Cefurabol^® (Powder) Instructions for Use

Marketing Authorization Holder

PFC Prebend, LLC (Russia)

ATC Code

J01DC02 (Cefuroxime)

Active Substance

Cefuroxime (Rec.INN registered by WHO)

Dosage Forms

	Cefurabol®	Powder for preparation of solution for intravenous and intramuscular administration 1.5 g: vial 1 or 5 pcs. in a set with solvent or without it
		Powder for preparation of solution for intravenous and intramuscular administration 750 mg: vial 1 or 5 pcs. in a set with solvent or without it

Dosage Form, Packaging, and Composition

Powder for preparation of solution for intravenous and intramuscular administration white or white with a yellowish tint.

Vials with a capacity of 10 ml (1) – cardboard packs.
Vials with a capacity of 10 ml (1) in a set with solvent (amp. 1 pc.) – cardboard packs.
Vials with a capacity of 10 ml (1) in a set with solvent (amp. 1 pc.) – contour cell packs (1) – cardboard packs.
Vials with a capacity of 10 ml (5) – cardboard packs.
Vials with a capacity of 10 ml (5) in a set with solvent (amp. 5 pcs.) – contour cell packs (1) – cardboard packs.

Powder for preparation of solution for intravenous and intramuscular administration white or white with a yellowish tint.

Vials with a capacity of 10 ml (1) – cardboard packs.
Vials with a capacity of 10 ml (1) in a set with solvent (amp. 1 pc.) – cardboard packs.
Vials with a capacity of 10 ml (1) in a set with solvent (amp. 1 pc.) – contour cell packs (1) – cardboard packs.
Vials with a capacity of 10 ml (5) – cardboard packs.
Vials with a capacity of 10 ml (5) in a set with solvent (amp. 5 pcs.) – contour cell packs (1) – cardboard packs.

Powder for preparation of solution for intravenous and intramuscular administration white or white with a yellowish tint.

Vials with a capacity of 20 ml (1) – cardboard packs.
Vials with a capacity of 20 ml (1) in a set with solvent (amp. 1 pc.) – cardboard packs.
Vials with a capacity of 20 ml (1) in a set with solvent (amp. 1 pc.) – contour cell packs (1) – cardboard packs.
Vials with a capacity of 20 ml (5) – cardboard packs.
Vials with a capacity of 20 ml (5) in a set with solvent (amp. 5 pcs.) – contour cell packs (1) – cardboard packs.

Clinical-Pharmacological Group

Second generation cephalosporin

Pharmacotherapeutic Group

Antibiotic-cephalosporin

Pharmacological Action

Cephalosporin antibiotic of the second generation for parenteral use. It acts bactericidally (disrupts the synthesis of the bacterial cell wall). It has a broad spectrum of antimicrobial activity.

It is highly active against: Gram-positive microorganisms Staphylococcus aureus, Staphylococcus epidermidis, including strains resistant to penicillins and except for methicillin-resistant strains, Streptococcus pyogenes and other beta-hemolytic streptococci, Streptococcus pneumoniae, Group B streptococci (Streptococcus agalactiae), Streptococcus mitis (viridans group), Bordetella pertussis, most Clostridium spp.); Gram-negative microorganisms Escherichia coli, Klebsiella spp., Proteus mirabilis, Providencia spp., Proteus rettgeri, Haemophilus influenzae, including strains resistant to ampicillin, Haemophilus parainfluenzae, including strains resistant to ampicillin, Moraxella catarrhalis, Neisseria gonorrhoeae, including penicillinase-producing and non-producing strains, Neisseria meningitidis, Salmonella spp., Bacteroides spp., Fusobacterium spp., Propionibacterium spp., Borrelia burgdorferi; Gram-positive and Gram-negative anaerobes: including Peptococcus spp., Peptostreptococcus spp.

The following are not susceptible to cefuroxime: Clostridium difficile, Pseudomonas spp., Campylobacter spp., Acinetobacter calcoaceticus, Listeria monocytogenes, methicillin-resistant strains of Staphylococcus aureus, methicillin-resistant strains of Staphylococcus epidermidis, Legionella spp., Streptococcus (Enterococcus) faecalis, Morganella morganii, Proteus vulgaris, Enterobacter spp., Citrobacter spp., Serratia spp., Bacteroides fragilis.

Pharmacokinetics

Parenteral administration: after intramuscular administration of 750 mg, C_max is reached within 15-60 minutes and is 27 mcg/ml. After intravenous administration of 750 mg and 1.5 g, C_max after 15 minutes is 50 and 100 mcg/ml, respectively. The therapeutic concentration is maintained for 5.3 and 8 hours, respectively.

T_1/2 after intravenous and intramuscular administration is 1.3 – 1.5 hours, in newborn children – 2-2.5 hours.

Plasma protein binding – 33-50%. It is not metabolized in the liver.

