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Cefixime

Pronunciation

Dosage Form: powder, for suspension

Indications and Usage for Cefixime


To reduce the development of drug resistant bacteria and maintain the effectiveness of Cefixime for oral suspension USP and other antibacterial drugs, Cefixime for oral suspension USP should be used only to treat 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 antimicrobial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Cefixime is a cephalosporin antibacterial drug indicated in the treatment of adults and pediatric patients six months of age or older with the following infections when caused by susceptible isolates of the designated bacteria:

Uncomplicated Urinary Tract Infections


Uncomplicated Urinary Tract Infections caused by Escherichia coli and Proteus mirabilis.

Otitis Media


Otitis Media caused by Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pyogenes. (Efficacy for Streptococcus pyogenes in this organ system was studied in fewer than 10 infections.)

Note: For patients with otitis media caused by Streptococcus pneumoniae, overall response was approximately 10% lower for Cefixime than for the comparator [see CLINICAL STUDIES (14)].

Pharyngitis and Tonsillitis


Pharyngitis and Tonsillitis caused by Streptococcus pyogenes. (Note: Penicillin is the usual drug of choice in the treatment of Streptococcus pyogenes infections. Cefixime for oral suspension USP is generally effective in the eradication of Streptococcus pyogenes from the nasopharynx; however, data establishing the efficacy of Cefixime for oral suspension USP in the subsequent prevention of rheumatic fever is not available.)

Acute Exacerbations of Chronic Bronchitis


Acute Exacerbations of Chronic Bronchitis caused by Streptococcus pneumoniae and Haemophilus influenzae.

Uncomplicated Gonorrhea (cervical/urethral)


Uncomplicated Gonorrhea (cervical/urethral) caused by Neisseria gonorrhoeae (penicillinase-and non-penicillinase-producing isolates).

Cefixime Dosage and Administration

Adults


The recommended dose of Cefixime is 400 mg daily. This may be given as a 400 mg tablet or capsule daily or the 400 mg tablet may be split and given as one half tablet every 12 hours. For the treatment of uncomplicated cervical/urethral gonococcal infections, a single oral dose of   400 mg is recommended. The capsule and tablet may be administered without regard to food.

In the treatment of infections due to Streptococcus pyogenes, a therapeutic dosage of Cefixime should be administered for at least 10 days.

Pediatric Patients (6 months or older)


The recommended dose is 8 mg/kg/day of the suspension. This may be administered as a single daily dose or may be given in two divided doses, as 4 mg/kg every 12 hours.


Note: A suggested dose has been determined for each pediatric weight range. Refer to Table 1. Ensure all orders that specify a dose in milliliters include a concentration, because Cefixime for oral suspension is available in three different concentrations (100 mg/5 mL, 200 mg/5 mL, and 500 mg/5 mL). 

            


Table 1. Suggested doses for pediatric patients

* The preferred concentrations of oral suspension to use are 100 mg/5 mL or 200 mg/5 mL for pediatric patients in these weight ranges.
PEDIATRIC DOSAGE CHART
Doses are suggested for each weight range and rounded for ease of administration
Cefixime for Oral Suspension
Cefixime Chewable Tablet
100 mg/5 mL
200 mg/5 mL
500 mg/5 mL
Patient Weight
(kg)
Dose/Day
(mg)
Dose/Day
(mL)
Dose/Day
(mL)
Dose/Day (mL)
Dose
5 to 7.5*
50
2.5
--
--
--
7.6 to 10*
80
4
2
--
--
10.1 to 12.5
100
5
2.5
1
1 tablet of 100 mg
12.6 to 20.5
150
7.5
4
1.5
1 tablet of 150 mg
20.6 to 28
200
10
5
2
1 tablet of 200 mg
28.1 to 33
250
12.5
6
2.5
1 tablet of 100 mg and 1 tablet of 150 mg
33.1 to 40
300
15
7.5
3
2 tablets of 150 mg
40.1 to 45
350
17.5
9
3.5
1 tablet of 150 mg and 1 tablet of 200 mg
45.1 or greater
400
20
10
4
2 tablets of 200 mg

Children weighing more than 45 kg or older than 12 years should be treated with the recommended adult dose. Cefixime chewable tablets must be chewed or crushed before swallowing.


