NDC 65862-752 Cefixime

Cefixime

NDC Product Code 65862-752

NDC CODE: 65862-752

Proprietary Name: Cefixime What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Cefixime What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.

Drug Use Information

Drug Use Information
The drug use information is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate. This information is not individual medical advice and does not substitute for the advice of a health care professional. Always ask a health care professional for complete information about this product and your specific health needs.

  • Cefixime is used to treat a wide variety of bacterial infections. This medication is known as a cephalosporin antibiotic. It works by stopping the growth of bacteria. This antibiotic treats only bacterial infections. It will not work for viral infections (such as common cold, flu). Using any antibiotic when it is not needed can cause it to not work for future infections.

Product Characteristics

Color(s):
WHITE (C48325 - OFF-WHITE TO PALE YELLOW)
Flavor(s):
STRAWBERRY (C73417)

NDC Code Structure

NDC 65862-752-50

Package Description: 50 mL in 1 BOTTLE

NDC 65862-752-75

Package Description: 75 mL in 1 BOTTLE

NDC Product Information

Cefixime with NDC 65862-752 is a a human prescription drug product labeled by Aurobindo Pharma Limited. The generic name of Cefixime is cefixime. The product's dosage form is powder, for suspension and is administered via oral form.

Labeler Name: Aurobindo Pharma Limited

Dosage Form: Powder, For Suspension - An intimate mixture of dry, finely divided drugs and/or chemicals, which, upon the addition of suitable vehicles, yields a suspension (a liquid preparation containing the solid particles dispersed in the liquid vehicle).

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Cefixime Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • CEFIXIME 200 mg/5mL

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
  • STRAWBERRY (UNII: 4J2TY8Y81V)
  • SUCROSE (UNII: C151H8M554)
  • XANTHAN GUM (UNII: TTV12P4NEE)
  • SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
  • STRAWBERRY (UNII: 4J2TY8Y81V)
  • SUCROSE (UNII: C151H8M554)
  • XANTHAN GUM (UNII: TTV12P4NEE)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Oral - Administration to or by way of the mouth.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Cephalosporin Antibacterial - [EPC] (Established Pharmacologic Class)
  • Cephalosporins - [CS]

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Aurobindo Pharma Limited
Labeler Code: 65862
FDA Application Number: ANDA204835 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: ANDA - A product marketed under an approved Abbreviated New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 04-14-2015 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2021 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N - NO What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA"s requests for correction to deficient or non-compliant submissions ("Y"), or because the listing certification is expired ("E"), or because the listing data was inactivated by FDA ("I"). Values = "Y", "N", "E", or "I".

* Please review the disclaimer below.

Information for Patients

Cefixime

Cefixime is pronounced as (sef ix' eem)

Why is cefixime medication prescribed?
Cefixime is used to treat certain infections caused by bacteria such as bronchitis (infection of the airway tubes leading to the lungs); gonorrhea (a sexually transmitted...
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* Please review the disclaimer below.

Cefixime Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

1.1 Uncomplicated Urinary Tract Infections

Cefixime for oral suspension is indicated in the treatment of adults and pediatric patients six months of age or older with uncomplicated urinary tract infections caused by susceptible isolates of Escherichia coli and Proteus mirabilis.

1.2 Otitis Media

Cefixime for oral suspension is indicated in the treatment of adults and pediatric patients six months of age or older with otitis media caused by susceptible isolates of 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)].

1.3 Pharyngitis And Tonsillitis

Cefixime for oral suspension is indicated in the treatment of adults and pediatric patients six months of age or older with pharyngitis and tonsillitis caused by susceptible isolates of Streptococcus pyogenes. (Note: Penicillin is the usual drug of choice in the treatment of Streptococcus pyogenes infections. Cefixime for oral suspension is generally effective in the eradication of Streptococcus pyogenes from the nasopharynx; however, data establishing the efficacy of cefixime for oral suspension in the subsequent prevention of rheumatic fever is not available.)

1.4 Acute Exacerbations Of Chronic Bronchitis

Cefixime for oral suspension is indicated in the treatment of adults and pediatric patients six months of age or older with acute exacerbations of chronic bronchitis caused by susceptible isolates of Streptococcus pneumoniae and Haemophilus influenzae.

1.5 Uncomplicated Gonorrhea (Cervical/Urethral)

Cefixime for oral suspension is indicated in the treatment of adults and pediatric patients six months of age or older with uncomplicated gonorrhea (cervical/urethral) caused by susceptible isolates of Neisseria gonorrhoeae (penicillinase-and non-penicillinase-producing isolates).

1.6 Usage

To reduce the development of drug resistant bacteria and maintain the effectiveness of cefixime for oral suspension and other antibacterial drugs, cefixime for oral suspension 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.

2.1 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.

