Cefuroxime combi

INSTRUCTIONS for medical use of the medicinal product cefuroxime combi (CefuroximE combi)

Composition:

Active substance: cefuroxime;

1 vial contains cefuroxime (as cefuroxime sodium) 0.75 g.

1 set for preparation of solution for intramuscular and intravenous injections contains:

1 vial: cefuroxime (as cefuroxime sodium) – 0.75 g;

1 ampoule of 10 ml solvent: water for injections.

Pharmaceutical form. Powder for solution for injection.

Main physico-chemical properties: white or slightly yellow powder.

Solvent: water for injections, solvent for parenteral use.

Main physico-chemical properties: colorless clear liquid.

Pharmacotherapeutic group. Antibacterial agents for systemic use.

Second-generation cephalosporins. ATC code J01D C02.

Pharmacological properties.

Pharmacodynamics.

Mechanism of action

Cefuroxime inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs). This inhibits the biosynthesis of the cell wall (peptidoglycan), leading to lysis and death of bacterial cells.

Mechanism of resistance

Bacterial resistance to cefuroxime may be associated with one or more of the following mechanisms:

• hydrolysis by beta-lactamases, including (but not limited to) extended-spectrum beta-lactamases (ESBLs) and AmpC enzymes, which may be inducible or stably expressed in certain aerobic Gram-negative bacterial species;
• reduced affinity of PBPs for cefuroxime;
• outer membrane impermeability, limiting access of cefuroxime to PBPs in Gram-negative bacteria;
• bacterial efflux pump systems.

Organisms that have developed resistance to other injectable cephalosporins are expected to be resistant to cefuroxime. Depending on the resistance mechanism, organisms with acquired resistance to penicillins may exhibit reduced susceptibility or resistance to cefuroxime.

Cefuroxime sodium breakpoints

• Breakpoint minimum inhibitory concentrations (MICs) for cefuroxime established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST):

Microorganism	Breakpoint concentrations (mg/l)
	Susceptible	Resistant
Enterobacteriaceae 1	≤82	>8
Staphylococcus spp.	Note 3	Note 3
Streptococcus A, B, C and G	Note 4	Note 4
Streptococcus pneumoniae	≤0.5	>1
Streptococcus (other)	≤0.5	>0.5
Haemophilus influenzae	≤1	>2
Moraxella catarrhalis	≤4	>8
Non-species-related breakpoint concentrations 1	≤45	>85
1 Breakpoint concentrations for determining cephalosporin activity against Enterobacteriaceae detect all clinically important resistance mechanisms (including ESBLs and plasmid-mediated AmpC). Some strains producing beta-lactamases may be susceptible or show intermediate resistance to 3rd or 4th generation cephalosporins according to these breakpoints and should be reported as determined; thus, the presence or absence of ESBLs alone does not affect susceptibility categorization. In many regions, detection and characterization of ESBLs are recommended or mandatory for infection control purposes. 2 Breakpoint concentrations apply only to the 1.5 g × 3 dosage and to E. coli, Proteus mirabilis, and Klebsiella spp. strains. 3 Staphylococcal susceptibility to cephalosporins follows methicillin susceptibility, except for ceftazidime, cefixime, and cefetibuten, which lack breakpoint concentrations and should not be used for treatment of staphylococcal infections. 4 Streptococcal susceptibility of groups A, B, C, and G to cephalosporins follows benzylpenicillin susceptibility. 5 Breakpoint concentrations apply to an intravenous daily dose of 750 mg × 3 and high-dose regimens of at least 1.5 g × 3.

Microbiological susceptibility

Acquired resistance to the antibiotic varies by region and over time for individual microorganisms. Local antibiotic susceptibility data should be consulted, especially when treating severe infections. If acquired resistance to the antibiotic is known and the benefit of using the medicinal product is at least questionable in the treatment of certain types of infections, consultation with a specialist is recommended.

