Axcel Cefuroxime

Cefuroxime axetil.

Capsule: Standard purple OP/Amethyst OP, hard gelatin capsule, size "O".
Each capsule contains: Cefuroxime Axetil equivalent to Cefuroxime 250 mg.
Tablet: White to off white, biconvex, capsule shaped tablet with a scoreline on one side and B032 on other side.
Each tablet contains: Cefuroxime Axetil equivalent to Cefuroxime 500 mg.
Oral suspension: Off white to pale yellow granules, which gives off white to pale yellow suspension with fruity flavor after reconstituted.
Each 5 ml contains: Cefuroxime Axetil equivalent to Cefuroxime 125 mg.

Pharmacology: Mechanism of Action: Capsule and Oral suspension: Cefuroxime axetil is an oral prodrug of the bactericidal cephalosporin antibiotic cefuroxime, which is resistant to most β-lactamases and is active against a wide range of Gram-positive and Gram-negative organisms. It is indicated for the treatment of infections caused by susceptible bacteria. Cefuroxime is a well-characterized 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. Cefuroxime is usually active against the following organisms in vitro: Aerobes, Gram-negative: Haemophilus influenzae (including ampicillin-resistant strains); Haemophilus parainfluenzae; Moraxella (Branhamella) catarrhalis; Escherichia coli; Klebsiella spp.; Proteus mirabilis; Proteus inconstans; Providencia rettgeri and Neisseria gonorrhoeae (including penicillinase and non-penicillinase-producing strains).
Aerobes, Gram-positive: Staphylococcus aureus (including penicillinase-producing strains but excluding methicillin-resistant strains), Staphylococcus epidermidis (including penicillinase-producing strains but excluding methicillin-resistant strains), Streptococcus pyogenes (and other β-haemolytic streptococci), Streptococcus pneumoniae, Streptococcus Group B (Streptococcus agalactiae).
Anaerobes, Gram-positive and Gram-negative cocci (including Peptococcus and Peptostreptococcus spp); Gram-positive bacilli (including Clostridium spp.) and Gram-negative bacilli (including Bacteroides and Fusobacterium spp); Propionibacterium spp.
Some strains of the following genera are not susceptible to Cefuroxime: Enterococcus (Streptococcus) faecalis, Morganella morganii, Proteus vulgaris, Enterobacter spp., Citrobacter spp., Serratia spp. and Bacteroides fragilis.
Oral suspension: Other organisms: Borrelia burgdorferi.
The following organisms are not susceptible to Cefuroxime: Clostridium difficile, Pseudomonas spp., Campylobacter spp., Acinetobacter calcoaceticus, Listeria monocytogenes, Methicillin-resistant strains of Staphylococcus aureus and Staphylococcus epidermidis and Legionella spp.
Tablet: Cefuroxime axetil undergoes hydrolysis by esterase enzymes to the active antibiotic, cefuroxime. 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) by extended-spectrum beta-lactamases (ESBLs), and AmpC enzymes that may be induced or stably derepressed in certain aerobic Gram-negative bacteria 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. 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. Cefuroxime is usually active against the following organisms in vitro. In vitro susceptibility of microorganisms to Cefuroxime where clinical efficacy of cefuroxime axetil has been demonstrated in clinical trials this is indicated with an asterisk (*): Commonly susceptible species: Gram-positive aerobes: Staphylococcus aureus (methicillin-susceptible)*, Coagulase negative staphylococcus (methicillin-susceptible), Streptococcus pyogenes, Beta-hemolytic streptococci.
Gram-negative aerobes: Haemophilus influenzae* including ampicillin-resistant strains, Haemophilus parainfluenzae*, Moraxella catarrhalis*, Neisseria gonorrhoea* including penicillinase and non-penicillinase producing strains.
Gram-Positive Anaerobes: Peptostreptococcus spp., Propionibacterium spp.
Spirochaetes: Borrelia burgdorferi*.
Microorganisms for which acquired resistance may be a problem: Gram-positive aerobes: Streptococcus pneumoniae*.
Gram-negative aerobes: Citrobacter spp. not including C. freundii, Enterobacter spp. not including E. aerogenes and E. cloacae, Escherichia coli*, Klebsiella spp. including Klebsiella pneumoniae*, Proteus mirabilis, Proteus spp. not including P. penneri and P. vulgaris, Providencia spp.
Gram-positive anaerobes: Clostridium spp. not including C. difficile.
Gram-negative anaerobes: Bacteroides spp. not including B. fragilis, Fusobacterium spp.
Inherently resistant microorganisms: 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 Pseudomonas aeruginosa, Serratia spp., Stenotrophomonas maltophilia.
Gram-Positive anaerobes: Clostridium difficile.
Gram-negative anaerobes: Bacteroides fragilis.
Others: Chlamydia species, Mycoplasma species, Legionella species.
Pharmacokinetics: Cefuroxime axetil is slowly absorbed from the gastrointestinal tract after oral administration and rapidly hydrolysed in the intestinal mucosa and blood to release cefuroxime into the circulation. Serum levels of cefuroxime are reduced by dialysis.
Capsule and Oral suspension: In presence of food, the absorption of Cefuroxime axetil is enhanced.
Tablet and Oral suspension: The absorption of cefuroxime from the suspension is more prolonged compared with tablets, leading to later, lower peak serum levels and slightly reduced systemic bioavailability (4-17% less). Post peak levels, the serum half-life is between 1 and 1.5 hours. Protein binding has been variously stated as 33-50% depending on the methodology used. Cefuroxime is not metabolised and is excreted by glomerular filtration and tubular secretion. Concurrent administration of probenecid increases the area under the mean serum concentrations time curve by 50%.
Capsule: Peak plasma concentrations are reported about 2 to 3 hours after an oral dose. Up to 50% of Cefuroxime in the circulation is bound to plasma proteins and the plasma half-life is about 70 minutes and is prolonged in patients with renal impairment and in neonates. Cefuroxime is distributed widely in the body including pleural fluid, sputum, bones, synovial fluid and aqueous humour. It crosses the placenta and has been detected in breast milk. Cefuroxime is excreted unchanged by glomerular filtration and renal tubular secretion, and high concentrations are achieved in the urine. Probenecid competes for renal tubular secretion with Cefuroxime resulting in higher and more prolonged plasma concentrations of Cefuroxime. Small amounts of Cefuroxime are excreted in bile.
Tablet: Optimum absorption occurs when it is administered shortly after a meal. Peak serum level (2.1 mg/l for a 125 mg dose, 4.1 mg/l for a 250 mg dose, 7.0 mg/l for a 500 mg dose and 13.6 mg/l for a 1 g dose) occur approximately two to three hours after dosing when taken after food, unlike iv dosing which peaks immediately.
Renal impairment: Cefuroxime pharmacokinetics have been investigated in patients with various degrees of renal impairment. Cefuroxime elimination half-life increases with decrease in renal function which serves as the basis for dosage adjustment recommendations in this group of patients (see Dosage & Administration). In patients undergoing haemodialysis, at least 60% of the total amount of cefuroxime present in the body at the start of dialysis will be removed during a 4-hour dialysis period. Therefore, an additional single dose of cefuroxime should be administered following the completion of haemodialysis.

