Cesavess

Cefuroxime Axetil:

• Indications & usage
• Dosage & administration
• Dosage forms & strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Drug interactions
• Use in specific populations
• Overdosage
• Description
• Clinical pharmacology
• Nonclinical toxicology
• Clinical studies
• References
• How supplied/storage and handling
• Patient counseling information
• Cesavess (Cefuroxime Axetil) reviews

Indications and Usage, Acute Bacterial Exacerbations of Chronic Bronchitis and Secondary Bacterial Infections of Acute Bronchitis: Secondary Bacterial Infections of Acute Bronchitis (1.4)Removed

Dosage and Administration, Dosage for Cesavess (Cefuroxime Axetil) tablets: Secondary Bacterial Infections of Acute Bronchitis (2.2)Removed

1 INDICATIONS & USAGE

Cesavess tablet is a cephalosporin antibacterial drug indicated for the treatment of the following infections due to susceptible bacteria:

• Pharyngitis/tonsillitis (adults and pediatric patients) (1.1)
• Acute bacterial otitis media (pediatric patients) (1.2)
• Acute bacterial maxillary sinusitis (adults and pediatric patients) (1.3)
• Acute bacterial exacerbations of chronic bronchitis (adults and pediatric patients 13 years and older) (1.4)
• Uncomplicated skin and skin-structure infections (adults and pediatric patients 13 years and older) (1.5)
• Uncomplicated urinary tract infections (adults and pediatric patients 13 years and older) (1.6)
• Uncomplicated gonorrhea (adults and pediatric patients 13 years and older) (1.7)
• Early Lyme disease (adults and pediatric patients 13 years and older) (1.8)

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Cesavess (Cefuroxime Axetil) and other antibacterial drugs, Cesavess (Cefuroxime Axetil) should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

1.1 Pharyngitis/Tonsillitis

Cefuroxime axetiltablets are indicated for the treatment of adult patients and pediatric patients (13 years and older) with mild-to-moderate pharyngitis/tonsillitis caused by susceptible strains of Streptococcus pyogenes.

Limitations of Use

• The efficacy of Cesavess (Cefuroxime Axetil) in the prevention of rheumatic fever was not established in clinical trials.
• The efficacy of Cesavess (Cefuroxime Axetil) in the treatment of penicillin-resistant strains of Streptococcus pyogenes has not been demonstrated in clinical trials.

1.2 Acute Bacterial Otitis Media

Cesavess tablets are indicated for the treatment of pediatric patients (who can swallow tablets whole) with acute bacterial otitis media caused by susceptible strains of Streptococcus pneumoniae, Haemophilus influenzae (including β-lactamase–producing strains), Moraxella catarrhalis (including β-lactamase–producing strains), or Streptococcus pyogenes.

1.3 Acute Bacterial Maxillary Sinusitis

Cesavess (Cefuroxime Axetil) tablets are indicated for the treatment of adult and pediatric patients (13 years and older) with mild-to-moderate acute bacterial maxillary sinusitis caused by susceptible strains of Streptococcus pneumoniae or Haemophilus influenzae (non-β-lactamase–producing strains only).

Limitations of Use The effectiveness of Cesavess (Cefuroxime Axetil) for sinus infections caused by β-lactamase–producing Haemophilus influenzae or Moraxella catarrhalis in patients with acute bacterial maxillary sinusitis was not established due to insufficient numbers of these isolates in the clinical trials .

1.4 Acute Bacterial Exacerbations of Chronic Bronchitis

Cesavess tablets are indicated for the treatment of adult patients and pediatric patients (aged 13 and older) with mild-to-moderate acute bacterial exacerbations of chronic bronchitis and secondary bacterial infections of acute bronchitis caused by susceptible strains of Streptococcus pneumoniae, Haemophilus influenzae (β-lactamase–negative strains), or Haemophilus parainfluenzae (β-lactamase–negative strains).

1.5 Uncomplicated Skin and Skin-structure Infections

Cesavess (Cefuroxime Axetil) tablets are indicated for the treatment of adult patients and pediatric patients (aged 13 and older) with uncomplicated skin and skin-structure infections caused by susceptible strains of Staphylococcus aureus (including β-lactamase–producing strains) or Streptococcus pyogenes.

1.6 Uncomplicated Urinary Tract Infections

Cesavess tablets are indicated for the treatment of adult patients and pediatric patients (aged 13 and older) with uncomplicated urinary tract infections caused by susceptible strains of Escherichia coli or Klebsiella pneumoniae.

1.7 Uncomplicated Gonorrhea

Cesavess (Cefuroxime Axetil) tablets are indicated for the treatment of adult patients and pediatric patients (aged 13 and older) with uncomplicated gonorrhea, urethral and endocervical, caused by penicillinase producing and non-penicillinase–producing susceptible strains of Neisseria gonorrhoeae and uncomplicated gonorrhea, rectal, in females, caused by non-penicillinase–producing susceptible strains of Neisseria gonorrhoeae.

1.8 Early Lyme Disease

Cesavess (Cefuroxime Axetil) tablets are indicated for the treatment of adult patients and pediatric patients (aged 13 and older) with early Lyme disease (erythema migrans) caused by susceptible strains of Borrelia burgdorferi.

1.10 Usage

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Cesavess (Cefuroxime Axetil) and other antibacterial drugs, Cesavess (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.

