity of the microorganism. In the absence of clinical improvement within 72 hours, parenteral administration of the drug should be continued. Before using Zinnat, you should read the instructions for use of this drug.
Use during pregnancy and breastfeeding. No data on the embryotoxic and teratogenic effects of cefuroxime have been heard, however, as with the use of other drugs, it should be prescribed with caution in the first months of pregnancy.
Cefuroxime passes into breast milk, so breastfeeding should be discontinued during use of the drug.
Ability to influence the reaction rate when driving vehicles or other mechanisms. There are no reports of the drug's effect on the reaction rate when driving vehicles or other mechanisms.
Interactions
Like other antibiotics, cefuroxime may affect the intestinal microflora, leading to reduced reabsorption of estrogens and reduced efficacy of combined oral contraceptives.
In patients taking Zinacef, it is recommended to use the glucose oxidase or hexokinase method to determine blood glucose levels. The drug does not affect the results of enzymatic methods for determining glucosuria.
Zinacef may slightly affect the results of copper reduction methods (Benedict, Fehling, Clinitest), but this does not lead to false-positive results, as with some other cephalosporins.
Incompatibility. Zinacef should not be mixed in the same syringe with aminoglycoside antibiotics. The pH of 2.74% sodium bicarbonate solution for injection significantly affects the color of the solution, so it is not recommended to use it for diluting Zinacef. However, if necessary, if the patient receives sodium bicarbonate solution by intravenous infusion, Zinacef can be administered directly into the dropper tube.
1.5 g of Zinacef dissolved in 15 ml of water for injection can be used together with metronidazole injection (500 mg/100 ml), both drugs retain their activity for 24 hours at temperatures below 25 °C.
1.5 g of Zinacef are compatible with 1 g (in 15 ml of solvent) or 5 g (in 50 ml of solvent) of azlocillin for 24 h at a temperature of 4 °C and 6 h at a temperature not exceeding 25 °C.
Zinacef (5 mg/ml) can be stored for 24 hours at 25°C in 5% or 10% p-rexylitol for injection.
Zinacef is compatible with solutions containing up to 1% lidocaine hydrochloride.
Zinacef is compatible with most commonly used solutions for intravenous injection. It retains its properties for 24 hours at room temperature in the following solutions: 0.9% sodium chloride solution for injection; 5% glucose solution for injection; 0.18% sodium chloride solution with 4% glucose solution for injection; 5% glucose solution with 0.9% sodium chloride solution for injection; 5% glucose solution with 0.45% sodium chloride solution for injection; 5% glucose solution with 0.225% sodium chloride solution for injection; 10% glucose solution for injection; 10% inverted glucose solution in water for injection; Ringer's solution; Ringer's lactate solution; M / 6 sodium lactate solution; Hartmann's solution.
The stability of Zinacef in 0.9% sodium chloride solution for injection with 5% glucose solution is not altered in the presence of hydrocortisone sodium phosphate.
Zinacef is also compatible for 24 hours at room temperature when diluted in an infusion solution:
with heparin (10 or 50 U/ml) in 0.9% sodium chloride solution for injection; with potassium chloride solution (10 or 40 mEq/l) in 0.9% sodium chloride solution for injection.
Overdose
Overdose of cephalosporin antibiotics may lead to symptoms of brain irritation, which may result in convulsions. Serum cefuroxime concentrations may be reduced by hemodialysis or peritoneal dialysis.
Storage conditions
Store the vial with dry powder in its original packaging at a temperature below 25 ° C. After dilution, the drug can be stored for up to 48 hours in a refrigerator (4 ° C) or up to 5 hours at a temperature not exceeding 25 ° C.
Information for the professional activities of medical and pharmaceutical workers.
You can obtain the complete instructions for the medical use of the drug by contacting GlaxoSmithKline Pharmaceuticals Ukraine LLC: 02152, Kyiv, Pavla Tychyny Ave., 1B, tel.: (044) 585-51-85, www.ua.gsk.com. You can report an adverse event to GlaxoSmithKline Pharmaceuticals Ukraine LLC by tel.: (044) 585-51-85 or e-mail: oax70065@gsk.com, you can report a complaint about the quality of the drug by tel.: (044) 585-51-85, +38 (050) 381-43-49 or e-mail: ua.complaints@gsk.com
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UA / AIN / 0017 / 18.12.13
