Canada - English - Health Canada
Cefixime tablets, Mfr. Std., 400 mg
Cefixime for oral suspension, Mfr. Std., 100 mg/5 mL
ODAN LABORATORIES LTD.
325 Stillview Ave.,
Date of Revision:
March 17, 2020
Submission Control No. : 233967
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Cefixime tablets, Mfr. Std., 400 mg
Cefixime for oral suspension, Mfr. Std., 100 mg/5 mL
ACTION AND CLINICAL PHARMACOLOGY
SUPRAX (cefixime) exerts its bactericidal effect by attaching to penicillin-binding proteins
(PBP) and inhibiting peptidoglycan synthesis, thus causing damage to the bacterial cell wall.
Following oral dosing, SUPRAX attains peak serum levels in approximately 4 hours. The
half-life is about 3 to 4 hours and is not dose dependent. Cefixime is excreted by renal and
biliary mechanisms. About 50% of the absorbed dose is excreted unchanged in the urine within
24 hours. There is no evidence of metabolism of cefixime
INDICATIONS AND USAGE
SUPRAX (cefixime) is indicated in the treatment of the following infections caused by
susceptible strains of the designated microorganisms:
Upper Respiratory Tract:
Pharyngitis and tonsillitis caused by
Otitis media caused by
S. pneumoniae, H. influenzae
(beta-lactamase positive and negative
) (beta-lactamase positive and negative strains)
Sinusitis caused by
S. pneumoniae, H. influenzae
(beta-lactamase positive and negative strains),
) (beta-lactamase positive and negative strains).
Lower Respiratory Tract:
(beta-lactamase positive and negative strains) and
(beta-lactamase positive and
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Acute uncomplicated cystitis and urethritis caused by
E. coli, P. mirabilis
gonorrhea (cervical/urethral and rectal) caused by
negative) producing strains.
Appropriate cultures should be taken for susceptibility testing before initiating treatment with
SUPRAX. If warranted, therapy may be instituted before susceptibility results are known;
however, once these are obtained, therapy may need to be adjusted.
SUPRAX and other antibacterial drugs, SUPRAX 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
antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns
may contribute to the empiric selection of therapy.
SUPRAX (cefixime) is contraindicated in patients with known allergies to the cephalosporin or
penicillin antibiotics or to any ingredients in the formulation or component of the container.
SENSITIVE TO BOTH. MEDICAL LITERATURE INDICATES THAT PATIENTS
Antibiotics, including SUPRAX, should be administered cautiously to any patient who has
demonstrated some form of allergy, particularly to drugs.
Severe Cutaneous Adverse Reactions:
Severe cutaneous adverse reactions (SCAR) such as acute generalized exanthematous pustulosis
(AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson
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syndrome (SJS), and toxic epidermal necrolysis (TEN) have been reported in association with beta-
lactam treatment. When SCAR is suspected, Suprax should be discontinued and appropriate
therapy and/or measures should be taken.
Clostridium Difficile-Associated Disease:
antibacterial agents, including SUPRAX (see ADVERSE REACTIONS). CDAD may range in
severity from mild diarrhea to fatal colitis. It is important to consider this diagnosis in patients
who present with diarrhea, or symptoms of colitis, pseudomembranous colitis, toxic megacolon,
or perforation of colon subsequent to the administration of any antibacterial agent. CDAD has
been reported to occur over 2 months after the administration of antibacterial agents.
Treatment with antibacterial agents may alter the normal flora of the colon and may permit
Clostridium difficile. C. difficile
produces toxins A and B, which contribute to
the development of CDAD. CDAD may cause significant morbidity and mortality. CDAD can
be refractory to antimicrobial therapy.
If the diagnosis of CDAD is suspected or confirmed, appropriate therapeutic measures should
be initiated. Mild cases of CDAD usually respond to discontinuation of antibacterial agents not
. In moderate to severe cases, consideration should be
given to management with fluids and electrolytes, protein supplementation, and treatment with
an antibacterial agent clinically effective against
. Surgical evaluation
should be instituted as clinically indicated, as surgical intervention may be required in certain
RECURRENCE OF HEMOLYSIS IS MUCH MORE SEVERE.
An immune mediated hemolytic anemia has been observed in patients receiving cephalosporin
class antibacterials, including SUPRAX. Severe cases of hemolytic anemia, including fatalities,
have been reported with cephalosporins in both adults and children. If a patient develops
anemia anytime during, or within 2-3 weeks subsequent to the administration of SUPRAX, the
diagnosis of a cephalosporin-associated anemia should be considered and the drug discontinued
until the etiology is determined.
Patients may benefit from periodic monitoring for signs and symptoms of hemolytic anemia,
including measurement of hematological parameters or drug-induced antibody testing, where
appropriate (see ADVERSE REACTIONS).
