- Approval Id
- 1fa994722ab886ad
- Drug Approval Emc Name
- Cefuroxime 1.5 g Powder for solution for injection vial
- Drug Name
- Cefuroxime 1.5 g Powder for solution for injection vial
- Company Name
- Reig Jofre UK Ltd
- Company Address
- Follaton House, Plymouth Road, Totnes, Devon, TQ9 5NE, UK
- Company Website
- //www.reigjofre.com/en
- Company Telephone
- 01803 300401
- Company Medical Info Direct Line
- 0330 1359 434
- Company Medical Info Email
- MedInfoUK@reigjofre.com
- Company Customer Care Direct Line
- 01803 300401
- Atc Code
- J01CD02
- Legal Category
- Prescription only medicine
- Authorisation Holder
- Reig Jofre UK Limited
Unit 9A Caddsdown Business Support Centre, Caddsdown Industrial Park,
Bideford, Devon, EX39 3DX, UK
- Authorisation Number
- PL 44095/0033
- Authorisation Date
- 23/01/2025
- Instruction Authorisation Holder
- Reig Jofre UK Limited
Unit 9A Caddsdown Business Support Centre, Caddsdown Industrial Park,
Bideford, Devon, EX39 3DX, UK
- Instruction Authorisation Number
- PL 44095/0033
- Instruction Authorisation Date
- 23/01/2025
- Instruction Composition
- Each vial contains 1.5 g cefuroxime (as sodium).
The total quantity of sodium per vial is 81 mg.
- Instruction Dosage Form
- Powder for solution for injection or infusion.
White or off-white powder.
- Instruction Clinical Particulars
- 4.1 Therapeutic indications
Cefuroxime is indicated for the treatment of the infections listed below in adults and children, including neonates (from birth) (see sections 4.4 and 5.1).
• Community acquired pneumonia
• Acute exacerbations of chronic bronchitis
• Complicated urinary tract infections, including pyelonephritis
• Soft-tissue infections: cellulitis, erysipelas and wound infections.
• Intra-abdominal infections (see section 4.4)
• Prophylaxis against infection in gastrointestinal (including oesophageal), orthopaedic, cardiovascular, and gynaecological surgery (including caesarean section).
In the treatment and prevention of infections in which it is very likely that anaerobic organisms will be encountered, cefuroxime should be administered with additional appropriate antibacterial agents.
Consideration should be given to official guidance on the appropriate use of antibacterial agents.4.2 Posology and method of administration
Posology
Table 1. Adults and children ≥ 40 kg
| | |
| --- | --- |
| Indication | Dosage |
| Community acquired pneumonia and acute exacerbations of chronic bronchitis | 750 mg every 8 hours (intravenously or intramuscularly) |
| Soft-tissue infections: cellulitis, erysipelas and 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) |
| Surgical prophylaxis for gastrointestinal, gynaecological surgery (including caesarean section) and orthopaedic operations | 1.5 g with the induction of anaesthesia. This may be supplemented with two 750 mg doses (intramuscularly) after 8 hours and 16 hours |
| Surgical prophylaxis for cardiovascular and oesophageal operations | 1.5 g with induction of anaesthesia followed by 750 mg (intramuscularly) every 8 hours for a further 24 hours |
Table 2. Children < 40 kg
| | | |
| --- | --- | --- |
| Indication | Infants and toddlers > 3 weeks and children < 40 kg | Infants (birth to 3 weeks) |
| Community acquired pneumonia | 30 to 100 mg/kg/day (intravenously) given as 3 or 4 divided doses; a dose of 60 mg/kg/day is appropriate for most infections | 30 to 100 mg/kg/day (intravenously) given as 2 or 3 divided doses (see section 5.2) |
| Complicated urinary tract infections, including pyelonephritis |
| Soft-tissue infections: cellulitis, erysipelas and wound infections |
| Intra-abdominal infections |
Renal impairment
Cefuroxime is primarily excreted by the kidneys. Therefore, as with all such antibiotics, in patients with markedly impaired renal function it is recommended that the dosage of cefuroxime should be reduced to compensate for its slower excretion.
Table 3. Recommended doses in renal impairment
| | | |
| --- | --- | --- |
| Creatinine clearance | T1/2 (hrs) | Dose (mg) |
| > 20 mL/min/1.73 m2 | 1.7-2.6 | It is not necessary to reduce the standard dose (750 mg to 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 on haemodialysis | 3.75 | A further 750 mg dose should be given intravenously or intramuscularly at the end of each dialysis; in addition to parenteral use, cefuroxime sodium can be incorporated into the peritoneal dialysis fluid (usually 250 mg for every 2 litres of dialysis fluid). |
| Patients in renal failure on continuous arteriovenous haemodialysis (CAVH) or high-flux haemofiltration (HF) in intensive therapy units | 7.9-12.6 (CAVH) 1.6 (HF) | 750 mg twice daily; for low-flux haemofiltration follow the dosage recommended under impaired renal function. |
Hepatic impairment
Cefuroxime is primarily eliminated by the kidney. In patients with hepatic dysfunction this is not expected to affect the pharmacokinetics of cefuroxime.
Method of administration
Cefuroxime should be administered by intravenous injection over a period of 3 to 5 minutes directly into a vein or via a drip tube or by deep intramuscular injection.
Intramuscular injections should be injected well within the bulk of a relatively large muscle and not more than 750 mg should be injected at one site. For doses greater than 1.5 g intravenous administration should be used.
For instructions on reconstitution of the medicinal product before administration, see section 6.6.4.3 Contraindications
Hypersensitivity to cefuroxime or to any of the cephalosporins.
Previous immediate and/or severe hypersensitivity (e.g. anaphylactic reaction) to any other type of beta-lactam antibacterial agent (penicillins, monobactams and carbapenems).4.4 Special warnings and precautions for use
Hypersensitivity reactions
As with all beta-lactam antibacterial agents, serious and occasionally fatal hypersensitivity reactions have been reported. There have been reports of hypersensitivity reactions which progressed to Kounis syndrome (acute allergic cornary asteriospasm that can result in myocardial infarction, see section 4.8). In case of severe hypersensitivity reactions, treatment with cefuroxime must be discontinued immediately and adequate emergency measures must be initiated.
Before beginning treatment, it should be established whether the patient has a history of severe hypersensitivity reactions to cefuroxime, to other cephalosporins or to any other type of beta-lactam agent. Caution should be used if cefuroxime is given to patients with a history of non-severe hypersensitivity to other beta-lactam agents.
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), which can be life-threatening or fatal, have been reported in association with cefuroxime treatment (see section 4.8).
