Cefuroxime 750 mg
Ukraine
Table of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT CEFOXIME 750 mg (CEFUROXIME 750 mg)
Composition:
Active substance: cefuroxime;
One vial contains sodium cefuroxime equivalent to cefuroxime 750 mg.
Dosage form. Powder for solution for injection.
Main physicochemical properties: crystalline powder, white to pale yellow in color.
Pharmacotherapeutic group. Antibacterial agents for systemic use. Second-generation cephalosporins. ATC code J01D C02.
Pharmacological properties.
Pharmacodynamics.
Cefuroxime is a bactericidal cephalosporin antibiotic with high activity against a broad spectrum of Gram-positive and Gram-negative bacteria, including strains producing β-lactamases. Cefuroxime is resistant to the action of β-lactamases and therefore demonstrates activity against many ampicillin- or amoxicillin-resistant strains. The primary mechanism of bactericidal action is inhibition of bacterial cell wall synthesis.
Acquired resistance to the antibiotic varies among different regions and may change over time, with significant differences observed even among individual strains. Local antibiotic susceptibility data should be consulted when available, especially in the treatment of severe infections.
The drug is highly active against Staphylococcus aureus (methicillin-sensitive strains) and coagulase-negative staphylococci (methicillin-sensitive strains), Haemophilus influenzae, Klebsiella spp., Enterobacter spp., Streptococcus pyogenes, Escherichia coli, Streptococcus mitis (Viridans group), Clostridium spp., Proteus mirabilis, Proteus rettgeri, Salmonella typhi, Salmonella typhimurium, and other Salmonella strains, Shigella spp., Neisseria spp. (including β-lactamase-producing strains of N. gonorrhoeae), and Bordetella pertussis. The drug shows moderate sensitivity against Proteus vulgaris, Morganella morganii (Proteus morganii), and Bacteroides fragilis.
Microorganisms insensitive to cefuroxime include: Clostridium difficile, Pseudomonas spp., Campylobacter spp., Acinetobacter calcoaceticus, Legionella spp., methicillin-resistant strains of Staphylococcus aureus, and coagulase-negative staphylococci.
Some strains of the following species have also been found to be insensitive to cefuroxime: Streptococcus faecalis, Morganella morganii, Proteus vulgaris, Enterobacter spp., Citrobacter spp., Serratia spp., and Bacteroides fragilis.
In vitro, cefuroxime in combination with aminoglycoside antibiotics exerts at least additive effects, sometimes showing signs of synergy.
Pharmacokinetics.
Maximum serum concentration of cefuroxime is achieved 30–45 minutes after intramuscular administration. The elimination half-life of cefuroxime following intravenous or intramuscular administration is approximately 70 minutes. Concurrent administration of probenecid slows the elimination of cefuroxime and results in increased serum concentrations.
Protein binding in serum ranges from 33% to 50%.
Within 24 hours after administration, the drug is almost completely (85–90%) excreted unchanged in urine, with the majority eliminated within the first 6 hours.
Cefuroxime is not metabolized and is excreted via glomerular filtration and tubular secretion.
Serum levels of cefuroxime decrease during dialysis.
Concentrations of cefuroxime exceeding the minimum inhibitory concentration (MIC) for most common pathogenic microorganisms are achieved in bone tissue, synovial fluid, and intraocular fluid. Cefuroxime crosses the blood-brain barrier during inflammation of the meninges.
Special patient groups
Sex
No differences in cefuroxime pharmacokinetics have been observed between men and women after a single 1000 mg intravenous bolus dose of cefuroxime as cefuroxime sodium.
Elderly patients
Following intramuscular or intravenous administration, absorption, distribution, and elimination of cefuroxime in elderly patients are similar to those in younger patients with equivalent renal function. Since elderly patients are more likely to have reduced renal function, cefuroxime dosage should be carefully selected and renal function monitored (see section "Dosage and administration").
Children
The elimination half-life of cefuroxime in serum is significantly prolonged in neonates depending on gestational age. However, in infants older than 3 weeks and in children, the serum elimination half-life of approximately 60–90 minutes is similar to that observed in adults.
Renal impairment
Cefuroxime is primarily eliminated by the kidneys. As with other similar antibiotics, patients with severe renal impairment (e.g., creatinine clearance < 20 mL/min) should receive reduced doses of cefuroxime to compensate for slower drug elimination (see section "Dosage and administration"). Cefuroxime is effectively removed by hemodialysis and peritoneal dialysis.