Upper respiratory tract infections (for example: ear, nose and throat infections, such as otitis media, sinusitis, tonsillitis and pharyngitis).
Lower respiratory tract infections (for example: pneumonia, acute bronchitis, and acute exacerbation of chronic bronchitis).
Genito-urinary tract infections (for example: pyelonephritis, cystitis and urethritis).
Gonorrhoea, acute uncomplicated gonococcal urethritis, and cervicitis.
Skin and soft tissue infections (for example: furunculosis, pyoderma and impetigo).
Tablet: Cefuroxime axetil is an oral prodrug of the bactericidal cephalosporin antibiotic cefuroxime, which is resistant to most β-lactamases and is active against a wide range of Gram-positive and Gram-negative organisms. It is indicated for the treatment of infections caused by susceptible bacteria. Susceptibility to Cefuroxime axetil will vary with geography and time and local susceptibility data should be consulted where available (see Pharmacology under Actions). This indicated for treatment of infections caused by sensitive bacteria which includes the previously mentioned.
Cefuroxime is also available as the sodium salt for parenteral administration. This permits the use of sequential therapy with the same antibiotic when a change from parenteral to oral therapy is clinically indicated. Where appropriate, Axcel Cefuroxime-500 mg Tablet is effective when used following initial parenteral Vaxcel Cefuroxime Injection (cefuroxime sodium) in the treatment of pneumonia and acute exacerbations of chronic bronchitis.
Oral suspension: Treatment of early Lyme disease and subsequent prevention of late Lyme disease in adults and children over 12 years old.