At the time of prescription patients should be advised of the signs and symptoms and monitored closely for skin reactions. If signs and symptoms suggestive of these reactions appear, cefuroxime should be withdrawn immediately and an alternative treatment considered. If the patient has developed a serious reaction such as SJS, TEN or DRESS with the use of cefuroxime, treatment with cefuroxime must not be restarted in this patient at any time.
Concurrent treatment with potent diuretics or aminoglycosides
Cephalosporin antibiotics at high dosage should be given with caution to patients receiving concurrent treatment with potent diuretics such as furosemide or aminoglycosides. Renal impairment has been reported during use of these combinations. Renal function should be monitored in the elderly and those with known pre-existing renal impairment (see section 4.2).
Overgrowth of non-susceptible microorganisms
Use of cefuroxime may result in the overgrowth of \*Candida\*. Prolonged use may also result in the overgrowth of other non-susceptible microorganisms (e.g. enterococci and \*Clostridium difficile\*), which may require interruption of treatment (see section 4.8).
Antibacterial agent–associated pseudomembranous colitis has been reported with use of cefuroxime and may range in severity from mild to life threatening. This diagnosis should be considered in patients with diarrhoea during or subsequent to the administration of cefuroxime (see section 4.8). Discontinuation of therapy with cefuroxime and the administration of specific treatment for \*Clostridium difficile\* should be considered. Medicinal products that inhibit peristalsis should not be given.
Intracameral use and eye disorders
Cefuroxime 1.5 g Powder for Solution for Injection or Infusion is not formulated for intracameral use. Individual cases and clusters of serious ocular adverse reactions have been reported following unapproved intracameral use of cefuroxime sodium compounded from vials approved for intravenous/intramuscular administration. These reactions included macular oedema, retinal oedema, retinal detachment, retinal toxicity, visual impairment, visual acuity reduced, vision blurred, corneal opacity and corneal oedema.
Intra-abdominal infections
Due to its spectrum of activity, cefuroxime is not suitable for the treatment of infections caused by Gram-negative non-fermenting bacteria (see section 5.1).
Interference with diagnostic tests
The development of a positive Coombs Test associated with the use of cefuroxime may interfere with cross matching of blood (see section 4.8).
Slight interference with copper reduction methods (Benedict's, Fehling's, Clinitest) may be observed. However, this should not lead to false-positive results, as may be experienced with some other cephalosporins.
As a false negative result may occur in the ferricyanide test, it is recommended that either the glucose oxidase or hexokinase methods are used to determine blood/plasma glucose levels in patients receiving cefuroxime sodium.
Important information about excipients
Cefuroxime 1.5 g Powder for Solution for Injection or Infusion contains 81 mg sodium per vial, equivalent to 4% of the WHO recommended maximum daily intake of 2 g sodium for an adult.4.5 Interaction with other medicinal products and other forms of interaction
Cefuroxime may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives.
Cefuroxime is excreted by glomerular filtration and tubular secretion. Concomitant use of probenecid is not recommended. Concurrent administration of probenecid prolongs the excretion of the antibiotic and produces an elevated peak serum level.
Potential nephrotoxic drugs and loop diuretics
High-dosage treatments with cephalosporins should be carried out with caution on patients who are taking strong-acting diuretics (such as furosemide) or potential nephrotoxic preparations (such as aminoglycoside antibiotics), since impairment of renal function through such combinations cannot be ruled out.
Other Interactions
Determination of blood/plasma glucose levels: refer to section 4.4.
Concomitant use with oral anticoagulants may give rise to increased international normalised ratio (INR).4.6 Fertility, pregnancy and lactation
Pregnancy
There are limited amounts of data from the use of cefuroxime in pregnant women. Studies in animals have shown no reproductive toxicity (see section 5.3).
Cefuroxime should be prescribed to pregnant women only if the benefit outweighs the risk.
Cefuroxime has been shown to cross the placenta and attain therapeutic levels in amniotic fluid and cord blood after intramuscular or intravenous dose to the mother.
Breast-feeding
Cefuroxime is excreted in human milk in small quantities. Adverse reactions at therapeutic doses are not expected, although a risk of diarrhoea and fungus infection of the mucous membranes cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from cefuroxime therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Fertility
There are no data on the effects of cefuroxime sodium on fertility in humans.
Reproductive studies in animals have shown no effects on fertility.4.7 Effects on ability to drive and use machines
No studies on the effects of cefuroxime on the ability to drive and use machines have been performed. However, based on known adverse reactions, cefuroxime is unlikely to have an effect on the ability to drive and use machines.4.8 Undesirable effects
The most common adverse reactions are neutropenia, eosinophilia, transient rise in liver enzymes or bilirubin, particularly in patients with pre-existing liver disease, but there is no evidence of harm to the liver and injection site reactions.
The frequency categories assigned to the adverse reactions below are estimates, as for most reactions suitable data for calculating incidence are not available. In addition the incidence of adverse reactions associated with cefuroxime sodium may vary according to the indication.
Data from clinical trials were used to determine the frequency of very common to rare adverse reactions. The frequencies assigned to all other adverse reactions (i.e. those occurring at <1/10,000) were mainly determined using post-marketing data, and refer to a reporting rate rather than a true frequency.
Treatment related adverse reactions, all grades, are listed below by MedDRA body system organ class, frequency and grade of severity.
Tabulated list of adverse reactions
The following convention has been used for the classification of frequency:
| | |
| --- | --- |
| Very common Common Uncommon Rare Very rare Not known | ≥1/10 ≥1/100 and <1/10 ≥1/1000 and <1/100 ≥1/10,000 and <1/1000 <1/10,000 (cannot be estimated from the available data). |
| | | | |
| --- | --- | --- | --- |
| \*\*System organ class\*\* | \*\*Common\*\* | \*\*Uncommon\*\* | \*\*Not known\*\* |
| Infections and infestations | | | \*Candida\* overgrowth, overgrowth of \*Clostridium difficile\* |
| Blood and lymphatic system disorders | neutropenia, eosinophilia, decreased haemoglobin concentration | leukopenia, positive Coombs test | thrombocytopenia, haemolytic anaemia |
| Immune system disorders | | | drug fever, interstitial nephritis, anaphylaxis, cutaneous vasculitis |
| Gastrointestinal disorders | | gastrointestinal disturbance | pseudomembranous colitis (see section 4.4) |
| Hepatobiliary disorders | transient rise in liver enzymes | transient rise in bilirubin | |
| Skin and subcutaneous tissue disorders | | skin rash, urticaria and pruritus | erythema multiforme, toxic epidermal necrolysis and Stevens-Johnson syndrome, angioneurotic oedema, drug reaction with eosinophilia and systemic symptoms (DRESS) |
| Renal and urinary disorders | | | elevations in serum creatinine, elevations in blood urea nitrogen and decreased creatinine clearance (see section 4.4) |
| General disorders and administration site conditions | injection site reactions which may include pain and thrombophlebitis | | |
| Cardiac disorders | | | Kounis syndrome |
\*Description of selected adverse reactions\*
Cephalosporins as a class tend to be absorbed onto the surface of red cell membranes and react with antibodies directed against the drug to produce a positive Coombs test (which can interfere with cross matching of blood) and very rarely haemolytic anaemia.