Hepatic impairment
Since cefuroxime is predominantly eliminated by the kidneys, hepatic impairment is not expected to significantly affect its pharmacokinetics.
Pharmacokinetic/pharmacodynamic interaction
For cephalosporins, the most important pharmacokinetic-pharmacodynamic index correlating with in vivo efficacy is the percentage of the dosing interval (%T) during which the concentration of the free fraction of the drug exceeds the MIC of cefuroxime for specific target strains (i.e., %T > MIC).
Clinical characteristics.
Indications.
Cefuroxime is indicated for the treatment of the following infections in adults and children, including neonates (from birth) (see sections "Pharmacological properties" and "Special instructions"):
- Community-acquired pneumonia.
- Exacerbations of chronic bronchitis.
- Complicated urinary tract infections, including pyelonephritis.
- Soft tissue infections: cellulitis, erysipelas, wound infections.
- Intra-abdominal infections (see section "Special instructions").
- Prophylaxis of postoperative infections following gastrointestinal tract surgery, including the esophagus, orthopedic, gynecological surgery (including cesarean section), and cardiovascular surgery.
When treating or preventing infections caused by anaerobic microorganisms, cefuroxime should be used in combination with appropriate additional antibacterial agents.
Official recommendations regarding the appropriate use of antibacterial agents should be taken into account.
Contraindications.
Hypersensitivity to cefuroxime or to any of the excipients of the medicinal product.
Hypersensitivity to cephalosporin antibiotics.
History of severe hypersensitivity (e.g., anaphylactic reactions) to other beta-lactam antibiotics (penicillins, monobactams, and carbapenems).
Interaction with other medicinal products and other forms of interaction.
Cefuroxime may affect the intestinal flora, leading to reduced reabsorption of estrogens and decreased efficacy of combined oral contraceptives.
Cefuroxime is eliminated via glomerular filtration and tubular secretion. Concomitant administration with probenecid is not recommended, as it prolongs the elimination half-life of the antibiotic and increases the maximum plasma concentration.
Potentially nephrotoxic agents and loop diuretics
Cephalosporin antibiotics in high doses should be administered with caution to patients receiving treatment with potent diuretics (such as furosemide) or potentially nephrotoxic agents (such as aminoglycoside antibiotics), as renal function impairment cannot be excluded with such combinations.
Other types of interactions
Information on plasma glucose measurement is provided in the section "Special instructions".
Concomitant use with oral anticoagulants may lead to an increased international normalized ratio (INR).
Special precautions for use.
Hypersensitivity reactions
As with other beta-lactam antibiotics, severe and occasionally fatal hypersensitivity reactions have been reported. Hypersensitivity reactions progressing to Kounis syndrome—acute allergic coronary artery spasm that may lead to myocardial infarction—have been documented (see section "Adverse reactions"). In case of severe hypersensitivity reactions, cefuroxime therapy must be discontinued immediately and appropriate emergency measures should be initiated.
Prior to initiating therapy, it is essential to determine whether the patient has a history of severe hypersensitivity reactions to cefuroxime, other cephalosporins, or other beta-lactam agents. The drug should be administered with caution in patients with a history of mild hypersensitivity reactions to other beta-lactam antibiotics.
Severe cutaneous adverse reactions (SCARs)
Severe cutaneous adverse reactions, including Stevens–Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), which may be life-threatening or fatal, have been reported during cefuroxime therapy (see section "Adverse reactions").
Patients receiving the drug should be informed about the signs and symptoms of such reactions and carefully monitored for skin reactions. If signs or symptoms suggestive of these reactions occur, cefuroxime must be discontinued immediately and alternative therapy considered. If a patient develops a serious reaction such as Stevens–Johnson syndrome, toxic epidermal necrolysis, or DRESS syndrome during cefuroxime treatment, cefuroxime must not be re-administered to this patient under any circumstances.
Concomitant therapy with potent diuretics or aminoglycosides
Cephalosporin antibiotics in high doses should be administered with caution in patients receiving therapy with potent diuretics such as furosemide or aminoglycoside antibiotics, as adverse effects on renal function have been reported with such combinations. Renal function should be monitored in these patients, as well as in elderly patients and those with renal impairment (see section "Posology and method of administration").