For oral administration only.
The usual course of therapy is seven days (range 5 to 10 days).
Cefuroxime axetil should be taken after food for optimum absorption.
Dosage in adults: Most infections: 250 mg twice daily.
Urinary tract infections: 125 mg or 250 mg twice daily.
Mild to moderate lower respiratory tract infections e.g. bronchitis: 250 mg twice daily.
More severe lower respiratory tract infections, or if pneumonia is suspected: 500 mg twice daily.
Pyelonephritis: 250 mg twice daily.
Uncomplicated gonorrhea: single dose of 1 g.
Oral suspension: Lyme disease in adults and children over the age of 12 years: 500 mg twice daily for 20 days.
Capsule and Tablet: Sequential therapy: Pneumonia: 1.5 g cefuroxime injection (cefuroxime sodium)/Vaxcel Cefuroxime twice daily (given i.v. or i.m.) for 48 to 72 hours, followed by 500 mg twice daily Axcel Cefuroxime Tablet (cefuroxime axetil) oral therapy for 7 to 10 days.
Acute exacerbations of chronic bronchitis: 750 mg cefuroxime injection (cefuroxime sodium)/Vaxcel Cefuroxime twice daily (given i.v. or i.m.) for 48 to 72 hours, followed by 500 mg twice daily Axcel Cefuroxime Tablet (cefuroxime axetil) oral therapy for 5 to 10 days. Duration of both parenteral and oral therapy is determined by the severity of the infection and the clinical status of the patient.
Dosage in children: Most infections: The usual dose is 125 mg twice daily or 10 mg/kg twice daily to a maximum of 250 mg daily.
For otitis media, in children less than 2 years of age, the usual dosage is 125 mg twice daily or 10 mg/kg bd to a maximum of 250 mg daily and in children over 2 years of age, 250 mg twice daily or 15 mg/kg twice daily to a maximum of 500 mg daily.
There is no experience or clinical trial data available on the use in children under 3 months of age.
Capsule: Elderly and patients with renal impairment: No special precautions are necessary in patients with renal impairment or on renal dialysis or in the elderly at dosages up to the normal maximum of 1 g per day. The usual course of therapy is seven days. Axcel Cefuroxime-250 Capsule should be taken after food for optimum absorption.
Oral suspension: Direction for mixing: Shake bottle well to loosen granules. Remove cap and Dose-Master adapter. Then, add some water to mix with the granules. After that, shake and top up to 50 ml mark. Place the Dose-Master adapter and cap. Shake the bottle well to mix the medicine properly.
Tablet: Renal impairment: Cefuroxime is primarily excreted by kidneys. In patients with markedly impaired renal function it is recommended that the dosage of cefuroxime be reduced to compensate for its slower excretion (see the table as follows). (See table.)

Click on icon to see table/diagram/image

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

Patients known to be hypersensitive to cephalosporin antibiotics.
Tablet: Hypersensitivity to cefuroxime or to any of the excipients.
History of severe hypersensitivity (e.g. anaphylactic reaction) to any other type of beta-lactam antibacterial agent (penicillins, monobactams and carbapenems).

Serious and occasionally fatal hypersensitivity reactions (including anaphylactoid and severe cutaneous adverse reactions) have been reported in patients receiving therapy with beta-lactams. Before initiating therapy with Axcel Cefuroxime, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, carbapenems or other beta-lactam agents. If an allergic reaction occurs, Axcel Cefuroxime must be discontinued immediately and appropriate alternative therapy instituted.
Capsule: This product should be given cautiously to penicillin-sensitive patients. Antibiotics should be administered with caution to any patient who has demonstrated some form of allergy, particularly to drugs.
Serious acute hypersensitivity reactions may require epinephrine and other emergency measures. Pseudomembranous colitis has been reported with nearly all antibacterial agents, including cefuroxime, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.