Acute Renal Failure:
tubulointerstitial nephritis. When acute renal failure occurs, SUPRAX should be discontinued
and appropriate therapy and/or measures should be taken.
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particularly in patients with renal impairment when the dosage was not reduced. If seizures
associated with SUPRAX occur, the drug should be discontinued. Anticonvulsant therapy can
Development of Drug Resistant Bacteria
Prescribing SUPRAX in the absence of a proven or strongly suspected bacterial infection is
unlikely to provide benefit to the patient and risks the development of drug-resistant bacteria.
If an allergic reaction to SUPRAX (cefixime) occurs, the drug should be discontinued, and, if
antihistamines, or corticosteroids.
The possibility of the emergence of resistant organisms, which might result in overgrowth,
observation of the patient is essential. If superinfection occurs during therapy, appropriate
measures should be taken.
Broad-spectrum antibiotics such as SUPRAX should be prescribed with caution in individuals
with a history of gastrointestinal disease.
Once daily dosing only must be used for urinary tract infections, since twice daily dosing was
shown to be not as effective in clinical studies.
Do not use SUPRAX to treat
as this strain of staphylococcus is resistant
SUPRAX should be used with particular care in the presence of severely impaired renal
function. Dose modification is recommended
for patients with moderate or severe
impairment (i.e., creatinine clearance of < 40 mL/min) (see PHARMACOLOGY and DOSAGE
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Bioavailability Differences between Tablet and Suspension:
The area under the time versus concentration curve is greater by approximately 26.4% and the
is greater by approximately 20.7% with the oral suspension when compared to the tablet
after doses of 400 mg. 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 particularly in the treatment of otitis media where
ADVERSE REACTIONS and PHARMACOLOGY).
A false-positive reaction for ketones in the urine may occur with tests using nitroprusside but
not with those using nitroferricyanide.
The administration of beta-lactams 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
) be used.
A false-positive direct Coombs test has been reported during treatment with cephalosporin
antibiotics; therefore, it should be recognized that a positive Coombs test may be due to the
Usage in Pregnancy:
The safety of SUPRAX in the treatment of infection in pregnant women has not been
Reproduction studies have been performed in mice and rats at doses up to 400 times the human
dose and have revealed no evidence of impaired fertility or harm to the fetus due to cefixime.
Because animal reproduction studies are not always predictive of human response, this drug
should be used during pregnancy only if the likely benefits of using SUPRAX outweigh the
potential risk to the fetus and/or the mother.
Labour and Delivery:
SUPRAX has not been studied for use during labour and delivery.
Reg. Trademark of Bayer Healthcare LLC subsidiary of Bayer Corporation.
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It is not known whether SUPRAX is excreted in human milk. Because many drugs are excreted
in human milk, caution should be exercised when SUPRAX is administered to a nursing
Usage in Children:
Safety and effectiveness of SUPRAX in children less than six months old have not been
Five percent (5%) of patients in the clinical trials discontinued therapy because of drug-related
adverse reactions. Thirty-six percent of the pediatric patient population experienced at least one
adverse reaction (mild 25%, moderate 9%, severe 2%). Forty-seven percent of the adult patients
experienced at least one adverse reaction (mild 24%, moderate 19%, severe 4%). The most
gastrointestinal events, which were reported in 37% of all adult patients treated (mild 21%,
moderate 13%, severe 3%). The predominant adverse events seen in adults in clinical trials with
SUPRAX (cefixime) were diarrhea 15%, (mild 7.2%, moderate 6.2%, severe 1.5%), headache
11%, stool changes 12%, nausea 9%, abdominal pain 5%, dyspepsia 3%, flatulence (3%),
dizziness (3%) and vomiting (2%). The rates of the most prevalent adverse reactions were
similar in the once a day and twice a day dosing regimens with the exception of headache,
which appears slightly more frequently in adults, dosed once a day (12.9%) versus twice a day
(8%). Other than for generally mild rashes or emesis, which were each observed in 5% of
suspension was generally comparable to the incidence seen in adult patients receiving tablets.
These symptoms usually responded to symptomatic therapy or ceased when SUPRAX was
Several patients developed severe diarrhea and/or documented pseudomembranous colitis, and
a few required hospitalization.
When SUPRAX was used as single 400 mg dose therapy in clinical trials in the treatment of
uncomplicated gonorrhoea, adverse reactions which were considered to be related to SUPRAX
therapy, were reported for 5.9% (21/358) of patients. Clinically mild gastrointestinal side
effects occurred in 3.7% of all patients, moderate events occurred in 0.9% of all patients and no
adverse reactions were reported as severe. Individual event rates included diarrhea 1% and
loose or frequent stools 1%. Incidence rates for all other adverse reactions reported for adults in
these trials were less than 1%.