Cefuroxime generally has in vitro activity against the following microorganisms:

Susceptible strains

Gram-positive aerobes: Staphylococcus aureus (methicillin-susceptible), Streptococcus pyogenes, Streptococcus agalactiae

Gram-negative aerobes: Haemophilus parainfluenzae, Moraxella catarrhalis

Microorganisms for which acquired resistance may be a problem

Gram-positive aerobes: Streptococcus pneumoniae, Streptococcus mitis (viridans group)

Gram-negative aerobes: Citrobacter spp., excluding C. freundii, Enterobacter spp., excluding E. aerogenes and E. cloacae, Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, Proteus mirabilis, Proteus spp., excluding P. penneri and Proteus vulgaris, Providencia spp., Salmonella spp.

Gram-positive anaerobes: Peptostreptococcus spp., Propionibacterium spp.

Gram-negative anaerobes: Fusobacterium spp., Bacteroides spp.

Microorganisms with inherent resistance

Gram-positive aerobes: Enterococcus faecalis, Enterococcus faecium

Gram-negative aerobes: Acinetobacter spp., Burkholderia cepacia, Campylobacter spp., Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, Morganella morganii, Proteus penneri, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescens, Stenotrophomonas maltophilia

Gram-positive anaerobes: Clostridium difficile

Gram-negative anaerobes: Bacteroides fragilis

Others: Chlamydia spp., Mycoplasma spp., Legionella spp.

$ All methicillin-resistant S. aureus are resistant to cefuroxime.

In vitro, cefuroxime in combination with aminoglycoside antibiotics exerts at least an additive effect, sometimes with evidence of synergy.

Pharmacokinetics

Absorption

After intramuscular (IM) administration of cefuroxime to healthy volunteers, mean peak serum concentrations were 27–35 mcg/mL for a 750 mg dose and 33–40 mcg/mL for a 1000 mg dose, achieved within 30–60 minutes after administration. Fifteen minutes after intravenous (IV) infusion of 750 mg and 1500 mg doses, serum concentrations were approximately 50 mcg/mL and 100 mcg/mL, respectively.

Following IM and IV administration, the area under the plasma concentration-time curve (AUC) and maximum concentration (Cmax) increase linearly with increasing dose within the single-dose range of 250 mg to 1000 mg. There was no evidence of cefuroxime accumulation in serum in healthy volunteers after repeated IV infusions of 1500 mg every 8 hours.

Distribution

Protein binding ranges from 33% to 50%, depending on the methodology used. The mean volume of distribution is 9.3–15.8 L/1.73 m² after IM or IV administration within the dose range of 250 mg to 1000 mg. Cefuroxime concentrations exceeding the MIC for most common pathogenic microorganisms are achieved in tonsillar tissue, nasal sinuses, bronchial mucosa, bone, pleural fluid, joint fluid, synovial fluid, interstitial fluid, bile, sputum, and intraocular fluid. Cefuroxime crosses the blood-brain barrier during meningitis.

Biotransformation

Cefuroxime is not metabolized.

Elimination

Cefuroxime is eliminated by glomerular filtration and tubular secretion. The serum elimination half-life after intramuscular or intravenous injection is approximately 70 minutes. Within 24 hours after administration, the drug is almost completely (85–90%) excreted unchanged in urine. The majority of the dose is excreted within the first 6 hours. Mean renal clearance ranges from 114 to 170 mL/min/1.73 m² after IM or IV injection within the 250–1000 mg dose range.

Special patient groups

Gender

No differences in cefuroxime pharmacokinetics were observed between men and women after a single 1000 mg intravenous bolus injection of cefuroxime as cefuroxime sodium.

Elderly patients

After intramuscular or intravenous administration, absorption, distribution, and excretion of cefuroxime in elderly patients are similar to those in younger patients with equivalent renal function. However, since elderly patients are more likely to have decreased renal function, cefuroxime dosage should be selected with caution in this population, and renal function should be monitored (see section "Dosage and administration").