Overgrowth of resistant microorganisms
Administration of cefuroxime may lead to overgrowth of Candida species. Prolonged use of cefuroxime may result in overgrowth of resistant microorganisms (such as Enterococci, Clostridium difficile), which may necessitate discontinuation of treatment (see section "Adive reactions").
Cases of pseudomembranous colitis, varying in severity from mild to life-threatening, have been reported with antibiotic use. Therefore, it is important to consider this diagnosis in patients who develop diarrhea during or after antibiotic therapy (see section "Adverse reactions"). Discontinuation of cefuroxime therapy and initiation of specific treatment against Clostridium difficile should be considered. Medicinal products that inhibit intestinal peristalsis are not recommended.
Intracameral administration and ocular adverse reactions
The medicinal product is not intended for intracameral administration. Individual cases and a number of serious ocular adverse reactions have been reported following intracameral administration of cefuroxime sodium intended for intravenous/intramuscular use. These reactions included macular edema, retinal edema, retinal detachment, retinal toxicity, visual disturbances, decreased visual acuity, blurred vision, corneal clouding, and corneal edema.
Intra-abdominal infections
Due to its spectrum of activity, cefuroxime is not used for the treatment of infections caused by gram-negative non-fermenting bacteria (see section "Pharmacodynamics").
Impact on diagnostic tests
Positive Coombs' test results have been reported during cefuroxime therapy. This phenomenon may interfere with cross-matching of blood (see section "Adverse reactions").
Minor interference with copper reduction methods (Benedict, Fehling, Clinitest) may occur. However, this should not lead to false-positive results as may be observed with some other cephalosporins.
As false-negative results may occur with the ferricyanide test, glucose oxidase or hexokinase methods are recommended for determination of glucose levels in blood/plasma of patients receiving cefuroxime sodium.
Excipients
This medicinal product contains sodium. This should be taken into account in patients on a controlled sodium diet.
Use during pregnancy or breastfeeding.
Pregnancy
Data on the use of cefuroxime in pregnant women are limited. Reproductive toxicity has not been observed in animal studies. Cefuroxime should be prescribed during pregnancy only when the potential benefit justifies the potential risk to the fetus.
Cefuroxime crosses the placenta and reaches therapeutic concentrations in amniotic fluid and umbilical cord blood after intramuscular or intravenous dosing in the mother.
Breastfeeding
Cefuroxime passes into breast milk in small amounts. Adverse reactions are not expected with therapeutic doses, but the risk of diarrhea or fungal mucosal infections in the infant cannot be excluded. Therefore, a decision on whether to discontinue breastfeeding or to discontinue/abstain from cefuroxime therapy should be made, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.
Fertility
There are no data on the effect of sodium cefuroxime on fertility in humans. Reproductive studies in animals have not shown any effect of this medicinal product on fertility.
Ability to affect reaction speed when driving or operating machinery.
No studies have been conducted on the effect of cefuroxime on the ability to drive vehicles or operate machinery. However, considering the known adverse reactions, it can be concluded that cefuroxime is unlikely to affect reaction speed when driving vehicles or operating machinery.
Method of administration and dosage.
Table 1
Adults and children with body weight ≥ 40 kg
| Indications |
Dosage |
| Community-acquired pneumonia and acute exacerbations of chronic bronchitis |
750 mg every 8 hours (intravenously or intramuscularly) |
| Soft tissue infections: cellulitis, erysipelas, wound infections |
|
| Intra-abdominal infections |
|
| Complicated urinary tract infections, including pyelonephritis |
1.5 g every 8 hours (intravenously or intramuscularly) |
| Severe infections |
750 mg every 6 hours (intravenously); 1.5 g every 8 hours (intravenously) |
| Prophylaxis of postoperative infections following gastrointestinal, orthopedic, gynecological surgeries (including cesarean section) |
1.5 g during induction of anesthesia; may be supplemented with two additional doses of 750 mg (intramuscularly) at 8 and 16 hours |
| Prophylaxis of postoperative infections following cardiovascular and esophageal surgeries |
1.5 g during induction of anesthesia, followed by 750 mg (intramuscularly) every 8 hours for additional 24 hours |
Table 2
Children with body weight < 40 kg
| Indications |
Infants and children older than 3 weeks of age and children with body weight < 40 kg |
Neonates (from birth to 3 weeks of age) |
| Community-acquired pneumonia |
30 to 100 mg/kg/day (intravenously), divided into 3 or 4 doses; for most infections, the optimal dose is 60 mg/kg/day |
30 to 100 mg/kg/day (intravenously), divided into 2 or 3 doses |
| Complicated urinary tract infections, including pyelonephritis |
||
| Soft tissue infections: cellulitis, erysipelas, wound infections |
||
| Intra-abdominal infections |
Renal function impairment
Cefuroxime is primarily excreted by the kidneys. Therefore, as with other similar antibiotics, patients with marked impairment of renal function should have the dose of cefuroxime reduced to compensate for the slower elimination of the drug.