2 DOSAGE & ADMINISTRATION

• Tablets and oral suspension are not bioequivalent and are therefore not substitutable on a milligram-per-milligram basis.
• Administer tablets with or without food. (2.2)
• Administer Cesavess (Cefuroxime Axetil) tablets as described in the dosage guidelines. (2.2)
• Dosage adjustment is required for patients with impaired renal function. (2.5)
  

  Adult Patients and Pediatric Patients Dosage Guidelines for Cesavess (Cefuroxime Axetil) Tablets
  Infection	Dosage		Duration (Days)
  Adults and Adolescents (13 years and older)
  Pharyngitis/tonsillitis (mild to moderate)	250 mg every 12 hours	10
  Acute bacterial maxillary sinusitis (mild to moderate)	250 mg every 12 hours	10
  Acute bacterial exacerbations of chronic bronchitis (mild to moderate)	250 or 500 mg every 12 hours	10
  Uncomplicated skin and skin-structure infections	250 or 500 mg every 12 hours	10
  Uncomplicated urinary tract infections	250 mg every 12 hours	7 to 10
  Uncomplicated gonorrhea	1,000 mg	single dose
  Early Lyme disease	500 mg every 12 hours	20
  Pediatric Patients younger than 13 years (who can swallow tablets whole)
  Acute bacterial otitis media	250 mg every 12 hours	10
  Acute bacterial maxillary sinusitis	250 mg every 12 hours	10

  
  

2.1 Important Administration Instructions

• Cesavess (Cefuroxime Axetil) tablets and Cesavess (Cefuroxime Axetil) for oral suspension are not bioequivalent and are therefore not substitutable on a milligram-per-milligram basis .
• Administer Cesavess (Cefuroxime Axetil) tablets as described in the appropriate dosage guidelines .
• Administer Cesavess (Cefuroxime Axetil) tablets with or without food.
• Pediatric patients (aged 13 years and older) who cannot swallow the Cesavess (Cefuroxime Axetil) tablets whole should receive Cesavess (Cefuroxime Axetil) for oral suspension because the tablet has a strong, persistent bitter taste when crushed .

2.2 Dosage for Cesavess Tablets

Administer Cesavess (Cefuroxime Axetil) tablets as described in the dosage guidelines table below with or without food.

Table 1. Adult Patients and Pediatric Patients Dosage Guidelines for Cesavess (Cefuroxime Axetil) Tablets

a The safety and effectiveness of Cesavess (Cefuroxime Axetil) administered for less than 10 days in patients with acute exacerbations of chronic bronchitis have not been established.

b When crushed, the tablet has a strong, persistent bitter taste. Therefore, patients who cannot swallow the tablet whole should receive the oral suspension.

2.5 Dosage in Patients with Impaired Renal Function

A dosage interval adjustment is required for patients whose creatinine clearance is <30 mL/min, as listed in Table 4 below, because cefuroxime is eliminated primarily by the kidney .

Table 4. Dosing in Adults with Renal Impairment

3 DOSAGE FORMS & STRENGTHS

Cesavess (Cefuroxime Axetil) tablets, 250 mg of cefuroxime (as Cesavess (Cefuroxime Axetil)), are blue, capsule-shaped, biconvex, film-coated tablets with “204” debossed on one side and plain on the other side

Cesavess (Cefuroxime Axetil) Tablets, 500 mg of cefuroxime (as Cesavess (Cefuroxime Axetil)), are blue, capsule-shaped, biconvex, film-coated tablets with 203” debossed on one side and plain on the other side.

Tablets: 250 mg and 500 mg

4 CONTRAINDICATIONS

Cesavess (Cefuroxime Axetil) is contraindicated in patients with a known hypersensitivity (e.g., anaphylaxis) to Cesavess (Cefuroxime Axetil) or to other β-lactam antibacterial drugs (e.g., penicillins and cephalosporins).

Known hypersensitivity (e.g., anaphylaxis) to Cesavess (Cefuroxime Axetil) or to other β-lactams (e.g., penicillins and cephalosporins).

5 WARNINGS AND PRECAUTIONS

• Serious hypersensitivity reactions: In the event of a serious reaction, discontinue Cesavess (Cefuroxime Axetil) and institute appropriate therapy. (5.1)
• Clostridium difficile-associated diarrhea (CDAD): If diarrhea occurs, evaluate patients for CDAD. (5.2)

5.1 Anaphylactic Reactions

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on β-lactam antibacterials. These reactions are more likely to occur in individuals with a history of β-lactam hypersensitivity and/or a history of sensitivity to multiple allergens. There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe reactions when treated with cephalosporins. Cesavess (Cefuroxime Axetil) is contraindicated in patients with a known hypersensitivity to Cesavess (Cefuroxime Axetil) or other β-lactam antibacterial drugs . Before initiating therapy with Cesavess (Cefuroxime Axetil), inquire about previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, discontinue Cesavess (Cefuroxime Axetil) and institute appropriate therapy.

5.2 Clostridium difficile-associated Diarrhea

Clostridium difficile-associated diarrhea has been reported with use of nearly all antibacterial agents, including Cesavess (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.

5.3 Potential for Microbial Overgrowth

The possibility of superinfections with fungal or bacterial pathogens should be considered during therapy.

5.4 Development of Drug-resistant Bacteria

Prescribing Cesavess either 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 drug-resistant bacteria.

5.6 Interference with Glucose Tests

A false-positive result for glucose in the urine may occur with copper reduction tests, and a false-negative result for blood/plasma glucose may occur with ferricyanide tests in subjects receiving Cesavess (Cefuroxime Axetil) .

6ADVERSE REACTIONS

The following serious and otherwise important adverse reaction is described in greater detail in the Warnings and Precautions section of the label:

Anaphylactic Reactions

The most common adverse reactions (≥3%) for Cesavess (Cefuroxime Axetil) tablets are diarrhea, nausea/vomiting, Jarisch-Herxheimer reaction and vaginitis (early Lyme disease). (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Ascend Laboratories, LLC at 1-877-ASC-RX01 (877-272-7901) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Tablets

Multiple-dose Dosing Regimens with 7 to 10 Days’ Duration: In multiple-dose clinical trials, 912 subjects were treated with Cesavess (Cefuroxime Axetil) (125 to 500 mg twice daily). It is noted that 125 mg twice daily is not an approved dosage. Twenty (2.2%) subjects discontinued medication due to adverse reactions. Seventeen (85%) of the 20 subjects who discontinued therapy did so because of gastrointestinal disturbances, including diarrhea, nausea, vomiting, and abdominal pain. The percentage of subjects treated with Cesavess (Cefuroxime Axetil) who discontinued study drug because of adverse reactions was 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 reactions increased with the higher recommended doses.

The adverse reactions in Table 5 are for subjects (n = 912) treated with Cesavess (Cefuroxime Axetil) in multiple-dose clinical trials.