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Clinical Trial and Post-Market Adverse Drug Reactions:
The following adverse reactions have been observed during clinical trial studies and/or during
Blood and lymphatic system disorders:
immune hemolytic anemia (see WARNINGS, Hemolytic Anemia).
Diarrhea, stool changes, nausea, abdominal pain, dyspepsia, flatulence, vomiting.
General disorders and administration site conditions:
Drug fever, face oedema.
Jaundice (cholestatic and/or hepatocellular).
Immune system disorders:
Serum sickness-like reaction, anaphylactic reactions (urticaria and angioedema).
Infections and infestations:
Vaginitis, candidiasis, pseudomembranous colitis.
Elevations of alanine aminotransferase (ALT or SGPT), aspartate aminotransferase (AST or
SGOT), alkaline phosphatase and bilirubin.
Elevations in Blood Urea Nitrogen (BUN) or creatinine.
Prolongation in prothrombin time.
Nervous system disorders:
Headaches, dizziness, convulsions.
Renal and urinary disorders:
Acute renal failure including tubulointerstitial nephritis.
Reproductive system and breast disorders:
Respiratory, thoracic and mediastinal disorders:
Dyspnea, respiratory distress.
Skin and subcutaneous tissue disorders:
Skin rashes, pruritus, urticaria, toxic epidermal necrolysis (TEN), drug rash with eosinophilia
and systemic symptoms (DRESS), bullous skin reactions (erythema multiforme and Stevens-
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In addition to the adverse reactions listed above which have been observed in patients treated
with SUPRAX the following adverse reactions and altered laboratory tests have been reported
dehydrogenase (LDH) and pancytopenia.
SYMPTOMS AND TREATMENT OF OVERDOSAGE
Activated charcoal may be administered to aid in the removal of unabsorbed drug. General
supportive measures are recommended.
For management of a suspected drug overdose, contact your regional Poison Control Centre.
No specific antidote exists. General supportive measures are recommended.
SUPRAX (cefixime) is not removed in significant quantities from the circulation by
hemodialysis or peritoneal dialysis.
DOSAGE AND ADMINISTRATION
The recommended dose of SUPRAX (cefixime) is 400 mg once daily. When necessary, a dose
of 200 mg (one-half of a 400 mg tablet) given twice daily may be considered except for urinary
tract infections where once daily dosing must be used.
Children (≥ 6 months):
The recommended dose of SUPRAX is 8 mg/kg/day once daily. When necessary, a dose of
4 mg/kg given twice daily may be considered except for urinary tract infections where once
daily dosing must be used.
Table 1 - Pediatric dosage chart
Children weighing more than 50 kg or older than 12
years should be treated with the
recommended adult dose. Safety and effectiveness in infants aged less than six months have not
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Otitis media should be treated with the suspension. Clinical studies of otitis media were
conducted with the suspension only and the suspension results in higher peak blood levels than
the tablet when administered at the same dose. Therefore, the tablet should not be substituted
for the suspension in the treatment of otitis media (see PRECAUTIONS).
Reconstitution Directions for Oral Suspension:
Suspend with 33 mL water.
Tap the bottle several times to loosen powder contents prior to reconstitution.
Add a total volume of 33 mL of water. The total volume of water (33 mL)
should be split into TWO SEPARATE PORTIONS when added to the powder.
Mix well after each addition. Provides 20 mg/mL.
refrigeration without significant loss of potency. Keep container tightly closed. Shake well
before using. Discard unused portion after 14 days.
Duration of Therapy:
Duration of dosage in clinical trials was 10 to 14 days. The duration of treatment should be
guided by the patient's clinical and bacteriological response.
In the treatment of infections due to
, a therapeutic dose of SUPRAX
should be administered for at least 10 days.
SUPRAX may be administered in the presence of impaired renal function. Normal dose and
schedule may be employed in patients with creatinine clearances of 40 mL/min or greater.
Patients whose clearance is between 20 and 40 mL/min should be given 75% of the standard
daily dosage. Patients whose creatinine clearance is less than 20 mL/min should be given 50%
of the standard daily dosage.
Experience in children with renal impairment is very limited.
Neither hemodialysis, nor peritoneal dialysis remove significant amounts of SUPRAX
from the body.
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Cefixime is a white to light yellow powder. Slightly soluble in water,
soluble in methanol, sparingly soluble in ethanol, practically insoluble
in ethyl acetate.
The pH of a 0.5 g in 10 mL suspension is between 2.6 and 4.1
SUPRAX (cefixime) is available in scored 400 mg film coated tablets and in powder for oral
suspension, which can be reconstituted to provide 100 mg/5 mL.
pregelatinized starch, sodium lauryl sulfate and titanium dioxide.
