Cefurus^® (Powder) Instructions for Use

Marketing Authorization Holder

Sintez PJSC (Russia)

Contact Information

SINTEZ PJSC Kurgan Joint Stock Company of Medical Preparations and Products (Russia)

ATC Code

J01DC02 (Cefuroxime)

Active Substance

Cefuroxime (Rec.INN registered by WHO)

Dosage Forms

	Cefurus®	Powder for solution for intravenous and intramuscular administration 0.75 g: vial 1 or 10 pcs.
		Powder for solution for intravenous and intramuscular administration 1.5 g: vial 1 or 10 pcs.

Dosage Form, Packaging, and Composition

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

0.75 g – vials with a capacity of 10 ml (1) – cardboard packs.
0.75 g – vials with a capacity of 10 ml (10) – cardboard boxes.

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

1.5 g – vials with a capacity of 20 ml (1) – cardboard packs.
1.5 g – vials with a capacity of 20 ml (10) – cardboard packs.

Clinical-Pharmacological Group

Second generation cephalosporin

Pharmacotherapeutic Group

Systemic antibacterial agents; other beta-lactam antibacterial agents; second-generation cephalosporins

Pharmacological Action

Cefuroxime belongs to the second-generation cephalosporin antibiotics for parenteral administration. Cefuroxime is active against a wide range of pathogens, including strains producing β-lactamases. The bactericidal action of cefuroxime is associated with the suppression of bacterial cell wall synthesis.

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

The following microorganisms are resistant to cefuroxime: Clostridium difficile, Pseudomonas spp., Campylobacter spp., Acinetobacter calcoaceticus, Listeria monocytogenes, methicillin-resistant strains of Staphylococcus aureus and Staphylococcus epidermidis, Enterococcus faecalis; Legionella spp., Morganella morganii, Proteus vulgaris, Enterobacter spp., Citrobacter spp., Serratia spp., Bacteroides fragilis.

Pharmacokinetics

Absorption

After intramuscular administration of the drug at a dose of 750 mg, C_max is reached within 15-60 minutes and is 27 µg/ml. With intravenous administration of the drug at doses of 750 mg and 1.5 g, C_max is reached within 15 minutes and is 50 µg/ml and 100 µg/ml, respectively. The therapeutic concentration in the blood is maintained for 5.3 and 8 hours, respectively.

Distribution and Metabolism

It is not metabolized in the liver.

Plasma protein binding is 33-50%. Therapeutic concentrations are achieved in pleural fluid, bile, sputum, myocardium, skin, and soft tissues. Concentrations of cefuroxime exceeding the minimum inhibitory concentration for most common microorganisms can be achieved in bone tissue, synovial fluid, and intraocular fluid. In meningitis, it penetrates the blood-brain barrier. It crosses the placental barrier and is excreted in breast milk.

Elimination

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

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

Indications

Bacterial infections caused by susceptible microorganisms:

• Respiratory tract infections (bronchitis, pneumonia, lung abscess, pleural empyema);
• ENT infections (sinusitis, tonsillitis, pharyngitis);
• Urinary tract infections (pyelonephritis, cystitis, symptomatic bacteriuria);
• Gonorrhea;
• Skin and soft tissue infections (erysipelas, pyoderma, impetigo, furunculosis, cellulitis, wound infection, erysipeloid);
• Bone and joint infections (osteomyelitis, septic arthritis);
• Pelvic organ infections (endometritis, adnexitis, cervicitis);
• Sepsis;
• Meningitis;
• Lyme disease (borreliosis).

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

ICD codes

Dosage Regimen

The drug is administered intramuscularly and intravenously (bolus or drip).

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

For children over 3 months 30-100 mg/kg/day in 3-4 administrations is prescribed. For most infections, the optimal dose is 60 mg/kg/day.

For newborns and children under 3 months 30 mg/kg/day in 2-3 administrations is prescribed.

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

For bacterial meningitis – intravenously 3 g every 8 hours; for infants and older children – 150-250 mg/kg/day in 3-4 administrations, for newborns – 100 mg/kg/day.

For pneumonia – intramuscularly or intravenously 1.5 g 2-3 times/day for 48-72 hours, then switch to oral administration (using oral dosage forms) 500 mg 2 times/day for 7-10 days.

For exacerbation of chronic bronchitis intramuscularly or intravenously 750 mg 2-3 times/day for 48-72 hours is prescribed, then switch to oral administration (using oral dosage forms) 500 mg 2 times/day for 5-10 days.

For the prevention of postoperative complications

• during operations on the heart, lungs, esophagus and blood vessels – intravenously 1.5 g 0.5-1 hour before surgery and 750 mg intravenously or intramuscularly every 8 hours during prolonged operations over the next 24-48 hours (for open-heart surgery, the total dose is up to 6 g);
• during operations on the abdomen, pelvic organs and during orthopedic operations – intravenously 1.5 g at induction of anesthesia, then additionally intramuscularly 750 mg at 8 and 16 hours after surgery;
• 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 adults with chronic renal failure dosage adjustment is necessary. For CrCl 10-20 ml/min intravenous or intramuscular 750 mg 2 times/day is prescribed, for CrCl less than 10 ml/min – 750 mg 1 time/day.