Transient rises in serum liver enzymes or bilirubin have been observed which are usually reversible.
Pain at the intramuscular injection site is more likely at higher doses. However it is unlikely to be a cause for discontinuation of treatment.
\*Paediatric population\*
The safety profile for cefuroxime sodium in children is consistent with the profile in adults.
\*\*Reporting of suspected adverse reactions\*\*
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.4.9 Overdose
Overdosage can lead to neurological sequelae including encephalopathy, convulsions and coma. Symptoms of overdose can occur if the dose is not reduced appropriately in patients with renal impairment (see sections 4.2 and 4.4).
Serum levels of cefuroxime can be reduced by haemodialysis or peritoneal dialysis.
- Instruction Pharmacology
- 5.1 Pharmacodynamic properties
Pharmacotherapeutic group: antibacterials for systemic use, second-generation cephalosporins, ATC Code: J01DC02
Mechanism of action
Cefuroxime inhibits bacterial cell wall synthesis following attachment to penicillin binding proteins (PBPs). This results in the interruption of cell wall (peptidoglycan) biosynthesis, which leads to bacterial cell lysis and death.
Mechanism of resistance
Bacterial resistance to cefuroxime may be due to one or more of the following mechanisms:
• hydrolysis by beta-lactamases including (but not limited to) extended-spectrum beta-lactamases (ESBLs), and by AmpC enzymes that may be induced or stably derepressed in certain aerobic Gram-negative bacterial species;
• reduced affinity of penicillin-binding proteins for cefuroxime
• outer membrane impermeability, which restricts access of cefuroxime to penicillin binding proteins in Gram-negative bacteria
• bacterial efflux pumps
Organisms that have acquired resistance to other injectable cephalosporins are expected to be resistant to cefuroxime. Depending on the mechanism of resistance, organisms with acquired resistance to penicillins may demonstrate reduced susceptibility or resistance to cefuroxime.
Cefuroxime sodium breakpoints:
Minimum inhibitory concentration (MIC) breakpoints established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) are as follows:
| | | |
| --- | --- | --- |
| Microorganism | Breakpoints (mg/L) | |
| | Susceptible | Resistant |
| Enterobacteriaceae1 | ≤82 | >8 |
| Staphylococcus spp. | Note3 | Note3 |
| Streptococcus A, B, C and G | Note4 | Note4 |
| Streptococcus pneumoniae | LJ0.5 | >1 |
| Streptococcus (other) | LJ0.5 | >0.5 |
| Haemophilus influenzae | LJ1 | >2 |
| Moraxella catarrhalis | LJ4 | >8 |
| Non-species related breakpoints1 | LJ45 | >85 |
| 1 The cephalosporin breakpoints for Enterobacteriaceae will detect all clinically important resistance mechanisms (including ESBL and plasmid mediated AmpC). Some strains that produce beta- lactamases are susceptible or intermediate to 3rd or 4th generation cephalosporins with these breakpoints and should be reported as found, i.e. the presence or absence of an ESBL does not in itself influence the categorization of susceptibility. In many areas, ESBL detection and characterization is recommended or mandatory for infection control purposes. 2 Breakpoint relates to a dosage of 1.5 g × 3 and to E. coli, P. mirabilis and Klebsiella spp. only 3 Susceptibility of staphylococci to cephalosporins is inferred from the methicillin susceptibility except for ceftazidme and cefixime and ceftibuten, which do not have breakpoints and should not be used for staphylococcal infections. 4 The susceptibility of streptococcus groups A, B, C and G to cephalosporins is inferred from the benzylpenicillin susceptibility. 5 Breakpoints apply to daily intravenous dose of 750 mg × 3 and a high dose of at least 1.5 g × 3. | | |
Microbiological Susceptibility:
The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.
Cefuroxime is usually active against the following microorganisms in vitro.
| |
| --- |
| Commonly susceptible species |
| Gram-positive aerobes: Staphylococcus aureus (methicillin-susceptible) $ Streptococcus agalactiae Streptococcus pyogenes |
| 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 species not including C. freundii Enterobacter species. not including E. aerogenes and E. cloacae Escherichia coli Haemophilus influenzae Klebsiella pneumoniae Proteus mirabilis Proteus spp. not including P. penneri and P. Vulgaris Providencia spp. Salmonella spp. |
| Gram-positive anaerobes: Peptostreptococcus spp. Propionibacterium spp. |
| Gram-negative anaerobes: Fusobacterium spp. Bacteroides spp. |
| Inherently resistant microorganisms |
| 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 the activities of cefuroxime sodium and aminoglycoside antibiotics in combination have been shown to be at least additive with occasional evidence of synergy.5.2 Pharmacokinetic properties
Absorption
After intramuscular (IM) injection of cefuroxime to normal volunteers, mean peak serum concentrations have been seen to range from 27 to 35 μg/mL for a 750 mg dose and from 33 to 40 μg/mL for a 1000 mg dose; achieved within 30 to 60 minutes after administration. Following intravenous (IV) doses of 750 and 1500 mg, serum concentrations were approximately 50 and 100 μg/mL, respectively, at 15 minutes.
AUC and Cmax appear to increase linearly with increase in dose over the single dose range of 250 to 1000 mg following IM and IV administration. There was no evidence of accumulation of cefuroxime in the serum from normal volunteers following repeat intravenous administration of 1500 mg doses every 8 hours.
Distribution
Protein binding has been stated as 33 to 50%, depending on the methodology used. The average volume of distribution ranges from 9.3 to 15.8 L/1.73 m2 following IM or IV administration over the dosage range of 250 to 1000 mg. Concentrations of cefuroxime in excess of the minimum inhibitory levels for common pathogens can be achieved in the tonsilla, sinus tissues, bronchial mucosa, bone, pleural fluid, joint fluid, synovial fluid, interstitial fluid, bile, sputum and aqueous humour. Cefuroxime passes the blood-brain barrier when the meninges are inflamed.
Biotransformation
Cefuroxime is not metabolised.
