Cefuroxime-Kotra is a bactericidal cephalosporin antibiotic which is resistant to most betalactamases and is active against a wide range of Gram-positive and Gram-negative organisms.

It is indicated for the treatment of infections before the infecting organism has been identified or when caused by sensitive bacteria. Susceptibility to Cefuroxime-Kotra will vary with geography and time and local susceptibility data should be consulted where available (see Pharmacodynamics).

Indications include:
- respiratory tract infections for example, acute exacerbation of chronic bronchitis, infected bronchiectasis, bacterial pneumonia, lung abscess and post-operative chest infections.
- ear, nose and throat infections for example, sinusitis, tonsillitis, pharyngitis and otitis media.
- urinary tract infections for example, acute and chronic pyelonephritis, cystitis and asymptomatic bacteriuria.
- soft-tissue infections for example, cellulitis, erysipelas and wound infections.
- bone and joint infections for example, osteomyelitis and septic arthritis.
- obstetric and gynaecological infections for example, pelvic inflammatory diseases.
- gonorrhoea particularly when penicillin is unsuitable.
- other infections including septicaemia, meningitis and peritonitis.
- prophylaxis against infection in abdominal, pelvic, orthopaedic, cardiac, pulmonary,oesophageal and vascular surgery where there is increased risk from infection
 

 

Cefuroxime-Kotra is for intravenous (IV) and/or intramuscular (IM) administration only.
Not more than 750 mg should be injected at one intramuscular site.
GENERAL DOSING RECOMMENDATIONS
Adults
Many infections respond to 750mg three times daily by IM or IV injection. For more severe
infections, this dose should be increased to 1.5g three times daily given IV. The frequency of administration may be increased to 6-hourly if necessary, giving total daily doses of 3g to 6g.
Infants and Children
Doses of 30 to 100mg/kg/day IV given as 3 or 4 divided doses. A dose of 60 mg/kg/day will be appropriate for most infections

Neonates
Doses of 30 to 100 mg/kg/day IV given as 2 or 3 divided doses (see Pharmacokinetics).

GONORRHOEA
Adults
1.5g as a single dose. This may be given as 2 x 750mg injections into different sites e.g. each buttock.

MENINGITIS
Cefuroxime-Kotra is suitable for sole therapy of bacterial meningitis due to sensitive strains.

• Adults:

  3g IV every 8 hours

• Infants and Children:

  200 to 240 mg/kg/day IV in 3 or 4 divided doses. This dosage may be reduced to 100 mg/kg/day IV after 3 days or when clinical improvement occurs.

• Neonates:

  The initial dosage should be 100 mg/kg/day IV. A reduction to 50 mg/kg/day IV may be made when clinically indicated

  
   

 

PROPHYLAXIS
The usual dose is 1.5g given IV with induction of anaesthesia for abdominal, pelvic and orthopaedic operations. This may be supplemented with two 750mg IM doses 8 and 16 hours later.
In cardiac, pulmonary, oesophageal and vascular operations, the usual dose is 1.5g given IV with induction of anaesthesia, continuing with 750mg given IM three times daily for a further 24 to 48 hours.
In total joint replacement, 1.5g Cefuroxime powder may be mixed dry with each pack of methyl methacrylate cement polymer before adding the liquid monomer.

 

RENAL IMPAIRMENT
Cefuroxime is 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-Kotra should be reduced to compensate for its slower excretion.
It is not necessary to reduce the standard dose (750mg to 1.5g three times daily) until the creatinine clearance falls below 20 ml/min.
In adults with marked impairment (creatinine clearance 10 to 20 ml/min) 750mg twice daily is recommended and with severe impairment (creatinine clearance <10 ml/min) 750mg once daily is adequate.

For patients on haemodialysis a further 750mg dose should be given IV or IM at the end of each dialysis. In addition to parenteral use, Cefuroxime-Kotra can be incorporated into the peritoneal dialysis fluid (usually 250mg for every 2 litres of dialysis fluid).