2.2 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 CHARTDoses are suggested for each weight range and rounded for ease of administrationCefixime for oral suspensionCefixime chewable tablet100 mg/5 mL200 mg/5 mL500 mg/5 mLPatient Weight(kg)Dose/Day(mg)Dose/Day(mL)Dose/Day(mL)Dose/Day (mL) Dose 5 to 7.5*502.5------7.6 to 10*8042----10.1 to 12.510052.511 tablet of 100 mg 12.6 to 20.51507.541.51 tablet of 150 mg 20.6 to 2820010521 tablet of 200 mg 28.1 to 3325012.562.51 tablet of 100 mg and 1 tablet of 150 mg 33.1 to 40300157.532 tablets of 150 mg 40.1 to 4535017.593.51 tablet of 150 mg and 1 tablet of 200 mg 45.1 or greater400201042 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.

2.3 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 dysfunctionRenal DysfunctionCefixime for oral suspensionTabletChewable tabletCreatinine Clearance (mL/min) 100 mg/5 mL200 mg/5 mL500 mg/5 mL400 mg200 mg Dose/Day (mL)Dose/Day (mL)Dose/Day (mL)Dose/DayDose/Day60 or greater Normal doseNormal doseNormal doseNormal doseNormal dose21 to 59* OR renal hemodialysis* 136.52.6Not AppropriateNot Appropriate20 or less OR continuous peritoneal dialysis8.64.41.80.5 tablet1 tablet

2.4 Reconstitution Directions For Oral Suspension

StrengthBottle SizeReconstitution Directions100 mg/5 mL 100 mLTo 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 mL75 mLTo 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 mL50 mLTo 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.

3 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.

4 Contraindications

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

5.1 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 antibacterial drugs 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.

5.2 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 antibacterial drug 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 antibacterial drug use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial drug treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

5.3 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)].

5.4 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.

5.5 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.

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 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.

6.2 Post-Marketing Experience

The following adverse reactions have been reported following the post-approval 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.

7.1 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.

7.2 Warfarin And Anticoagulants

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

7.3 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.

8.1 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.

8.2 Labor And Delivery

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

8.3 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.

8.4 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.

8.5 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.

8.6 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)].

10 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.

11 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 cefixime powder for oral suspension USP are: colloidal silicon dioxide, strawberry guarana flavor, sucrose, and xanthan gum.

12.1 Mechanism Of Action

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

12.3 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 SubjectsPharmacokinetic parameterYoungElderlyCmax (mg/L)4.74 ± 1.435.68 ± 1.83Tmax (h)*3.9 ± 0.34.3 ± 0.6AUC (mg.h/L)*34.9 ± 12.249.5 ± 19.1T½ (h)*3.5 ± 0.64.2 ± 0.4Cave (mg/L)*1.42 ± 0.51.99 ± 0.75However, 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.

12.4 Microbiology

Mechanism of ActionAs 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. ResistanceResistance 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 ActivityCefixime 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 coliHaemophilus influenzaeMoraxella catarrhalisNeisseria gonorrhoeaeProteus mirabilisThe 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 caused by these bacteria has not been established in adequate and well-controlled clinical trials. Gram-positive Bacteria Streptococcus agalactiaeGram-negative Bacteria Citrobacter amalonaticusCitrobacter diversusHaemophilus parainfluenzaeKlebsiella oxytocaKlebsiella pneumoniaePasteurella multocidaProteus vulgarisProvidencia speciesSalmonella speciesSerratia marcescensShigella species Susceptibility TestingFor specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.

13.1 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.

14 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 antibacterial drug) 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 antibacterial drug. 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 OutcomeOrganismCefixime(a)4 mg/kg BIDCefixime(a)8 mg/kg QDControl(a)drugsStreptococcus pneumoniae48/70 (69%)18/22 (82%)82/100 (82%)Haemophilus influenzaebeta-lactamase negative24/34 (71%)13/17 (76%)23/34 (68%)Haemophilus influenzaebeta-lactamase positive17/22 (77%)9/12 (75%)1/1 (b)Moraxella catarrhalis26/31 (84%)5/518/24 (75%)S. pyogenes5/53/36/7All Isolates120/162 (74%)48/59 (81%)130/166 (78%)

16 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.

17.1 Information For Patients

Counsel patients 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. Advise patients that diarrhea is a common problem caused by antibacterial drugs which usually ends when the antibacterial drug is discontinued. Sometimes after starting treatment with antibacterial drugs, 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 antibacterial drug. If this occurs, patients should contact their physician as soon as possible. Distributed by:Aurobindo Pharma USA, Inc. 2400 Route 130 North Dayton, NJ 08810 Manufactured by:Aurobindo Pharma Limited Hyderabad-500 038, India Revised: 04/2018

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