Elimination
Cefuroxime is excreted by glomerular filtration and tubular secretion. The serum half- life after either intramuscular or intravenous injection is approximately 70 minutes.
There is almost complete recovery (85 to 90%) of unchanged cefuroxime in the urine within 24 hours of administration, the major part being eliminated in the first six hours. The average renal clearance ranges from 114 to 170 mL/min/1.73 m2 following IM or IV administration over the dosage range of 250 to 1000 mg.
Special patient populations
Gender
No differences in the pharmacokinetics of cefuroxime were observed between males and females following a single IV bolus injection of 1000 mg of cefuroxime as the sodium salt.
Elderly
Following IM or IV administration, the absorption, distribution and excretion of cefuroxime in elderly patients are similar to younger patients with equivalent renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in cefuroxime dose selection, and it may be useful to monitor renal function (see section 4.2).
Paediatrics
The serum half-life of cefuroxime has been shown to be substantially prolonged in neonates according to gestational age. However, in older infants (aged >3 weeks) and in children, the serum half-life of 60 to 90 minutes is similar to that observed in adults.
Renal impairment
Cefuroxime is primarily excreted by the kidneys. As with all such antibiotics, in patients with markedly impaired renal function (i.e. C1cr <20 mL/minute) it is recommended that the dosage of cefuroxime should be reduced to compensate for its slower excretion (see section 4.2). Cefuroxime is effectively removed by haemodialysis and peritoneal dialysis.
Hepatic impairment
Since cefuroxime is primarily eliminated by the kidney, hepatic dysfunction is not expected to have an effect on the pharmacokinetics of cefuroxime.
PK/PD relationship
For cephalosporins, the most important pharmacokinetic-pharmacodynamic index correlating with in vivo efficacy has been shown to be the percentage of the dosing interval (%T) that the unbound concentration remains above the minimum inhibitory concentration (MIC) of cefuroxime for individual target species (i.e. %T>MIC).5.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and toxicity to reproduction and development. No carcinogenicity studies have been performed; however, there is no evidence to suggest carcinogenic potential.
Gamma glutamyl transpeptidase activity in rat urine is inhibited by various cephalosporins, however the level of inhibition is less with cefuroxime. This may have significance in the interference in clinical laboratory tests in humans.
- Instruction Pharmaceutical Particulars
- 6.1 List of excipients
None.6.2 Incompatibilities
Cefuroxime is compatible with most commonly used intravenous fluids and electrolyte solutions.
The pH of 2.74% w/v sodium bicarbonate injection BP considerably affects the colour of solutions and therefore this solution is not recommended for the dilution of Cefuroxime. However, if required, for patients receiving sodium bicarbonate injection by infusion the Cefuroxime may be introduced into the tube of the giving set.
Cefuroxime should not be mixed in the syringe with aminoglycoside antibiotics.6.3 Shelf life
Un-opened dry powder: 3 years
Reconstituted solution: Store at 2-8°C and use within 24 hours
From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless reconstitution/dilution (etc) has taken place in controlled and validated aseptic conditions.6.4 Special precautions for storage
Un-opened dry powder: Store below 30°C. Store in the original package.
For storage conditions after reconstitution of the medicinal product, see section 6.3.6.5 Nature and contents of container
A type II transparent, colourless glass vial, with a bromobutyl stopper and a green aluminum and polypropylene flip off cap with adhesive labels.
Cefuroxime 1.5 g Powder for Injection or Infusion is available in 20 and 100 ml vial packs of 1, 10 or 20 vials. Not all pack sizes may be marketed6.6 Special precautions for disposal and other handling
Cefuroxime 1.5 g when dissolved in Water for Injections forms an off-white, opaque suspension for intramuscular use or a yellowish, clear solution for intravenous administration.
On reconstitution, the product must be mixed gently for at least 90 seconds prior to withdrawing into the syringe; and if not given immediately, again just prior to administration.
Intramuscular injection
1.5 g of cefuroxime should be dissolved in 6 mL of Water for Injections. Shake gently to produce an opaque suspension. Not more than 750 mg cefuroxime should be injected at one site, see section 4.2.
Intravenous injection
1.5 g of cefuroxime should be dissolved in 15 mL of Water for Injections. Shake gently to produce a clear solution. This solution may be given directly into the vein or introduced into the tubing of the giving set if the patient is receiving parenteral fluids.
Intravenous infusion
20 ml vial: 1.5 g of cefuroxime should be dissolved in 15 mL of Water for Injections. Shake gently to produce a clear solution. The reconstituted solution should then be added to 50 or 100 mL of compatible infusion fluid (see information on compatibility, below).
100 ml vial: 1.5 g of cefuroxime should be dissolved in 50 mL of Water for Injections. Shake gently to produce a clear solution.
Addition volumes and concentrations which may be useful when fractional doses are required.
When Water for Injections is added to 1.5 g cefuroxime the resulting volume is affected by the displacement factor of the drug substance, giving the approximate concentrations in mg/mL detailed in the table below.
| | | | |
| --- | --- | --- | --- |
| Route of administration | Amount of water added (mL) | Physical state | Approximate cefuroxime concentration (mg/mL) |
| Intramuscular | 6 mL | suspension | 216 |
| Intravenous bolus | 15 mL | solution | 94 |
| Intravenous infusion | 15 mL\\* | solution | 94 |
\\* Reconstituted solution to be added to 50 or 100 mL of compatible infusion fluid (see information on compatibility, below)
Compatibility
1.5 g cefuroxime sodium constituted with 15 mL Water for Injection may be added to metronidazole injection (500 mg/100 mL) and both retain their activity for up to 24 hours below 25°C.
1.5 g cefuroxime sodium is compatible with azlocillin 1 g (in 15 mL) or 5 g (in 50 mL) for up to 24 hours at 4°C or 6 hours below 25°C.
Cefuroxime sodium (5 mg/mL) in 5% w/v or 10% w/v xylitol injection may be stored for up to 24 hours at 25°C.
Cefuroxime sodium is compatible with aqueous solutions containing up to 1% lidocaine hydrochloride.
Cefuroxime sodium is compatible with the following infusion fluids. It will retain potency for up to 24 hours at room temperature in:
| | |
| --- | --- |
| | 0.9% w/v Sodium Chloride Injection BP 5% Dextrose Injection BP 0.18% w/v Sodium Chloride plus 4% Dextrose Injection BP 5% Dextrose and 0.9% w/v Sodium Chloride Injection BP 5% Dextrose and 0.45% Sodium Chloride Injection 5% Dextrose and 0.225% Sodium Chloride Injection 10% Dextrose Injection 10% Invert Sugar in Water for Injection Ringer's Injection USP Lactated Ringer's Injection USP M/6 Sodium Lactate Injection Compound Sodium Lactate Injection BP (Hartmann's Solution). |
The stability of cefuroxime sodium in 0.9% w/v Sodium Chloride Injection BP and in 5% Dextrose Injection is not affected by the presence of hydrocortisone sodium phosphate.
