Cefuroxime axetil (oral)

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# Overview
Cefuroxime axetil (oral) is a 2nd generation cephalosporin, antibiotic, anti-infective agent that is FDA approved for the treatment of pharyngitis/tonsillitis, acute bacterial otitis media, acute bacterial maxillary sinusitis, acute bacterial exacerbations of chronic bronchitis and secondary bacterial infections of acute bronchitis, uncomplicated skin and skin structure infections, uncomplicated urinary tract infections, uncomplicated gonorrhea, early lyme disease (erythema migrans) and impetigo.   Common adverse reactions include diarrhea, nausea, vomiting, and vaginitis..

# Adult Indications and Dosage

## FDA-Labeled Indications and Dosage (Adult)
- To reduce the development of drugresistant bacteria and maintain the effectiveness of Cefuroxime axetil and other antibacterial drugs, Cefuroxime axetil should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

### Cefuroxime axetil Tablets
- Cefuroxime axetil Tablets are indicated for the treatment of patients with mild to moderate infections caused by susceptible strains of the designated microorganisms in the conditions listed below:
- Caused by Streptococcus pyogenes
- NOTE: The usual drug of choice in the treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever, is penicillin given by the intramuscular route. Cefuroxime axetil Tablets are generally effective in the eradication of streptococci from the nasopharynx; however, substantial data establishing the efficacy of cefuroxime in the subsequent prevention of rheumatic fever are not available. Please also note that in all clinical trials, all isolates had to be sensitive to both penicillin and cefuroxime. There are no data from adequate and wellcontrolled trials to demonstrate the effectiveness of cefuroxime in the treatment of penicillinresistant strains of Streptococcus pyogenes.
- Caused by Streptococcus pneumoniae, Haemophilus influenzae (including beta-lactamaseproducing strains), Moraxella catarrhalis (including beta-lactamaseproducing strains), or Streptococcus pyogenes.
- Caused by Streptococcus pneumoniae or Haemophilus influenzae (non-beta-lactamaseproducing strains only).
- NOTE: In view of the insufficient numbers of isolates of beta -lactamaseproducing strains of Haemophilus influenzae and Moraxella catarrhalis that were obtained from clinical trials with Cefuroxime axetil Tablets for patients with acute bacterial maxillary sinusitis, it was not possible to adequately evaluate the effectiveness of Cefuroxime axetil Tablets for sinus infections known, suspected, or considered potentially to be caused by beta -lactamaseproducing Haemophilus influenzae or Moraxella catarrhalis.
- Caused by Streptococcus pneumoniae, Haemophilus influenzae (beta-lactamase negative strains), or Haemophilus parainfluenzae (betalactamase negative strains).
- Caused by Staphylococcus aureus (including beta-lactamaseproducing strains) or Streptococcus pyogenes.
- Caused by Escherichia coli or Klebsiella pneumoniae.
- Caused by penicillinase-producing and non-penicillinaseproducing strains of Neisseria gonorrhoeae and uncomplicated gonorrhea, rectal, in females, caused by non-penicillinaseproducing strains of Neisseria gonorrhoeae.
- Caused by Borrelia burgdorferi

### Dosing Information
NOTE: Cefuroxime axetil Tablets and Cefuroxime axetil for oral suspension are not bioequivalent and are not substitutable on a milligrampermilligram basis.
- Because cefuroxime is eliminated primarily by the kidney, a dosage interval adjustment is required for patients whose creatinine clearance is <30 mL/min.

## Off-Label Use and Dosage (Adult)

### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Cefuroxime axetil in adult patients.

### NonGuideline-Supported Use
There is limited information regarding Off-Label NonGuideline-Supported Use of Cefuroxime axetil in adult patients.

# Pediatric Indications and Dosage

## FDA-Labeled Indications and Dosage (Pediatric)

### Cefuroxime axetil for Oral Suspension
- Cefuroxime axetil for Oral Suspension is indicated for the treatment of pediatric patients 3 months to 12 years of age with mild to moderate infections caused by susceptible strains of the designated microorganisms in the conditions listed below. The safety and effectiveness of Cefuroxime axetil for Oral Suspension in the treatment of infections other than those specifically listed below have not been established either by adequate and wellcontrolled trials or by pharmacokinetic data with which to determine an effective and safe dosing regimen.
- NOTE: The usual drug of choice in the treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever, is penicillin given by the intramuscular route. Cefuroxime axetil for Oral Suspension is generally effective in the eradication of streptococci from the nasopharynx; however, substantial data establishing the efficacy of cefuroxime in the subsequent prevention of rheumatic fever are not available. Please also note that in all clinical trials, all isolates had to be sensitive to both penicillin and cefuroxime. There are no data from adequate and wellcontrolled trials to demonstrate the effectiveness of cefuroxime in the treatment of penicillinresistant strains of Streptococcus pyogenes.
- Caused by Streptococcus pneumoniae, Haemophilus influenzae (including beta-lactamaseproducing strains), Moraxella catarrhalis (including beta-lactamaseproducing strains), or Streptococcus pyogenes.
- Caused by Staphylococcus aureus (including beta-lactamaseproducing strains) or Streptococcus pyogenes.