Otitis media should be treated with the chewable tablets or suspension. Clinical trials of otitis media were conducted with the chewable tablets or suspension, and the chewable tablets or suspension results in higher peak blood levels than the tablet when administered at the same dose.


Therefore, the tablet or capsule should not be substituted for the chewable tablets or suspension in the treatment of otitis media [see  CLINICAL PHARMACOLOGY (12.3)].


In the treatment of infections due to Streptococcus pyogenes, a therapeutic dosage of Cefixime should be administered for at least 10 days.

Renal Impairment


Cefixime for oral suspension may be administered in the presence of impaired renal function. Normal dose and schedule may be employed in patients with creatinine clearances of 60 mL/min or greater. Refer to Table 2 for dose adjustments for adults with renal impairment. Neither hemodialysis nor peritoneal dialysis removes significant amounts of drug from the body.

Table 2. Doses for Adults with Renal Impairment
* The preferred concentrations of oral suspension to use are 200 mg/5 mL or 500 mg/5 mL for patients with this renal dysfunction
Renal Dysfunction
Cefixime for Oral Suspension
Tablet
Chewable Tablet
Creatinine Clearance (mL/min)
100 mg/5 mL
200 mg/5 mL
500 mg/5 mL
400 mg
200 mg
 
Dose/Day (mL)
Dose/Day (mL)
Dose/Day (mL)
Dose/Day
Dose/Day
60 or greater
Normal dose
Normal dose
Normal dose
Normal dose
Normal dose
21 to 59*
OR renal hemodialysis*
13
6.5
2.6
Not Appropriate
Not Appropriate
20 or less OR continuous peritoneal dialysis
8.6
4.4
1.8
0.5 tablet
1 tablet

Reconstitution Directions for Oral Suspension


Strength
Bottle Size
Reconstitution Directions
100 mg/5 mL
100 mL
To reconstitute, suspend with 70 mL water. Method: Tap the bottle several times to loosen powder contents prior to reconstitution. Add approximately half the total amount of water for reconstitution and shake well. Add the remainder of water and shake well.
200 mg/5 mL
75 mL
To reconstitute, suspend with 52.5 mL water. Method: Tap the bottle several times to loosen powder contents prior to reconstitution. Add approximately half the total amount of water for reconstitution and shake well. Add the remainder of water and shake well.
100 mg/5 mL and
 
200 mg/5 mL
50 mL
To reconstitute, suspend with 35 mL water. Method: Tap the bottle several times to loosen powder contents prior to reconstitution. Add approximately half the total amount of water for reconstitution and shake well. Add the remainder of water and shake well.

After reconstitution, the suspension may be kept for 14 days either at room temperature, or under refrigeration, without significant loss of potency. Keep tightly closed. Shake well before using. Discard unused portion after 14 days.

Dosage Forms and Strengths


Cefixime is available for oral administration in the following strengths:

  • Powder for oral suspension, when reconstituted, provides either 100 mg/5 mL or 200 mg/5 mL of Cefixime as trihydrate. The powder has an off-white to pale yellow color and is strawberry flavored.

Contraindications

Cefixime for oral suspension is contraindicated in patients with known allergy to Cefixime or other cephalosporins.

Warnings and Precautions

Hypersensitivity Reactions


Anaphylactic/anaphylactoid reactions (including shock and fatalities) have been reported with the use of Cefixime.

Before therapy with Cefixime is instituted, careful inquiry should be made to determine whether the patient has had previous hypersensitivity reactions to cephalosporins, penicillins, or other drugs. If this product is to be given to penicillin-sensitive patients, caution should be exercised because cross hypersensitivity among beta-lactam antibiotics has been clearly documented and may occur in up to 10% of patients with a history of penicillin allergy. If an allergic reaction to Cefixime occurs, discontinue the drug.

Clostridium difficile-Associated Diarrhea


Clostridium difficile
associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Cefixime, 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 isolates 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 two 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.

Dose Adjustment in Renal Impairment


The dose of Cefixime should be adjusted in patients with renal impairment as well as those undergoing continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD). Patients on dialysis should be monitored carefully [see DOSAGE AND ADMINISTRATION (2)].

Coagulation Effects


Cephalosporins, including Cefixime, 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.