Cefuroxime sodium has also been found compatible for 24 hours at room temperature when admixed in IV infusion with:
| | |
| --- | --- |
| | Heparin (10 and 50 units/mL) in 0.9% w/v Sodium Chloride Injection BP; Potassium Chloride (10 and 40 mEqL) in 0.9% w/v Sodium Chloride Injection BP. |
Any unused product or waste material should be disposed of in accordance with local requirements.
- Instruction Content
- ## Composition
Each vial contains 1.5 g cefuroxime (as sodium).
The total quantity of sodium per vial is 81 mg.
## Pharmaceutical Form
Powder for solution for injection or infusion.
White or off-white powder.
## Clinical Particulars
4.1 Therapeutic indications
Cefuroxime is indicated for the treatment of the infections listed below in adults and children, including neonates (from birth) (see sections 4.4 and 5.1).
• Community acquired pneumonia
• Acute exacerbations of chronic bronchitis
• Complicated urinary tract infections, including pyelonephritis
• Soft-tissue infections: cellulitis, erysipelas and wound infections.
• Intra-abdominal infections (see section 4.4)
• Prophylaxis against infection in gastrointestinal (including oesophageal), orthopaedic, cardiovascular, and gynaecological surgery (including caesarean section).
In the treatment and prevention of infections in which it is very likely that anaerobic organisms will be encountered, cefuroxime should be administered with additional appropriate antibacterial agents.
Consideration should be given to official guidance on the appropriate use of antibacterial agents.4.2 Posology and method of administration
Posology
Table 1. Adults and children ≥ 40 kg
| | |
| --- | --- |
| Indication | Dosage |
| Community acquired pneumonia and acute exacerbations of chronic bronchitis | 750 mg every 8 hours (intravenously or intramuscularly) |
| Soft-tissue infections: cellulitis, erysipelas and 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) |
| Surgical prophylaxis for gastrointestinal, gynaecological surgery (including caesarean section) and orthopaedic operations | 1.5 g with the induction of anaesthesia. This may be supplemented with two 750 mg doses (intramuscularly) after 8 hours and 16 hours |
| Surgical prophylaxis for cardiovascular and oesophageal operations | 1.5 g with induction of anaesthesia followed by 750 mg (intramuscularly) every 8 hours for a further 24 hours |
Table 2. Children < 40 kg
| | | |
| --- | --- | --- |
| Indication | Infants and toddlers > 3 weeks and children < 40 kg | Infants (birth to 3 weeks) |
| Community acquired pneumonia | 30 to 100 mg/kg/day (intravenously) given as 3 or 4 divided doses; a dose of 60 mg/kg/day is appropriate for most infections | 30 to 100 mg/kg/day (intravenously) given as 2 or 3 divided doses (see section 5.2) |
| Complicated urinary tract infections, including pyelonephritis |
| Soft-tissue infections: cellulitis, erysipelas and wound infections |
| Intra-abdominal infections |
Renal impairment
Cefuroxime is primarily excreted by the kidneys. Therefore, as with all such antibiotics, in patients with markedly impaired renal function it is recommended that the dosage of cefuroxime should be reduced to compensate for its slower excretion.
Table 3. Recommended doses in renal impairment
| | | |
| --- | --- | --- |
| Creatinine clearance | T1/2 (hrs) | Dose (mg) |
| > 20 mL/min/1.73 m2 | 1.7-2.6 | It is not necessary to reduce the standard dose (750 mg to 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 on haemodialysis | 3.75 | A further 750 mg dose should be given intravenously or intramuscularly at the end of each dialysis; in addition to parenteral use, cefuroxime sodium can be incorporated into the peritoneal dialysis fluid (usually 250 mg for every 2 litres of dialysis fluid). |
| Patients in renal failure on continuous arteriovenous haemodialysis (CAVH) or high-flux haemofiltration (HF) in intensive therapy units | 7.9-12.6 (CAVH) 1.6 (HF) | 750 mg twice daily; for low-flux haemofiltration follow the dosage recommended under impaired renal function. |
Hepatic impairment
Cefuroxime is primarily eliminated by the kidney. In patients with hepatic dysfunction this is not expected to affect the pharmacokinetics of cefuroxime.
Method of administration
Cefuroxime should be administered by intravenous injection over a period of 3 to 5 minutes directly into a vein or via a drip tube or by deep intramuscular injection.
Intramuscular injections should be injected well within the bulk of a relatively large muscle and not more than 750 mg should be injected at one site. For doses greater than 1.5 g intravenous administration should be used.
For instructions on reconstitution of the medicinal product before administration, see section 6.6.4.3 Contraindications
Hypersensitivity to cefuroxime or to any of the cephalosporins.
Previous immediate and/or severe hypersensitivity (e.g. anaphylactic reaction) to any other type of beta-lactam antibacterial agent (penicillins, monobactams and carbapenems).4.4 Special warnings and precautions for use
Hypersensitivity reactions
As with all beta-lactam antibacterial agents, serious and occasionally fatal hypersensitivity reactions have been reported. There have been reports of hypersensitivity reactions which progressed to Kounis syndrome (acute allergic cornary asteriospasm that can result in myocardial infarction, see section 4.8). In case of severe hypersensitivity reactions, treatment with cefuroxime must be discontinued immediately and adequate emergency measures must be initiated.
Before beginning treatment, it should be established whether the patient has a history of severe hypersensitivity reactions to cefuroxime, to other cephalosporins or to any other type of beta-lactam agent. Caution should be used if cefuroxime is given to patients with a history of non-severe hypersensitivity to other beta-lactam agents.
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), which can be life-threatening or fatal, have been reported in association with cefuroxime treatment (see section 4.8).
At the time of prescription patients should be advised of the signs and symptoms and monitored closely for skin reactions. If signs and symptoms suggestive of these reactions appear, cefuroxime should be withdrawn immediately and an alternative treatment considered. If the patient has developed a serious reaction such as SJS, TEN or DRESS with the use of cefuroxime, treatment with cefuroxime must not be restarted in this patient at any time.
Concurrent treatment with potent diuretics or aminoglycosides
Cephalosporin antibiotics at high dosage should be given with caution to patients receiving concurrent treatment with potent diuretics such as furosemide or aminoglycosides. Renal impairment has been reported during use of these combinations. Renal function should be monitored in the elderly and those with known pre-existing renal impairment (see section 4.2).