### Dosing Information
- Cefuroxime axetil for Oral Suspension may be administered to pediatric patients ranging in age from 3 months to 12 years, according to dosages in the table given below:
- Prepare a suspension at the time of dispensing as follows:
- Shake the bottle to loosen the powder.
- Remove the cap.
- Add the total amount of water for reconstitution (see Table 12) and replace the cap.
- Invert the bottle and vigorously rock the bottle from side to side so that water rises through the powder.
- Once the sound of the powder against the bottle disappears, turn the bottle upright and vigorously shake it in a diagonal direction.
- NOTE: Shake the oral suspension well before each use. Replace cap securely after each opening. Store the reconstituted suspension between 2 and 8C (36 and 46F) (in a refrigerator). Discard after 10 days.

## Off-Label Use and Dosage (Pediatric)

### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Cefuroxime axetil in pediatric patients.

### NonGuideline-Supported Use
There is limited information regarding Off-Label NonGuideline-Supported Use of Cefuroxime axetil in pediatric patients.

# Contraindications
- Cefuroxime axetil products are contraindicated in patients with known allergy to the cephalosporin group of antibiotics.

# Warnings
- Cefuroxime axetil tablets and Cefuroxime axetil for oral suspension are not bioequivalent and are therefore not substitutable on a milligrampermilligram basis.
- Before therapy with Cefuroxime axetil products is instituted, careful inquiry should be made to determine whether the patient has had previous hypersensitivity reactions to Cefuroxime axetil products, other cephalosporins, penicillins, or other drugs. If this product is to be given to penicillinsensitive patients, caution should be exercised because crosshypersensitivity among betalactam antibiotics has been clearly documented and may occur in up to 10% of patients with a history of penicillin allergy. If a clinically significant allergic reaction to Cefuroxime axetil products occurs, discontinue the drug and institute appropriate therapy. Serious acute hypersensitivity reactions may require treatment with epinephrine and other emergency measures, including oxygen, intravenous fluids, intravenous antihistamines, corticosteroids, pressor amines, and airway management, as clinically indicated.
- Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Cefuroxime axetil, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
- C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over 2 months after the administration of antibacterial agents.
- If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

### PRECAUTIONS
- As with other broadspectrum antibiotics, prolonged administration of cefuroxime axetil may result in overgrowth of nonsusceptible microorganisms. If superinfection occurs during therapy, appropriate measures should be taken.
- Cephalosporins, including cefuroxime axetil, should be given with caution to patients receiving concurrent treatment with potent diuretics because these diuretics are suspected of adversely affecting renal function.
- Cefuroxime axetil, as with other broadspectrum antibiotics, should be prescribed with caution in individuals with a history of colitis. The safety and effectiveness of cefuroxime axetil have not been established in patients with gastrointestinal malabsorption. Patients with gastrointestinal malabsorption were excluded from participating in clinical trials of cefuroxime axetil.
- Cephalosporins may be associated with a fall in prothrombin activity. Those at risk include patients with renal or hepatic impairment or poor nutritional state, as well as patients receiving a protracted course of antimicrobial therapy, and patients previously stabilized on anticoagulant therapy. Prothrombin time should be monitored in patients at risk and exogenous Vitamin K administered as indicated.
- Prescribing Cefuroxime axetil in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drugresistant bacteria.
- Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as 2 or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

# Adverse Reactions

## Clinical Trials Experience

### Multiple-Dose Dosing Regimens
- Using multiple doses of cefuroxime axetil tablets, 912 patients were treated with cefuroxime axetil (125 to 500 mg twice daily). There were no deaths or permanent disabilities thought related to drug toxicity. Twenty (2.2%) patients discontinued medication due to adverse events thought by the investigators to be possibly, probably, or almost certainly related to drug toxicity. Seventeen (85%) of the 20 patients who discontinued therapy did so because of gastrointestinal disturbances, including diarrhea, nausea, vomiting, and abdominal pain. The percentage of cefuroxime axetil tablettreated patients who discontinued study drug because of adverse events was very similar at daily doses of 1,000, 500, and 250 mg (2.3%, 2.1%, and 2.2%, respectively). However, the incidence of gastrointestinal adverse events increased with the higher recommended doses.
- The following adverse events were thought by the investigators to be possibly, probably, or almost certainly related to cefuroxime axetil tablets in multipledose clinical trials (n = 912 cefuroxime axetiltreated patients).
- Table Adverse ReactionsCefuroxime axetil Tablets:
- In clinical trials using Cefuroxime axetil in a dose of 250 mg twice daily in the treatment of secondary bacterial infections of acute bronchitis, 399 patients were treated for 5 days and 402 patients were treated for 10 days. No difference in the occurrence of adverse events was found between the 2 regimens.
- Two multicenter trials assessed cefuroxime axetil tablets 500 mg twice a day for 20 days. The most common drugrelated adverse experiences were diarrhea (10.6% of patients), JarischHerxheimer reaction (5.6%), and vaginitis (5.4%). Other adverse experiences occurred with frequencies comparable to those reported with 7 to 10 days dosing.