Special care is indicated in patients who have experienced an allergic or anaphylactic reaction to penicillin or other beta-lactams. As with other antibiotics, prolonged use of Cefuroxime may result in overgrowth of non-susceptible organisms (eg. Candida, Enterococci, Clostridium difficile), which may require interruption of treatment.
Tablet and Oral suspension: Pseudomembranous colitis has been reported with the use of broad-spectrum antibiotics; therefore, it is important to consider its diagnosis in patients who develop serious diarrhea during or after antibiotic use.
Effects on Ability to Drive and Use Machines: As this medicine may cause dizziness, patients should be warned to be cautious when driving or operating machinery.
Capsule: Cephalosporin antibiotics may in general be given safely to patients who are hypersensitive to penicillins, although cross-reactions have been reported. Cephalosporin antibiotics at high dosage should be given with caution to patients receiving concurrent treatment with potent diuretics such as frusemide, as these combinations are suspected of adversely affecting renal function. Clinical experience with Cefuroxime has shown that this is not likely to be a problem at the recommended dose levels.
Tablet: 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. Refer to the relevant prescribing information for cefuroxime sodium before initiating sequential therapy.

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 axetil is administered to a nursing mother.
Tablet and Oral suspension: There is no experimental evidence of embryopathic or teratogenic effects which refer to cefuroxime axetil.

Tablet and Oral suspension: Adverse reaction to Cefuroxime Axetil is generally mild and transient in nature.
Capsule and Oral suspension: Gastrointestinal disturbances, including diarrhoea, nausea and vomiting, have occurred in some patients receiving Cefuroxime Axetil. As with other broad-spectrum antibiotics, there have been reports of pseudomembranous colitis. Headache has also been reported. There have been rare reports of erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, thrombocytopenia, leucopenia, jaundice, haemolytic anaemia and hypersensitive reactions including skin rashes, urticaria, pruritus, drug fever, serum sickness and very rarely anaphylaxis. Eosinophilia and transient increases of hepatic enzyme levels (ALT and AST) have been noted during Cefuroxime therapy.
Tablet: The incidence of adverse reactions associated with Cefuroxime Axetil may vary according to the indication. The following side effects have been observed: Infections and infestations: overgrowth of candida.
Blood and lymphatic system disorders: Eosinophilia, Positive Coombs test, thrombocytopenia, leukopenia (sometimes profound) and Haemolytic anaemia. Cephalosporin tend be absorbed onto the surface of red cells membranes and react with antibodies directed against the drug to produce a positive Coombs test (interfere with cross-matching of blood) and very rarely haemolytic anaemia.
Immune system disorders: Hypersensitivity reactions including rashes, urticaria, pruritus, drug fever, serum sickness, and anaphylaxis.
Nervous system disorders: Headache, dizziness.
Gastrointestinal disorders: Gastrointestinal disturbances including diarrhoea, nausea, abdominal pain, vomiting, and Pseudomembranous colitis.
Hepatobiliary disorders: Transient increases of hepatic enzyme levels, [ALT (SGPT), AST (SGOT), LDH], jaundice (predominantly cholestatic), and hepatitis.
Skin and subcutaneous tissue disorders: Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (exanthematic necrolysis), see immune system disorders as previously mentioned.
Axcel Cefuroxime-500 mg Tablet may cause severe allergy and serious skin reactions. Stop using Axcel Cefuroxime-500 mg Tablet and seek medical assistance immediately if the patient experiences any of the following symptoms: skin reddening, blisters, rash, fever, sore throat or eye irritation.
Oral suspension: There have been rare reports of thrombocytopenia and leucopenia (sometimes profound). As with other cephalosporins, jaundice has been reported very rarely. Cephalosporins as a class tend to be absorbed onto the surface of red cells 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.

Drugs which reduce gastric acidity may result in a lower bioavailability of this antibiotic compared with that of the fasting state and tend to cancel the effect of enhanced absorption after food.
Cefuroxime may cause false negative results in the ferricyanide test, it is recommended that either glucose oxidase or hexokinase method are used to determine blood/plasma glucose levels in patients receiving Cefuroxime. The antibiotic does not interfere the alkaline picrate assay for creatinine.
Capsule: Drug-lab Interaction: A positive Coombs' test has been reported during treatment with cephalosporins this phenomena can interfere with cross-matching of blood. Cefuroxime 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.
Tablet: Similar with other antibiotics, Axcel Cefuroxime-500 mg Tablet may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives.

Store below 30°C. Protect from light and moisture.
Oral suspension: Keep container well closed. Store below 30°C. Protect from light.
After reconstitution, refrigerate between 2°C - 8°C and use within 10 days.

Cephalosporins

J01DC02 - cefuroxime ; Belongs to the class of second-generation cephalosporins. Used in the systemic treatment of infections.

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