Overgrowth of non-susceptible microorganisms
Use of cefuroxime may result in the overgrowth of \*Candida\*. Prolonged use may also result in the overgrowth of other non-susceptible microorganisms (e.g. enterococci and \*Clostridium difficile\*), which may require interruption of treatment (see section 4.8).
Antibacterial agent–associated pseudomembranous colitis has been reported with use of cefuroxime and may range in severity from mild to life threatening. This diagnosis should be considered in patients with diarrhoea during or subsequent to the administration of cefuroxime (see section 4.8). Discontinuation of therapy with cefuroxime and the administration of specific treatment for \*Clostridium difficile\* should be considered. Medicinal products that inhibit peristalsis should not be given.
Intracameral use and eye disorders
Cefuroxime 1.5 g Powder for Solution for Injection or Infusion is not formulated for intracameral use. Individual cases and clusters of serious ocular adverse reactions have been reported following unapproved intracameral use of cefuroxime sodium compounded from vials approved for intravenous/intramuscular administration. These reactions included macular oedema, retinal oedema, retinal detachment, retinal toxicity, visual impairment, visual acuity reduced, vision blurred, corneal opacity and corneal oedema.
Intra-abdominal infections
Due to its spectrum of activity, cefuroxime is not suitable for the treatment of infections caused by Gram-negative non-fermenting bacteria (see section 5.1).
Interference with diagnostic tests
The development of a positive Coombs Test associated with the use of cefuroxime may interfere with cross matching of blood (see section 4.8).
Slight interference with copper reduction methods (Benedict's, Fehling's, Clinitest) may be observed. However, this should not lead to false-positive results, as may be experienced with some other cephalosporins.
As a false negative result may occur in the ferricyanide test, it is recommended that either the glucose oxidase or hexokinase methods are used to determine blood/plasma glucose levels in patients receiving cefuroxime sodium.
Important information about excipients
Cefuroxime 1.5 g Powder for Solution for Injection or Infusion contains 81 mg sodium per vial, equivalent to 4% of the WHO recommended maximum daily intake of 2 g sodium for an adult.4.5 Interaction with other medicinal products and other forms of interaction
Cefuroxime may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives.
Cefuroxime is excreted by glomerular filtration and tubular secretion. Concomitant use of probenecid is not recommended. Concurrent administration of probenecid prolongs the excretion of the antibiotic and produces an elevated peak serum level.
Potential nephrotoxic drugs and loop diuretics
High-dosage treatments with cephalosporins should be carried out with caution on patients who are taking strong-acting diuretics (such as furosemide) or potential nephrotoxic preparations (such as aminoglycoside antibiotics), since impairment of renal function through such combinations cannot be ruled out.
Other Interactions
Determination of blood/plasma glucose levels: refer to section 4.4.
Concomitant use with oral anticoagulants may give rise to increased international normalised ratio (INR).4.6 Fertility, pregnancy and lactation
Pregnancy
There are limited amounts of data from the use of cefuroxime in pregnant women. Studies in animals have shown no reproductive toxicity (see section 5.3).
Cefuroxime should be prescribed to pregnant women only if the benefit outweighs the risk.
Cefuroxime has been shown to cross the placenta and attain therapeutic levels in amniotic fluid and cord blood after intramuscular or intravenous dose to the mother.
Breast-feeding
Cefuroxime is excreted in human milk in small quantities. Adverse reactions at therapeutic doses are not expected, although a risk of diarrhoea and fungus infection of the mucous membranes cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from cefuroxime therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Fertility
There are no data on the effects of cefuroxime sodium on fertility in humans.
Reproductive studies in animals have shown no effects on fertility.4.7 Effects on ability to drive and use machines
No studies on the effects of cefuroxime on the ability to drive and use machines have been performed. However, based on known adverse reactions, cefuroxime is unlikely to have an effect on the ability to drive and use machines.4.8 Undesirable effects
The most common adverse reactions are neutropenia, eosinophilia, transient rise in liver enzymes or bilirubin, particularly in patients with pre-existing liver disease, but there is no evidence of harm to the liver and injection site reactions.
The frequency categories assigned to the adverse reactions below are estimates, as for most reactions suitable data for calculating incidence are not available. In addition the incidence of adverse reactions associated with cefuroxime sodium may vary according to the indication.
Data from clinical trials were used to determine the frequency of very common to rare adverse reactions. The frequencies assigned to all other adverse reactions (i.e. those occurring at <1/10,000) were mainly determined using post-marketing data, and refer to a reporting rate rather than a true frequency.
Treatment related adverse reactions, all grades, are listed below by MedDRA body system organ class, frequency and grade of severity.
Tabulated list of adverse reactions
The following convention has been used for the classification of frequency:
| | |
| --- | --- |
| Very common Common Uncommon Rare Very rare Not known | ≥1/10 ≥1/100 and <1/10 ≥1/1000 and <1/100 ≥1/10,000 and <1/1000 <1/10,000 (cannot be estimated from the available data). |
| | | | |
| --- | --- | --- | --- |
| \*\*System organ class\*\* | \*\*Common\*\* | \*\*Uncommon\*\* | \*\*Not known\*\* |
| Infections and infestations | | | \*Candida\* overgrowth, overgrowth of \*Clostridium difficile\* |
| Blood and lymphatic system disorders | neutropenia, eosinophilia, decreased haemoglobin concentration | leukopenia, positive Coombs test | thrombocytopenia, haemolytic anaemia |
| Immune system disorders | | | drug fever, interstitial nephritis, anaphylaxis, cutaneous vasculitis |
| Gastrointestinal disorders | | gastrointestinal disturbance | pseudomembranous colitis (see section 4.4) |
| Hepatobiliary disorders | transient rise in liver enzymes | transient rise in bilirubin | |
| Skin and subcutaneous tissue disorders | | skin rash, urticaria and pruritus | erythema multiforme, toxic epidermal necrolysis and Stevens-Johnson syndrome, angioneurotic oedema, drug reaction with eosinophilia and systemic symptoms (DRESS) |
| Renal and urinary disorders | | | elevations in serum creatinine, elevations in blood urea nitrogen and decreased creatinine clearance (see section 4.4) |
| General disorders and administration site conditions | injection site reactions which may include pain and thrombophlebitis | | |
| Cardiac disorders | | | Kounis syndrome |
\*Description of selected adverse reactions\*
Cephalosporins as a class tend to be absorbed onto the surface of red cell membranes and react with antibodies directed against the drug to produce a positive Coombs test (which can interfere with cross matching of blood) and very rarely haemolytic anaemia.
