Zinacef, 1500 mg

Pharmacodynamics

Cephalosporin II generation. Cefuroxime is active against a wide range of pathogens, including strains producing β-lactamases. Bactericidal action of cefuroxime is connected with inhibition of bacterial cell wall synthesis as a result of binding to main target proteins.

Cefuroxime in vitro is active against Gram-negative aerobes: Haemophilus influenzae(including ampicillin-resistant strains), Haemophilus parainfluenzae, Moraxella catarrhalis, Esherichia coli, Klebsiella spp., Proteus mirabilis, Providencia spp, Proteus rettgeri and Neisseria gonorrhoeae (including penicillinase-producing and non-producing strains), Neisseria meningitidis, Salmonella spp: Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes (and other β-hemolytic streptococci), Streptococcus group B (Streptococcus agalactiae), Streptococcus mitis (viridans group), Bordetella pertussis; anaerobes: Peptococcus spp., Peptostreptococcus spp., Clostridium spp., Bacteroides spp., Fusobacterium spp., Propionibacterium spp.; other microorganisms: Borrelia burgdorferi.

The following microorganisms are not sensitive to cefuroxime: Clostridium difficile, Pseudomonas spp., Campylobacter spp., Acinetobacter calcoaceticus, Listeria monocytogenes, methicillin-resistant strains of Staphylococcus aureus and Staphylococcus epidermidis, Legionella spp.

Pharmacokinetics

Intake

C_max of cefuroxime in plasma after intravenous administration, noted between 30 and 45 minutes, is 27 µg/mL and persists for 5.3 h.

Distribution

Cefuroxime penetrates the HEB, the placental barrier and is excreted with the breast milk. Therapeutic concentrations of cefuroxime are produced in bone, skin, soft tissues, synovial, pleural, intraocular fluid, bile, sputum and myocardium. Concentrations of cefuroxime in excess of the minimum inhibitory concentration for most microorganisms can be achieved in bone tissue, synovial and intraocular fluid.

The binding to plasma proteins is 33-50%.

Metabolism and excretion

Cefuroxime is not metabolized. The T_1/2 of cefuroxime after parenteral administration is approximately 70 minutes. In newborn children, the T_1/2 of cefuroxime may be 3-5 times longer than in adults.

Extracted by the kidneys through glomerular filtration and tubular secretion. Within 24 hours after parenteral administration cefuroxime is eliminated almost completely (85-90%) in unchanged form in the urine, most of the drug – during the first 6 hours. Serum levels of cefuroxime decrease with dialysis.

Indications

Treatment of diseases caused by cefuroxime-sensitive bacteria:

Prevention of infectious complications during abdominal and pelvic surgeries, orthopedic surgeries, surgeries on the heart, lungs, esophagus and vessels.

Active ingredient

Composition

1 vial contains:

Active ingredients:

cefuroxime (in the form of sodium salt) 1.5 g.

In a vial 1.5 g powder.

There is 1 vial in the carton.

How to take, the dosage

Adults are administered v/m or intravenously 750 mg 3 times/day. In more severe cases the drug is administered by IV in a dose of 1.5 g 3 times/day. If necessary, Zinacef may be administered every 6 hours, and the daily dose may be 3 to 6 g.

In some infections, it is effective to prescribe Zinacef in a dose of 750 mg or 1.5 g 2 times/day (w/v or iv) followed by an oral dose of Zinnate.

In children the drug is prescribed in a dose of 30-100 mg/kg/day in 3-4 doses. For most infections the optimal dose is 60 mg/kg/day.

In newborns 30-100 mg/kg/day in 2-3 doses.

To treat gonorrhea, 1.5 g is prescribed once (two doses of 750 mg w/o in different sites, e.g., both gluteal muscles).

In meningitis, adults are prescribed 3 g v/v every 8 hours; children, 150-250 mg/kg/day v/v in 3-4 doses; newborns, 100 mg/kg/day v/v.

