cefixime 200 MG per 5 ML Oral Suspension
Generic Name: CEFIXIME
Brand Name: Cefixime
- Substance Name(s):
- CEFIXIME
DRUG INTERACTIONS
7 Elevated carbamazepine levels have been reported in postmarketing experience when cefixime is administered concomitantly.
(7.1) Increased prothrombin time, with or without clinical bleeding, has been reported when cefixime is administered concomitantly with warfarin and anticoagulants.
(7.2) 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.
OVERDOSAGE
10 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.
DESCRIPTION
11 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, 7 2 -( Z )-[ O -(carboxy methyl) oxime] trihydrate.
Molecular weight = 507.50 as the trihydrate.
Chemical Formula is C 16 H 15 N 5 O 7 S 2 .3H 2 O.
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.
Chemical Structure
CLINICAL STUDIES
14 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 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%)
HOW SUPPLIED
16 /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.
GERIATRIC USE
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.
DOSAGE FORMS AND STRENGTHS
3 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.
Oral Suspension: 100 mg/5 mL and 200 mg/5 mL (3)
MECHANISM OF ACTION
12.1 Mechanism of Action Cefixime is a semisynthetic cephalosporin antibacterial drug [see Microbiology (12.4) ].
INDICATIONS AND USAGE
1 Cefixime for oral suspension is a cephalosporin antibacterial drug indicated in the treatment of adults and pediatric patients six months and older with the following infections: Uncomplicated Urinary Tract Infections (1.1) Otitis Media (1.2) Pharyngitis and Tonsillitis (1.3) Acute Exacerbations of Chronic Bronchitis (1.4) Uncomplicated Gonorrhea (cervical/urethral) (1.5) 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 bacteria.
(1.6) 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.
PEDIATRIC USE
8.4 Pediatric Use Safety and effectiveness of cefixime in pediatric patients younger than 6 months of age 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.
PREGNANCY
8.1 Pregnancy Risk Summary Available data from published observational studies, case series, and case reports over several decades with cephalosporin use, including cefixime, in pregnant women have not established drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data) .
Reproduction studies have been performed in mice and rats at doses equivalent to 40 and 80 times, respectively, the adult human recommended dose and have revealed no evidence of harm to the fetus due to cefixime (see Data ).
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S.
general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Maternal gonorrhea may be associated with preterm birth, low neonatal birth weight, chorioamnionitis, intrauterine growth restriction, small for gestational age and premature rupture of membranes.
Perinatal transmission of gonorrhea to the offspring can result in infant blindness, joint infections, and bloodstream infections.
Data Human Data While available studies cannot definitively establish the absence of risk, published data from prospective cohort studies, case series, and case reports over several decades have not identified a consistent association with cephalosporin use, including cefixime, during pregnancy, and major birth defects, miscarriage, or other adverse maternal or fetal outcomes.
Available studies have methodological limitations, including small sample size, retrospective data collection, and inconsistent comparator groups.
Animal data The results of embryo-fetal development studies in mice and rats show that cefixime, at doses up to 3200 mg/kg/day administered during the period of organogenesis did not adversely affect development.
In these studies, in mice and rats, cefixime did not affect postnatal development or reproductive capacity of the F 1 generation or fetal development of the F 2 generation.
In an embryo-fetal development study in rabbits, cefixime at doses of 3.2, 10 or 32 mg/kg given daily during the period of organogenesis (gestation days 6 through 18) resulted in abortions and/or maternal deaths at doses > 10 mg/kg (typically associated with the administration of antibiotics in this species), but no malformations were reported at lower doses.
A pre- and post-natal development study of cefixime at oral doses up to 3200 mg/kg/day in rats demonstrated no effect on the duration of pregnancy, process of parturition, development and viability of offspring, or reproductive capacity of the F 1 generation and development of their fetuses (F 2 ).
WARNING AND CAUTIONS
5 WARNINGS AND PRECAUTIONS Hypersensitivity reactions including shock and fatalities have been reported with cefixime.
Discontinue use if a reaction occurs.
(5.1) Clostridium difficile associated diarrhea: Evaluate if diarrhea occurs.
(5.2) 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.
INFORMATION FOR PATIENTS
17 PATIENT COUNSELING INFORMATION Drug Resistance 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 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 .
279 Princeton-Hightstown Road East Windsor, NJ 08520 Manufactured by: Aurobindo Pharma Limited Hyderabad-500 038, India Revised: 12/2019
DOSAGE AND ADMINISTRATION
2 Adults: 400 mg daily (2.1) Pediatric patients (6 months and older): 8 mg/kg/day (2.2) 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 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.
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 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 2.4 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.