Transient rises in serum liver enzymes or bilirubin have been observed which are usually reversible.
Pain at the intramuscular injection site is more likely at higher doses. However it is unlikely to be a cause for discontinuation of treatment.
\*Paediatric population\*
The safety profile for cefuroxime sodium in children is consistent with the profile in adults.
\*\*Reporting of suspected adverse reactions\*\*
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.4.9 Overdose
Overdosage can lead to neurological sequelae including encephalopathy, convulsions and coma. Symptoms of overdose can occur if the dose is not reduced appropriately in patients with renal impairment (see sections 4.2 and 4.4).
Serum levels of cefuroxime can be reduced by haemodialysis or peritoneal dialysis.
## Pharmacological Properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: antibacterials for systemic use, second-generation cephalosporins, ATC Code: J01DC02
Mechanism of action
Cefuroxime inhibits bacterial cell wall synthesis following attachment to penicillin binding proteins (PBPs). This results in the interruption of cell wall (peptidoglycan) biosynthesis, which leads to bacterial cell lysis and death.
Mechanism of resistance
Bacterial resistance to cefuroxime may be due to one or more of the following mechanisms:
• hydrolysis by beta-lactamases including (but not limited to) extended-spectrum beta-lactamases (ESBLs), and by AmpC enzymes that may be induced or stably derepressed in certain aerobic Gram-negative bacterial species;
• reduced affinity of penicillin-binding proteins for cefuroxime
• outer membrane impermeability, which restricts access of cefuroxime to penicillin binding proteins in Gram-negative bacteria
• bacterial efflux pumps
Organisms that have acquired resistance to other injectable cephalosporins are expected to be resistant to cefuroxime. Depending on the mechanism of resistance, organisms with acquired resistance to penicillins may demonstrate reduced susceptibility or resistance to cefuroxime.
Cefuroxime sodium breakpoints:
Minimum inhibitory concentration (MIC) breakpoints established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) are as follows:
| | | |
| --- | --- | --- |
| Microorganism | Breakpoints (mg/L) | |
| | Susceptible | Resistant |
| Enterobacteriaceae1 | ≤82 | >8 |
| Staphylococcus spp. | Note3 | Note3 |
| Streptococcus A, B, C and G | Note4 | Note4 |
| Streptococcus pneumoniae | LJ0.5 | >1 |
| Streptococcus (other) | LJ0.5 | >0.5 |
| Haemophilus influenzae | LJ1 | >2 |
| Moraxella catarrhalis | LJ4 | >8 |
| Non-species related breakpoints1 | LJ45 | >85 |
| 1 The cephalosporin breakpoints for Enterobacteriaceae will detect all clinically important resistance mechanisms (including ESBL and plasmid mediated AmpC). Some strains that produce beta- lactamases are susceptible or intermediate to 3rd or 4th generation cephalosporins with these breakpoints and should be reported as found, i.e. the presence or absence of an ESBL does not in itself influence the categorization of susceptibility. In many areas, ESBL detection and characterization is recommended or mandatory for infection control purposes. 2 Breakpoint relates to a dosage of 1.5 g × 3 and to E. coli, P. mirabilis and Klebsiella spp. only 3 Susceptibility of staphylococci to cephalosporins is inferred from the methicillin susceptibility except for ceftazidme and cefixime and ceftibuten, which do not have breakpoints and should not be used for staphylococcal infections. 4 The susceptibility of streptococcus groups A, B, C and G to cephalosporins is inferred from the benzylpenicillin susceptibility. 5 Breakpoints apply to daily intravenous dose of 750 mg × 3 and a high dose of at least 1.5 g × 3. | | |
Microbiological Susceptibility:
The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.
Cefuroxime is usually active against the following microorganisms in vitro.
| |
| --- |
| Commonly susceptible species |
| Gram-positive aerobes: Staphylococcus aureus (methicillin-susceptible) $ Streptococcus agalactiae Streptococcus pyogenes |
| 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 species not including C. freundii Enterobacter species. not including E. aerogenes and E. cloacae Escherichia coli Haemophilus influenzae Klebsiella pneumoniae Proteus mirabilis Proteus spp. not including P. penneri and P. Vulgaris Providencia spp. Salmonella spp. |
| Gram-positive anaerobes: Peptostreptococcus spp. Propionibacterium spp. |
| Gram-negative anaerobes: Fusobacterium spp. Bacteroides spp. |
| Inherently resistant microorganisms |
| 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 the activities of cefuroxime sodium and aminoglycoside antibiotics in combination have been shown to be at least additive with occasional evidence of synergy.5.2 Pharmacokinetic properties
Absorption
After intramuscular (IM) injection of cefuroxime to normal volunteers, mean peak serum concentrations have been seen to range from 27 to 35 μg/mL for a 750 mg dose and from 33 to 40 μg/mL for a 1000 mg dose; achieved within 30 to 60 minutes after administration. Following intravenous (IV) doses of 750 and 1500 mg, serum concentrations were approximately 50 and 100 μg/mL, respectively, at 15 minutes.
AUC and Cmax appear to increase linearly with increase in dose over the single dose range of 250 to 1000 mg following IM and IV administration. There was no evidence of accumulation of cefuroxime in the serum from normal volunteers following repeat intravenous administration of 1500 mg doses every 8 hours.
Distribution
Protein binding has been stated as 33 to 50%, depending on the methodology used. The average volume of distribution ranges from 9.3 to 15.8 L/1.73 m2 following IM or IV administration over the dosage range of 250 to 1000 mg. Concentrations of cefuroxime in excess of the minimum inhibitory levels for common pathogens can be achieved in the tonsilla, sinus tissues, bronchial mucosa, bone, pleural fluid, joint fluid, synovial fluid, interstitial fluid, bile, sputum and aqueous humour. Cefuroxime passes the blood-brain barrier when the meninges are inflamed.
Biotransformation
Cefuroxime is not metabolised.
Elimination
Cefuroxime is excreted by glomerular filtration and tubular secretion. The serum half- life after either intramuscular or intravenous injection is approximately 70 minutes.
There is almost complete recovery (85 to 90%) of unchanged cefuroxime in the urine within 24 hours of administration, the major part being eliminated in the first six hours. The average renal clearance ranges from 114 to 170 mL/min/1.73 m2 following IM or IV administration over the dosage range of 250 to 1000 mg.
Special patient populations
Gender
No differences in the pharmacokinetics of cefuroxime were observed between males and females following a single IV bolus injection of 1000 mg of cefuroxime as the sodium salt.
Elderly
Following IM or IV administration, the absorption, distribution and excretion of cefuroxime in elderly patients are similar to younger patients with equivalent renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in cefuroxime dose selection, and it may be useful to monitor renal function (see section 4.2).