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Powder for Oral Suspension:
The powder for oral suspension contains artificial strawberry flavour, sodium benzoate, sucrose
and xanthan gum.
SUPRAX (cefixime) tablets 400 mg are biconvex, oblong, white film coated tablets, with
rounded flattened corners, breaking scores on both sides and engraved EM 400 on one side. The
400 mg tablet can be split into two equal parts of 200 mg.
The 400 mg tablets are supplied as follows:
Blister packs of 7 tablets;
Blister packs of 10 tablets
The tablet contains cefixime as trihydrate, corresponding to 400 mg cefixime anhydrous.
Powder for Oral Suspension:
SUPRAX (cefixime) Powder for Oral Suspension is a white to cream-coloured-granulated
The powder for oral suspension is packaged in bottle containing cefixime as trihydrate,
corresponding to 1 g cefixime anhydrous. Once reconstituted as directed, the suspension
contains 100 mg/5 mL cefixime (50 mL of suspension).
The tablets and powder for oral suspension should be stored at controlled room temperature
15 - 30
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activity of SUPRAX (cefixime) against various gram-positive and gram-negative
organisms is presented in Table 2.
Table 2 - Activity of cefixime against clinical isolates of bacteria
(formerly Branhamella catarrhalis)
Table 2- Activity of cefixime against clinical isolates of bacteria (cont’d)
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Geometric mean MIC for 50% and 90% of the isolates.
Abbreviation: MIC, minimal inhibitory concentration.
The following organisms are resistant to cefixime:
strains of group D streptococci (including enterococci)
most strains of staphylococci (including methicillin-resistant strains)
most strains of
most strains of
Susceptibility Tests: Diffusion Techniques:
Quantitative methods that require measurement of zone diameters give an estimate of antibiotic
susceptibility to cefixime. Interpretation involves correlation of the diameters obtained in the
disk test with the minimum inhibitory concentration (MIC) for cefixime.
Reports from the laboratory giving results of the standard single-disk susceptibility test with a
5 µg cefixime disk should be interpreted according to the following criteria:
Table 3 - Recommended Susceptibility Ranges: Agar Disk Diffusion
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> 31 mm
All other organisms
< 15 mm
> 19 mm
Using GC Agar Base with a defined 1% supplement with cysteine.
A report of "Susceptible" indicates that the pathogen is likely to be inhibited by generally
concentrations of the antibiotic may well be achieved if high dosage is used or if the infection is
confined to tissues and fluids (e.g., urine) in which high antibiotic levels are attained. A report
of "Resistant" indicates that achievable concentrations of the antibiotic are unlikely to be
inhibitory and other therapy should be selected.
Standardized procedures require the use of laboratory control organisms. The 5 µg disk should
give the following zone diameter:
Table 4 - Control organisms: Agar Disk Diffusion
Zone Diameter (mm)
Using GC Agar Base with a defined 1% supplement with cysteine.
The class disk for cephalosporin susceptibility testing (the cephalothin disk) is not appropriate
because of spectrum differences with cefixime. The 5 µg cefixime disk should be used for all
testing of isolates.
Broth or agar dilution methods can be used to determine the minimum inhibitory concentration
(MIC) value for susceptibility of bacterial isolates to cefixime. The recommended susceptibility
breakpoints are as follows:
Table 5 - MIC Interpretive Standards (µg /mL)
All other organisms
As with standard diffusion methods, dilution procedures require the use of laboratory control
organisms. Standard cefixime powder should give the following MIC ranges in daily testing of
quality control organisms:
Table 6 - Control organisms: Dilution technique
Using GC Agar Base with a defined 1% supplement with cysteine.
0.004 - 0.03
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C-labelled cefixime was distributed (in order of descending amounts) to the kidneys,
lungs, liver, heart, spleen, and brain at 1 hour following a single oral dose of cefixime and to the
kidneys, urinary bladder, blood, liver, and lungs at 5 minutes after a single intravenous dose. In
dogs, tissue radioactivity was noted in bile, kidney, liver, lung, testes, heart, and brain after
single or multiple intravenous dosing with
After multiple oral dosing, accumulation of cefixime was negligible in the serum and urine of
adult rats and dogs. The doses used in these studies were 100 and 1000 mg/kg/day administered
for 1 month to rats and up to 400 mg/kg/day (100, 200 and 400 mg/kg/day) for 53 weeks to
dogs. In addition, there was no evidence of drug accumulation in serum or urine after two
weeks of intravenous dosing (320 and 1000 mg/kg/day) in adult dogs.
In animal studies, it was noted that cefixime is excreted in the bile in excess of 10% of the
SUPRAX (cefixime), given orally, is about 40% to 50% absorbed.
