Axetine (Powder) Instructions for Use

Marketing Authorization Holder

Medochemie, Ltd. (Cyprus)

Contact Information

MEDOCHEMIE Ltd. (Cyprus)

ATC Code

J01DC02 (Cefuroxime)

Active Substance

Cefuroxime (Rec.INN registered by WHO)

Dosage Forms

	Axetine	Powder for preparation of solution for intravenous and intramuscular administration 1.5 g: vial 1 or 100 pcs.
		Powder for preparation of solution for intravenous and intramuscular administration 750 mg: vial 1 or 100 pcs.

Dosage Form, Packaging, and Composition

Powder for preparation of solution for IV and IM administration from white to light yellow color.

Glass vials (1) – cardboard boxes.
Glass vials (100) – cardboard boxes.

Clinical-Pharmacological Group

Second generation cephalosporin

Pharmacotherapeutic Group

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

Pharmacological Action

Cephalosporin antibiotic of the II generation for parenteral administration. 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 Streptococcus (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 (Branhamella) catarrhalis, Neisseria gonorrhoeae, including both penicillinase-producing and non-penicillinase-producing strains, Neisseria meningitidis, Salmonella spp., Bacteroides spp. (except Bacteroides fragilis), Fusobacterium spp., Propionibacterium spp., Borrelia burgdorferi; gram-positive and gram-negative anaerobic microorganisms (including Peptococcus spp. and Peptostreptococcus spp.).

The following microorganisms are resistant 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

Absorption

After IM administration of the drug at a dose of 750 mg, C_max of cefuroxime in blood plasma is reached within 15-60 minutes and is 27 mcg/ml. After IV administration at doses of 750 mg and 1.5 g, C_max is reached after 15 minutes and is 50 and 100 mcg/ml, respectively. The therapeutic concentration persists for 5.3 and 8 hours, respectively.

Distribution

Plasma protein binding is 33-50%.

Therapeutic concentrations are determined in pleural fluid, bile, sputum, myocardium, skin, and soft tissues. Cefuroxime concentrations exceeding the MIC for most common microorganisms are achieved in bone tissue, synovial fluid, and intraocular fluid.

It penetrates the placental barrier and is excreted in breast milk.

Metabolism

It is not metabolized in the liver.

Excretion

T_1/2 after IM and IV administration is 80 minutes; in newborns, it increases by 3-5 times.

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

Pharmacokinetics in special clinical cases

In newborns, T_1/2 is longer by 3-5 times.

In meningitis, it penetrates the BBB.

Indications

Infectious and inflammatory diseases caused by microorganisms sensitive to the drug

• Respiratory tract infections (including bronchitis, pneumonia, lung abscess, pleural empyema);
• ENT organ infections (including sinusitis, tonsillitis, pharyngitis);
• Urinary tract infections (including pyelonephritis, cystitis, symptomatic bacteriuria, gonorrhea);
• Skin and soft tissue infections (including erysipelas);
• Bone and joint infections (including osteomyelitis, septic arthritis);
• Pelvic organ infections (in obstetrics and gynecology);
• Septicemia;
• Meningitis.

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

ICD codes

Dosage Regimen

IM and IV for adults, the drug is prescribed at 750 mg 3 times/day; 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, it is prescribed 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. For newborns and children under 3 months of age, the drug is prescribed at a dose of 30 mg/kg/day in 2-3 divided doses.

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

For bacterial meningitis – IV 3 g every 8 hours; for younger and older children – 150-250 mg/kg/day in 3-4 divided doses, for newborns – 100 mg/kg/day.

For abdominal, pelvic, and orthopedic surgeries – IV 1.5 g at induction of anesthesia, then additionally – IM 750 mg after 8 and 16 hours after surgery.

For heart, lung, esophageal, and vascular surgeries – IV 1.5 g at induction of anesthesia, then – IM 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 methylmethacrylate polymer cement before adding the liquid monomer.