In order to prevent infectious complications during abdominal, pelvic and orthopedic surgeries Zinacef is administered in dose of 1.5 g by IV fluids during induction anesthesia. Eight hours and 16 hours after surgery, 750 mg of Zinacef may be administered additionally by intravenous injection.

In order to prevent infectious complications during cardiac, pulmonary, esophageal and vascular surgeries during induction anesthesia Zinacef is administered in 1.5 g dose by IV and then 750 mg 3 times per day by IV for 24-48 hours.

In case of total joint replacement, 1.5 g of cefuroxime powder can be mixed with a polymer packet of methyl methacrylate cement before adding the liquid polymer.

Stage therapy

In pneumonia, Zinacef is given in a dose of 1.5 g 2-3 times/day (IV or IM) for 48-72 h, followed by administration of Zinnate (oral) in a dose of 500 mg 2 times/day for 7-10 days.

In exacerbation of chronic bronchitis Zinacef is prescribed at a dose of 750 mg 2-3 times/day (IV or IM) for 48-72 hours followed by administration of Zinnate (oral) 500 mg 2 times/day for 5-10 days.

The duration of each period (parenteral therapy and oral administration) is determined by the severity of the infection and the overall condition of the patient.

Renal failure

In cases of renal failure, a reduction in the dose of Zinacef is recommended. However, it is not necessary to decrease the standard dose of the drug (0.75-1.5 g 3 times/day) in patients with CKR over 20 ml/min.

Zinacef dose adjustment in adult renal failure

Creatinine clearance

Zinacef dose

>20 ml/min

0.75-1.5 g 3 times/day

10-20 ml/min

750 mg 2 times/day

Interaction

Simultaneous use with “loop” diuretics (furosemide) and aminoglycosides slows down tubular secretion, reduces renal clearance, increases plasma concentrations and increases T1/2 cefuroxime, which increases the risk of nephrotoxic effects. Zinacef in combination with aminoglycosides acts additively, but synergism may sometimes be observed.

Pharmaceutical interactions

When a solution of cefuroxime (1.5 g in 15 ml of water for injection) and metronidazole (500 mg/100 ml) is mixed, both components retain their activity for up to 24 hours at a temperature not exceeding 25°C. Zinacef in dose 1.5 g is compatible with azlocillin solution (1 g in 15 ml or 5 g in 50 ml); both components retain their activity for up to 24 hours at 4°C or up to 6 hours at a temperature not exceeding 25°C. A solution of Zinacef (5 mg/ml) in 5% or 10% xylitol solution can be stored for up to 24 h at a temperature not exceeding 25°C.

Zinacef is compatible with aqueous solutions containing up to 1% lidocaine hydrochloride.

Zinacef is compatible with the most commonly used infusion solutions.

When mixed with the following solutions the drug is stable for up to 24 hours at room temperature: 0.9% sodium chloride solution; 5% dextrose solution for injection; 0.18% sodium chloride solution and 4% dextrose solution for injection; 5% dextrose solution and 0.9% sodium chloride solution; 5% dextrose solution and 0.45% sodium chloride solution; 5% dextrose solution and 0.225% sodium chloride solution; 10% dextrose solution for injection; Ringer’s solution; Ringer’s lactate solution; Hartmann’s solution.

The stability of cefuroxime in 0.9% sodium chloride solution and 5% dextrose solution is not impaired in the presence of hydrocortisone sodium phosphate.

The following solutions of Zinacef are compatible and stable for 24 h at room temperature: heparin (10 U/ml and 50 U/ml) in 0.9% sodium chloride solution; potassium chloride (10 mEq/L and 40 mEq/L) in 0.9% sodium chloride solution.

Zinacef should not be mixed in the same syringe with antibiotics from the group of aminoglycosides.

Sodium bicarbonate solution 2.74% has a pH value that significantly affects the color of the cefuroxime solution, so it is not recommended to use it to dilute Zinacef. However, if the patient is administered sodium bicarbonate solution by infusion, Zinacef can be injected directly into the tube of the infusion system if needed.

