Cefuroxime axetil tablet, film coated

Recent major changes

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 11/2016

Dosage and Administration, Dosage for Cefuroxime Axetil Tablets: Secondary Bacterial Infections of Acute Bronchitis (2.2)-Removed 11/2016

1 indications and usage

Cefuroxime axetil is a cephalosporin antibacterial drug indicated for the treatment of the following infections due to susceptible bacteria: ( 1)

  • 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 cefuroxime axetil tablets and other antibacterial drugs, cefuroxime axetil tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

2 dosage and administration

  • Tablets and oral suspension are not bioequivalent and are therefore not substitutable on a milligram-per-milligram basis. ( 2.1)
  • Administer tablets with or without food. ( 2.2)
  • Administer 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 Cefuroxime Axetil Tablets
Infection
Dosage
Duration ( Days )
Adults and Adolescents ( 13 years and older )
Pharyngitis/tonsillitis
(mildtomoderate)
250mg
every12hours
10
Acutebacterialmaxillarysinusitis
(mildtomoderate)
250mg
every12hours
10
Acutebacterialexacerbationsof
chronicbronchitis(mildtomoderate)
250or500mg
every12hours
10
Uncomplicatedskinand
skin-structureinfections
250or500mg
every12hours
10
Uncomplicatedurinarytractinfections
250mg
every12hours
7to10
Uncomplicatedgonorrhea
1,000mg
singledose
EarlyLymedisease
500mg
every12hours
20
Pediatric Patients younger than 13 years ( who can swallow tablets whole )
Acutebacterialotitismedia
250mg
every12hours
10
Acutebacterialmaxillarysinusitis
250mg
every12hours
10

3 dosage forms and strengths

  • Tablets: 125 mg, 250 mg and 500 mg ( 3)

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Cefuroxime axetil tablets are white film-coated round-shaped biconvex unscored tablets available in the following strengths:

  • 125 mg of cefuroxime as cefuroxime axetil embossed with W920 on one side and other side plain.
  • 250 mg of cefuroxime as cefuroxime axetil embossed with W921 on one side and other side plain.
  • 500 mg of cefuroxime as cefuroxime axetil embossed with W922 on one side and other side plain.

4 contraindications

Known hypersensitivity (e.g., anaphylaxis) to cefuroxime axetil tablets or to other -lactams (e.g., penicillins and cephalosporins). ( 4)

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Cefuroxime axetil tablets are contraindicated in patients with a known hypersensitivity (e.g., anaphylaxis) to cefuroxime axetil or to other -lactam antibacterial drugs (e.g., penicillins and cephalosporins).

5 warnings and precautions

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

6 adverse reactions

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

To report SUSPECTED ADVERSE REACTIONS, contact Wockhardt USA LLC. at 1-800-346-6854 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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

Anaphylactic Reactions [ see Warnings and Precautions (5.1)]

7 drug interactions

  • Oral Contraceptives: Effects on gut flora may lower estrogen reabsorption and reduce efficacy of oral contraceptives. ( 7.1)
  • Drugs that reduce gastric acidity may lower the bioavailability of cefuroxime axetil tablets. ( 7.2)
  • Coadministration with probenecid increases systemic exposure to cefuroxime axetil tablets and is therefore not recommended. ( 7.3)

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, cefuroxime axetil tablets 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 cefuroxime axetil.

8.3 nursing mothers

Because cefuroxime is excreted in human milk, caution should be exercised when cefuroxime axetil is administered to a nursing woman.

8.4 pediatric use

The safety and effectiveness of cefuroxime axetil tablets 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 tablets 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. [ See Indications and Usage (1), Dosage and Administration (2), Adverse Reactions (6), Clinical Pharmacology (12.3).]

8.5 geriatric use

Of the total number of subjects who received cefuroxime axetil tablets in 20 clinical trials, 375 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.