Table 3
Recommended doses of Cefuroxime 750 mg in renal function impairment
| Creatinine clearance |
T½ (hours) |
Dosage (mg) |
| > 20 mL/min/1.73 m² |
1.7–2.6 |
No need to reduce the standard dose (750 mg–1.5 g three times daily). |
| 10–20 mL/min/1.73 m² |
4.3–6.5 |
750 mg twice daily |
| < 10 mL/min/1.73 m² |
14.8–22.3 |
750 mg once daily |
| Patients undergoing hemodialysis |
3.75 |
During hemodialysis, 750 mg of cefuroxime sodium should be administered intravenously or intramuscularly at the end of each dialysis session. In addition to parenteral administration, cefuroxime sodium may be added to peritoneal dialysis fluid (usually 250 mg per 2 liters of dialysis fluid). |
| Patients with renal impairment undergoing continuous arteriovenous hemodialysis (CAVH) or high-flux hemofiltration (HFH) in intensive care units |
7.9–12.6 (CAVH) |
750 mg twice daily. Patients undergoing low-flux hemofiltration should follow the dosing regimen appropriate for renal dysfunction. |
Hepatic impairment
Cefuroxime is primarily eliminated by the kidneys. No influence on the pharmacokinetics of cefuroxime has been observed in patients with hepatic dysfunction.
After reconstitution, the preparation can be stored for up to 48 hours in a refrigerator (4 °C) or for up to 5 hours at temperatures up to 25 °C.
Route of administration
Cefuroxime should be administered by intravenous injection over 3–5 minutes directly into the vein, or via an intravenous infusion line or infusion over 30–60 minutes, or by deep intramuscular injection.
The site for intramuscular injection is the large gluteal muscle; no more than 750 mg should be administered at a single site. Doses exceeding 1.5 g should be administered intravenously.
Instructions for reconstituting the medicinal product prior to administration
Table 4
| Additional volumes and concentrations that may be useful when fractionated doses are required |
||||
| Flacon volume |
Routes of administration |
Physical state |
Amount of water to be added (ml) |
Approximate cefuroxime concentration (mg/ml)** |
| 750 mg powder for solution for injection or infusion |
||||
| 750 mg |
intramuscular intravenous bolus intravenous infusion |
suspension solution solution |
3 ml at least 6 ml at least 6 ml* |
216 116 116 |
* Reconstituted solution for addition to 50 ml or 100 ml of a compatible infusion fluid (see compatibility information below).
** The resulting volume of cefuroxime solution in the reconstituted medium increases due to the displacement factor of the active substance, resulting in the listed concentrations in milligrams per milliliter (mg/ml).
Compatibility
Sodium cefuroxime (5 mg/ml) can be stored for 24 hours at 25 °C in 5 % or 10 % xylose injection solution (for intravenous use only).
Sodium cefuroxime is compatible with aqueous solutions containing up to 1 % lidocaine hydrochloride (for intramuscular use only).
Sodium cefuroxime is compatible with the following infusion fluids and retains its properties for 24 hours at room temperature in these solutions: 0.9 % sodium chloride injection solution; 5 % glucose injection solution; 0.18 % sodium chloride with 4 % glucose injection solution; 5 % glucose with 0.9 % sodium chloride injection solution; 5 % glucose with 0.45 % sodium chloride injection solution; 5 % glucose with 0.225 % sodium chloride injection solution; 10 % glucose injection solution; Ringer’s lactate solution; M/6 sodium lactate solution; Hartmann’s solution.
The stability of cefuroxime in 0.9 % sodium chloride injection solution with 5 % glucose is not affected by the presence of sodium hydrocortisone phosphate.
Cefuroxime is also compatible for 24 hours at room temperature when diluted in infusion solution:
- with heparin (10 or 50 units/ml) in 0.9 % sodium chloride injection solution;
- with potassium chloride solution (10 or 40 mEq/L) in 0.9 % sodium chloride injection solution.