Development of Drug-Resistant Bacteria


Prescribing Cefixime in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Adverse Reactions

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 to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The most commonly seen adverse reactions in U.S. trials of the tablet formulation were gastrointestinal events, which were reported in 30% of adult patients on either the twice daily or the once daily regimen. Five percent (5%) of patients in the U.S. clinical trials discontinued therapy because of drug-related adverse reactions. Individual adverse reactions included diarrhea 16%, loose or frequent stools 6%, abdominal pain 3%, nausea 7%, dyspepsia 3%, and flatulence 4%. The incidence of gastrointestinal adverse reactions, including diarrhea and loose stools, in pediatric patients receiving the suspension was comparable to the incidence seen in adult patients receiving tablets.

Post-marketing Experience

 

The following adverse reactions have been reported following the use of Cefixime. Incidence rates were less than 1 in 50 (less than 2%).

Gastrointestinal

Several cases of documented pseudomembranous colitis were identified in clinical trials. The onset of pseudomembranous colitis symptoms may occur during or after therapy.

Hypersensitivity Reactions

Anaphylactic/anaphylactoid reactions (including shock and fatalities), skin rashes, urticaria, drug fever, pruritus, angioedema, and facial edema. Erythema multiforme, Stevens-Johnson syndrome, and serum sickness-like reactions have been reported.

Hepatic

Transient elevations in SGPT, SGOT, alkaline phosphatase, hepatitis, jaundice.

Renal

Transient elevations in BUN or creatinine, acute renal failure.

Central Nervous System

Headaches, dizziness, seizures.

Hemic and Lymphatic System

Transient thrombocytopenia, leukopenia, neutropenia, prolongation in prothrombin time, elevated LDH, pancytopenia, agranulocytosis, and eosinophilia.

Abnormal Laboratory Tests

Hyperbilirubinemia.

Other Adverse Reactions

Genital pruritus, vaginitis, candidiasis, toxic epidermal necrolysis.

Adverse Reactions Reported for Cephalosporin-class Drugs

Allergic reactions, superinfection, renal dysfunction, toxic nephropathy, hepatic dysfunction including cholestasis, aplastic anemia, hemolytic anemia, hemorrhage, and colitis.

Several cephalosporins have been implicated in triggering seizures, particularly in patients with renal impairment when the dosage was not reduced [see DOSAGE AND ADMINISTRATION (2)  and OVERDOSAGE (10)]. If seizures associated with drug therapy occur, the drug should be discontinued. Anticonvulsant therapy can be given if clinically indicated.

Drug Interactions

Carbamazepine


Elevated carbamazepine levels have been reported in postmarketing experience when Cefixime is administered concomitantly. Drug monitoring may be of assistance in detecting alterations in carbamazepine plasma concentrations.

Warfarin and Anticoagulants


Increased prothrombin time, with or without clinical bleeding, has been reported when Cefixime is administered concomitantly.

Drug/Laboratory Test Interactions


A false-positive reaction for ketones in the urine may occur with tests using nitroprusside but not with those using nitroferricyanide.

The administration of Cefixime may result in a false-positive reaction for glucose in the urine using Clinitest®**, Benedict’s solution, or Fehling’s solution. It is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as Clinistix®** or TesTape®**) be used. A false-positive direct Coombs test has been reported during treatment with other cephalosporins; therefore, it should be recognized that a positive Coombs test may be due to the drug.

** Clinitest® and Clinistix® are registered trademarks of Ames Division, Miles Laboratories, Inc. Tes-Tape® is a registered trademark of Eli Lilly and Company.

USE IN SPECIFIC POPULATIONS

Pregnancy

Teratogenic Effects

Pregnancy Category B. Reproduction studies have been performed in mice and rats at doses up to 40 times the human dose and have revealed no evidence of harm to the fetus due to Cefixime. There are no adequate and well-controlled 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.

Labor and Delivery


Cefixime has not been studied for use during labor and delivery. Treatment should only be given if clearly needed.

Nursing Mothers


It is not known whether Cefixime is excreted in human milk. Consideration should be given to discontinuing nursing temporarily during treatment with this drug.

Pediatric Use


Safety and effectiveness of Cefixime in children aged less than six months old have not been established. The incidence of gastrointestinal adverse reactions, including diarrhea and loose stools, in the pediatric patients receiving the suspension, was comparable to the incidence seen in adult patients receiving tablets.