Children

The serum elimination half-life of cefuroxime 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 excretion (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 (unbound) 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 precautions for use"):

• 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 precautions for use").
• Prophylaxis of postoperative infections following gastrointestinal tract surgery, including esophageal surgery, 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 other 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 types of interactions.

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 of probenecid is not recommended. Simultaneous administration of probenecid slows elimination of the antibiotic and results in increased serum concentrations.

Potentially nephrotoxic drugs 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 drugs (such as aminoglycoside antibiotics), as renal function impairment cannot be excluded with such combinations.

Other types of interactions

Regarding determination of plasma glucose levels: see section "Special precautions for use".

Concomitant use with oral anticoagulants may lead to increased international normalized ratio (INR).

Special precautions for use.

Hypersensitivity reactions

Severe and occasionally fatal hypersensitivity reactions have been observed during treatment with beta-lactam antibiotics, including cefuroxime. Hypersensitivity reactions progressing to Kounis syndrome (acute allergic coronary artery spasm that may lead to myocardial infarction — see section "Adverse reactions") have been reported. If severe hypersensitivity reactions occur, cefuroxime therapy must be discontinued immediately and appropriate emergency measures should be initiated.

Prior to initiating therapy, it is necessary to ascertain whether the patient has a history of severe hypersensitivity reactions to cefuroxime, other cephalosporins, or other beta-lactam drugs. The drug should be administered with caution in patients with a history of hypersensitivity reactions to other beta-lactam antibiotics.

Concomitant treatment with potent diuretics or aminoglycosides

Cephalosporin antibiotics administered in high doses should be used with caution in patients receiving concomitant treatment with potent diuretics such as furosemide or aminoglycosides. Cases of impaired renal function have been reported with this combination of drugs. Renal function should be monitored in these patients, as in elderly patients and in those with pre-existing renal impairment (see section "Dosage and administration").

Overgrowth of resistant microorganisms

Cefuroxime use 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 require discontinuation of therapy (see section "Adverse reactions").

Cases of pseudomembranous colitis of varying severity, ranging from mild to life-threatening, have been reported during antibiotic therapy. Therefore, it is important to consider this diagnosis in patients who develop diarrhea during or after antibiotic use (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

Cefuroxime combi is not intended for intracameral administration. Individual cases and series of serious ocular adverse reactions have been reported after intracameral use of sodium cefuroxime intended for intravenous/intramuscular administration. These reactions included macular edema, retinal edema, retinal detachment, retinal toxicity, visual disturbances, decreased visual acuity, blurred vision, corneal opacity, and corneal edema.

Intra-abdominal infections

Due to its spectrum of activity, cefuroxime is not suitable for treatment of infections caused by gram-negative non-fermenting bacteria (see section "Pharmacodynamics").

Severe cutaneous adverse reactions (SCARs)

Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), which were life-threatening or resulted in fatal outcomes, have been reported in association with cefuroxime therapy (see section "Adverse reactions").

Patients should be informed about the signs and symptoms of these reactions, and careful monitoring for skin reactions should be performed during treatment. If symptoms suggestive of these reactions occur, cefuroxime should be discontinued immediately and alternative therapy considered. Re-administration of cefuroxime to a patient who has experienced a serious reaction such as SJS, TEN, or DRESS syndrome is absolutely contraindicated.

Effect on diagnostic tests

Positive Coombs test results have been reported during cefuroxime therapy. This phenomenon may affect cross-matching of blood (see section "Adverse reactions").

Minor interference with copper reduction methods (Benedict’s, Fehling’s, Clinitest) may occur. However, this should not lead to false-positive results as may occur with some other cephalosporins.

Because false-negative results may occur with the ferricyanide test, glucose oxidase or hexokinase methods are recommended for determination of blood/plasma glucose levels in patients receiving sodium cefuroxime.

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 combi should be administered to pregnant women only when the potential benefit justifies the potential risk to the fetus.

Cefuroxime crosses the placenta and reaches therapeutic levels in amniotic fluid and umbilical cord blood after intramuscular or intravenous dosing in the mother.

