Zinacef^® (Powder) Instructions for Use

ATC Code

J01DC02 (Cefuroxime)

Active Substance

Cefuroxime (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Second generation cephalosporin

Pharmacotherapeutic Group

Antibiotic-cephalosporin

Pharmacological Action

A second-generation cephalosporin. Cefuroxime is active against a wide range of pathogens, including strains producing beta-lactamases. The bactericidal action of cefuroxime is associated with the suppression of bacterial cell wall synthesis as a result of binding to the main target proteins.

Cefuroxime in vitro is active against gram-negative aerobes: Haemophilus influenzae (including ampicillin-resistant strains), Haemophilus parainfluenzae, Moraxella catarrhalis, Escherichia coli, Klebsiella spp., Proteus mirabilis, Providencia spp., Proteus rettgeri and Neisseria gonorrhoeae (including penicillinase-producing and non-producing strains), Neisseria meningitidis, Salmonella spp.; gram-positive aerobes: Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes (and other beta-hemolytic streptococci), Group B streptococci (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 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

Absorption

The C_max of cefuroxime in plasma after intramuscular administration is observed between 30 and 45 minutes, is 27 µg/ml and persists for 5.3 hours.

Distribution

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

Plasma protein binding 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 infants, the T_1/2 of cefuroxime may be 3-5 times longer than in adults.

It is excreted by the kidneys via glomerular filtration and tubular secretion. Within 24 hours after parenteral administration, Cefuroxime is almost completely (85-90%) excreted unchanged in the urine, with the majority of the drug excreted within the first 6 hours. Serum levels of cefuroxime are reduced by dialysis.

Indications

Treatment of diseases caused by bacteria sensitive to cefuroxime

• Infections of the upper and lower respiratory tract (pneumonia, bronchitis, infected bronchiectasis, lung abscess, postoperative chest infections);
• Infections of the ENT organs (otitis media, sinusitis, tonsillitis, pharyngitis);
• Urinary tract infections (pyelonephritis, cystitis, asymptomatic bacteriuria, gonorrhea);
• Skin and soft tissue infections (furunculosis, erysipelas and wound infections);
• Bone and joint infections (osteomyelitis and septic arthritis);
• Pelvic infections;
• Septicemia;
• Meningitis;
• Peritonitis.

Prevention of infectious complications during operations on the abdominal organs, pelvis, during orthopedic operations, operations on the heart, lungs, esophagus and blood vessels.

ICD codes

Dosage Regimen

Powder

Adults are administered 750 mg IM or IV 3 times/day. In more severe cases, the drug is administered IV at a dose of 1.5 g 3 times/day. If necessary, Zinacef^® can be administered every 6 hours, and the daily dose can range from 3 to 6 g.

For some infections, administration of Zinacef^® at a dose of 750 mg or 1.5 g 2 times/day (IM or IV) followed by oral administration of Zinnat is effective.

Children are prescribed the drug at a dose of 30-100 mg/kg/day in 3-4 divided doses. For most infections, the optimal dose is 60 mg/kg/day.

Newborns are prescribed 30-100 mg/kg/day in 2-3 divided doses.

For the treatment of gonorrhea, 1.5 g is prescribed as a single dose (two doses of 750 mg IM in different sites, for example, in both gluteal muscles).

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

For the prevention of infectious complications during operations on the abdominal organs, pelvis and orthopedic interventions, Zinacef^® at a dose of 1.5 g is administered IV during induction anesthesia. An additional 750 mg of Zinacef^® may be administered IM 8 hours and 16 hours after surgery.

For the prevention of infectious complications during operations on the heart, lungs, esophagus and blood vessels during induction anesthesia, Zinacef^® is administered IV at a dose of 1.5 g, and then 750 mg 3 times/day IM for 24-48 hours.

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

Step-down therapy

For pneumonia, Zinacef^® is prescribed at a dose of 1.5 g 2-3 times/day (IV or IM) for 48-72 hours, followed by Zinnat (orally) at a dose of 500 mg 2 times/day for 7-10 days.

For 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 Zinnat (orally) 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 general condition of the patient.

Renal impairment

In renal impairment, a reduction in the dose of Zinacef^® is recommended. However, there is no need to reduce the standard dose of the drug (0.75-1.5 g 3 times/day) in patients with a creatinine clearance greater than 20 ml/min.

Dosage adjustment of Zinacef^® in adults with renal impairment

Patients on hemodialysis should be given an additional dose of Zinacef^® equal to 750 mg at the end of each hemodialysis session.

For patients in the intensive care unit on continuous hemodialysis using an arteriovenous shunt or on high-speed hemofiltration, a dose of 750 mg 2 times/day is recommended. If low-speed hemofiltration is used, then doses as for renal impairment are applied.

Rules for preparation of injection solution

To prepare a solution for IM administration, add 1 ml of water for injections to 250 mg of Zinacef^® or 3 ml of water for injections to 750 mg of Zinacef^®. Shake gently to form a suspension.

To prepare a solution for IV administration, dissolve 250 mg of Zinacef^® in 2 ml or more of water for injections, 750 mg of Zinacef^® in 6 ml or more of water for injections, 1.5 g of Zinacef^® in 15 ml or more of water for injections.

To prepare a solution for short-term IV infusions (up to 30 minutes), 1.5 g of the drug is dissolved in 50 ml of water for injections. These solutions can be administered directly into a vein or into the tube of an infusion system.

Adverse Reactions

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

From the hematopoietic system eosinophilia, leukopenia, neutropenia, thrombocytopenia, agranulocytosis, hemolytic anemia.

From the central nervous system and sensory organs seizures, hearing loss.