Geriatric Use


Clinical studies did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently than younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. A pharmacokinetic study in the elderly detected differences in pharmacokinetic parameters [see CLINICAL PHARMACOLOGY (12.3)]. These differences were small and do not indicate a need for dosage adjustment of the drug in the elderly.

Renal Impairment


The dose of Cefixime should be adjusted in patients with renal impairment as well as those undergoing continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD). Patients on dialysis should be monitored carefully [see DOSAGE AND ADMINISTRATION (2.3)].

Overdosage


Gastric lavage may be indicated; otherwise, no specific antidote exists. Cefixime is not removed in significant quantities from the circulation by hemodialysis or peritoneal dialysis. Adverse reactions in small numbers of healthy adult volunteers receiving single doses up to 2 g of Cefixime did not differ from the profile seen in patients treated at the recommended doses.

Cefixime Description


Cefixime is a semisynthetic, cephalosporin antibacterial for oral administration. Chemically, it is (6R,7R) - 7 - [2 - (2 - Amino - 4 - thiazolyl)glyoxylamido] - 8 - oxo - 3 - vinyl - 5 - thia - 1 - azabicyclo [4.2.0] oct-2-­ene-2-carboxylic acid, 72-(Z)-[O-(carboxy methyl) oxime] trihydrate.

Molecular weight = 507.50 as the trihydrate. Chemical Formula is C16H15N5O7S2.3H2O.

The structural formula for Cefixime is:



  • Inactive ingredients contained in the powder for oral suspension are: colloidal silicon dioxide, strawberry Guarana flavor, sucrose, and xanthan gum.

Cefixime - Clinical Pharmacology

Mechanism of Action


Cefixime is a semisynthetic cephalosporin antibacterial drug [see Microbiology (12.4)].

Pharmacokinetics


Cefixime chewable tablets are bioequivalent to oral suspension.



Cefixime tablets and suspension, given orally, are about 40% to 50% absorbed whether administered with or without food; however, time to maximal absorption is increased approximately 0.8 hours when administered with food. A single 200 mg tablet of Cefixime produces an average peak serum concentration of approximately 2 mcg/mL (range 1 to 4 mcg/mL); a single 400 mg tablet produces an average peak concentration of approximately   3.7 mcg/mL (range 1.3 to 7.7 mcg/mL). The oral suspension produces average peak concentrations approximately 25% to 50% higher than the tablets, when tested in normal adult volunteers. Two hundred and 400 mg doses of oral suspension produce average peak concentrations of 3 mcg/mL (range 1 to 4.5 mcg/mL) and 4.6 mcg/mL (range 1.9 to 7.7 mcg/mL), respectively, when tested in normal adult volunteers. The area under the time versus concentration curve (AUC) is greater by approximately 10% to 25% with the oral suspension than with the tablet after doses of 100 to 400 mg, when tested in normal adult volunteers. This increased absorption should be taken into consideration if the oral suspension is to be substituted for the tablet. Because of the lack of bioequivalence, tablets should not be substituted for oral suspension in the treatment of otitis media [see DOSAGE AND ADMINISTRATION (2)]. Cross-over studies of tablet versus suspension have not been performed in children.

The 400 mg capsule is bioequivalent to the 400 mg tablet under fasting conditions. However, food reduces the absorption following administration of the capsule by approximately 15% based on AUC and 25% based on Cmax.

Peak serum concentrations occur between 2 and 6 hours following oral administration of a single 200 mg tablet, a single 400 mg tablet or 400 mg of Cefixime suspension. Peak serum concentrations occur between 2 and 5 hours following a single administration of 200 mg of suspension. Peak serum concentrations occur between 3 and 8 hours following oral administration of a single 400 mg capsule.

Distribution



Serum protein binding is concentration independent with a bound fraction of approximately 65%. In a multiple dose study conducted with a research formulation which is less bioavailable than the tablet or suspension, there was little accumulation of drug in serum or urine after dosing for 14 days. Adequate data on CSF levels of Cefixime are not available.

Metabolism and Excretion



There is no evidence of metabolism of Cefixime in vivo. Approximately 50% of the absorbed dose is excreted unchanged in the urine in 24 hours. In animal studies, it was noted that Cefixime is also excreted in the bile in excess of 10% of the administered dose. The serum half-life of Cefixime in healthy subjects is independent of dosage form and averages 3 to 4 hours but may range up to 9 hours in some normal volunteers.