In adults a single 200 mg tablet of SUPRAX produces an average peak serum concentration of
approximately 2 µg/mL (range 1 to 4 µg/mL); a single 400 mg tablet produces an average
concentration of approximately 3.5 µg/mL (range 1.3 to 7.7 µg/mL). The oral suspension, in
adults, following 200 mg and 400 mg doses produces average concentrations of 2.8 µg/mL
(range 1 to 4.5 µg/mL) and 4.4 µg/mL (range 1.9 to 7.7 µg/mL), respectively. The area under
the time versus concentration curve is greater by approximately 26.4% with the oral suspension
than with the tablet after doses of 400 mg. This increased absorption should be taken into
consideration if the oral suspension is to be substituted for the tablet.
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 suspension of SUPRAX. Peak serum
concentrations occur between 2 and 5 hours following a single administration of 200 mg
suspension. See Tables 7 and 8.
Table 7 - Serum Levels of Cefixime in Adults after Administration of Tablets (µg/mL)
* ½ x 200 mg tablets
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Table 8 - Serum Levels of Cefixime in Adults after Administration of Oral Suspension
The serum half-life of cefixime in healthy subjects is independent of dosage form and averaged
3 to 4 hours but may range up to 9 hours in some normal volunteers.
There is no evidence of metabolism of cefixime
Cefixime is excreted by renal and biliary mechanisms.
The urinary recoveries of orally administered 200 mg and 400 mg doses of cefixime in
12 healthy men are presented in Table 9. Over a 24 hour period, approximately 20% and 16%
of a 200 mg and 400 mg dose of cefixime, respectively
was excreted in the urine. An additional
10% or more was recovered from bile.
Table 9 - Mean urinary excretion of cefixime after 200 and 400 mg dose in 12 healthy men
24-h Urinary Recovery of
Cefixime (% of
Maximum Concentration of
Cefixime in Urine (µg/mL)
Distribution and Accumulation:
Cefixime appears to be widely distributed; however, adequate tissue concentration data relating
to tablet and suspension are not available.
Serum protein binding is concentration independent with a bound fraction of approximately
65%. Multiple dose studies conducted with 200 mg or 400 mg tablets in normal volunteers
showed there was little or no accumulation of drug in serum or urine after dosing for 14 days.
Adequate data on cerebrospinal fluid (CSF) levels of cefixime are not available.
Factors Affecting Pharmacokinetics:
In patients 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.
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The dose proportionality of SUPRAX suspension was evaluated in 42 pediatric patients who
were 6 months of age or older. With doses of 4, 6, and 8 mg/kg, serum concentrations at a
dose-proportional manner. In particular, the 8 mg/kg dose did not produce twice the serum level
observed with the 4 mg/kg dose. The mean serum concentrations following the 4 mg/kg dose
2.2 to 2.6 µg/mL.
2.5 to 4.8 µg/mL. (Table 10).
Table 10 - Mean pharmacokinetic values in 42 pediatric patients following administration
of a single dose of SUPRAX suspension
Mean Serum Concentration (µg/mL) at 3.5 h after administration
at the following age ranges (yr)
0.5 to 2
> 2 to < 6
AGE (ELDERLY PATIENTS)
comparative pharmacokinetic study in 12 healthy men over 64 years of age and in 12 men 18 to
35 years of age used a 400 mg dose of SUPRAX administered once daily for 5 days. Blood and
concentration-time profiles of cefixime. C
and AUC were greater in the elderly on the first
(4.77 µg/mL and 41.0 µg.h/mL) and fifth (5.45 µg/mL and 49.5 µg.h/mL) days of dosing when
compared with corresponding values in the young subjects on day 1 (3.64 µg/mL and 28.6
µg.h/mL) and day 5 (4.53 µg/mL and 34.9 µg.h/mL). These differences were statistically
significant, but their magnitude was too small to be of clinical significance. T
values were not
different between the two groups.
Table 11 - Mean pharmacokinetic parameters for cefixime on day 5 in young and elderly
subjects given 400 mg daily for 5 days
peak serum concentration;
time to reach maximum serum concentration;
area under the serum concentration versus time curve;
urinary recovery of cefixime expressed as a fraction of the administered
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FOOD (EFFECT OF FOOD ON ABSORPTION)
There was no clinically significant effect of food on the absorption of cefixime. SUPRAX was
administered as a single 400 mg dose with and without food in a crossover study in 20 healthy
values were 4.22 and 4.24 µg/mL in the fed and fasted states, respectively. Food
slowed the time to reach C
by about 1 hour (3.8 hours versus 4.8 hours). This effect is of no
clinical significance and probably reflects a small delay in gastric emptying due to the presence
of food. Urinary recovery was unaffected by the presence of food: 18.4% (fed) and 17.7%
(fasted) of the doses were recovered in 24 hours.