### =Single Dose Regimen for Uncomplicated gonorrhea
- In clinical trials using a single dose of cefuroxime axetil tablets, 1,061 patients were treated with the recommended dosage of cefuroxime axetil (1,000 mg) for the treatment of uncomplicated gonorrhea. There were no deaths or permanent disabilities thought related to drug toxicity in these studies.
- The following adverse events were thought by the investigators to be possibly, probably, or almost certainly related to cefuroxime axetil in 1,000mg singledose clinical trials of cefuroxime axetil tablets in the treatment of uncomplicated gonorrhea conducted in the United States.
- Table Adverse ReactionsCefuroxime axetil Tablets
- In clinical trials using multiple doses of cefuroxime axetil powder for oral suspension, pediatric patients (96.7% of whom were younger than 12 years of age) were treated with the recommended dosages of cefuroxime axetil (20 to 30 mg/kg/day divided twice a day up to a maximum dose of 500 or 1,000 mg/day, respectively). There were no deaths or permanent disabilities in any of the patients in these studies. Eleven US patients (1.2%) discontinued medication due to adverse events thought by the investigators to be possibly, probably, or almost certainly related to drug toxicity. The discontinuations were primarily for gastrointestinal disturbances, usually diarrhea or vomiting. During clinical trials, discontinuation of therapy due to the taste and/or problems with administering this drug occurred in 13 (1.4%) pediatric patients enrolled at centers in the United States.
- The following adverse events were thought by the investigators to be possibly, probably, or almost certainly related to cefuroxime axetil for oral suspension in multipledose clinical trials (n = 931 cefuroxime axetiltreated US patients).
- Table Adverse ReactionsCefuroxime axetil for Oral Suspension:
- In addition to the adverse reactions listed above that have been observed in patients treated with cefuroxime axetil, the following adverse reactions and altered laboratory tests have been reported for cephalosporinclass antibiotics: Toxic nephropathy, aplastic anemia, hemorrhage, increased BUN, increased creatinine, falsepositive test for urinary glucose, increased alkaline phosphatase, neutropenia, elevated bilirubin, and agranulocytosis.
- Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced. If seizures associated with drug therapy occur, the drug should be discontinued.
- Anticonvulsant therapy can be given if clinically indicated.

## Postmarketing Experience

### POSTMARKETING EXPERIENCE WITH Cefuroxime axetil PRODUCTS
- In addition to adverse events reported during clinical trials, the following events have been identified during clinical practice in patients treated with Cefuroxime axetil Tablets or with Cefuroxime axetil for Oral Suspension and were reported spontaneously. Data are generally insufficient to allow an estimate of incidence or to establish causation.
- The following hypersensitivity reactions have been reported: Anaphylaxis, angioedema, pruritus, rash, serum sicknesslike reaction, urticaria.
- Pseudomembranous colitis
- Hemolytic anemia, leukopenia, pancytopenia, thrombocytopenia, and increased prothrombin time.
- Hepatic impairment including hepatitis and cholestasis, jaundice.
- Seizure, encephalopathy.
- Erythema multiforme, StevensJohnson syndrome, toxic epidermal necrolysis.
- Renal dysfunction

# Drug Interactions
- Concomitant administration of probenecid with cefuroxime axetil tablets increases the area under the serum concentration versus time curve by 50%. The peak serum cefuroxime concentration after a 1.5g single dose is greater when taken with 1 g of probenecid (mean = 14.8 mcg/mL) than without probenecid (mean = 12.2 mcg/mL).
- Drugs that reduce gastric acidity may result in a lower bioavailability of Cefuroxime axetil compared with that of fasting state and tend to cancel the effect of postprandial absorption.
- In common with other antibiotics, cefuroxime axetil may affect the gut flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives.
- A falsepositive reaction for glucose in the urine may occur with copper reduction tests (Benedict's or Fehling's solution or with CLINITEST tablets), but not with enzymebased tests for glycosuria (e.g., CLINISTIX). As a falsenegative result may occur in the ferricyanide test, it is recommended that either the glucose oxidase or hexokinase method be used to determine blood/plasma glucose levels in patients receiving cefuroxime axetil. The presence of cefuroxime does not interfere with the assay of serum and urine creatinine by the alkaline picrate method.

