Cefuaxit

Cefuaxit

cefuroxime

Manufacturer:

Nectar Lifesciences

Distributor:

Royal Distribution

Marketer:

ESTI Pharma
Full Prescribing Info
Contents
Tablet: Cefuroxime Axetil. Injection: Cefuroxime Sodium.
Description
Tablet: Each film coated Tablet Contains: Cefuroxime Axetil USP Equivalent to Cefuroxime 250 mg/500 mg.
Injection: Each Vial Contains: Sterile Cefuroxime Sodium USP equivalent to Anhydrous Cefuroxime 750 mg.
Excipients/Inactive Ingredients: Tablet: q.s.
Colour: Titanium Dioxide USP.
Action
Pharmacotherapeutic group: Antibacterials for systemic use, second-generation cephalosporins. ATC Code: J01DC02.
Pharmacology: Pharmacodynamics: Mechanism of action: 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.
Pharmacokinetics: Absorption: After oral administration cefuroxime axetil is absorbed from the gastrointestinal tract and rapidly hydrolysed in the intestinal mucosa and blood to release cefuroxime into the circulation. Optimum absorption occurs when it is administered shortly after a meal.
Following administration of cefuroxime axetil tablets peak serum levels (2.9 µg/mL for a 125 mg dose, 4.4 µg/mL for a 250 mg dose, 7.7 µg/mL for a 500 mg dose and 13.6 µg/mL for a 1000 mg dose) occur approximately 2.4 hours after dosing when taken with food. The rate of absorption of cefuroxime from the suspension is reduced compared with the tablets, leading to later, lower peak serum levels and reduced systemic bioavailability (4 to 17% less). Cefuroxime axetil oral suspension was not bioequivalent to cefuroxime axetil tablets when tested in healthy adults and therefore is not substitutable on a milligramper-milligram basis. The pharmacokinetics of cefuroxime is linear over the oral dosage range of 125 to 1000 mg. No accumulation of cefuroxime occurred following repeat oral doses of 250 to 500 mg.
After intramuscular (IM) injection of cefuroxime to normal volunteers, the mean peak serum concentrations ranged from 27 to 35 µg/mL for a 750 mg dose and from 33 to 40 µg/mL for a 1000 mg dose, and were 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.
Following a single dose of Cefuroxime axetil 500 mg tablet to 12 healthy volunteers, the apparent volume of distribution was 50 L (CV% = 28%). 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.
Tablet: The serum half-life is between 1 and 1.5 hours. The renal clearance is in the region of 125 to 148 mL/min/1.73 m2.
Injection: The serum half-life after either intramuscular or intravenous injection is approximately 70 minutes. There is an almost complete recovery (85 to 90%) of unchanged cefuroxime in urine within 24 hours of administration. The majority of the cefuroxime is excreted within the first 6 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: Tablet: No differences in the pharmacokinetics of cefuroxime were observed between males and females.
Injection: 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: Tablet: No special precaution is necessary in the elderly patients with normal renal function at dosages up to the normal maximum of 1g per day. Elderly patients are more likely to have decreased renal function; therefore, the dose should be adjusted in accordance with the renal function in the elderly.
Injection: 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.
Paediatrics: Tablet: In older infants (aged >3 months) and in children, the pharmacokinetics of cefuroxime ae similar to that observed in adults.
There is no clinical trial data available on the use of cefuroxime axetil in children under the age of 3 months.
Injection: 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: Tablet: The safety and efficacy of cefuroxime axetil in patients with renal failure have not been established.
Cefuroxime is primarily excreted by the kidneys. Therefore, as with all such antibiotics, in patients with markedly impaired renal function (i.e. Clcr <30 mL/minute) it is recommended that the dosage of cefuroxime should be reduced to compensate for its slower excretion. Cefuroxime is effectively removed by dialysis.
Injection: Cefuroxime is primarily excreted by the kidneys. As with all such antibiotics, in patients with markedly impaired renal function (i.e. Clcr <20 mL/minute) it is recommended that the dosage of cefuroxime should be reduced to compensate for its slower excretion. Cefuroxime is effectively removed by haemodialysis and peritoneal dialysis.
Hepatic impairment: Tablet: There are no data available for patients with hepatic impairment. Since cefuroxime is primarily eliminated by the kidney, the presence of hepatic dysfunction is expected to have no effect on the pharmacokinetics of cefuroxime.
Injection: 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).
Toxicology: 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.
Microbiology: 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.
Cefuroxime axetil breakpoints: Tablet: Minimum inhibitory concentration (MIC) breakpoints established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) are as follows: See Table 1.