For patients in renal failure on continuous arteriovenous haemodialysis or high-flux haemofiltration in intensive therapy units, a suitable dosage is 750 mg twice daily. For low-flux haemofiltration follow the dosage recommended under impaired renal function.

Compatibility and Stability:
Protect from light. Cefuroxime should not be mixed in the syringe with aminoglycoside
antibiotics.

*Reconstituted solution to be added to 50 or 100mL of compatible infusion fluid (see
information on compatibility below)
 

Cefuroxime Sodium (5 mg/mL) in 5% w/v or 10% w/v xylitol injection may used.
 

Cefuroxime-Kotra may be constituted for i.m use with aqueous solutions containing up to 1%
lidocaine hydrochloride.
 

Cefuroxime-Kotra is compatible with the following more commonly used i.v. infusion fluids:
• 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% Sodium Chloride Injection
• 5% Dextrose and 0.45% Sodium Chloride Injection
• 5% Dextrose and 0.225% Sodium Chloride Injection
• 10% Dextrose Injection
• Lactated Ringer's Injection USP
• M/6 Sodium Lactate Injection
• Compound Sodium Lactate Injection BP (Hartmann's Solution)
 

The stability of Cefuroxime-Kotra 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-Kotra has also been found compatible admixed in i.v. infusion with: Heparin (10 and 50 units/ml) in 0.9% w/v Sodium Chloride Injection; Potassium Chloride (10 and 40 mEqL) in
0.9% w/v Sodium Chloride Injection.

(see Instruction for use and handling)
 

 

 

Patients known to be hypersensitive to Cephalosporin antibiotics.

Special care is indicated in patients who have experienced an allergic reaction to penicillins or other beta-lactams.
Cephalosporin antibiotics at high dosage should be given with caution to patients receiving concurrent treatment with potent diuretics such as furosemide or aminoglycosides, as renal
impairment has been reported with these combinations. Renal function should be monitored in these patients, the elderly, and those with pre-existing renal impairment (see Posology and
method of administration)
 

As with other therapeutic regimens used in the treatment of meningitis, mild-to-moderate hearing loss has been reported in a few paediatric patients treated with Cefuroxime-Kotra. Persistence of positive cerebral spinal fluid (CSF) cultures of Haemophilus influenzae at 18-36 hours has also been noted with Cefuroxime-Kotra, as well as with other antibiotic therapies; however, the clinical relevance of this is unknown.
 

As with other antibiotics, use of Cefuroxime-Kotra may result in the overgrowth of Candida.
 

Prolonged use may also result in the overgrowth of other non-susceptible organisms (e.g.enterococci and Clostridioides difficile), which may require interruption of treatment.
 

Pseudomembranous colitis has been reported with the use of antibiotics and may range in severity from mild to life-threatening. Therefore, it is important to consider its diagnosis in
patients who develop diarrhoea during or after antibiotic use. If prolonged or significant diarrhoea occurs or the patient experiences abdominal cramps, treatment should be discontinued
immediately and the patient investigated further

 

Intracameral use and ocular toxicity
Serious ocular toxicity, including corneal opacity, retinal toxicity and visual impairment has been reported following off-label intracameral use of Cefuroxime-Kotra. Cefuroxime-Kotra should not be administered intracamerally.

With a sequential therapy regime the timing of change to oral therapy is determined by severity of the infection, clinical status of the patient and susceptibility of the pathogens involved. If there is no clinical improvement within 72 hours, then the parenteral course of treatment must be continued.
 

 

In common with other antibiotics, Cefuroxime-Kotra may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives.

Cefuroxime-Kotra does not interfere in enzyme-based tests for glycosuria.
 

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.

It is recommended that either the glucose oxidase or hexokinase methods are used to determine blood/plasma glucose levels in patients receiving Cefuroxime-Kotra.