From the genitourinary system impaired renal function with increased levels of creatinine and/or blood urea nitrogen and decreased creatinine clearance, perineal itching, vaginitis (with the development of candidiasis).

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

Laboratory parameters false-positive Coombs test.

Local reactions with IM administration – pain, irritation and infiltrate at the injection site, with IV administration – phlebitis, thrombophlebitis.

Long-term use of Zinacef^® may be accompanied by overgrowth of non-susceptible microorganisms, including fungi of the genus Candida with the development of oral and vaginal candidiasis (itching, discharge).

Contraindications

• Hypersensitivity to cephalosporin antibiotics, penicillins and carbapenems.

Use with caution in renal failure, gastrointestinal diseases (including history and nonspecific ulcerative colitis), when necessary for concomitant use with “loop” diuretics and aminoglycosides, during pregnancy and lactation, as well as in newborn infants (especially premature ones).

Use in Pregnancy and Lactation

The drug belongs to category B. The drug should be used with caution during pregnancy.

Cefuroxime is excreted in breast milk, so 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.

Use in Renal Impairment

Renal impairment

In renal impairment, a reduction in the dose of Zinacef^® is recommended. However, there is no need to reduce the standard dose of the drug (0.75-1.5 g 3 times/day) in patients with a creatinine clearance greater than 20 ml/min.

Dosage adjustment of Zinacef^® in adults with renal impairment

Patients on hemodialysis should be given an additional dose of Zinacef^® equal to 750 mg at the end of each hemodialysis session.

For patients in the intensive care unit on continuous hemodialysis using an arteriovenous shunt or on high-speed hemofiltration, a dose of 750 mg 2 times/day is recommended. If low-speed hemofiltration is used, then doses as for renal impairment are applied.

Pediatric Use

According to indications and in doses taking into account the patient’s age.

Special Precautions

The drug should be prescribed with caution to patients with a history of an anaphylactic reaction to penicillins and other beta-lactam antibiotics.

When taken concomitantly with aminoglycosides and diuretics, the risk of nephrotoxic effects increases, so renal function should be monitored when using such a combination of drugs, especially in elderly patients, patients with kidney disease and those receiving the drug in a high dose.

When treating meningitis with Zinacef^®, mild to moderate hearing loss was observed in some children, with positive cultures of Haemophilus influenzae detected in the cerebrospinal fluid after 18-36 hours of therapy. Similar phenomena have also been observed with the use of other antibiotics; their clinical significance is unknown.

Pseudomembranous colitis is observed with the use of broad-spectrum antibiotics; the possibility of its occurrence must be considered in patients with severe diarrhea that occurs during or after a course of antibiotic treatment.

Cefuroxime is also available in the form of axetil (Zinnat) in tablets, which allows for the sequential administration of the same antibiotic when a switch from parenteral to oral therapy is necessary.

For the treatment of pneumonia and exacerbation of chronic bronchitis, a course of treatment with Zinacef^®, an antibiotic for parenteral administration, before using Zinnat orally (step-down therapy method) is effective.

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

Before starting step-down therapy, consult available reference sources for information on cefuroxime axetil.

Zinacef^® does not affect the results of urine glucose determination using enzymatic methods. However, when using other methods (Benedict’s, Fehling’s, Clinitest) interaction may occur, not leading to false-positive results.

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 picrate method.

Each vial of Zinacef^® 750 mg contains 42 mg of sodium.

Effect on the ability to drive vehicles and mechanisms

No reports.

Overdose

Symptoms increased excitability of the cerebral cortex with the development of convulsions.

Treatment symptomatic therapy, hemodialysis, peritoneal dialysis are performed.

Drug Interactions

Concomitant administration with loop diuretics (furosemide) and aminoglycosides slows tubular secretion, reduces renal clearance, increases plasma concentration and increases the T_1/2 of cefuroxime, which increases the risk of nephrotoxic effects. Zinacef^® in combination with aminoglycosides has an additive effect, but sometimes synergism of action may be observed.

Pharmaceutical interactions

When a solution of cefuroxime (1.5 g in 15 ml of water for injections) and metronidazole (500 mg/100 ml) are mixed, both components retain their activity for up to 24 hours at a temperature not exceeding 25°C (77°F). Zinacef^® at a dose of 1.5 g is compatible with a solution of azlocillin (1 g in 15 ml or 5 g in 50 ml); both components retain their activity for up to 24 hours at a temperature of 4°C (39.2°F) or up to 6 hours at a temperature not exceeding 25°C (77°F).

A solution of Zinacef^® (5 mg/ml) in 5% or 10% xylitol solution can be stored for up to 24 hours at a temperature not exceeding 25°C (77°F).

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

Zinacef^® is compatible with the most widely 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 injections; 0.18% sodium chloride and 4% dextrose solution for injections; 5% dextrose and 0.9% sodium chloride solution; 5% dextrose and 0.45% sodium chloride solution; 5% dextrose and 0.225% sodium chloride solution; 10% dextrose solution for injections; Ringer’s solution; Ringer’s lactate solution; Hartmann’s solution.

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

With the following solutions, Zinacef^® is compatible and stable for 24 hours at room temperature: heparin (10 units/ml and 50 units/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 aminoglycoside group.

A 2.74% sodium bicarbonate solution has a pH that significantly affects the color of the cefuroxime solution, so it is not recommended for diluting Zinacef^®. However, if a patient is receiving a sodium bicarbonate solution by infusion, Zinacef^® can, if necessary, be administered directly into the tube of the infusion system.

Storage Conditions

The drug should be stored in a place protected from light, out of the reach of children, at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life is 2 years.

After reconstitution, the solution is stored for 5 hours at a temperature not exceeding 25°C (77°F) and for 48 hours at a temperature of 4°C (39.2°F) (in a refrigerator).

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.