# Use in Specific Populations

### Pregnancy
Pregnancy Category (FDA): B
- Reproduction studies have been performed in mice at doses up to 3,200 mg/kg/day (14 times the recommended maximum human dose based on mg/m2) and in rats at doses up to 1,000 mg/kg/day (9 times the recommended maximum human dose based on mg/m2) and have revealed no evidence of impaired fertility or harm to the fetus due to cefuroxime axetil. There are, however, no adequate and wellcontrolled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Cefuroxime axetil in women who are pregnant.

### Labor and Delivery
Cefuroxime axetil has not been studied for use during labor and delivery.

### Nursing Mothers
- Because cefuroxime is excreted in human milk, consideration should be given to discontinuing nursing temporarily during treatment with cefuroxime axetil.

### Pediatric Use
- The safety and effectiveness of Cefuroxime axetil have been established for pediatric patients aged 3 months to 12 years for acute bacterial maxillary sinusitis based upon its approval in adults. Use of Cefuroxime axetil in pediatric patients is supported by pharmacokinetic and safety data in adults and pediatric patients, and by clinical and microbiological data from adequate and wellcontrolled studies of the treatment of acute bacterial maxillary sinusitis in adults and of acute otitis media with effusion in pediatric patients. It is also supported by postmarketing adverse events surveillance.

### Geriatic Use
- Of the total number of subjects who received cefuroxime axetil in 20 clinical studies of Cefuroxime axetil, 375 were 65 and older while 151 were 75 and older. No overall differences in safety or effectiveness were observed between these subjects and younger adult subjects. The geriatric patients reported somewhat fewer gastrointestinal events and less frequent vaginal candidiasis compared with patients aged 12 to 64 years old; however, no clinically significant differences were reported between the elderly and younger adult patients. Other reported clinical experience has not identified differences in responses between the elderly and younger adult patients.

### Gender
There is no FDA guidance on the use of Cefuroxime axetil with respect to specific gender populations.

### Race
There is no FDA guidance on the use of Cefuroxime axetil with respect to specific racial populations.

### Renal Impairment
There is no FDA guidance on the use of Cefuroxime axetil in patients with renal impairment.

### Hepatic Impairment
There is no FDA guidance on the use of Cefuroxime axetil in patients with hepatic impairment.

### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Cefuroxime axetil in women of reproductive potentials and males.

### Immunocompromised Patients
There is no FDA guidance one the use of Cefuroxime axetil in patients who are immunocompromised.

# Administration and Monitoring

### Administration
- Oral
- Tablets
- Oral Powder for Suspension

### Monitoring
- Cephalosporins may be associated with a fall in prothrombin activity. Those at risk include patients with renal or hepatic impairment or poor nutritional state, as well as patients receiving a protracted course of antimicrobial therapy, and patients previously stabilized on anticoagulant therapy. Prothrombin time should be monitored in patients at risk and exogenous Vitamin K administered as indicated.

# IV Compatibility
There is limited information regarding IV Compatibility of Cefuroxime axetil in the drug label.

# Overdosage
- Overdosage of cephalosporins can cause cerebral irritation leading to convulsions or encephalopathy. Serum levels of cefuroxime can be reduced by hemodialysis and peritoneal dialysis.

# Pharmacology

## Mechanism of Action
- Cefuroxime axetil is a bactericidalagent that acts by inhibition of bacterial cell wall synthesis. Cefuroxime axetil has activity in the presence of some betalactamases, both penicillinases and cephalosporinases, of Gramnegative and Grampositive bacteria.

## Structure
- Cefuroxime axetil Tablets and Cefuroxime axetil for Oral Suspension contain cefuroxime as cefuroxime axetil. Cefuroxime axetil is a semisynthetic, broadspectrum cephalosporin antibiotic for oral administration.
- Chemically, cefuroxime axetil, the 1-(acetyloxy) ethyl ester of cefuroxime, is (RS)-1-hydroxyethyl (6R ,7R)-7--3-(hydroxymethyl)-8-oxo-5-thia-1-azabicyclo-oct-2-ene-2-carboxylate, 72-(Z)-(O-methyl-oxime), 1-acetate 3-carbamate. Its molecular formula is C20H22N4O10S, and it has a molecular weight of 510.48.
- Cefuroxime axetil is in the amorphous form and has the following structural formula:

## Pharmacodynamics

### Microbiology
- Resistance to cefuroxime axetil is primarily through hydrolysis by betalactamase, alteration of penicillin-binding proteins (PBPs), decreased permeability and the presence of bacterial efflux pumps.
- Susceptibility to cefuroxime axetil will vary with geography and time; local susceptibility data should be consulted, if available. Cefuroxime axetil has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections as described in the Indications and Usage section:
- Grampositive bacteria
- Staphylococcus aureus (methicillinsusceptible isolates only)
- Streptococcus pneumoniae
- Streptococcus pyogenes
- Gramnegative bacteria
- Escherichia colia
- Klebsiella pneumoniaea
- Haemophilus influenzaeb
- Haemophilus parainfluenzae
- Moraxella catarrhalis
- Neisseria gonorrhoeae
- Most extended spectrum betalactamase (ESBL)producing and carbapenemaseproducing isolates are resistant to cefuroxime axetil.
- Betalactamasenegative, ampicillin resistant (BLNAR) isolates of H. influenzae must be considered resistant to cefuroxime axetil.
- Spirochetes
- Borrelia burgdorferi
- The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following microorganisms exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for cefuroxime axetil. However, the efficacy of cefuroxime axetil in treating clinical infections due to these microorganisms has not been established in adequate and well controlled clinical trials.
- Grampositive bacteria
- Staphylococcus epidermidis (methicillinsusceptible isolates only)
- Staphylococcus saprophyticus (methicillinsusceptible isolates only)
- Streptococcus agalactiae
- Gramnegative bacteria
- Morganella morganii
- Proteus inconstans
- Proteus mirabilis
- Providencia rettgeri
- Anaerobic bacteria
- Peptococcus niger
- When available, the clinical microbiology laboratory should provide the results of in vitro susceptibility test results for antimicrobial drug products used in resident hospitals to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting an antibacterial drug product for treatment.
- Dilution Techniques:Quantitative methods are used to determine antimicrobial minimal inhibitory concentrations (MICs). These MICs provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized test method (broth or agar)1,2. The MIC values should be interpreted according to criteria provided in Table 4.
- Diffusion Techniques: Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size provides an estimate of the susceptibility of bacteria to antimicrobial compounds. The zone size should be determined using a standardized test method4. This procedure uses paper disks impregnated with 30 mcg cefuroxime axetil to test the susceptibility of microorganisms to cefuroxime axetil. The disk diffusion interpretive criteria are provided in Table 4.
- Susceptibility of staphylococci to cefuroxime axetil may be deduced from testing only penicillin and either cefoxitin or oxacillin.
- Susceptibility of Streptococcus pyogenes may be deduced from testing penicillin.
- A report of Susceptible indicates that the antimicrobial is likely to inhibit growth of the pathogen if the antimicrobial compound reaches the concentration at the infection site necessary to inhibit growth of the pathogen . A report of Intermediate indicates that the result should be considered equivocal, and if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where a high dosage of drug can be used. This category also provides a buffer zone that prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of Resistant indicates that the antimicrobial is not likely to inhibit growth of the pathogen if the antimicrobial compound reaches the concentrations usually achievable at the infection site; other therapy should be selected.
- Standardized susceptibility test procedures require the use of laboratory controls to monitor and ensure the accuracy and precision of supplies and reagents used in the assay, and the techniques of the individual performing the test1,2,4. The QC ranges for MIC and disk diffusion testing using the 30 mcg disk are provided in Table 5.

## Pharmacokinetics

### Absorption and Metabolism
- After oral administration, cefuroxime axetil is absorbed from the gastrointestinal tract and rapidly hydrolyzed by nonspecific esterases in the intestinal mucosa and blood to cefuroxime. Cefuroxime is subsequently distributed throughout the extracellular fluids. The axetil moiety is metabolized to acetaldehyde and acetic acid.

### Pharmacokinetics
- Approximately 50% of serum cefuroxime is bound to protein. Serum pharmacokinetic parameters for Cefuroxime axetil Tablets and Cefuroxime axetil for Oral Suspension are shown in Tables 1 and 2.
- A 250 mg/5 mLdose of Cefuroxime axetil Suspension is bioequivalent to 2 times 125 mg/5 mLdose of Cefuroxime axetil Suspension when administered with food (see Table 3). Cefuroxime axetil for Oral Suspension was not bioequivalent to Cefuroxime axetil Tablets when tested in healthy adults. The tablet and powder for oral suspension formulations are NOT substitutable on a milligrampermilligram basis. The area under the curve for the suspension averaged 91% of that for the tablet, and the peak plasma concentration for the suspension averaged 71% of the peak plasma concentration of the tablets. Therefore, the safety and effectiveness of both the tablet and oral suspension formulations had to be established in separate clinical trials.
- Absorption of the tablet is greater when taken after food (absolute bioavailability of Cefuroxime axetil Tablets increases from 37% to 52%). Despite this difference in absorption, the clinical and bacteriologic responses of patients were independent of food intake at the time of tablet administration in 2 studies where this was assessed.
- All pharmacokinetic and clinical effectiveness and safety studies in pediatric patients using the suspension formulation were conducted in the fed state. No data are available on the absorption kinetics of the suspension formulation when administered to fasted pediatric patients.
- Cefuroxime is excreted unchanged in the urine; in adults, approximately 50% of the administered dose is recovered in the urine within 12 hours. The pharmacokinetics of cefuroxime in the urine of pediatric patients have not been studied at this time. Until further data are available, the renal pharmacokinetic properties of cefuroxime axetil established in adults should not be extrapolated to pediatric patients.
- In a study of 28 adults with normal and markedly impaired renal function, the elimination half-life of cefuroxime was prolonged in relation to severity of renal impairment. In a study of 16 adult hemodialysis patients with endstage renal disease, the majority of a cefuroxime dose was removed by hemodialysis. In a study of 20 elderly patients (mean age = 83.9 years) having a mean creatinine clearance of 34.9 mL/min, the mean serum elimination halflife was 3.5 hours. Despite the lower elimination of cefuroxime in geriatric patients, dosage adjustment based on age is not necessary.