Special Instructions

Patients with a history of anaphylactic reactions to penicillins and other beta-lactam antibiotics should be treated with caution.

The simultaneous use of aminoglycosides and diuretics increases the risk of nephrotoxic effects; therefore, renal function should be monitored when using this combination of drugs, especially in elderly patients with renal disease and those receiving the drug in high doses.

When treating meningitis with Zinacef some children had mild to moderate hearing loss with positive cultures of Haemophilus influenzae detected in the cerebrospinal fluid after 18-36 hours of therapy. Similar phenomena have also been observed with other antibiotics, and their clinical significance is not known.

Pseudomembranous colitis is seen with a wide range of antibiotics, and the possibility of its occurrence should be kept in mind in patients with severe diarrhea that occurred during or after antibiotic treatment.

Cefuroxime is also available in axetil (Zinnate) tablet form, which allows the same antibiotic to be prescribed sequentially when switching from parenteral to oral therapy is necessary.

In the treatment of pneumonia and exacerbations of chronic bronchitis, it is effective to prescribe a course of treatment with Zinacef, an antibiotic for parenteral administration, before using Zinnate orally (stepped therapy technique).

In step therapy, the time of transition to oral therapy is determined by the severity of the infection, the clinical condition of patients and the sensitivity of the pathogen. If there is no clinical effect within 72 hours of treatment initiation, parenteral therapy should be continued.

Before starting stepwise therapy, consult available references for cefuroxime axetil.

Zinacef has no effect on urine glucose results using enzymatic methods. However, there may be an interaction when using other methods (Benedict, Fehling, Clinitest) that does not lead to false positives.

In patients receiving Zinacef, it is recommended to use the glucose oxidase or hexokinase method to determine blood/plasma glucose levels.

Zinacef does not affect the quantitative determination of creatinine by the alkaline-precision method.

Zinacef has 42 mg of sodium in each 750 mg bottle.

Impact on the ability to drive vehicles and other mechanisms requiring increased concentration

No reports.

Contraindications

With caution: the drug should be used in renal failure, GI diseases (including history of non-specific ulcerative colitis. history and in case of nonspecific ulcerative colitis), in case of necessity of combined administration with “loop” diuretics and aminoglycosides, in pregnancy and during lactation as well as in newborns (especially in prematurely born children).

Side effects

Digestive system disorders: nausea, vomiting, diarrhea, abdominal cramps and pain, pseudomembranous colitis, oral candidiasis, increased activity of liver enzymes (ALT, AST, LDH, ALP), hyperbilirubinemia.

Hematopoietic system disorders: eosinophilia, leukopenia, neutropenia, thrombocytopenia, agranulocytosis, hemolytic anemia.

CNS and sensory organs: seizures, decreased hearing.

Urogenital system disorders: renal dysfunction with increased creatinine and/or urea nitrogen levels and decreased CK, itching in the perineum, vaginitis (if candidiasis develops).

Allergic reactions: erythema multiforme exudative (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell syndrome), skin rash (including urtic), skin itching, fever, bronchospasm, serum sickness; very rarely – anaphylactic shock.

Laboratory indicators: false positive Coombs test.

Local reactions: pain, irritation and infiltration at the injection site when injected, phlebitis, thrombophlebitis when injected intravenously.

Long-term use of Zinaceph may be accompanied by excessive growth of insensitive microorganisms, including fungi of genus Candida with the development of oral and vaginal candidiasis (itching, discharge).

Overdose

Symptoms: increased cortical excitability with the development of convulsions.

Treatment: symptomatic therapy, hemodialysis, peritoneal dialysis.

Pregnancy use

The drug is classified as category B. Caution should be exercised when prescribing the drug in pregnancy.

Cefuroxime is excreted with breast milk, therefore caution should be exercised when prescribing the drug to nursing mothers.

There are no data on the development of embryotoxic or teratogenic effects of cefuroxime.

Similarities