A four-way crossover study in 12 healthy men evaluated the pharmacokinetics of SUPRAX
when administered with, before, and after aluminum/magnesium containing antacids. The
administration of antacid did not significantly alter the pharmacokinetic parameters of cefixime.
In a protein-binding interaction study using human serum, there was no statistically significant
change in the fraction of unbound cefixime with the addition of acetaminophen, heparin,
concentrations. With salicylic acid there was a significant, approximately two fold increase
from 35% to 66% in the unbound fraction. When the interaction was studied in dogs, it was
confirmed that ASA-related products (i.e. salicylic acid) caused an increase in the unbound
fraction of cefixime, which ultimately resulted in an increase in the volume of distribution and
the clearance of the drug. However, since the volume of distribution and clearance increased to
the same extent, there was no net effect on the elimination half-life of cefixime.
administration of ASA (650 mg) with SUPRAX 400 mg tablet had no effect on protein binding,
half-life, or renal clearance of SUPRAX. ASA did, however, appear to decrease absorption of
SUPRAX as evidenced by a 26% reduction in C
and 19% reduction in AUC values.
values were > 10 g/kg for mice (5-10/sex/group), rats (5-10/sex/group) and rabbits
(5/sex/group). In 13 dogs, lethal dose determination was limited by emesis occurring at a single
oral dose of 0.32 g/kg or higher; there was no mortality among these dogs. After intravenous,
intraperitoneal, or subcutaneous injection, LD
values were greater than 3, 7, or 10 g/kg,
(5-10/sex/group). The tolerated intravenous dose in rabbits (3M/group) was 0.32 g/kg. In one
male dog, a total intravenous infusion dose of 5.5 g/kg was not associated with lethality. Signs
of toxicity in this dog were decreased blood pressure and respiratory
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Following oral dosing in young animals (10/sex/group), LD
values were 3 g/kg in 4-day old
mice, 7 g/kg in 4-day old rats, and > 10 g/kg in 20- and 34-day old rats. Oral doses of 3.2 g/kg
in 2 week old dogs (2M/1F) and 8-week old dogs (1M/2F) were not lethal, did not affect body
weight and were not associated with gross postmortem or histopathologic changes. Young dogs
were able to tolerate higher doses of cefixime without emesis than were older dogs due to the
incomplete maturation of the emetic centre in young dogs.
Multiple-dose oral toxicity studies were conducted for periods of 4 weeks to 1 year in rats and
dogs. Studies in rats utilized doses up to 3200 mg/kg administered once daily (15-20/sex/group)
or up to 500 mg/kg given twice daily (12/sex/group). Studies in dogs (4-5/sex/group) employed
doses up to 200 mg/kg administered twice daily. In addition, studies of 2 weeks duration were
ascending intravenous doses of 80 to 2500 mg/kg was conducted to assess the nephrotoxic
potential of cefixime. The results of these studies follow.
Soft feces, enlargement of the cecum and increased cecal weights were seen across all rat
studies. These are common findings in rats following treatment with antibiotics. Decreased
urobilinogen was also observed and is considered to be related to changes in the intestinal flora
resulting in reduced production of urobilinogen from bilirubin. The chronic nephropathy of
(1000 mg/kg/day) for 53 weeks. In dog studies, emesis, which was related to treatment, was
noted in some animals receiving cefixime orally; there were no other findings related to
cefixime following oral administration. In an 8-day, ascending intravenous dose study in dogs,
cefixime was not lethal at a cumulative dose of 7295 mg/kg. In this study, emesis and
nephrotoxicity (i.e. elevated blood urea nitrogen and serum creatinine; protein, glucose, and
ketones in the urine; tubular degeneration and necrosis of kidneys) were seen.