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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 known and 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 pyogenes, Streptococcus agalactiae.
Injection: Streptococcus mitis (viridans group).
Gram-negative aerobes: Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis.
Spirochaetes: Tablet: Borrelia burgdorferi.
Microorganisms for which acquired resistance may be a problem: Gram-positive aerobes: Streptococcus pneumoniae.
Gram-negative aerobes: Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus spp. (other than P. vulgaris), Providencia spp, Salmonella spp. (for Injection only).
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., Campylobacter spp. (for Tablet only), Morganella morganii, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescens.
Gram-positive anaerobes: Injection: Clostridium difficile.
Gram-negative anaerobes: Bacteroides fragilis.
Others: Chlamydia spp., Mycoplasma spp., Legionella spp.
* All methicillin-resistant S. aureus are resistant to cefuroxime.
Injection: In vitro, the activities of cefuroxime sodium and aminoglycoside antibiotics in combination have been shown to beat least additive with occasional evidence of synergy.
Indications/Uses
Tablet: Cefuroxime axetil is indicated for the treatment of the infections listed as follows in adults and children from the age of 3 months: Acute streptococcal tonsillitis and pharyngitis; Acute bacterial sinusitis; Acute otitis media; Acute exacerbations of chronic bronchitis; Cystitis; Pyelonephritis; Uncomplicated skin and soft tissue infections; Treatment of early Lyme disease.
Injection: Cefuroxime for Injection USP 750 mg is indicated for the treatment of the infections listed as follows in adults and children, including neonates: 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; 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.
Dosage/Direction for Use
Posology: Tablet: course of therapy is seven days (may range from five to ten days). (See Tables 2 and 3.)

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There is no experience of using Cefuroxime axetil in children under the age of 3 months.
Injection: See Tables 4 and 5.

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Renal impairment: Tablet: The safety and efficacy of cefuroxime axetil in patients with renal failure have not been established.
Cefuroxime is primarily excreted by the kidneys. In patients with markedly impaired renal function it is recommended that the dosage of cefuroxime should be reduced to compensate for its slower excretion. Cefuroxime is effectively removed by dialysis. (See Table 6.)

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Injection: 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 Cefuaxit should be reduced to compensate for its slower excretion. (See Table 7.)