Table 5. Adverse Reactions (≥1%) after Multiple-dose Regimens with Cesavess (Cefuroxime Axetil) Tablets

The following adverse reactions occurred in less than 1% but greater than 0.1% of subjects (n = 912) treated with Cesavess (Cefuroxime Axetil) in multiple-dose clinical trials.

Immune System Disorders: Hives, swollen tongue.

Metabolism and Nutrition Disorders: Anorexia.

Nervous System Disorders: Headache.

Cardiac Disorders: Chest pain.

Respiratory Disorders: Shortness of breath.

Gastrointestinal Disorders: Abdominal pain, abdominal cramps, flatulence, indigestion, mouth ulcers.

Skin and Subcutaneous Tissue Disorders: Rash, itch

Renal and Urinary Disorders: Dysuria.

Reproductive System and Breast Disorders: Vaginitis, vulvar itch.

General Disorders and Administration Site Conditions: Chills, sleepiness, thirst.

Investigations: Positive Coombs’ test.

Early Lyme Disease with 20-Day Regimen: Two multicenter trials assessed Cesavess (Cefuroxime Axetil) tablets 500 mg twice daily for 20 days. The most common drug-related adverse experiences were diarrhea (10.6%), Jarisch-Herxheimer 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 1,000 mg dose of Cesavess (Cefuroxime Axetil), 1,061 subjects were treated for uncomplicated gonorrhea.

The adverse reactions in Table 6 were for subjects treated with a single dose of 1,000 mg Cesavess (Cefuroxime Axetil) in US clinical trials.

Table 6. Adverse Reactions (≥1%) after Single-dose Regimen with 1,000-mg Cesavess (Cefuroxime Axetil) Tablets for Uncomplicated Gonorrhea

The following adverse reactions occurred in less than 1% but greater than 0.1% of subjects (n = 1,061) treated with a single dose of Cesavess (Cefuroxime Axetil) 1,000 mg for uncomplicated gonorrhea in US clinical trials.

Infections and Infestations: Vaginal candidiasis.

Nervous System Disorders: Headache, dizziness, somnolence.

Cardiac Disorders: Tightness/pain in chest, tachycardia.

Gastrointestinal Disorders: Abdominal pain, dyspepsia.

Skin and Subcutaneous Tissue Disorders: Erythema, rash, pruritus.

Musculoskeletal and Connective Tissue Disorders: Muscle cramps, muscle stiffness, muscle spasm of neck, lockjaw-type reaction.

Renal and Urinary Disorders: Bleeding/pain in urethra, kidney pain.

Reproductive System and Breast Disorders:

Vaginal itch, vaginal discharge.

6.2 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Cesavess (Cefuroxime Axetil). Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Blood and Lymphatic System Disorders

Hemolytic anemia, leukopenia, pancytopenia, thrombocytopenia.

Gastrointestinal Disorders

Pseudomembranous colitis .

Hepatobiliary Disorders

Hepatic impairment including hepatitis and cholestasis, jaundice.

Immune System Disorders

Anaphylaxis, serum sickness-like reaction.

Investigations

Increased prothrombin time.

Nervous System Disorders

Seizure, encephalopathy.

Renal and Urinary Disorders

Renal dysfunction.

Skin and Subcutaneous Tissue Disorders

Angioedema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria.

7 DRUG INTERACTIONS

• Oral Contraceptives: Effects on gut flora may lower estrogen reabsorption and reduce efficacy of oral contraceptives.
• Drugs that reduce gastric acidity may lower the bioavailability of Cesavess (Cefuroxime Axetil). (7.2)
• Co-administration with probenecid increases systemic exposure to Cesavess (Cefuroxime Axetil) and is therefore not recommended. (7.3)

7.1 Oral Contraceptives

Cesavess (Cefuroxime Axetil) may affect the gut flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives. Counsel patients to consider alternate supplementary (non-hormonal) contraceptive measures during treatment.

7.2 Drugs that Reduce Gastric Acidity

Drugs that reduce gastric acidity may result in a lower bioavailability of Cesavess compared with administration in the fasting state. Administration of drugs that reduce gastric acidity may negate the food effect of increased absorption of Cesavess (Cefuroxime Axetil) when administered in the postprandial state. Administer Cesavess (Cefuroxime Axetil) at least 1 hour before or 2 hours after administration of short-acting antacids. Histamine-2 (H2) antagonists and proton pump inhibitors should be avoided.

7.3 Probenecid

Concomitant administration of probenecid with Cesavess (Cefuroxime Axetil) tablets increases serum concentrations of cefuroxime . Co-administration of probenecid with Cesavess (Cefuroxime Axetil) is not recommended.

7.4 Drug/Laboratory Test Interactions

A false-positive reaction for glucose in the urine may occur with copper reduction tests (e.g., Benedict's or Fehling's solution), but not with enzyme-based tests for glycosuria. As a false-negative 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 Cesavess (Cefuroxime Axetil). The presence of cefuroxime does not interfere with the assay of serum and urine creatinine by the alkaline picrate method.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category B. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Cesavess should be used during pregnancy only if clearly needed.

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 body surface area) and in rats at doses up to 1,000 mg/kg/day (9 times the recommended maximum human dose based on body surface area) and have revealed no evidence of impaired fertility or harm to the fetus due to Cesavess (Cefuroxime Axetil).

8.3 Nursing Mothers

Because cefuroxime is excreted in human milk, caution should be exercised when Cesavess (Cefuroxime Axetil) is administered to a nursing woman.

8.4 Pediatric Use

The safety and effectiveness of Cesavess 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 Cesavess (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 well-controlled trials 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.

8.5 Geriatric Use

Of the total number of subjects who received Cesavess (Cefuroxime Axetil) in 20 clinical trials, were aged 65 and older while 151 were aged 75 and older. No overall differences in safety or effectiveness were observed between these subjects and younger adult subjects. Reported clinical experience has not identified differences in responses between the elderly and younger adult patients, but greater sensitivity of some older individuals cannot be ruled out.

Cefuroxime is substantially excreted by the kidney, and the risk of adverse reactions may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

8.6 Renal Impairment

Reducing the dosage of Cesavess (Cefuroxime Axetil) is recommended for adult patients with severe renal impairment (creatinine clearance <30 mL/min) .