It is excreted by the kidneys through glomerular filtration and tubular secretion, 85-90% unchanged within 8 hours (the majority of the drug is excreted within the first 6 hours, creating high concentrations in the urine); it is completely excreted within 24 hours (50% by tubular secretion, 50% by glomerular filtration).

Therapeutic concentrations are recorded in pleural fluid, bile, sputum, myocardium, skin and soft tissues. Concentrations of cefuroxime exceeding the MIC for most microorganisms can be achieved in bone tissue, synovial and intraocular fluids. In meningitis, it penetrates the blood-brain barrier. It crosses the placenta and passes into breast milk.

Indications

Bacterial infections caused by susceptible microorganisms:

• Infectious diseases of the respiratory tract (bronchitis, pneumonia, lung abscess, pleural empyema, etc.);
• Infections of the ENT organs (sinusitis, tonsillitis, pharyngitis, otitis, etc.);
• Urinary tract infections (pyelonephritis, cystitis, symptomatic bacteriuria);
• Gonorrhea;
• Skin and soft tissue infections (erysipelas, pyoderma, impetigo, furunculosis, cellulitis, wound infection, erysipeloid, etc.);
• Bone and joint infections (osteomyelitis, septic arthritis, etc.);
• Pelvic organ infections (in obstetrics and gynecology);
• Septicemia;
• Meningitis;
• Lyme disease (borreliosis).

Prevention of infectious complications during operations on the chest, abdominal, pelvic organs, joints (including operations on the lungs, heart, esophagus; in vascular surgery with a high risk of infectious complications, in orthopedic surgeries).

ICD codes

Dosage Regimen

Intravenous and intramuscularly, adults are prescribed 750 mg 3 times/day; for severe infections – the dose is increased to 1.5 g 3-4 times a day (if necessary, the interval between administrations can be reduced to 6 hours). The average daily dose is 3-6 g.

Children are prescribed 30-100 mg/kg/day in 3-4 divided doses. For most infections, the optimal dose is 60 mg/kg/day. Newborns and children under 3 months are prescribed 30 mg/kg/day in 2-3 divided doses.

For gonorrhea – intramuscularly, 1.5 g as a single dose (or as 2 injections of 750 mg administered into different areas, for example, into both gluteal muscles).

For bacterial meningitis – intravenously, 3 g every 8 hours; younger and older children – 150-250 mg/kg/day in 3-4 divided doses, newborns – 100 mg For abdominal, pelvic and orthopedic surgeries – intravenously, 1.5 g at induction of anesthesia, then additionally – intramuscularly, 750 mg, 8 and 16 hours after surgery.

For heart, lung, esophageal and vascular surgeries – intravenously, 1.5 g at induction of anesthesia, then – intramuscularly, 750 mg 3 times/day for the next 24-48 hours.

For total joint replacement – 1.5 g of powder is mixed in dry form with each packet of methyl methacrylate polymer cement before adding the liquid monomer.

For pneumonia – intramuscularly or intravenously, 1.5 g 2-3 times/day for 48-72 hours, then switch to oral administration, 500 mg 2 times/day for 7-10 days. For exacerbation of chronic bronchitis, it is prescribed intramuscularly or intravenously, 750 mg 2-3 times/day for 48-72 hours, then switch to oral administration, 500 mg 2 times/day for 5-10 days.

In case of chronic renal failure, dosage adjustment is necessary: with CC 10-20 ml/min, intravenous or intramuscular administration of 750 mg 2 times/day is prescribed, with CC less than 10 ml/min – 750 mg once/day.

Patients on continuous hemodialysis using an arteriovenous shunt or on high-speed hemofiltration in intensive care units are prescribed 750 mg 2 times a day: for patients on low-speed hemofiltration, doses recommended for renal impairment are prescribed.

Preparation of injection solution.

Solution for intramuscular injections

Add 1 ml of water for injections to 250 mg of Cefurabol^® or 3 ml of water for injections to 750 mg of Cefurabol^®. Gently shake until a suspension is formed.

Solution for intravenous administration

Dissolve 250 mg of Cefurabol^® in 2 or more ml of water for injections; 750 mg of Cefurabol^® in 6 or more ml of water for injections; 1.5 g of Cefurabol^® in 15 or more ml of water for injections.

For short-term intravenous 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.

When mixing a solution of Cefurabol^® (1.5 g in 15 ml of water for injections) and metronidazole (50 mg/100 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 below 25°C (77°F). A solution of Cefurabol^® (5 mg/ml) in 5% or 10% xylitol solution can be stored for up to 24 hours at a temperature below 25°C (77°F).

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

Cefurabol^® is compatible with the most widely used intravenous fluids. The drug is stable for up to 24 hours at room temperature when mixed with the following solutions: 0.9% sodium chloride solution, 5% dextrose solution, Ringer’s solution, Hartmann’s solution.

Cefurabol^® remains stable in 0.9% sodium chloride solution and in 5% dextrose solution in the presence of hydrocortisone sodium phosphate.