Paediatrics
The serum half-life of cefuroxime has been shown to be substantially prolonged in neonates according to gestational age. However, in older infants (aged >3 weeks) and in children, the serum half-life of 60 to 90 minutes is similar to that observed in adults.
Renal impairment
Cefuroxime is primarily excreted by the kidneys. As with all such antibiotics, in patients with markedly impaired renal function (i.e. C1cr <20 mL/minute) it is recommended that the dosage of cefuroxime should be reduced to compensate for its slower excretion (see section 4.2). Cefuroxime is effectively removed by haemodialysis and peritoneal dialysis.
Hepatic impairment
Since cefuroxime is primarily eliminated by the kidney, hepatic dysfunction is not expected to have an effect on the pharmacokinetics of cefuroxime.
PK/PD relationship
For cephalosporins, the most important pharmacokinetic-pharmacodynamic index correlating with in vivo efficacy has been shown to be the percentage of the dosing interval (%T) that the unbound concentration remains above the minimum inhibitory concentration (MIC) of cefuroxime for individual target species (i.e. %T>MIC).5.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and toxicity to reproduction and development. No carcinogenicity studies have been performed; however, there is no evidence to suggest carcinogenic potential.
Gamma glutamyl transpeptidase activity in rat urine is inhibited by various cephalosporins, however the level of inhibition is less with cefuroxime. This may have significance in the interference in clinical laboratory tests in humans.
## Pharmaceutical Particulars
6.1 List of excipients
None.6.2 Incompatibilities
Cefuroxime is compatible with most commonly used intravenous fluids and electrolyte solutions.
The pH of 2.74% w/v sodium bicarbonate injection BP considerably affects the colour of solutions and therefore this solution is not recommended for the dilution of Cefuroxime. However, if required, for patients receiving sodium bicarbonate injection by infusion the Cefuroxime may be introduced into the tube of the giving set.
Cefuroxime should not be mixed in the syringe with aminoglycoside antibiotics.6.3 Shelf life
Un-opened dry powder: 3 years
Reconstituted solution: Store at 2-8°C and use within 24 hours
From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless reconstitution/dilution (etc) has taken place in controlled and validated aseptic conditions.6.4 Special precautions for storage
Un-opened dry powder: Store below 30°C. Store in the original package.
For storage conditions after reconstitution of the medicinal product, see section 6.3.6.5 Nature and contents of container
A type II transparent, colourless glass vial, with a bromobutyl stopper and a green aluminum and polypropylene flip off cap with adhesive labels.
Cefuroxime 1.5 g Powder for Injection or Infusion is available in 20 and 100 ml vial packs of 1, 10 or 20 vials. Not all pack sizes may be marketed6.6 Special precautions for disposal and other handling
Cefuroxime 1.5 g when dissolved in Water for Injections forms an off-white, opaque suspension for intramuscular use or a yellowish, clear solution for intravenous administration.
On reconstitution, the product must be mixed gently for at least 90 seconds prior to withdrawing into the syringe; and if not given immediately, again just prior to administration.
Intramuscular injection
1.5 g of cefuroxime should be dissolved in 6 mL of Water for Injections. Shake gently to produce an opaque suspension. Not more than 750 mg cefuroxime should be injected at one site, see section 4.2.
Intravenous injection
1.5 g of cefuroxime should be dissolved in 15 mL of Water for Injections. Shake gently to produce a clear solution. This solution may be given directly into the vein or introduced into the tubing of the giving set if the patient is receiving parenteral fluids.
Intravenous infusion
20 ml vial: 1.5 g of cefuroxime should be dissolved in 15 mL of Water for Injections. Shake gently to produce a clear solution. The reconstituted solution should then be added to 50 or 100 mL of compatible infusion fluid (see information on compatibility, below).
100 ml vial: 1.5 g of cefuroxime should be dissolved in 50 mL of Water for Injections. Shake gently to produce a clear solution.
Addition volumes and concentrations which may be useful when fractional doses are required.
When Water for Injections is added to 1.5 g cefuroxime the resulting volume is affected by the displacement factor of the drug substance, giving the approximate concentrations in mg/mL detailed in the table below.
| | | | |
| --- | --- | --- | --- |
| Route of administration | Amount of water added (mL) | Physical state | Approximate cefuroxime concentration (mg/mL) |
| Intramuscular | 6 mL | suspension | 216 |
| Intravenous bolus | 15 mL | solution | 94 |
| Intravenous infusion | 15 mL\\* | solution | 94 |
\\* Reconstituted solution to be added to 50 or 100 mL of compatible infusion fluid (see information on compatibility, below)
Compatibility
1.5 g cefuroxime sodium constituted with 15 mL Water for Injection may be added to metronidazole injection (500 mg/100 mL) and both retain their activity for up to 24 hours below 25°C.
1.5 g cefuroxime sodium is compatible with azlocillin 1 g (in 15 mL) or 5 g (in 50 mL) for up to 24 hours at 4°C or 6 hours below 25°C.
Cefuroxime sodium (5 mg/mL) in 5% w/v or 10% w/v xylitol injection may be stored for up to 24 hours at 25°C.
Cefuroxime sodium is compatible with aqueous solutions containing up to 1% lidocaine hydrochloride.
Cefuroxime sodium is compatible with the following infusion fluids. It will retain potency for up to 24 hours at room temperature in:
| | |
| --- | --- |
| | 0.9% w/v Sodium Chloride Injection BP 5% Dextrose Injection BP 0.18% w/v Sodium Chloride plus 4% Dextrose Injection BP 5% Dextrose and 0.9% w/v Sodium Chloride Injection BP 5% Dextrose and 0.45% Sodium Chloride Injection 5% Dextrose and 0.225% Sodium Chloride Injection 10% Dextrose Injection 10% Invert Sugar in Water for Injection Ringer's Injection USP Lactated Ringer's Injection USP M/6 Sodium Lactate Injection Compound Sodium Lactate Injection BP (Hartmann's Solution). |
The stability of cefuroxime sodium in 0.9% w/v Sodium Chloride Injection BP and in 5% Dextrose Injection is not affected by the presence of hydrocortisone sodium phosphate.
Cefuroxime sodium has also been found compatible for 24 hours at room temperature when admixed in IV infusion with:
| | |
| --- | --- |
| | Heparin (10 and 50 units/mL) in 0.9% w/v Sodium Chloride Injection BP; Potassium Chloride (10 and 40 mEqL) in 0.9% w/v Sodium Chloride Injection BP. |
Any unused product or waste material should be disposed of in accordance with local requirements.