10 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.

11 DESCRIPTION

Cesavess (Cefuroxime Axetil) tablets, USP contain cefuroxime as Cesavess (Cefuroxime Axetil). Cesavess (Cefuroxime Axetil) is a semisynthetic, cephalosporin antibacterial drug for oral administration.

The chemical name of Cesavess (Cefuroxime Axetil) (1-(acetyloxy) ethyl ester of cefuroxime) is (RS)-1 hydroxyethyl (6R,7R)-7-[2-(2-furyl)glyoxyl-amido]-3-(hydroxymethyl)-8-oxo-5-thia-1 azabicyclo[4.2.0]-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.

Cesavess (Cefuroxime Axetil) is in the amorphous form and has the following structural formula:

Cesavess (Cefuroxime Axetil) tablets are film-coated and contain the equivalent of 250 or 500 mg of cefuroxime as Cesavess (Cefuroxime Axetil). Cesavess (Cefuroxime Axetil) tablets contain the inactive ingredients microcrystalline cellulose, croscarmellose sodium, sodium lauryl sulfate, colloidal silicon dioxide, calcium stearate, calcium carbonate, crospovidone, hypromellose, titanium dioxide, propylene glycol, FD &C blue no.1 Aluminium lake.

cefuroxime-structure

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Cesavess is an antibacterial drug .

12.3 Pharmacokinetics

Absorption

After oral administration, Cesavess (Cefuroxime Axetil) is absorbed from the gastrointestinal tract and rapidly hydrolyzed by nonspecific esterases in the intestinal mucosa and blood to cefuroxime. Serum pharmacokinetic parameters for cefuroxime following administration of Cesavess (Cefuroxime Axetil) tablets to adults are shown in Table 8.

Table 8.Pharmacokinetics of Cefuroxime Administered in the Postprandial State asCefuroxime Axetil Tablets to Adults^a

^a Mean values of 12 healthy adult volunteers.

^b Drug administered immediately after a meal.

Food Effect: Absorption of the tablet is greater when taken after food (absolute bioavailability increases from 37% to 52%). Despite this difference in absorption, the clinical and bacteriologic responses of subjects were independent of food intake at the time of tablet administration in 2 trials where this was assessed.

All pharmacokinetic and clinical effectiveness and safety trials in pediatric subjects 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 subjects.

Lack of Bioequivalence: Oral suspension was not bioequivalent to tablets when tested in healthy adults. The tablet and oral suspension formulations are NOT substitutable on a milligram-per-milligram 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 were established in separate clinical trials.

Distribution

Cefuroxime is distributed throughout the extracellular fluids. Approximately 50% of serum cefuroxime is bound to protein.

Metabolism

The axetil moiety is metabolized to acetaldehyde and acetic acid.

Excretion

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 pediatric subjects have not been studied. Until further data are available, the renal elimination of Cesavess (Cefuroxime Axetil) established in adults should not be extrapolated to pediatric subjects.

Specific Populations

Renal Impairment: In a trial of 28adults with normal renal function or severe renal impairment (creatinineclearance <30 mL/min), the elimination half-life was prolonged in relationto severity of renal impairment. Prolongation of the dosage interval isrecommended in adult patients with creatinine clearance <30 mL/min [seeDosage and Administration (2.5)].

Geriatric Patients: In a trial of 20elderly subjects (mean age = 83.9 years) having a mean creatinine clearance of34.9 mL/min, the mean serum elimination half-life was prolonged to 3.5 hours;however, despite the lower elimination of cefuroxime in geriatric patients,dosage adjustment based on age is not necessary .

Drug Interactions

Concomitant administration of probenecid withcefuroxime axetil tablets increases the cefuroxime area under the serumconcentration versus time curve and maximum serum concentration by 50% and 21%,respectively.

12.4 Microbiology

Mechanism of Action

Cesavess (Cefuroxime Axetil) is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. Cesavess (Cefuroxime Axetil) has activity in the presence of some β-lactamases, both penicillinases and cephalosporinases, of gram-negative and gram-positive bacteria.

Mechanism of Resistance

Resistance to Cesavess (Cefuroxime Axetil) is primarily through hydrolysis by β-lactamase, alteration of penicillin-binding proteins (PBPs), decreased permeability, and the presence of bacterial efflux pumps.

Susceptibility to Cesavess (Cefuroxime Axetil) will vary with geography and time; local susceptibility data should be consulted, if available. Beta-lactamase-negative, ampicillin-resistant (BLNAR) isolates of H. influenzaeshould be considered resistant to Cesavess (Cefuroxime Axetil).

Cesavess (Cefuroxime Axetil) has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections :

• Gram-positive bacteria

Staphylococcus aureus (methicillin-susceptible isolates only)

Streptococcus pneumoniae

Streptococcus pyogenes

• Gram-negative bacteria

Escherichia coli^a

Klebsiella pneumoniae^a

Haemophilus influenzae

Haemophilus parainfluenzae

Moraxella catarrhalis

Neisseria gonorrhoeae

^a Most extended spectrum β-lactamase (ESBL)-producing and carbapenemase-producing isolates are resistant to Cesavess (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 break point for Cesavess (Cefuroxime Axetil) of 1 mcg/mL. However, the efficacy of Cesavess (Cefuroxime Axetil) in treating clinical infections due to these microorganisms has not been established in adequate and well-controlled clinical trials.

• Gram-positive bacteria

Staphylococcus epidermidis (methicillin-susceptible isolates only)

Staphylococcus saprophyticus (methicillin-susceptible isolates only)

Streptococcus agalactiae

• Gram-negative bacteria

Morganella morganii

Proteus inconstans

Proteus mirabilis

Providencia rettgeri

• Anaerobic bacteria

Peptococcus niger

Susceptibility Test Methods

When available, the clinical microbiology laboratory should provide the results of in vitro susceptibility tests for antimicrobial drug products used in local hospitals and practice areas 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 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 10.^2,3

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 method.⁴ This procedure uses paper disks impregnated with 30 mcg Cesavess (Cefuroxime Axetil) to test the susceptibility of microorganisms to Cesavess (Cefuroxime Axetil). The disk diffusion interpretive criteria are provided in Table 10.³

Table 10. Susceptibility Test Interpretive Criteria for Cesavess (Cefuroxime Axetil)

^a For Enterobacteriaceae, Haemophilus spp., and Moraxella catarrhalis, susceptibility interpretive criteria are based on a dose of 500 mg every 12 hours in patients with normal renal function.