Special Populations



Geriatrics
: Average AUCs at steady state in elderly patients are approximately 40% higher than average AUCs in other healthy adults. Differences in the pharmacokinetic parameters between 12 young and 12 elderly subjects who received 400 mg of Cefixime once daily for 5 days are summarized as follows:


* Difference between age groups was significant. (p<0.05)
Pharmacokinetic Parameters (mean ± SD) for Cefixime in Both Young & Elderly Subjects
Pharmacokinetic parameter
Young
Elderly
Cmax (mg/L)
4.74 ± 1.43
5.68 ± 1.83
Tmax (h)*
3.9 ± 0.3
4.3 ± 0.6
AUC (mg.h/L)*
34.9 ± 12.2
49.5 ± 19.1
T½ (h)*
3.5 ± 0.6
4.2 ± 0.4
Cave (mg/L)*
1.42 ± 0.5
1.99 ± 0.75

However, these  increases  were  not  clinically  significant  [see  DOSAGE   AND ADMINISTRATION (2)].

Renal Impairment
: In subjects with moderate impairment of renal function (20 to 40 mL/min creatinine clearance), the average serum half-life of Cefixime is prolonged to 6.4 hours. In severe renal impairment (5 to 20 mL/min creatinine clearance), the half-life increased to an average of 11.5 hours. The drug is not cleared significantly from the blood by hemodialysis or peritoneal dialysis. However, a study indicated that with doses of 400 mg, patients undergoing hemodialysis have similar blood profiles as subjects with creatinine clearances of 21 to 60 mL/min.

Microbiology

Mechanism of Action

As with other cephalosporins, the bactericidal action of Cefixime results from inhibition of cell wall synthesis. Cefixime is stable in the presence of certain beta-lactamase enzymes. As a result, certain organisms resistant to penicillins and some cephalosporins due to the presence of beta-lactamases may be susceptible to Cefixime.


Resistance

Resistance to Cefixime in isolates of Haemophilus influenzae and Neisseria gonorrhoeae is most often associated with alterations in penicillin-binding proteins (PBPs). Cefixime may have limited activity against Enterobacteriaceae producing extended spectrum beta-lactamases (ESBLs). Pseudomonas species, Enterococcus species, strains of Group D streptococci, Listeria monocytogenes, most strains of staphylococci (including methicillin-resistant strains), most strains of Enterobacter species, most strains of Bacteroides fragilis, and most strains of Clostridium species are resistant to Cefixime.


Antimicrobial Activity

Cefixime has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections [see INDICATIONS AND USAGE (1)].


Gram-positive Bacteria

Streptococcus pneumoniae

Streptococcus pyogenes


Gram-negative Bacteria

Escherichia coli

Haemophilus influenzae

Moraxella catarrhalis

Neisseria gonorrhoeae

Proteus mirabilis

The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for Cefixime against isolates of similar genus or organism group. However, the efficacy of Cefixime in treating clinical infections due to these bacteria has not been established in adequate and well-controlled clinical trials.


Gram-positive Bacteria

Streptococcus agalactiae


Gram-negative Bacteria

Citrobacter amalonaticus

Citrobacter diversus

Haemophilus parainfluenzae

Klebsiella oxytoca

Klebsiella pneumoniae

Pasteurella multocida

Proteus vulgaris

Providencia species

Salmonella species

Serratia marcescens

Shigella species


Susceptibility Test Methods

When available, the clinical microbiology laboratory should provide cumulative reports of in vitro susceptibility test results for antimicrobial drugs 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 for treatment.

Dilution techniques:

Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized test method1,2 (broth and/or agar). The MIC values should be interpreted according to criteria provided in Table 3.


Diffusion techniques:


Quantitative methods that require measurement of zone diameters can also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size should be determined using a standardized test method.2.3 This procedure uses paper disks impregnated with 5 mcg Cefixime to test the susceptibility of bacteria to Cefixime. The disc diffusion breakpoints are provided in Table 3.