Any unused medicinal product or waste material must be disposed of in accordance with local requirements.
Children.
Can be used in children from the first days of life. The safety profile of cefuroxime in children corresponds to that in adult patients.
Overdose.
Overdose with cephalosporins may cause neurological complications, including encephalopathy, seizures, and coma.
Symptoms of overdose may occur if the drug dose has not been appropriately adjusted in patients with impaired renal function (see sections "Special precautions for use" and "Dosage and administration").
Serum levels of cefuroxime can be reduced by hemodialysis or peritoneal dialysis.
Adverse Reactions
The most commonly observed adverse reactions are neutropenia, eosinophilia, and transient elevations in liver enzymes or bilirubin, particularly in patients with pre-existing liver disease. However, there is no evidence of harmful effects on the liver or injection site reactions.
The frequency of adverse reactions listed below is approximate, as sufficient data for precise calculation are lacking for most reactions. In addition, the frequency of adverse events varies depending on the indication.
Data from clinical trials were used to classify adverse reactions from very common to rare. The frequency of other adverse reactions (e.g., <1 in 10,000) is primarily based on post-marketing experience and reflects the frequency of reporting rather than the actual incidence.
All treatment-related adverse reactions are listed below by system organ class, frequency of occurrence, and severity according to the MedDRA classification. The following frequency classification is used: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); and frequency not known (cannot be estimated from available data).
Infections and infestations
Frequency not known – overgrowth of Candida or Clostridium difficile.
Blood and lymphatic system disorders
Common – neutropenia, eosinophilia, decreased hemoglobin levels.
Uncommon – leukopenia, positive Coombs test.
Frequency not known – thrombocytopenia, hemolytic anemia.
Cephalosporins as a class may adsorb onto the surface of red blood cell membranes and interact with antibodies, leading to a positive Coombs test. This may interfere with cross-matching blood and very rarely result in hemolytic anemia.
Immune system disorders
Frequency not known – drug fever, interstitial nephritis, anaphylaxis, cutaneous vasculitis.
Cardiac disorders
Frequency not known – Kounis syndrome.
Gastrointestinal disorders
Uncommon – gastrointestinal discomfort.
Frequency not known – pseudomembranous colitis (see section "Special warnings and precautions for use").
Hepatobiliary disorders
Common – transient elevation of liver enzymes.
Uncommon – transient elevation of bilirubin levels.
Transient elevations in serum liver enzymes or bilirubin were reversible in nature.
Skin and subcutaneous tissue disorders
Uncommon – skin rashes, urticaria, pruritus.
Frequency not known – erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, angioneurotic edema, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome).
Renal and urinary disorders
Frequency not known – increased serum creatinine, blood urea nitrogen (BUN), and decreased creatinine clearance (see section "Special warnings and precautions for use").
General disorders and administration site conditions
Common – reactions at the injection site, which may include pain and thrombophlebitis.
The likelihood of pain at the intramuscular injection site increases with higher doses, but this is unlikely to lead to discontinuation of treatment.
Reporting suspected adverse reactions
Reporting of suspected adverse reactions after marketing authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, or their legal representatives, should report any suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.
Shelf life.
2 years.
Storage conditions.
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of the reach and sight of children.
Incompatibilities.
Cefuroxime must not be mixed in the same syringe with aminoglycoside antibiotics.
The pH of a 2.74% solution of sodium bicarbonate for injection significantly affects the color of the solution; therefore, this solution is not recommended for diluting cefuroxime. However, if necessary and when a patient is receiving sodium bicarbonate solution intravenously by infusion, cefuroxime may be administered directly into the infusion line.
Packaging.
Vials of 750 mg. Pack of 1 or 10 vials in a cardboard box.
Prescription status.
Prescription only.
Manufacturer.
Zeiss Pharmaceuticals Pvt. Ltd. / Zeiss Pharmaceuticals Pvt. Ltd.
Manufacturer's address and place of business.
Plot No. 72, EPIP, Phase-I, Jharmajri, Baddi, Distt. Solan, (H. P.), India.
Marketing Authorization Holder.
AAR PHARMA FZ-LLC, United Arab Emirates / AAR PHARMA FZ-LLC, United Arab Emirates.
Address of the Marketing Authorization Holder.
Premises 702, 7th Floor, Building: DSC Tower, Post Box - 478837, Dubai, United Arab Emirates.