## Nonclinical Toxicology
There is limited information regarding Nonclinical Toxicology of Cefuroxime axetil in the drug label.

# Clinical Studies

### Cefuroxime axetil Tablets
- One adequate and wellcontrolled study was performed in patients with acute bacterial maxillary sinusitis. In this study each patient had a maxillary sinus aspirate collected by sinus puncture before treatment was initiated for presumptive acute bacterial sinusitis. All patients had to have radiographic and clinical evidence of acute maxillary sinusitis. As shown in the following summary of the study, the general clinical effectiveness of Cefuroxime axetil Tablets was comparable to an oral antimicrobial agent that contained a specific beta-lactamase inhibitor in treating acute maxillary sinusitis. However, sufficient microbiology data were obtained to demonstrate the effectiveness of Cefuroxime axetil Tablets in treating acute bacterial maxillary sinusitis due only to Streptococcus pneumoniae or nonbetalactamaseproducing Haemophilus influenzae. An insufficient number of betalactamaseproducing Haemophilus influenzae and Moraxella catarrhalis isolates were obtained in this trial to adequately evaluate the effectiveness of Cefuroxime axetil Tablets in the treatment of acute bacterial maxillary sinusitis due to these 2 organisms.
- This study enrolled 317 adult patients, 132 patients in the United States and 185 patients in South America. Patients were randomized in a 1:1 ratio to cefuroxime axetil 250 mg twice daily or an oral antimicrobial agent that contained a specific betalactamase inhibitor. An intent-to-treat analysis of the submitted clinical data yielded the following results:
- a 95% Confidence interval around the success difference .
- b 95% Confidence interval around the success difference .
- In this trial and in a supporting maxillary puncture trial, 15 evaluable patients had non-betalactamaseproducing Haemophilus influenzae as the identified pathogen. Ten (10) of these 15 patients (67%) had their pathogen (non-betalactamaseproducing Haemophilus influenzae) eradicated. Eighteen (18) evaluable patients had Streptococcus pneumoniae as the identified pathogen. Fifteen (15) of these 18 patients (83%) had their pathogen (Streptococcus pneumoniae) eradicated.
- The incidence of drugrelated gastrointestinal adverse events was statistically significantly higher in the control arm (an oral antimicrobial agent that contained a specific betalactamase inhibitor) versus the cefuroxime axetil arm (12% versus 1%, respectively; P<.001), particularly drug-related diarrhea (8% versus 1%, respectively; P  = .001).
- Two adequate and wellcontrolled studies were performed in patients with early Lyme disease. In these studies all patients had to present with physician-documented erythema migrans, with or without systemic manifestations of infection. Patients were randomized in a 1:1 ratio to a 20day course of treatment with cefuroxime axetil 500 mg twice daily or doxycycline 100 mg 3 times daily. Patients were assessed at 1 month posttreatment for success in treating early Lyme disease (Part I) and at 1 year posttreatment for success in preventing the progression to the sequelae of late Lyme disease (Part II).
- A total of 355 adult patients (181 treated with cefuroxime axetil and 174 treated with doxycycline) were enrolled in the 2 studies. In order to objectively validate the clinical diagnosis of early Lyme disease in these patients, 2 approaches were used: 1) blinded expert reading of photographs, when available, of the pretreatment erythema migrans skin lesion; and 2) serologic confirmation (using enzyme-linked immunosorbent assay  and immunoblot assay ) of the presence of antibodies specific to Borrelia burgdorferi, the etiologic agent of Lyme disease. By these procedures, it was possible to confirm the physician diagnosis of early Lyme disease in 281 (79%) of the 355 study patients. The efficacy data summarized below are specific to this validated patient subset, while the safety data summarized below reflect the entire patient population for the 2 studies.
- Analysis of the submitted clinical data for evaluable patients in the validated patient subset yielded the following results:
- a 95% confidence interval around the satisfactory difference for Part I (-0.08, +0.05).
- b 95% confidence interval around the satisfactory difference for Part II (-0.13, +0.07).
c ns  include patients assessed as unsatisfactory clinical outcomes (failure + recurrence) in Part I (Cefuroxime axetil - 11 ; doxycycline - 8 ).
d Satisfactory clinical outcome includes cure + improvement (Part I) and success + improvement (Part II).
- Cefuroxime axetil and doxycycline were effective in prevention of the development of sequelae of late Lyme disease.
- Drugrelated adverse events affecting the skin were reported significantly more frequently by patients treated with doxycycline than by patients treated with cefuroxime axetil (12% versus 3%, respectively; P = .002), primarily reflecting the statistically significantly higher incidence of drug-related photosensitivity reactions in the doxycycline arm versus the cefuroxime axetil arm (9% versus 0%, respectively; P<.001). While the incidence of drug-related gastrointestinal adverse events was similar in the 2 treatment groups (cefuroxime axetil - 13%; doxycycline - 11%), the incidence of drug-related diarrhea was statistically significantly higher in the cefuroxime axetil arm versus the doxycycline arm (11% versus 3%, respectively; P = .005).
- Four randomized, controlled clinical studies were performed comparing 5 days versus 10 days of Cefuroxime axetil for the treatment of patients with secondary bacterial infections of acute bronchitis. These studies enrolled a total of 1,253 patients (CAE516 n = 360; CAE517 n = 177; CAEA4001 n = 362; CAEA4002 n = 354). The protocols for CAE516 and CAE517 were identical and compared Cefuroxime axetil 250 mg twice daily for 5 days, Cefuroxime axetil 250 mg twice daily for 10 days, and AUGMENTIN 500 mg 3 times daily for 10 days. These 2 studies were conducted simultaneously. CAEA4001 and CAEA4002 compared Cefuroxime axetil 250 mg twice daily for 5 days, Cefuroxime axetil 250 mg twice daily for 10 days, and CECLOR 250 mg 3 times daily for 10 days. They were otherwise identical to CAE516 and CAE517 and were conducted over the following 2 years. Patients were required to have polymorphonuclear cells present on the Gram stain of their screening sputum specimen, but isolation of a bacterial pathogen from the sputum culture was not required for inclusion. The following table demonstrates the results of the clinical outcome analysis of the pooled studies CAE516/CAE517 and CAEA4001/CAEA4002, respectively:
- a 95% Confidence interval around the success difference .
- b 95% Confidence interval around the success difference .
- The response rates for patients who were both clinically and bacteriologically evaluable were consistent with those reported for the clinically evaluable patients.
- In these clinical trials, 399 patients were treated with Cefuroxime axetil for 5 days and 402 patients with Cefuroxime axetil for 10 days. No difference in the occurrence of adverse events was observed between the 2 regimens.