10 overdosage

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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

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Cefuroxime axetil tablets, USP contain cefuroxime as cefuroxime axetil. Cefuroxime axetil is a semisynthetic, cephalosporin antibacterial drug for oral administration.

The chemical name of cefuroxime axetil (1-(acetyloxy) ethyl ester of cefuroxime) is ( RS)-1-hydroxyethyl (6 R,7 R)-7-[2-(2-furyl)glyoxyl-amido]-3-(hydroxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]-oct-2-ene-2-carboxylate, 7 2-( Z)-( O-methyl-oxime), 1-acetate 3-carbamate. Its molecular formula is C 20H 22N 4O 10S, and it has a molecular weight of 510.48.

Cefuroxime axetil is in the amorphous form and has the following structural formula:

Structure

Cefuroxime axetil tablets, USP are film-coated and contain the equivalent of 125, 250, or 500 mg of cefuroxime as cefuroxime axetil. Cefuroxime axetil tablets, USP contain the inactive ingredients colloidal silicon dioxide, prosolv SMCC 50, sodium lauryl sulfate, croscarmellose sodium, hydrogenated castor oil, hypromellose, propylene glycol, titanium dioxide, dewaxed shellac powder, dibutyl sebacate and polysorbate 80.

12 clinical pharmacology

12.1 mechanism of action

Cefuroxime axetil is an antibacterial drug [ see Clinical Pharmacology (12.4)].

12.3 pharmacokinetics

Absorption

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. Serum pharmacokinetic parameters for cefuroxime following administration of cefuroxime axetil tablets to adults are shown in Table 8.

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

aMean values of 12 healthy adult volunteers.

bDrug administered immediately after a meal.

Dose b ( Cefuroxime Equivalent )
Peak Plasma Concentration ( mcg / mL )
Time of Peak Plasma Concentration ( h )
Mean Elimination Half - life ( h )
AUC ( mcg( h / mL )
125mg
2.1
2.2
1.2
6.7
250mg
4.1
2.5
1.2
12.9
500mg
7
3
1.2
27.4
1,000mg
13.6
2.5
1.3
50

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 cefuroxime axetil established in adults should not be extrapolated to pediatric subjects.

Specific Populations

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

Geriatric Patients:In a trial of 20 elderly subjects (mean age = 83.9 years) having a mean creatinine clearance of 34.9 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 [ see Use in Specific Populations (8.5)].

Drug Interactions

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

12.4 microbiology

Mechanism of Action

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

Mechanism of Resistance

Resistance to cefuroxime axetil is primarily through hydrolysis by -lactamase, 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. Beta-lactamase -negative, ampicillin-resistant (BLNAR) isolates of H. influenzaeshould be considered resistant to cefuroxime axetil.

Cefuroxime axetil has been shown to be active against most isolates of the following bacteria, both in vitroand in clinical infections [ see Indications and Usage (1)]:

  • 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 -lactamase (ESBL) -producing and carbapenemase-producing isolates are resistant to cefuroxime axetil.

  • Spirochetes

Borrelia burgdorferi

The following in vitrodata are available, but their clinical significance is unknown. At least 90 percent of the following microorganisms exhibit an in vitrominimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for cefuroxime axetil of 1 mcg/mL. 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.

  • 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 vitrosusceptibility 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). 1,2The 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. 4This 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 10. 3

Table 10. Susceptibility Test Interpretive Criteria for Cefuroxime Axetil

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

b Haemophilusspp. includes only isolates of H . influenzaeand H . parainfluenzae.

Pathogen
Minimum Inhibitory
Concentrations ( mcg / mL )
Disk Diffusion
Zone Diameters ( mm )

( S )
Susceptible
( I )
Intermediate
( R )
Resistant
( S )
Susceptible
( I )
Intermediate
( R )
Resistant
Enterobacteriaceae a
4
8to16
32
23
15to22
14
Haemophilusspp. a , b
4
8
16
20
17to19
16
Moraxella catarrhalis a
4
8
16
-
-
-
Streptococcus pneumoniae
1
2
4
-
-
-

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

Susceptibility of Streptococcus pyogenesmay 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. 1,2,4The 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 Cefuroxime Axetil

ATCC = American Type Culture Collection.