For children with chronic renal failure the dosage regimen should be adjusted according to the recommendations for adults.

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

Preparation of suspension and solution for parenteral administration

To prepare a suspension for intramuscular administration, add 3 ml of water for injections to 750 mg (10 ml vial), to 1.5 g (20 ml vial) – 6 ml of water for injections. Shake gently until a suspension is formed.

To prepare a solution for intravenous bolus administration, add 9 ml of water for injections to 750 mg (10 ml vial); to 1.5 g (20 ml vial) – 14 ml of water for injections.

To prepare a solution for intravenous infusion – short-term intravenous infusions (e.g., up to 30 minutes) – 1.5 g is dissolved in 50 ml of water for injections. This solution can be administered directly into a vein or into an infusion system if the patient is receiving parenteral fluids.

Adverse Reactions

Allergic reactions chills, rash, itching, urticaria; rarely – erythema multiforme, bronchospasm, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome), bronchospasm, drug fever, serum sickness, anaphylactic shock, cutaneous vasculitis.

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

From the reproductive system perineal itching, vaginitis.

From the urinary system impaired renal function (decreased creatinine clearance, increased blood creatinine and/or urea nitrogen), dysuria, interstitial nephritis.

From the hematopoietic system eosinophilia, leukopenia, neutropenia, thrombocytopenia, agranulocytosis, hemolytic anemia, decreased hemoglobin and hematocrit.

From the nervous system convulsions.

From the sensory organs hearing loss.

Local reactions with intramuscular administration – pain, irritation and infiltrate at the injection site; with intravenous administration – phlebitis, thrombophlebitis.

Laboratory parameters false-positive Coombs test, hypoprothrombinemia, prolonged prothrombin time.

Contraindications

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

With caution the drug should be prescribed to newborns (including premature infants), with chronic renal failure, bleeding and gastrointestinal diseases (including in history, nonspecific ulcerative colitis), to debilitated and exhausted patients, during pregnancy, during lactation, with simultaneous use with aminoglycosides, “loop” diuretics.

Use in Pregnancy and Lactation

Use of the drug during pregnancy and breastfeeding is possible if the expected benefit to the mother outweighs the potential risk to the fetus and child.

Use in Renal Impairment

In chronic renal failure dosage adjustment is necessary. For CrCl 10-20 ml/min intravenous or intramuscular 750 mg 2 times/day is prescribed, for CrCl less than 10 ml/min – 750 mg 1 time/day.

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

Pediatric Use

With caution the drug should be prescribed to newborns (including premature infants).

For children over 3 months the drug is administered intravenously and intramuscularly at 30-100 mg/kg/day in 3-4 administrations. For most infections, the optimal dose is 60 mg/kg/day.

For newborns and children under 3 months 30 mg/kg/day in 2-3 administrations is prescribed.

For bacterial meningitis – intravenously for infants and older children – 150-250 mg/kg/day in 3-4 administrations, for newborns – 100 mg/kg/day.

Geriatric Use

In elderly patients, renal function monitoring is necessary during treatment.

Special Precautions

Patients with a history of allergic reactions to penicillins may exhibit hypersensitivity to cephalosporin antibiotics.

During treatment, monitoring of renal function is necessary, especially in patients receiving the drug in high doses, in elderly patients, with a history of kidney disease, with simultaneous use with aminoglycosides and “loop” diuretics.

Treatment is continued for 48-72 hours after the symptoms disappear.

In case of infections caused by Streptococcus 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 test for glucose are possible. In patients receiving Cefuroxime, it is recommended to use glucose oxidase or hexokinase tests when determining blood glucose concentration.

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 occurred during or after a course of antibiotic treatment.

Ethanol should not be consumed during treatment.

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 there is no clinical effect within 72 hours from the start of treatment, the parenteral course of therapy should be continued.

Effect on the ability to drive vehicles and machinery

During the treatment period, caution must be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms: CNS excitation, convulsions.

Treatment: symptomatic therapy, 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 cefuroxime.

When used concomitantly with aminoglycosides and diuretics, the risk of nephrotoxic effects increases.

Pharmaceutical interaction

Pharmaceutically compatible with aqueous solutions containing up to 1% lidocaine hydrochloride, 0.9% sodium chloride solution, 5% and 10% dextrose (glucose) solution, 0.18% sodium chloride and 4% dextrose (glucose) solution, 5% dextrose (glucose) solution and 0.9% sodium chloride solution, Ringer’s solution, sodium lactate solution, Hartmann’s solution, heparin (10 IU/ml and 50 IU/ml) in 0.9% sodium chloride solution.

Pharmaceutically incompatible with aminoglycosides, 2.74% sodium bicarbonate solution.

Storage Conditions

The drug should be stored in a dry, light-protected place, 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, it can be stored at room temperature for 7 hours, in a refrigerator for 48 hours. The use of a solution that has turned yellow during storage is allowed.

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.