Mechanism Of Action
Cefixime is a semisynthetic cephalosporin antibacterial drug [see Microbiology].
SUPRAX chewable tablets are bioequivalent to oral suspension.
SUPRAX 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]. 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.
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.
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:
|Pharmacokinetic Parameters (mean ± SD) for Cefixime in Both Young & Elderly Subjects
||4.74 ± 1.43
||5.68 ± 1.83
||3.9 ± 0.3
||4.3 ± 0.6`
||34.9 ± 12.2
||49.5 ± 19.1
||3.5 ± 0.6
||4.2 ± 0.4
||1.99 ± 0.75
|*Difference between age groups was significant. (p<0.05)
However, these increases were not clinically significant [see DOSAGE AND ADMINISTRATION].
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
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 betalactamases
may be susceptible to cefixime.
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.
Cefixime has been shown to be active against most isolates of the following microorganisms,
both in vitro and in clinical infections [see INDICATIONS].
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 caused by these
bacteria has not been established in adequate and well-controlled clinical trials.
For specific information regarding susceptibility test interpretive criteria and associated test
methods and quality control standards recognized by FDA for this drug, please see:
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%-31% of patients
had evidence of either treatment failure or recurrent disease.
|Bacteriological Outcome of Otitis Media at Two to Four Weeks Post-Therapy Based on Repeat Middle Ear
Fluid Culture or Extrapolation from Clinical Outcome
4 mg/kg BID
8 mg/kg QD
|(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
Bacteriological Outcome of Otitis Media at Two to Four Weeks Post-Therapy Based on Repeat Middle Ear