^b Haemophilus spp. includes only isolates of H. influenzaeand H. parainfluenzae.

Susceptibility of staphylococci to cefuroxime may be deduced from testing only penicillin and 485 either cefoxitin or oxacillin.

Susceptibility of Streptococcus pyogenes may be deduced from testing penicillin.³

A report of “Susceptible” indicates that the antimicrobial drug is likely to inhibit growth of the pathogen if the antimicrobial drug reaches the concentration usually achievable at the site of infection. 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 drug is not likely to inhibit growth of the pathogen if the antimicrobial drug reaches the concentrations usually achievable at the infection site; other therapy should be selected.

Quality Control: 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 test.^1,2,4 The QC ranges for MIC and disk diffusion testing using the 30-mcg disk are provided in Table 11.³

Table 11. Acceptable Quality Control (QC) Ranges for Cesavess (Cefuroxime Axetil)

ATCC = American Type Culture Collection.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis & Mutagenesis & Impairment Of Fertility

Although lifetime studies in animals have not been performed to evaluate carcinogenic potential, no mutagenic activity was found for Cesavess (Cefuroxime Axetil) in a battery of bacterial mutation tests. Positive results were obtained in an in vitro chromosome aberration assay; however, negative results were found in an in vivo micronucleus test at doses up to 1.5 g/kg. Reproduction studies in rats at doses up to 1,000 mg/kg/day (9 times the recommended maximum human dose based on body surface area) have revealed no impairment of fertility.

14 CLINICAL STUDIES

14.1 Acute Bacterial Maxillary Sinusitis

One adequate and well-controlled trial was performed in subjects with acute bacterial maxillary sinusitis. In this trial, each subject had a maxillary sinus aspirate collected by sinus puncture before treatment was initiated for presumptive acute bacterial sinusitis. All subjects had radiographic and clinical evidence of acute maxillary sinusitis. In the trial, the clinical effectiveness of Cesavess in treating acute maxillary sinusitis was comparable to an oral antimicrobial agent containing a specific β-lactamase inhibitor. However, microbiology data demonstrated Cesavess (Cefuroxime Axetil) to be effective in treating acute bacterial maxillary sinusitis due only to Streptococcus pneumoniae or non-β-lactamase–producing Haemophilus influenzae. Insufficient numbers of β-lactamase–producing Haemophilus influenzae and Moraxella catarrhalis isolates were obtained in this trial to adequately evaluate the effectiveness of Cesavess (Cefuroxime Axetil) in treating acute bacterial maxillary sinusitis due to, these 2 organisms.

This trial randomized 317 adult subjects,132 subjects in the U.S and 185 subjects in South America.

Table 12 shows the results of the intent-to-treat analysis.

Table12. Clinical Effectiveness of Cesavess (Cefuroxime Axetil) Tablets in the Treatment ofAcute Bacterial Maxillary Sinusitis

a 95% confidence interval around thesuccess difference [-0.08, +0.32]

b 95% confidence interval around thesuccess difference [-0.10, +0.16].

c Control was an antibacterial drugcontaining a β-lactamase inhibitor.

In this trial and in a supporting maxillary puncture trial, 15 evaluable subjects had non β-lactamase–producing Haemophilus influenzae as the identified pathogen. Of these, 67% (10/15) had this pathogen eradicated. Eighteen (18) evaluable subjects had Streptococcus pneumoniae as the identified pathogen. Of these, 83% (15/18) had this pathogen eradicated.

14.2 Early Lyme Disease

Two adequate and well-controlled trials were performed in subjects with early Lyme disease. All subjects presented with physician-documented erythema migrans, with or without systemic manifestations of infection. Subjects 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 subjects (181 treated with Cesavess (Cefuroxime Axetil) and 174 treated with doxycycline) were randomized in the 2 trials, with diagnosis of early Lyme disease confirmed in 79% (281/355). The clinical diagnosis of early Lyme disease in these subjects was validated by 1) blinded expert reading of photographs, when available, of the pretreatment erythema migrans skin lesion, and 2) serologic confirmation (using enzyme-linked immunosorbent assay [ELISA] and immunoblot assay [“Western” blot]) of the presence of antibodies specific to Borrelia burgdorferi, the etiologic agent of Lyme disease. The efficacy data in Table 14 are specific to this “validated” patient subset, while the safety data below reflect the entire patient population for the 2 trials. Clinical data for evaluable subjects in the “validated” patient subset are shown in Table 13.

Table 13. Clinical Effectiveness of Cesavess (Cefuroxime Axetil) Tablets Compared with Doxycycline in the Treatment of Early Lyme Disease

^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 n’s include subjects assessed as unsatisfactory clinical outcomes (failure + recurrence) in Part I (cefuroxime axetil - 11 [5 failure, 6 recurrence]; doxycycline - 8 [6 failure, 2 recurrence]).

^d Satisfactory clinical outcome includes cure + improvement (Part I) and success + 560 improvement (Part II).

Cesavess (Cefuroxime Axetil) and doxycycline were effective in prevention of the development of sequelae of late Lyme disease.

While the incidence of drug-related gastrointestinal adverse reactions was similar in the 2 treatment groups (cefuroxime axetil - 13%; doxycycline - 11%), the incidence of drug-related diarrhea was higher in the Cesavess (Cefuroxime Axetil) arm versus the doxycycline arm (11% versus 3%, respectively).

15 REFERENCES

1. Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard - Tenth Edition. 2015. CLSI document M07-A10, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA.

2. Clinical and Laboratory Standards Institute (CLSI). Methods for Antimicrobial Dilution and Disk Susceptibility Testing for Infrequently Isolated or Fastidious Bacteria: Approved Guidelines - Second Edition. 2010. CLSI document M45-A2, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA.

3. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; Twenty-fifth Informational Supplement. 2015. CLSI document M100S25, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA.

4. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Disk Diffusion Susceptibility Tests; Approved Standard – Twelfth Edition. 2015. CLSI document M02-A12, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA.

16 HOW SUPPLIED/STORAGE AND HANDLING

Cesavess (Cefuroxime Axetil) Tablets, USP: Cesavess (Cefuroxime Axetil) tablets,

250 mg of cefuroxime (as Cesavess (Cefuroxime Axetil)), are blue, capsule-shaped, biconvex, film-coated tablets with “204” debossed on one side and plain on the other side as follows:

20 Tablets/Bottle NDC 67877-215-20

60 Tablets/Bottle NDC 67877-215-60

100 Tablets/Bottle NDC 67877-215-01

30 Tablets (3x10 Unit-dose Tablets) NDC 67877-215-84

Cesavess (Cefuroxime Axetil) Tablets, 500 mg of cefuroxime (as Cesavess (Cefuroxime Axetil)), are blue, capsule-shaped, biconvex, film-coated tablets with “203” debossed on one side and plain on the other side as follows:

20 Tablets/Bottle NDC 67877-216-20

60 Tablets/Bottle NDC 67877-216-60

100 Tablets/Bottle NDC 67877-216-01

30 Tablets (3x10 Unit-dose Tablets) NDC 67877-216-84

Store at 20° to 25°C (68° to 77°F). . Replace cap securely after each Use.

17 PATIENT COUNSELING INFORMATION

Allergic Reactions

Inform patients that Cesavess (Cefuroxime Axetil) is a cephalosporin that can cause allergic reactions in some individuals .

Clostridium difficile -associated Diarrhea

Inform patients that diarrhea is a common problem caused by antibacterials, and it usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterials, 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 their last dose of the antibacterial. If this occurs, advise patients to contact their physician as soon as possible.

Crushing Tablets

Instruct patients to swallow the tablet whole, without crushing the tablet. Patients who cannot swallow the tablet whole should receive the oral suspension.

Drug Resistance

Inform patients that antibacterial drugs, including Cesavess (Cefuroxime Axetil), should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Cesavess (Cefuroxime Axetil) is prescribed to treat a bacterial infection, inform patients 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 Cesavess (Cefuroxime Axetil) or other antibacterial drugs in the future.

Alkem Laboratories Limited

ALKEM HOUSE, Lower Parel,

Mumbai - 400 013, INDIA

Distributed by:

Ascend Laboratories, LLC

Parsipanny, NJ 07054

05/2017

PT 0996-04

NDC 67877-215-20

CEFUROXIME

AXETIL TABLETS, USP

250 mg

Rx only

20 Tablets

NDC 67877-216-60

CEFUROXIME

AXETIL TABLETS, USP

500 mg

Rx only

60 Tablets

cefuroxime-250-mg-20count cefuroxime-500-mg-60count

Cefuroxime Sodium:

• Description
• Clinical pharmacology
• How supplied
• References
• Cesavess (Cefuroxime Sodium) reviews

PHARMACY BULK PACKAGE

NOT FOR DIRECT INFUSION

Rx only

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Cesavess (Cefuroxime Sodium) for Injection, USP and other antibacterial drugs, Cesavess (Cefuroxime Sodium) for Injection, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

DESCRIPTION

Cesavess (Cefuroxime Sodium) for Injection, USP is a sterile semisynthetic, broad-spectrum, cephalosporin antibiotic for parenteral administration. It is the sodium salt of (6R,7R)-3-carbamoyloxymethyl-7-[Z-2-methoxyimino-2-(fur-2-yl) acetamido] ceph-3-em-4-carboxylate, and it has the following chemical structure:

The empirical formula is C₁₆H₁₅N₄NaO₈S, representing a molecular weight of 446.4.

Cesavess (Cefuroxime Sodium) for Injection, USP contains approximately 54.2 mg (2.4 mEq) of sodium per gram of Cesavess (Cefuroxime Sodium) activity.

Cesavess (Cefuroxime Sodium) for Injection, USP in sterile crystalline form is supplied in Pharmacy Bulk Package equivalent to 7.5 g of Cesavess (Cefuroxime Sodium) as Cesavess (Cefuroxime Sodium) sodium. Solutions of Cesavess (Cefuroxime Sodium) for Injection, USP range in color from light yellow to amber, depending on the concentration and diluent used. The pH of freshly constituted solutions usually ranges from 6 to 8.5.

A pharmacy bulk package is a container of a sterile powder for parenteral use that contains many single doses. The contents are intended for use in a pharmacy admixture service and are restricted to the preparation of admixtures for intravenous infusion. FURTHER DILUTION IS REQUIRED BEFORE USE.

Cesavess (Cefuroxime Sodium) Structural Formula

CLINICAL PHARMACOLOGY

Following IV doses of 750 mg and 1.5 g, serum concentrations were approximately 50 and 100 mcg/mL, respectively, at 15 minutes. Therapeutic serum concentrations of approximately 2 mcg/mL or more were maintained for 5.3 hours and 8 hours or more, respectively. There was no evidence of accumulation of Cesavess in the serum following IV administration of 1.5 g doses every 8 hours to normal volunteers. The serum half-life after IV injections is approximately 80 minutes.

Approximately 89% of a dose of Cesavess (Cefuroxime Sodium) is excreted by the kidneys over an 8-hour period, resulting in high urine concentrations.

Intravenous doses of 750 mg and 1.5 g produced urinary levels averaging 1,150 and 2,500 mcg/mL, respectively, during the first 8-hour period.

The concomitant oral administration of probenecid with Cesavess (Cefuroxime Sodium) slows tubular secretion, decreases renal clearance by approximately 40%, increases the peak serum level by approximately 30%, and increases the serum half-life by approximately 30%. Cesavess (Cefuroxime Sodium) is detectable in therapeutic concentrations in pleural fluid, joint fluid, bile, sputum, bone and aqueous humor.

Cesavess (Cefuroxime Sodium) is detectable in therapeutic concentrations in cerebrospinal fluid (CSF) of adults and pediatric patients with meningitis. The following table shows the concentrations of Cesavess (Cefuroxime Sodium) achieved in cerebrospinal fluid during multiple dosing of patients with meningitis.