# How Supplied

### Cefuroxime axetil Tablets
- Cefuroxime axetil Tablets, 250 mg of cefuroxime (as cefuroxime axetil), are white, capsuleshaped, filmcoated tablets engraved with "GX ES7" on one side and blank on the other side as follows:

### Cefuroxime axetil for Oral Suspension
- Cefuroxime axetil for Oral Suspension is provided as dry, white to offwhite, tutti-fruttiflavored powder. When reconstituted as directed, Cefuroxime axetil for Oral Suspension provides the equivalent of 125 mg or 250 mg of cefuroxime (as cefuroxime axetil) per 5 mL of suspension. It is supplied in amber glass bottles as follows:
125 mg/5 mL:
100mL Suspension NDC 0173-0740-00
250 mg/5 mL:
50-mL Suspension NDC 0173-0741-10
100-mL Suspension NDC 0173-0741-00

## Storage

### Cefuroxime axetil Tablets
- Store the tablets between 15 and 30C (59 and 86F). Replace cap securely after each opening.

### Cefuroxime axetil for Oral Suspension
- Before reconstitution, store dry powder between 2 and 30C (36 and 86F).
- After reconstitution, immediately store suspension between 2 and 8C (36 and 46F), in a refrigerator. DISCARD AFTER 10 DAYS.