Breastfeeding period

Cefuroxime passes into breast milk in small amounts. Adverse reactions are not expected with therapeutic doses, but the possibility 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 benefits of breastfeeding for the infant and the benefits of therapy for the woman.

Fertility

There are no data on the effect of sodium cefuroxime on fertility in humans. Studies on reproductive function in animals have not shown any effect of this medicinal product on fertility.

Ability to affect reaction speed when driving vehicles 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 the speed of reaction when driving vehicles or operating machinery.

Method of administration and dosage.

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 surgery, orthopedic and gynecological surgeries (including cesarean section)	1.5 g during induction of anesthesia; may be supplemented with two additional doses of 750 mg (intramuscularly) given at 8 and 16 hours
Prophylaxis of postoperative infections following cardiovascular surgery and esophageal surgery	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 and children with body weight <40 kg	Neonates (from birth to 3 weeks)
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, erysipeloïd, wound infections
Intra-abdominal infections

Renal function impairment

Cefuroxime is primarily eliminated via the kidneys. Therefore, as with other similar antibiotics, patients with marked renal impairment should receive reduced doses of the medicinal product Cefuroxime combi to compensate for the slower drug excretion.

Table 3

Recommended doses of the medicinal product Cefuroxime combi in renal impairment

Creatinine clearance	T1/2 (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, administer 750 mg intravenously or intramuscularly at the end of each dialysis session. In addition to parenteral administration, sodium cefuroxime may be added to peritoneal dialysis fluid (usually 250 mg per 2 liters of dialysis fluid).
Patients with renal insufficiency undergoing continuous arteriovenous hemodialysis (CAVH) or high-flux hemofiltration (HFH) in intensive care units	7.9–12.6 (CAVH) 1.6 (HFH)	750 mg twice daily. Patients undergoing low-flux hemofiltration should follow the dosing regimen appropriate for impaired renal function.

Hepatic impairment

Cefuroxime is primarily excreted by the kidneys. No influence on the pharmacokinetics of cefuroxime has been observed in patients with hepatic dysfunction.

Method of administration

Cefuroxime Combi should be administered by intravenous injection over 3–5 minutes directly into the vein or via an infusion line 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 injected at a single site. Doses exceeding 1.5 g must be administered intravenously.

Instructions for dilution of the medicinal product prior to administration

	Additional volumes and concentrations that may be useful when fractional doses are required
Vial volume	Routes of administration	Physical state	Volume 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
	1.5 g powder for solution for injection or infusion
1.5 g	intramuscular intravenous bolus intravenous infusion	suспension solution solution	6 ml at least 15 ml 15 ml *	216 94 94

* 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, leading to the stated concentrations in milligrams per milliliter (mg/ml).

Compatibility

1.5 g of Cefuroxime Comb can be used together with metronidazole injection (500 mg/100 ml); both drugs retain their activity for 24 hours at temperatures below 25 °C.

1.5 g of Cefuroxime Comb is compatible with 1 g of azlocillin (in 15 ml solvent) or with 5 g (in 50 ml solvent) for 24 hours at 4 °C and for 6 hours at temperatures up to 25 °C.

The medicinal product Cefuroxime Comb (5 mg/ml) can be stored for 24 hours at 25 °C in 5% or 10% xylitol injection solution.

Cefuroxime Comb is compatible with solutions containing up to 1% lidocaine hydrochloride.

Cefuroxime Comb is compatible with most commonly used intravenous infusion solutions. It remains stable for 24 hours at room temperature in the following 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; 10% invert sugar solution in water for injection; Ringer's solution; Ringer's lactate solution; M/6 sodium lactate solution; Hartmann's solution.

The stability of Cefuroxime Comb in 0.9% sodium chloride injection solution with 5% glucose is not affected by the presence of sodium hydrocortisone phosphate.

The medicinal product Cefuroxime Comb is also compatible for 24 hours at room temperature when diluted in infusion solutions:

• 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 observed in adult patients.

Overdose.