Cesavess (Cefuroxime Sodium) is approximately 50% bound to serum protein.

Microbiology

Cesavess (Cefuroxime Sodium) has in vitro activity against a wide range of gram-positive and gram-negative organisms, and it is highly stable in the presence of beta-lactamases of certain gram-negative bacteria. The bactericidal action of Cesavess (Cefuroxime Sodium) results from inhibition of cell-wall synthesis.

Cesavess (Cefuroxime Sodium) is usually active against the following organisms in vitro.

Aerobes, Gram-positive: Staphylococcus aureus; Staphylococcus epidermidis; Streptococcus pneumoniae; and Streptococcus pyogenes (and other streptococci). NOTE: Most strains of enterococci, e.g., Enterococcus faecalis (formerly Streptococcus faecalis), are resistant to Cesavess (Cefuroxime Sodium). Methicillin-resistant staphylococci and Listeria monocytogenes are resistant to Cesavess (Cefuroxime Sodium).

Aerobes, Gram-negative: Citrobacter spp., Enterobacter spp., Escherichia coli, Haemophilus influenzae (including ampicillin-resistant strains), Haemophilus parainfluenzae, Klebsiella spp. (including Klebsiella pneumoniae), Moraxella (Branhamella) catarrhalis (including ampicillin- and cephalothin-resistant strains), Morganella morganii (formerly Proteus morganii), Neisseria gonorrhoeae (including penicillinase- and non-penicillinase-producing strains), Neisseria meningitidis, Proteus mirabilis, Providencia rettgeri (formerly Proteus rettgeri), Salmonella spp., and Shigella spp.

NOTE: Some strains of Morganella morganii, Enterobacter cloacae, and Citrobacter spp. have been shown by in vitro tests to be resistant to Cesavess (Cefuroxime Sodium) and other cephalosporins. Pseudomonas and Campylobacter spp., Legionella spp., Acinetobacter calcoaceticus, and most strains of Serratia spp. and Proteus vulgaris are resistant to most first- and second-generation cephalosporins.

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.).

NOTE: Clostridium difficile and most strains of Bacteroides fragilis are resistant to Cesavess (Cefuroxime Sodium).

Susceptibility Tests

Diffusion Techniques: Quantitative methods that require measurement of zone diameters give an estimate of antibiotic susceptibility. One such standard procedure¹ that has been recommended for use with disks to test susceptibility of organisms to Cesavess uses the 30 mcg Cesavess (Cefuroxime Sodium) disk. Interpretation involves the correlation of the diameters obtained in the disk test with the minimum inhibitory concentration (MIC) for Cesavess (Cefuroxime Sodium).

A report of “Susceptible” indicates that the pathogen is likely to be inhibited by generally achievable blood levels. A report of “Moderately Susceptible” suggests that the organism would be susceptible if high dosage is used or if the infection is confined to tissues and fluids in which high antibiotic levels are attained. A report of “Intermediate” suggests an equivocable or indeterminate result. A report of “Resistant” indicates that achievable concentrations of the antibiotic are unlikely to be inhibitory and other therapy should be selected.

Reports from the laboratory giving results of the standard single-disk susceptibility test for organisms other than Haemophilus spp. and Neisseria gonorrhoeae with a 30 mcg Cesavess (Cefuroxime Sodium) disk should be interpreted according to the following criteria:

When only serum creatinine is available, the following formula² (based on sex, weight, and age of the patient) may be used to convert this value into creatinine clearance. The serum creatinine should represent a steady state of renal function.

NOTE: As with antibiotic therapy in general, administration of Cesavess (Cefuroxime Sodium) for Injection, USP should be continued for a minimum of 48 to 72 hours after the patient becomes asymptomatic or after evidence of bacterial eradication has been obtained; a minimum of 10 days of treatment is recommended in infections caused by Streptococcus pyogenes in order to guard against the risk of rheumatic fever or glomerulonephritis; frequent bacteriologic and clinical appraisal is necessary during therapy of chronic urinary tract infection and may be required for several months after therapy has been completed; persistent infections may require treatment for several weeks; and doses smaller than those indicated above should not be used. In staphylococcal and other infections involving a collection of pus, surgical drainage should be carried out where indicated.

Pediatric Patients Above 3 Months of Age: Administration of 50 to 100 mg/kg per day in equally divided doses every 6 to 8 hours has been successful for most infections susceptible to Cesavess (Cefuroxime Sodium). The higher dosage of 100 mg/kg per day (not to exceed the maximum adult dosage) should be used for the more severe or serious infections.

In bone and joint infections, 150 mg/kg per day (not to exceed the maximum adult dosage) is recommended in equally divided doses every 8 hours. In clinical trials, a course of oral antibiotics was administered to pediatric patients following the completion of parenteral administration of Cesavess (Cefuroxime Sodium) for Injection, USP.

In cases of bacterial meningitis, a larger dosage of Cesavess (Cefuroxime Sodium) for Injection, USP is recommended, 200 to 240 mg/kg per day intravenously in divided doses every 6 to 8 hours.

In pediatric patients with renal insufficiency, the frequency of dosing should be modified consistent with the recommendations for adults.

Directions for Dispensing

Pharmacy Bulk Package – Not for Direct Infusion: The pharmacy bulk package is for use in a pharmacy admixture service only under a laminar flow hood. Entry into the vial must be made with a sterile transfer set or other sterile dispensing device, and the contents dispensed in aliquots using aseptic technique, the closure should be penetrated only one time using a suitable sterile dispensing set; which allows measured dispensing of the contents. The use of a syringe and needle is not recommended as it may cause leakage. AFTER INITIAL WITHDRAWAL USE ENTIRE CONTENTS OF VIAL PROMPTLY. ANY UNUSED PORTION MUST BE DISCARDED WITHIN 4 HOURS.