# Images

## Drug Images

## Package and Label Display Panel
NDC 0173-0387-00
Cefuroxime axetil Tablets
(cefuroxime axetil tablets)
250 mg 20 Tablets
Rx only
See package insert for Dosage and Administration.
Store between 15o and 30oC (59o and 86oF).
Replace cap securely after each opening.
GlaxoSmithKline
Research Triangle Park, NC 27709
Made in England
Rev. 2/02
NDC 0173-0394-00
Cefuroxime axetil Tablets
(cefuroxime axetil tablets)
500 mg
Rx only
20 Tablets
- Each tablet contains cefuroxime axetil equivalent to 500 mg of cefuroxime.
See package insert for Dosage and Administration.
Store between 15o and 30oC (59o and 86oF). Replace cap securely after each opening.
GlaxoSmithKline
Research Triangle Park, NC 27709
Made in England
4141667 Rev. 12/01
NDC 0173-0740-00
Cefuroxime axetil for Oral Suspension
(cefuroxime axetil powder for oral suspension)
For Oral Use Only
125 mg per 5 mL
100 mL (when reconstituted)
Rx only
Contains 3.0 g cefuroxime axetil equivalent to 2.5 g of cefuroxime.
Phenylketonurics: Contains Phenylalanine 11.8 mg per 5 mL (1 teaspoonful) constituted suspension.
See package insert for Dosage and Administration.
- Directions for Mixing Oral Suspension: Prepare the suspension at time of dispensing. Shake the bottle to loosen the powder. Remove the cap. Add 37 mL of water for reconstitution and replace the cap. Invert bottle and vigorously rock it from side to side so that water rises through the powder. Once the sound of powder against the bottle disappears, turn the bottle upright and vigorously shake it in a diagonal direction.
Before reconstitution, store dry powder between 2o and 30oC (36o and 86oF).
After reconstitution, store suspension between 2o and 8oC (36o and 46oF), in a refrigerator. SHAKE WELL BEFORE EACH USE. Replace cap securely after each opening. Discard after 10 days.
GlaxoSmithKline
Research Triangle Park, NC 27709
Made in England
10000000022540 Rev. 12/05
NDC 0173-0741-10
Ceftin for Oral Suspension
(cefuroxime axetil powder for oral suspension)
For Oral Use Only
250 mg per 5 mL
50 mL (when reconstituted)
Contains 3.6 g cefuroxime axetil equivalent to 3 g of cefuroxime.
Phenylketonurics: Contains Phenylalanine 25.2 mg per 5 mL (1 teaspoonful) constituted suspension.
See package insert for Dosage and Administration.
- Directions for Mixing Oral Suspension: Prepare the suspension at time of dispensing. Shake the bottle to loosen the powder. Remove the cap. Add 19 mL of water for reconstitution and replace the cap. Invert bottle and vigorously rock it from side to side so that water rises through the powder. Once the sound of powder against the bottle disappears, turn the bottle upright and vigorously shake it in a diagonal direction.
Before reconstitution, store dry powder between 2o and 30oC (36o and 86oF).
After reconstitution, store suspension between 2o and 8oC (36o and 46oF), in a refrigerator. SHAKE WELL BEFORE EACH USE. Replace cap securely after each opening. Discard after 10 days.
GlaxoSmithKline
Research Triangle Park, NC 27709
Made in England
10000000022489 Rev. 12/05
NDC Item Code: 0173-0387-00
Standard Name: Cefuroxime 250 MG Oral Tablet 
Shape: OVAL
Size: 15mm
Color: WHITE
Scored: 1
Imprint: GX;ES7
NDC Item Code: 0173-0394-00
Standard Name: Cefuroxime 500 MG Oral Tablet 
Shape: OVAL
Size: 20mm
Color: WHITE
Scored: 1
Imprint: GX;EG2

# Patient Counseling Information
- Cefuroxime axetil for Oral Suspension 125 mg/5 mL contains phenylalanine 11.8 mg per 5 mL (1 teaspoonful) constituted suspension. Cefuroxime axetil for Oral Suspension 250 mg/5 mL contains phenylalanine 25.2 mg per 5 mL (1 teaspoonful) constituted suspension.
- During clinical trials, the tablet was tolerated by pediatric patients old enough to swallow the cefuroxime axetil tablet whole. The crushed tablet has a strong, persistent, bitter taste and should not be administered to pediatric patients in this manner. Pediatric patients who cannot swallow the tablet whole should receive the oral suspension.
- Discontinuation of therapy due to taste and/or problems of administering this drug occurred in 1.4% of pediatric patients given the oral suspension. Complaints about taste (which may impair compliance) occurred in 5% of pediatric patients.
- Patients should be counseled that antibacterial drugs, including Cefuroxime axetil, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Cefuroxime axetil is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may: (1) decrease the effectiveness of the immediate treatment, and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Cefuroxime axetil or other antibacterial drugs in the future.

# Precautions with Alcohol
- Alcohol-Cefuroxime axetil interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

# Brand Names
- CEFTIN 

# Look-Alike Drug Names
There is limited information regarding Cefuroxime axetil (oral) Look-Alike Drug Names in the drug label.

# Drug Shortage Status

# Price