Neurological complications including encephalopathy, seizures, and coma may occur in case of overdose. Symptoms of overdose may arise if the dose of the medicinal product 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 and peritoneal dialysis.

Adverse reactions

The most commonly reported adverse reactions are neutropenia, eosinophilia, and transient elevations in liver enzymes or bilirubin, particularly in patients with pre-existing liver disease; however, there are no data indicating harmful effects on the liver or injection site reactions.

The frequency of adverse reactions listed below is approximate, as there are insufficient data to determine exact frequencies for most reactions. In addition, the frequency of adverse reactions associated with cefuroxime varies depending on the indication.

Classification of adverse reactions from very common to rare is based on clinical trial data. The frequency of other adverse reactions (e.g., <1 in 10,000) is primarily derived from post-marketing experience and reflects the reporting rate rather than the actual incidence.

All treatment-related adverse reactions are listed below by system organ class, frequency, and severity according to the MedDRA classification. The following frequency classification is used: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10,000, <1/1000); very rare (<1/10,000); frequency not known (cannot be estimated from available data).

Organ system class	Common	Uncommon	Frequency not known
Infections and infestations			Overgrowth of Candida or Clostridium difficile
Cardiac disorders			Kounis syndrome
Blood and lymphatic system disorders	Neutropenia, eosinophilia, decreased hemoglobin levels	Leukopenia, positive Coombs test	Thrombocytopenia, hemolytic anemia
Immune system disorders			Drug fever, interstitial nephritis, anaphylaxis, cutaneous vasculitis
Gastrointestinal disorders		Discomfort in the gastrointestinal tract	Pseudomembranous colitis (see section "Special precautions")
Hepatobiliary disorders	Transient elevation of liver enzymes	Transient elevation of bilirubin levels
Skin and subcutaneous tissue disorders		Skin rashes, urticaria, pruritus	Multiform erythema, toxic epidermal necrolysis, Stevens–Johnson syndrome, angioneurotic edema, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome)
Renal and urinary disorders			Increased serum creatinine and blood urea nitrogen levels, decreased creatinine clearance (see section "Special precautions")
General disorders and administration site reactions	Administration site reactions, which may include pain and thrombophlebitis
Description of selected adverse reactions Cephalosporins as a class have the property of being absorbed on the surface of erythrocyte membranes and interacting with antibodies, which may lead to a positive Coombs test result (which may affect cross-matching blood compatibility), very rarely – to hemolytic anemia. Transient elevations in serum liver enzymes or bilirubin levels were reversible in nature. The likelihood of pain at the site of intramuscular injection is greater when higher doses are administered, although this is unlikely to be a reason for discontinuation of treatment.

Shelf life. 3 years.

Water for injections – 4 years.

The shelf life is determined by the component of the medicinal product (powder or solvent) with the shorter expiration date.

Storage conditions. No special storage conditions required.

After reconstitution, the solution may be stored for up to 48 hours in a refrigerator (from 2 to 8 °C) or up to 5 hours at a temperature not exceeding 25 °C. Keep out of the reach of children.

Incompatibility.

Cefuroxime Combi must not be mixed in the same syringe with aminoglycoside antibiotics.

The pH of 2.74% sodium bicarbonate solution for injection significantly affects the color of the solution; therefore, this solution is not recommended for reconstitution of Cefuroxime Combi. However, if necessary, when a patient is receiving sodium bicarbonate solution by intravenous infusion, Cefuroxime Combi may be administered directly into the infusion line.

Packaging. 0.75 g of cefuroxime powder in a vial; 1 vial with 0.75 g powder and 1 ampoule of solvent (10 ml water for injections) in a blister pack, 1 blister pack in a carton.

Prescription status. Prescription only.

Manufacturers. Private Joint Stock Company "Lekhim-Kharkiv". LLC "Lekhim-Obukhiv".

Manufacturer's address and location of business activity.

36 Severina Pototskoho Street, Kharkiv, Kharkiv region, 61115, Ukraine.

126A Kyivska Street, Obukhiv, Kyiv region, 08700, Ukraine.