QC Strain
Minimum Inhibitory
Concentrations
( mcg / mL )
Disk Diffusion
Zone Diameters
( mm )
Escherichia coliATCC25922
2to8
20to26
Staphylococcus aureusATCC25923
-
27to35
Staphylococcus aureusATCC29213
0.5to2
-
Streptococcus pneumoniaeATCC49619
0.25to1
-
Haemophilus influenzaeATCC49766
0.25to1
28to36
Neisseria gonorrhoeaeATCC49226
0.25to1
33to41

13 nonclinical toxicology

14 clinical studies

15 references

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  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 M100-S25, 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

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Cefuroxime axetil tablets USP, 500 mg of cefuroxime as cefuroxime axetil, are white film-coated, round-shaped biconvex unscored tablets embossed with W922 on one side and plain on other side as follows:

20 Tablets/ Bottle NDC 43063-307-20

Store at 20 - 25C (68 - 77F). Replace cap securely after each opening.

17 patient counseling information

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Allergic Reactions

Inform patients that cefuroxime axetil tablets is a cephalosporin that can cause allergic reactions in some individuals [ see Warnings and Precautions (5.1)].

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 cefuroxime axetil tablets, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When cefuroxime axetil tablets are 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 cefuroxime axetil tablets or other antibacterial drugs in the future.

Trademarks are the property of their respective owners.

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Manufactured by:

Wockhardt Limited

Plot No. B-15/2, M.I.D.C. Area, Waluj,

Aurangabad, Maharashtra,

India.

Distributed by:

Wockhardt USA LLC.

20 Waterview Blvd.

Parsippany, NJ 07054

USA.

Rev.011117

Ingredients and appearance - Product information

Cefuroxime axetil tablet, film coated- Cefuroxime axetil

Product information

Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC: 43063-307
Route of Administration Oral

Active Ingredient/Active Moiety

Ingredient Name Strength
Cefuroxime axetil ( UNII: Z49QDT0J8Z)( Cefuroxime - UNII: O1R9FJ93ED ) 500 mgin 1

Inactive Ingredients

Ingredient Name Code
Croscarmellose sodium ( UNII: M28OL1HH48)
Dibutyl sebacate ( UNII: 4W5IH7FLNY)
Hydrogenated castor oil ( UNII: ZF94AP8MEY)
Hypromelloses ( UNII: 3NXW29V3WO)
Polysorbate 80 ( UNII: 6OZP39ZG8H)
Propylene glycol ( UNII: 6DC9Q167V3)
Shellac ( UNII: 46N107B71O)
Silicon dioxide ( UNII: ETJ7Z6XBU4)
Smcc ( UNII: B357P1G1IF)
Sodium lauryl sulfate ( UNII: 368GB5141J)
Titanium dioxide ( UNII: 15FIX9V2JP)

Product Characteristics

Color white (white) Shape CAPSULE (capsule)
Size 20 mm Score 1
Imprint Code W;922

Packaging

# Item Code Package Description Marketing Start Date
1 NDC: 43063-307-20 20 in 1 BOTTLE, PLASTIC 2012/02/02

Marketing Information

Marketing Category Application Number or Monograph Citation Territorial Authority Marketing Start Date
ANDA ANDA065166 USA 2012/02/02

Labeler - PD-Rx Pharmaceuticals, Inc.( 156893695)

Establishment

Name ID/FEI Business Operations
PD-Rx Pharmaceuticals, Inc. 156893695 repack( 43063-307)

Package label.principal display panel

DRUG: Cefuroxime Axetil

GENERIC: Cefuroxime Axetil

DOSAGE: Film-coated Tablets