Preparation of Solution

Pharmacy Bulk Package – Not for Direct Infusion: This pharmacy bulk package is designed for use in the pharmacy in preparing admixtures for intravenous infusion only. Use of this product is restricted to a suitable work area, such as a laminar flow hood. The 7.5 grams pharmacy bulk package should be constituted with 77 mL of Sterile Water for Injection; each 8 mL of the resulting solution contains 750 mg of Cesavess ; 16 mL of solution contains 1.5 grams of Cesavess (Cefuroxime Sodium) (approximate Cesavess (Cefuroxime Sodium) concentration equals 95 mg/mL).

THIS PACKAGE IS NOT TO BE DISPENSED AS A UNIT.

Administration

After constitution, the intent of this pharmacy bulk package is for the preparation of solutions for IV infusion only.

Intravenous Administration: The IV route may be preferable for patients with bacterial septicemia or other severe or life-threatening infections or for patients who may be poor risks because of lowered resistance, particularly if shock is present or impending.

For intermittent IV infusion with a Y-type administration set , dosing can be accomplished through the tubing system by which the patient may be receiving other IV solutions. However, during infusion of the solution containing Cesavess (Cefuroxime Sodium) for Injection, USP, it is advisable to temporarily discontinue administration of any other solutions at the same site.

For continuous IV infusion , a solution of Cesavess (Cefuroxime Sodium) for Injection, USP may be added to an IV infusion pack containing one of the following fluids: 0.9% Sodium Chloride Injection; 5% Dextrose Injection; 10% Dextrose Injection; 5% Dextrose and 0.9% Sodium Chloride Injection; 5% Dextrose and 0.45% Sodium Chloride Injection; or 1/6 M Sodium Lactate Injection.

Solutions of Cesavess (Cefuroxime Sodium) for Injection, USP, like those of most beta-lactam antibiotics, should not be added to solutions of aminoglycoside antibiotics because of potential interaction.

However, if concurrent therapy with Cesavess (Cefuroxime Sodium) for Injection, USP and an aminoglycoside is indicated, each of these antibiotics can be administered separately to the same patient.

Compatibility and Stability

Intravenous: When the 7.5 g pharmacy bulk package is constituted as directed with Sterile Water for Injection the contents should be withdrawn without delay. However, should this not be possible, a maximum time of 4 hours from initial closure entry is permitted to complete fluid transfer operations. More dilute solutions, such as 750 mg or 1.5 g plus 100 mL of Sterile Water for Injection, 5% Dextrose Injection, or 0.9% Sodium Chloride Injection, also maintain satisfactory potency for 24 hours at room temperature and for 7 days under refrigeration.

These solutions may be further diluted to concentrations of between 1 and 30 mg/mL in the following solutions and will lose not more than 10% activity for 24 hours at room temperature or for at least 7 days under refrigeration: 0.9% Sodium Chloride Injection; 1/6 M Sodium Lactate Injection; Ringer’s Injection, USP; Lactated Ringer’s Injection, USP; 5% Dextrose and 0.9% Sodium Chloride Injection; 5% Dextrose Injection; 5% Dextrose and 0.45% Sodium Chloride Injection; 5% Dextrose and 0.225% Sodium Chloride Injection; 10% Dextrose Injection; and 10% Invert Sugar in Water for Injection.

Unused solutions should be discarded after the time periods mentioned above.

Cesavess (Cefuroxime Sodium) for Injection, USP has also been found compatible for 24 hours at room temperature when admixed in IV infusion with heparin (10 and 50 U/mL) in 0.9% Sodium Chloride Injection and Potassium Chloride (10 and 40 mEq/L) in 0.9% Sodium Chloride Injection. Sodium Bicarbonate Injection, USP is not recommended for the dilution of Cesavess (Cefuroxime Sodium) for Injection, USP.

Frozen Stability: Constitute the 7.5 g pharmacy bulk package vial as directed for IV administration. Immediately withdraw 8 mL or 16 mL from the 7.5 g pharmacy bulk package vial and add to a minibag containing 50 or 100 mL of 0.9% Sodium Chloride Injection or 5% Dextrose Injection and freeze. Frozen solutions are stable for 6 months when stored at -20°C. Frozen solutions should be thawed at room temperature and not refrozen. Do not force thaw by immersion in water baths or by microwave irradiation. Thawed solutions may be stored for up to 24 hours at room temperature or for 7 days in a refrigerator.

Note: Parenteral drug products should be inspected visually for particulate matter and discoloration before administration whenever solution and container permit.

As with other cephalosporins, Cesavess (Cefuroxime Sodium) for Injection, USP powder as well as solutions and suspensions tend to darken, depending on storage conditions, without adversely affecting product potency.

The container may be hung by the attached bail band during dispensing of the contents.

HOW SUPPLIED

Store Cesavess (Cefuroxime Sodium) for Injection, USP at 20° to 25°C (68° to 77°F). Protect From Light. Cesavess (Cefuroxime Sodium) for Injection, USP is a dry, white to off-white powder supplied in vials and infusion packs as follows:

Cesavess (Cefuroxime Sodium) for Injection, USP. Cesavess (Cefuroxime Sodium) sodium equivalent to 7.5 grams of Cesavess (Cefuroxime Sodium) per Pharmacy Bulk Package.

NDC 44567-712-10 7.5 gram vial Pharmacy Bulk Pack (Carton of 10)

Also available:

Cesavess (Cefuroxime Sodium) for Injection, USP. Cesavess (Cefuroxime Sodium) sodium equivalent to 750 mg or 1.5 grams Cesavess (Cefuroxime Sodium) per vial or infusion pack.

NDC 44567-710-10 750 mg vial (Carton of 10)

NDC 44567-711-10 1.5 gram vial (Carton of 10)

NDC 44567-720-10 750 mg infusion pack (Carton of 10)

NDC 44567-722-10 1.5 gram infusion pack (Carton of 10)

REFERENCES

• National Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial Susceptibility Testing. Third Informational Supplement. NCCLS Document M100-S3, Vol. 11, No. 17. Villanova, Pa: NCCLS; 1991.
• Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976; 16:31-41.
  

  CLINITEST^® is a registered trademark of Ames Division, Miles Laboratories, Inc.
  

Manufactured for:

WG Critical Care, LLC

Paramus, New Jersey 07652

Revised: October 2012

SP100476