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Hepatic impairment: Tablet: There are no data available for patients with hepatic impairment. Since cefuroxime is primarily eliminated by the kidney, the presence of hepatic dysfunction is expected to have no effect on the pharmacokinetics of cefuroxime.
Injection: 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: Tablet: For oral administration.
Cefuroxime axetil tablets should be taken after food for optimum absorption.
Cefuroxime axetil tablets should not be crushed and are therefore unsuitable for treatment of patients who cannot swallow tablets. In children Cefuroxime axetil oral suspension may be used.
Injection: Intravenous/Intramuscular.
Overdosage
Tablet: Overdose 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.
Serum levels of cefuroxime can be reduced by haemodialysis and peritoneal dialysis.
Contraindications
Patients with known hypersensitivity to cephalosporin antibiotics.
History of severe hypersensitivity (e.g. anaphylactic reaction) to any other type of beta-lactam antibacterial agent (penicillins, monobactams and carbapenems).
Special Precautions
Hypersensitivity reactions: As with all beta-lactam antibacterial agents, serious and occasionally fatal hypersensitivity reactions have been reported. 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.
Tablet: Special care is indicated in patients who have experienced an allergic reaction to penicillins or other beta-lactam antibiotics because there is a risk of cross-sensitivity.
Jarisch-Herxheimer reaction: Tablet: The Jarisch-Herxheimer reaction has been seen following cefuroxime axetil treatment of Lyme disease. It results directly from the bactericidal activity of cefuroxime axetil on the causative bacteria of Lyme disease, the spirochaete Borrelia burgdorferi.
Patients should be reassured that this is a common and usually self-limiting consequence of antibiotic treatment of Lyme disease.
Overgrowth of non-susceptible microorganisms: As with other antibiotics, 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.
Antibacterial agent-associated pseudomembranous colitis has been reported with nearly all antibacterial agents, including 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. 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.
Interference with diagnostic tests: The development of a positive Coombs' Test associated with the use of cefuroxime may interfere with cross matching of blood.
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 axetil/sodium.
Injection: 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.
Concurrent treatment with potent diuretics or aminoglycosides: Injection: 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.
Intra-abdominal infections: Injection: Due to its spectrum of activity, Cefuroxime is not suitable for the treatment of infections caused by Gram-negative non-fermenting bacteria.
Effects on ability to drive and use machines: Tablet: No studies on the effects on the ability to drive and use machines have been performed. However, as this medicine may cause dizziness, patients should be warned to be cautious when driving or operating machinery.
Injection: 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.
Use In Pregnancy & Lactation
Pregnancy: Tablet: There are limited data from the use of cefuroxime in pregnant women. Studies in animals have shown no harmful effects on pregnancy, embryonal or foetal development, parturition or postnatal development. Cefuroxime axetil should be prescribed to pregnant women only if the benefit outweighs the risk.
Injection: There are limited amounts of data from the use of cefuroxime in pregnant women. Studies in animals have shown no reproductive toxicity. Cefuaxit 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.
Breastfeeding: Tablet: Cefuroxime is excreted in human milk in small quantities. Adverse effects at therapeutic doses are not expected, although a risk of diarrhoea and fungus infection of the mucous membranes cannot be excluded. Breastfeeding might have to be discontinued due to these effects. The possibility of sensitisation should be taken into account. Cefuroxime should only be used during breastfeeding after benefit/risk assessment by the physician in charge.
Injection: 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 axetil/sodium on fertility in humans. Reproductive studies in animals have shown no effects on fertility.
Adverse Reactions
Tablet: The most common adverse reactions are Candida overgrowth, eosinophilia, headache, dizziness, gastrointestinal disturbances and transient rise in liver enzymes.
The frequency categories assigned to the adverse reactions as follows are estimates, as for most reactions suitable data (for example from placebo-controlled studies) for calculating incidence were not available. In addition the incidence of adverse reactions associated with cefuroxime axetil may vary according to the indication.
Data from large 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 postmarketing data, and refer to a reporting rate rather than true frequency. Placebo-controlled trial data were not available. Where incidences have been calculated from clinical trial data, these were based on drug-related (investigator assessed) data. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Treatment related adverse reactions, all grades, are listed as follows by MedDRA body system organ class, frequency and grade of severity. The following convention has been utilised for the classification of frequency: very common ≥ 1/10; common ≥ 1/100 to < 1/10, uncommon ≥ 1/1,000 to < 1/100; rare ≥ 1/10,000 to < 1/1,000; very rare < 1/10,000 and not known (cannot be estimated from the available data). (See Table 8.)

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Injection: 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 as follows 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 as follows by MedDRA body system organ class, frequency and grade of severity. The following convention has been utilised for the classification of frequency: very common ≥ 1/10; common ≥ 1/100 to < 1/10, uncommon ≥ 1/1,000 to < 1/100; rare ≥ 1/10,000 to < 1/1,000; very rare < 1/10,000 and not known (cannot be estimated from the available data). (See Table 9.)

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Paediatric population: The safety profile for cefuroxime axetil/sodium in children is consistent with the profile in adults.
Drug Interactions
Tablet: Drugs which reduce gastric acidity may result in a lower bioavailability of cefuroxime axetil compared with that of the fasting state and tend to cancel the effect of enhanced absorption after food.
Cefuroxime axetil 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 significantly increases the peak concentration, area under the serum concentration time curve and elimination half-life of cefuroxime.
Concomitant use with oral anticoagulants may give rise to increased INR.
Injection: 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: Injection: 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: Injection: Determination of blood/plasma glucose levels.
Concomitant use with oral anticoagulants may give rise to increased international normalised ratio (INR).
Caution For Usage
Special precautions for disposal and other handling: Tablet: None.
Directions for use: Injection: Cefuroxime for Injection 750 mg should be constituted with 6 ml of SWFI for I.V use and 3 ml of SWFI for I.M use.
Storage
Store in dry place at temperatures below 30°C.
Protect from light.
MIMS Class
ATC Classification
J01DC02 - cefuroxime ; Belongs to the class of second-generation cephalosporins. Used in the systemic treatment of infections.
Presentation/Packing
FC tab 250 mg x 6's, 10's. 500 mg x 6's, 10's. Inj (vial) 750 mg (+ 10 mL SWFI) x 1's.
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