 

This antibiotic does not interfere in the alkaline picrate assay for creatinine.
 

There is no experimental evidence of embryopathic or teratogenic effects attributable to cefuroxime, but, as with all drugs, it should be administered with caution during the early months
of pregnancy. Cefuroxime is excreted in human milk, and consequently caution should be exercised when Cefuroxime-Kotra is administered to a nursing mother
 

Not applicable

 

 

 

Adverse drug reactions are very rare (<1/10,000) and are generally mild and transient in nature.

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-Kotra may vary according to the indication.

Data from clinical trials were used to determine the frequency of very common to rare undesirable effects. The frequencies assigned to all other undesirable effects (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.

The following convention has been used for the classification of frequency:
Very common ≥1/10,
Common ≥1/100 to <1/10,
Uncommon ≥1/1000 to <1/100,
Rare ≥1/10,000 to <1/1000, Very rare <1/10,000.

Infections and infestations
Rare: Candida overgrowth
Blood and lymphatic system disorders
Common: Neutropenia, eosinophilia.
Uncommon: Leukopenia, decreased haemoglobin concentration, positive Coomb’s test.
Rare: Thrombocytopenia.
Very rare: Haemolytic anaemia.
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 Coomb’s Test (which can interferewith cross matching of blood) and very rarely haemolytic anaemia.

Immune system disorders
Hypersensitivity reactions including
Uncommon: Skin rash, urticaria and pruritus.
Rare: Drug fever.
Very rare: Interstitial nephritis, anaphylaxis, cutaneous vasculitis.
See also Skin and subcutaneous tissue disorders and Renal and urinary disorders.
 

Gastrointestinal disorders
Uncommon: Gastrointestinal disturbance.
Very rare: Pseudomembranous colitis (see Warnings and Precautions)
 

Hepatobiliary disorders
Common: Transient rise in liver enzymes.
Uncommon: Transient rise in bilirubin.

Transient rises in serum liver enzymes or bilirubin occur, particularly in patients with preexisting liver disease, but there is no evidence of harm to the liver.
 

Skin and subcutaneous tissue disorders
Very rare: Erythema multiforme, toxic epidermal necrolysis and Stevens Johnson Syndrome.

See also Immune system disorders.

Renal and urinary disorders
Very rare: Elevations in serum creatinine, elevations in blood urea nitrogen and decreased
creatinine clearance (see Warnings and Precautions).

See also Immune system disorders.

General disorders and administration site conditions
Common: Injection site reactions which may include pain and thrombophlebitis.

Pain at the intramuscular injection site is more likely at higher doses. However, it is unlikely to
be a cause for discontinuation of treatment

To report any side effect(s):

-Saudi Arabia: National Pharmacovigilance Centre (NPC) SFDA call center: 19999 E-mail: npc.drug@sfda.gov.sa Website: https://ade.sfda.gov.sa/ - Other GCC states: Please contact the relevant competent  authority.

Overdosage of cephalosporins can cause cerebral irritation leading to convulsions. Serum levels of Cefuroxime can be reduced by haemodialysis and peritoneal dialysis.

Cefuroxime is a well characterised and effective antibacterial agent which has bactericidal activity against a wide range of common pathogens, including β-lactamase producing strains.
Cefuroxime has good stability to bacterial β-lactamase, and consequently is active against many ampicillin-resistant or amoxycillin-resistant strains.

The bactericidal action of cefuroxime results from inhibition of cell wall synthesis by binding to essential target proteins.

The prevalence of acquired resistance is geographically and time dependent and for select species may be very high. Local information on resistance is desirable, particularly when
treating severe infections.

Commonly Susceptible Species
Gram-Positive Aerobes:
Staphylococcus aureus (methicillin susceptible)
Coagulase negative staphylococcus (methicillin susceptible) Streptococcus pyogenes
Betahemolytic streptococci

Gram-Negative Aerobes:
Haemophilus influenzae including ampicillin resistant strains
Haemophilus parainfluenzae
Moraxella catarrhalis
Neisseria gonorrhoea including penicillinase and non-penicillinase producing strains
Neisseria meningitidis Shigella spp

Gram-Positive Anaerobes:
Peptostreptococcus spp.
Propionibacterium spp.