With the following solutions, Cefurabol^® is compatible 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. Cefurabol^® should not be mixed in the same syringe with antibiotics from the aminoglycoside group.

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

Adverse Reactions

Allergic reactions: chills, rash, itching, urticaria; rarely – multiform exudative erythema (including Stevens-Johnson syndrome), bronchospasm, malignant exudative erythema, anaphylactic shock.

From the digestive system: diarrhea or constipation, nausea, vomiting, flatulence, cramps and abdominal pain, ulceration of the oral mucosa, oral candidiasis, glossitis, pseudomembranous enterocolitis, impaired liver function (increased activity of liver enzymes in plasma – ALT, AST, ALP, LDH, bilirubin level), cholestasis.

From the genitourinary system: impaired renal function (decreased creatinine clearance, increased blood creatinine and blood urea nitrogen), dysuria, perineal itching and vaginitis.

From the hematopoietic system: decreased hemoglobin and hematocrit, anemia (aplastic or hemolytic), eosinophilia, neutropenia, leukopenia, agranulocytosis, thrombocytopenia, hypoprothrombinemia, prolonged prothrombin time.

Local reactions: irritation, infiltration and pain at the injection site, phlebitis.

From the central nervous system: convulsions.

From the sensory organs: hearing loss.

Contraindications

• Hypersensitivity (including to other cephalosporins, penicillins and carbapenems).

With caution the drug is used in newborns and premature infants; during pregnancy and lactation; in debilitated and emaciated patients; in chronic renal failure, bleeding and gastrointestinal diseases (including a history of nonspecific ulcerative colitis).

Use in Pregnancy and Lactation

With caution the drug is used during pregnancy and lactation.

Use in Renal Impairment

In case of chronic renal failure, dosage adjustment is necessary: with CC 10-20 ml/min, intravenous or intramuscular administration of 750 mg 2 times/day is prescribed, with CC less than 10 ml/min – 750 mg once/day.

For patients on continuous hemodialysis using an arteriovenous shunt or on high-speed hemofiltration in intensive care units, 750 mg twice daily is prescribed; for patients on low-speed hemofiltration, doses recommended for renal impairment are prescribed.

Pediatric Use

The drug should be used with caution in newborns and premature infants.

Children are prescribed 30-100 mg/kg/day in 3-4 divided doses. For most infections, the optimal dose is 60 mg/kg/day. Newborns and infants under 3 months are prescribed 30 mg/kg/day in 2-3 divided doses.

Special Precautions

Patients with a history of allergic reactions to penicillins may have hypersensitivity to cephalosporin antibiotics. During treatment, monitoring of renal function is necessary, especially in patients receiving the drug in high doses. Treatment should be continued for 48-72 hours after the symptoms disappear; in case of infections caused by Streptoccocus pyogenes, the course of treatment should be at least 7-10 days.

During treatment, a false-positive direct Coombs test and a false-positive urine glucose test are possible.

The ready-to-use solution can be stored at room temperature for 7 hours, in the refrigerator for 48 hours. The use of a solution that has turned yellow during storage is allowed.

In patients receiving Cefurabol^®, when determining blood glucose concentration, it is recommended to use tests with glucose oxidase or hexokinase. During the treatment of meningitis in children, hearing loss is possible. When switching from parenteral administration to oral administration, the severity of the infection, the sensitivity of microorganisms, and the general condition of the patient should be taken into account. If no improvement is observed 72 hours after oral administration of cefuroxime, parenteral administration should be continued.

Overdose

Symptoms CNS excitation, convulsions.

Treatment administration of antiepileptic drugs, monitoring and maintenance of vital body functions, hemodialysis and peritoneal dialysis.

Drug Interactions

Concomitant oral administration of “loop” diuretics slows tubular secretion, reduces renal clearance, increases plasma concentration, and increases the T_1/2 of Cefurabol^®.

When used concomitantly with aminoglycosides and diuretics, the risk of nephrotoxic effects increases. It is pharmaceutically compatible with metronidazole, azlocillin, xylitol, with aqueous solutions containing up to 1% lidocaine hydrochloride, 0.9% sodium chloride solution, 5% and 10% dextrose solution, 0.18% sodium chloride and 4% dextrose solution, 5% dextrose and 0.9% sodium chloride solution, Ringer’s solution, Hartmann’s solution, sodium lactate solution, heparin (10 IU/ml and 50 IU/ml) in 0.9% sodium chloride solution.

It is pharmaceutically incompatible with aminoglycosides, sodium bicarbonate solution.

Storage Conditions

List B. In a dry place, protected from light, out of reach of children, at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life is 2 years. Do not use after the expiration date printed on the package. The freshly prepared solution of the drug is suitable for use for 24 hours at a temperature not exceeding 25°C (77°F), for 96 hours when stored in a refrigerator.

Dispensing Status

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.