Table 3: Susceptibility Interpretive Criteria for Cefixime
1 Do not test Morganella species by disk diffusion
2 Test Haemophilus influenzae using Haemophilus Test Medium (HTM)
3 The current absence of resistant isolates precludes defining any results other than "susceptible" Isolates yielding results other than susceptible should be subjected to additional testing.
4 Test Neisseria gonorrhoeae using GC agar base and 1% defined growth supplement. Minimum inhibitory concentrations are determined using the agar dilution method.
Pathogen
Minimum Inhibitory Concentrations (mcg/mL)
Disk Diffusion Zone Diameter (mm)
S
I
R
S
I
R
Enterobacteriaceae1
≤1
2
≥4
≥19
16 to 18
≤15
Haemophilus influenzae2,3
<1
NA
NA
≥21
NA
NA
Neisseria gonorrhoeae3,4
≤0.25
NA
NA
≥31
NA
NA

A report of Susceptible (S) 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 (I) 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 the 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 (R) indicates that the antimicrobial drug is not likely to inhibit growth of the pathogen if the antimicrobial drug reaches the concentration 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 individuals performing the test.1, 2, 3 Standard Cefixime powder should provide the following range of MIC values noted in Table 4. For the diffusion technique using the 5 mcg disk, the criteria in Table 4 should be achieved.

Table 4: Acceptable Quality Control Ranges for Cefixime
ATCC = American Type Culture Collection
Quality Control Organisms
Minimum Inhibitory Concentrations (mcg/mL)
Disk Diffusion Zone Diameter (mm)
E. coli ATCC 25922
0.25 to 1
23 to 27
H. influenzae ATCC 49247
0.12 to 1
25 to 33
N. gonorrhoeae ATCC 49226
0.004 to 0.03
37 to 45
S. pneumoniae ATCC 49619
NA
16 to 23
S. aureus ATCC 29213
8 to 32
NA

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility


Lifetime studies in animals to evaluate carcinogenic potential have not been conducted. Cefixime did not cause point mutations in bacteria or mammalian cells, DNA damage, or chromosome damage in vitro and did not exhibit clastogenic potential in vivo in the mouse micronucleus test. In rats, fertility and reproductive performance were not affected by Cefixime at doses up to 25 times the adult therapeutic dose.

Clinical Studies


Comparative clinical trials of otitis media were conducted in nearly 400 children between the ages of 6 months to 10 years. Streptococcus pneumoniae was isolated from 47% of the patients, Haemophilus influenzae from 34%, Moraxella catarrhalis from 15% and S. pyogenes from 4%.

The overall response rate of Streptococcus pneumoniae to Cefixime was approximately 10% lower and that of Haemophilus influenzae or Moraxella catarrhalis approximately 7% higher (12% when beta-lactamase positive isolates of H. influenzae are included) than the response rates of these organisms to the active control drugs.

In these studies, patients were randomized and treated with either Cefixime at dose regimens of   4 mg/kg twice a day or 8 mg/kg once a day, or with a comparator. Sixty-nine to 70% of the patients in each group had resolution of signs and symptoms of otitis media when evaluated 2 to 4 weeks post-treatment, but persistent effusion was found in 15% of the patients. When evaluated at the completion of therapy, 17% of patients receiving Cefixime and 14% of patients receiving effective comparative drugs (18% including those patients who had Haemophilus influenzae resistant to the control drug and who received the control antibiotic) were considered to be treatment failures. By the 2 to 4 week follow-up, a total of 30% to 31% of patients had evidence of either treatment failure or recurrent disease.


(a)  Number eradicated/number isolated.
(b) An additional 20 beta-lactamase positive isolates of Haemophilus influenzae were isolated, but were excluded from this analysis because they were resistant to the control antibiotic. In nineteen of these, the clinical course could be assessed and a favorable outcome occurred in 10. When these cases are included in the overall bacteriological evaluation of therapy with the control drugs, 140/185 (76%) of pathogens were considered to be eradicated.
Bacteriological Outcome of Otitis Media at Two to Four Weeks Post-Therapy Based on Repeat Middle Ear Fluid Culture or Extrapolation from Clinical Outcome
Organism
Cefixime(a)
4 mg/kg BID
Cefixime(a)
8 mg/kg QD
Control(a)
drugs
Streptococcus pneumoniae
48/70 (69%)
18/22 (82%)
82/100 (82%)
Haemophilus influenzae
beta-lactamase negative
24/34 (71%)
13/17 (76%)
23/34 (68%)
Haemophilus influenzae
beta-lactamase positive
17/22 (77%)
9/12 (75%)
1/1 (b)
Moraxella catarrhalis
26/31 (84%)
5/5
18/24 (75%)
S. pyogenes
5/5
3/3
6/7
All Isolates
120/162 (74%)
48/59 (81%)
130/166 (78%)

REFERENCES

  1. Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard - Tenth Edition. CLSI document M07-A10, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2015.
  2. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; Twenty-fifth Informational Supplement, CLSI document M100-S25, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2015.
  3. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Disk Diffusion Susceptibility Tests; Approved Standard - Twelfth Edition. CLSI document M02-A12, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2015.