The multiple-dose oral toxicity of cefixime was also investigated in young rats (15/sex/group)
and dogs (3/sex/group) at doses up to 3200 mg/kg and 400 mg/kg, respectively, administered
once daily for 5 weeks. In addition, the oral toxicity of cefixime was investigated in young
dogs (7/sex/group) at single daily doses of up to 180 mg/kg or 60 mg/kg administered twice
daily for 5 weeks. The rat study showed cecal effects similar to those seen in the studies with
adult animals. Soft feces were noted in all dose groups. Results of the dog studies showed no
drug-related toxicity at doses up to 400 mg/kg/day in adult animals and up to 180 mg/kg/day in
Cefixime did not exhibit mutagenic or clastogenic potential in a battery of genetic toxicology
tests. Drug concentrations of 0.001 to 1.0 µg/plate were used in microbial mutagencity tests,
3200 µg/mL in a mammalian point mutation assay, 1 to 2500 µg/mL in an unscheduled DNA
synthesis test, and 6000 to 10 000 µg/mL in an
cytogenetics test. Two investigational
product (IP) doses of 100 to 3200 mg/kg were given to mice in an
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Fertility and general reproductive performance, teratology, and perinatal/postnatal studies were
conducted in animals. In the fertility and reproductive performance study in rats, no difference
between control and drug-treated animals was detected in mating behavior, pregnancy rate,
litter parameters (determined at sacrifice on day 13 of pregnancy), length of pregnancy or
delivery at oral doses up to 1000 mg/kg/day administered to males (for 68 days prior to pairing
and during the cohabitation period) and females (for 14 days before pairing to weaning). The
results of teratology studies in mice and rats show that cefixime, at doses up to 3200 mg/kg/day
development or reproductive capacity of the F
generation or fetal development of the F
generation. In studies designed to assess the teratogenic potential of cefixime in rabbits,
cefixime at doses of 3.2, 10 or 32 mg/kg given daily on days 6 through 18 of pregnancy was not
associated with the administration of antibiotics in this species were elicited at > 10 mg/kg. The
results of studies in rats designed to assess the effect of cefixime administered to dams during
the perinatal and postnatal periods, at oral doses up to 3200 mg/kg/day, show that cefixime does
not affect the duration of pregnancy, process of parturition, or development and viability of
offspring. In addition, reproductive capacity of the F
generation and development of their
) were not affected.
Results of tests in mice, rats, rabbits, and guinea pigs show that cefixime alone has no antigenic
potential when administered orally and only weak antigenic potential when administered
parenterally with adjuvants or carrier proteins. There was no cross-reactivity detected between
cefixime and several other cephalosporin antibiotics.
Lifetime studies in animals to evaluate carcinogenic potential have not been conducted.
Page 22 of 30
Asmar, B., Barone, J., Clark, P., Simpkins, D. A comparative trial of cefixime and
International Congress of Chemotherapy, July l987. Advances in Experimental and Clinical
Chemotherapy l988; l: 44-48.
Barry, A.L., Jones, R.N. Cefixime: spectrum of antibacterial activity against l6,0l6 clinical
isolates. Pediatric Infectious Disease l987; 6: 954-957.
infections. International Journal of Clinical Pharmacology l989; 27: 30-33.
Bergeron, M.G., Lavoie, G.Y., Boucher, F.D.W. Comparative bactericidal activity of
cefixime, carumonan, enoxacin and roxithromycin with those of other antibiotics against
Antimicrobial Chemotherapy l987; 20: 663-669.
Bialer, M., Tonelli, A.P., Kantrowitz, J.D., Yacobi, A. Serum protein binding of a new oral
cephalosporin, CL 284,635, in various species. Drug Metabolism and Disposition l986;
Bialer, M., Wu, W.H., Faulkner, R.D., Silbert, B.M., Yacobi, A.
interaction studies involving cefixime. Biopharmaceutics and Drug Disposition l988; 9:
Bowie, W.R., Shaw, C.E., Chan, D.G.W., Boyd, J., Black, W.A.
difloxacin hydrochloride (A566l9), A56620 and cefixime (CL 284,635; FK027) against
selected genital pathogens. Antimicrobial Agents and Chemotherapy l986; 30: 590-593.
Brittain, D.C., Scully, B.E., Hirose, T., Neu, H.C. The pharmacokinetic and bactericidal
Carenfelt, C. Melen, I., Odkvist, L., Olsson, O., Prellner, K., Rudblad, S., Savolainen, S.,
Skaftason, S., Sorri, M., Synnerstad, B. Treatment of Sinus Empyema in Adults. Acta
Otolaryngol (StockH) 1990; 110: 128-135.
10. Centers of Disease Control. Plasmid-mediated antimicrobial resistance in
United States; 1988 and 1989. MMWR 1990; 39:284-293.
11. Counts, G.W., Baugher, L.K., Ulness, B.K., Hamilton, D.J. Comparative
the new oral cephalosporin cefixime. European Journal of Clinical Microbiology and
Infectious Disease l988; 7: 428-431.
Page 23 of 30
12. Cullman, W., Dick, W., Opferkuch, W. Antibacterial activity of cefixime with regard to
Chemotherapy l985; l: 9-14.
13. Dornbusch, K. Kronvall, G., Goransson, E. Comparative
antibacterial activity and
Chemotherapy, July l987. Advances in Experimental and Clinical Chemotherapy l988;
Dorow, P. Safety and efficacy of cefixime in comparison to cefaclor in respiratory tract
infections. Workshop, l5th International Congress of Chemotherapy, July l987. Advances
in Experimental and Clinical Chemotherapy l988; l: 33-37.