Spirochetes:
Borrelia burgdorferi
 

Organisms for which acquired resistance may be a problem
Gram-Positive Aerobes:
Streptococcus pneumoniae
Viridans group streptococcus
Gram-Negative Aerobes:
Bordetella pertussis
Citrobacter spp. not including C. freundii
Enterobacter spp. not including E. aerogenes and E. cloacae
Escherichia coli
Klebsiella spp. including K. pneumoniae
Proteus mirabilis
Proteus spp. not including P. penneri and P. vulgaris Providencia spp

Salmonella spp
 

Gram-Positive Anaerobes:
Clostridium spp.

Gram-Negative Anaerobes:
Bacteroides spp. not including B. fragilis Fusobacterium spp.

Inherently resistant organisms
Gram-Positive Aerobes:
Enterococcus spp. including E. faecalis and E. faecium
Listeria monocytogenes

Gram-Negative Aerobes:
Acinetobacter spp. Burkholderia cepacia Campylobacter spp.
Citrobacter freundii
Enterobacter aerogenes
Enterobacter cloacae
Morganella morganii
Proteus penneri
Proteus vulgaris
Pseudomonas spp. including P. aeruginosa Serratia spp.
Stenotrophomonas maltophilia

Gram-Positive Anaerobes:
Clostridioides difficile

Gram-Negative Anaerobes:
Bacteroides fragilis

Others:
Chlamydia species
Mycoplasma species
Legionella species
 

 

Peak levels of cefuroxime are achieved within 30 to 45 minutes after intramuscular
administration. The serum half-life after either intramuscular or intravenous injection is
approximately 70 minutes. Concurrent administration of probenecid prolongs the excretion of
the antibiotic and produces and elevated peak serum level. There is almost complete recovery
of unchanged cefuroxime in the urine within 24 hours of administration, the major part being
eliminated in the first six hours. Approximately 50% is excreted through the renal tubules and
approximately 50% by glomerular filtration. Concentrations of cefuroxime in excess of the
minimum inhibitory levels for common pathogens can be achieved in bone, synovial fluid and
aqueous humor. Cefuroxime passes the blood-brain barrier when the meninges are inflamed.
Cefuroxime is approximately 50% bound to serum protein.
 

Not applicable

None.
 

Cefuroxime Injection should not be mixed in the syringe with aminoglycoside antibiotics.
 

3 years. The unopened pack storage temperature requirements are indicated on the packaging. When reconstituted for injection, it can be stored for 5 hours if stored below 25°C, or 72 hours if stored at 2° to 8°C. When reconstituted for infusion, it can be stored for 3 hours if stored below 25°C, or 72 hours if stored at 2° to 8°C. From a microbiological point of view, the medicinal product should be used immediately. (see Compatibility and Stability)

Keep container well closed. Store below 30ºC. Protect from light.
 

The sterile white or almost white to faintly yellow powder is packed in glass vial USP type I with
rubber bung and aluminium flip-off seal.
 

Administration Intramuscular:
Add 1ml Water for Injections to 250mg Cefuroxime or 3ml Water for Injections to 750mg
Cefuroxime. Shake gently to produce an opaque suspension.

Administration Intravenous:
Dissolved Cefuroxime in Water for Injections using at least 2ml for 250mg, at least 6ml for
750mg, or 15ml for 1.5g. For short intravenous infusion (e.g. up to 30minutes), 1.5g may be
dissolved in 50ml Water for Injections. These solutions may be given directly into the vein or
introduced into the tubing of the giving set if the patient is receiving parenteral fluids.
Cefuroxime is compatible with the more commonly used intravenous fluids.