How Supplied/Storage and Handling


Cefixime for oral suspension USP 100 mg/5 mL
is off-white to pale yellow colored powder - Each 5 mL of reconstituted off-white to pale yellow, strawberry flavored suspension contains Cefixime trihydrate equivalent to 100 mg Cefixime.

        50 mL Bottles                  NDC 65862-751-50
        100 mL Bottles                NDC 65862-751-01

Cefixime for oral suspension USP 200 mg/5 mL
is off-white to pale yellow colored powder - Each 5 mL of reconstituted off-white to pale yellow, strawberry flavored suspension contains Cefixime trihydrate equivalent to 200 mg Cefixime.

        50 mL Bottles                  NDC 65862-752-50
        75 mL Bottles                  NDC 65862-752-75

Storage

Prior to Reconstitution
: Store drug powder at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

After Reconstitution
: Store at room temperature or under refrigeration. Shake well before using. Discard unused portion after 14 days.

Keep tightly closed.

Patient Counseling Information

Information for Patients


Patients should be counseled that antibacterial drugs, including Cefixime, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Cefixime 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 Cefixime for oral suspension or other antibacterial drugs in the future.

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 two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Manufactured for:
Aurobindo Pharma USA, Inc.
2400 Route 130 North
Dayton, NJ 08810

Manufactured by:
Aurobindo Pharma Limited
Chitkul (V), 502307, India

Revised: 03/2016

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 100 mg/5 mL (50 mL Bottle)

NDC 65862-751-50
Cefixime for
Oral Suspension, USP
100 mg/5 mL
when reconstituted
FOR ORAL USE ONLY
SHAKE WELL BEFORE USING
Rx only           50 mL
                     (when reconstituted)
AUROBINDO


PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 200 mg/5 mL (50 mL Bottle)

NDC 65862-752-50
Cefixime for
Oral Suspension, USP
200 mg/5 mL
when reconstituted
FOR ORAL USE ONLY
SHAKE WELL BEFORE USING
Rx only           50 mL
              (when reconstituted)
AUROBINDO

Cefixime 
Cefixime powder, for suspension
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:65862-751
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Cefixime (Cefixime ANHYDROUS) Cefixime ANHYDROUS 100 mg  in 5 mL
Inactive Ingredients
Ingredient Name Strength
SILICON DIOXIDE  
STRAWBERRY  
SUCROSE  
XANTHAN GUM  
Product Characteristics
Color WHITE (Off-white to pale yellow) Score     
Shape Size
Flavor STRAWBERRY Imprint Code
Contains         
Packaging
# Item Code Package Description
1 NDC:65862-751-50 50 mL in 1 BOTTLE
2 NDC:65862-751-01 100 mL in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA204835 04/14/2015
Cefixime 
Cefixime powder, for suspension
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:65862-752
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Cefixime (Cefixime ANHYDROUS) Cefixime ANHYDROUS 200 mg  in 5 mL
Inactive Ingredients
Ingredient Name Strength
SILICON DIOXIDE  
STRAWBERRY  
SUCROSE  
XANTHAN GUM  
Product Characteristics
Color WHITE (Off-white to pale yellow) Score     
Shape Size
Flavor STRAWBERRY Imprint Code
Contains         
Packaging
# Item Code Package Description
1 NDC:65862-752-50 50 mL in 1 BOTTLE
2 NDC:65862-752-75 75 mL in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA204835 04/14/2015
Labeler - Aurobindo Pharma Limited (650082092)
Establishment
Name Address ID/FEI Operations
Aurobindo Pharma Limited 918917639 ANALYSIS(65862-751, 65862-752), MANUFACTURE(65862-751, 65862-752)
Establishment
Name Address ID/FEI Operations
Aurobindo Pharma Limited 918917647 API MANUFACTURE(65862-751, 65862-752)
Revised: 03/2016
 
Aurobindo Pharma Limited
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