For pneumonia – IM or IV 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, it is prescribed IM or IV 750 mg 2-3 times/day for 48-72 hours, then switch to oral administration (using oral dosage forms) 500 mg 2 times/day for 5-10 days.

In chronic renal failure, dosage adjustment is necessary. For CrCl 10-20 ml/min, prescribe IV or IM 750 mg 2 times/day, for CrCl less than 10 ml/min – 750 mg once/day.

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

Adverse Reactions

Allergic reactions chills, rash, itching, urticaria; rarely – multiform erythema, bronchospasm, Stevens-Johnson syndrome, anaphylactic shock.

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 activity of liver enzymes in plasma – AST, ALT, ALP, LDH; bilirubin), cholestasis.

From the urinary system: impaired renal function (decreased CrCl, increased blood creatinine and urea nitrogen), dysuria.

From the reproductive system perineal itching, 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.

Contraindications

• Hypersensitivity to cefuroxime and other cephalosporins, to penicillins and carbapenems.

With caution, the drug should be prescribed to newborn children, premature infants, in chronic renal failure, bleeding and gastrointestinal diseases (including in history, including UC), debilitated and exhausted patients.

Use in Pregnancy and Lactation

The drug should be prescribed with caution during pregnancy and lactation.

Use in Renal Impairment

In chronic renal failure, dosage adjustment is necessary. For CrCl 10-20 ml/min, prescribe IV or IM 750 mg 2 times/day, for CrCl less than 10 ml/min – 750 mg once/day.

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

Pediatric Use

The drug should be prescribed with caution to newborns and premature infants.

Special Precautions

In patients with a history of allergic reactions to penicillins, there may be hypersensitivity to cephalosporin antibiotics.

During treatment, renal function monitoring is necessary, especially in patients receiving the drug in high doses. Treatment is recommended to continue for 48-72 hours after the symptoms disappear; in case of infections caused by Streptococcus pyogenes, it is recommended to continue treatment for at least 10 days.

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

After reconstitution, it 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.

During treatment, alcohol consumption should be avoided.

In patients receiving Cefuroxime, it is recommended to use glucose oxidase or hexokinase tests when determining blood glucose levels.

During treatment of meningitis in children, hearing loss is possible.

When switching from parenteral administration to oral administration, the severity of the infection, sensitivity of microorganisms, and the general condition of the patient should be taken into account. If no clinical improvement is observed 72 hours after oral administration of cefuroxime, it is necessary to continue parenteral administration.

Overdose

Symptoms CNS excitation, convulsions.

Treatment: administration of anticonvulsants, ensuring lung ventilation and cardiovascular system function, monitoring and maintaining vital body functions, hemodialysis and peritoneal dialysis.

Drug Interactions

With simultaneous oral administration of “loop” diuretics, tubular secretion is slowed, renal clearance is reduced, plasma concentration is increased, and T_1/2 of cefuroxime is increased.

With simultaneous use with aminoglycosides and diuretics, the risk of nephrotoxic effects increases.

Drugs that reduce gastric acidity reduce the absorption and bioavailability of cefuroxime.

Pharmaceutical interaction

Pharmaceutically compatible with metronidazole, azlocillin, xylitol, with aqueous solutions containing up to 1% lidocaine hydrochloride, 0.9% sodium chloride solution, 5% dextrose solution, 0.18% sodium chloride and 4% dextrose solution, 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; 10% inverted sugar in water for injections, Ringer’s solution, sodium lactate solution, Hartmann’s solution, 0.9% sodium chloride solution, 5% dextrose and hydrocortisone, 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.

Pharmaceutically incompatible with aminoglycosides, 2.74% sodium bicarbonate solution.

Storage Conditions

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

Shelf Life

Shelf life – 2 years.

Dispensing Status

The drug is dispensed by prescription.

Dispensing Status

Rx Only

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.