15. Easmon, C.S.F., Ison, C.A.
: a versatile pathogen. J. Clin Pathol
Faulkner, R.D., Bohaychuk, W., Desjardins, R.E., Look, Z.M., Haynes, J.D., Weiss, A.I.,
Silber, B.M. Pharmacokinetics of cefixime after once-a-day and twice-a-day dosing to
steady state. Journal of Clinical Pharmacology l987; 27: 807-812.
Faulkner, R.D., Bohaychuk, W., Haynes, J.D., Desjardins, R.E., Yacobi, A., Silber, B.M.
Pharmacokinetics of cefixime in the fasted and fed state. European Journal of Clinical
Pharmacology l988; 34: 525-528.
Faulkner, R.D., Bohaychuk, W., Lane, R.A., Haynes, J.D., Desjardins, R.E., Yacobi, A.,
Antimicrobial Chemotherapy l988; 21: 787-794.
Faulkner, R.D., Fernandez, P., Lawrence, G., Sia, L.L., Falkowski, A.J., Weiss, A.I.,
Yacobi, A., Silber, B.M. Absolute bioavailability of cefixime in man. The Journal of
Clinical Pharmacology l988; 28: 700-706.
Faulkner, R.D., Yacobi, L.A., Barone J.S., Kaplan S.A., Silber, B.M. Pharmacokinetic
profile of cefixime in man. Pediatric Infectious Disease l987; 6: 963-970.
21. Finegold, S.M., Ingram-Drake, L., Gee, R., Reinhardt, J., Edelstein, M.A.C., MacDonald,
K., Wexler, H. Bowel flora changes in humans receiving cefixime (CL 284,635) or
cefaclor. Antimicrobial Agents and Chemotherapy l987; 3l: 443-446.
22. Fuchs, P.C., Jones, R.N., Barry, A.L., Thornsberry, C., Ayers, L.W., Gavan, L., Gerlach,
evaluation of cefixime (FK 027, FR l7027, CL 284,635): Spectrum against
recent clinical isolates, comparative antimicrobial activity, beta-lactamase stability and
preliminary susceptibility testing criteria. Diagnostic Microbiology and Infectious Diseases
l986; 5: l5l-l62.
Page 24 of 30
Experimental and Clinical Chemotherapy l988; l: 2l-23.
24. Hegran, D.W., Lefebvre, K., Willetts, V., Bowie, W.R. Single-dose oral cefixime versus
Antimicrob Agents Chemother 1990; 34:355-357.
Department of Medicine, University of Washington, Harborview Medical Center, Seattle,
Washington. Letter of January 7, 1985 addressed to Al Dornbush with data.
26. Howie, V.M., Owen, M.J. Bacteriologic and clinical efficacy of cefixime compared with
amoxicillin in acute otitis media. Pediatric Infectious Disease l987; 6: 989-99l.
comparative study of the safety and efficacy of cefixime versus amoxicillin in the treatment
of acute urinary tract infections in adult patients. American Journal of Medicine l988; 85
(Suppl. 3A): 27-25.
28. Janda, Wm., Department of Medical Laboratory Sciences, The University of Illinois at
Chicago, Chicago, Ill. Letter of September 23, 1988 addressed to Lynne Fredericks, with
29. Jones, R.N., Department of Pathology, The University of Iowa Hospitals and Clinics, Iowa
City, Iowa. Letter of October 4, 1990 addressed to Lynne Fredericks, with data.
30. Kamidono, S., Arakawa, S., Kataoka, N., Hikosaka, K., Mita, T., Ishigami, J.
clinical evaluation of FK027 for the treatment of urinary tract infections. l4th International
Congress of Chemotherapy, Kyoto, 23-28 June, l985. Japan Convention Services, Inc.,
31. Kamimura, T., Kojo, H., Matsumoto, Y., Mine, Y., Goto S., Kuwahara, S.
antibacterial properties of FK027, a new orally active cephem antibiotic. Antimicrobial
Agents and Chemotherapy l984; 25: 98-l04.
32. Kawamura, S., Fujimaki, Y., Sugita, R., Watanabe, I., Nakamura, M., Asai, S. Tissue
International Congress of Chemotherapy, July l987. Advances in Experimental Clinical
Chemotherapy l988; l: 24-32.
33. Kenna, M., Bluestone, C.D., Fall, P., Stephenson, J., Kurs-Lasky, M., Wucher, F.P.,
Blatter, M.M., Reisinger, K.S. Cefixime vs cefactor in the treatment of acute otitis media in
infants and children. Pediatric Infectious Disease l987; 6: 992-996.
Page 25 of 30
34. Kiani, R., Johnson, D., Nelson, B. Clinical results of cefixime 200mg bid in the treatment
of patients with acute respiratory tract infections. Workshop, l5th International Congress of
Chemotherapy, July l987. Advances in Experimental and Clinical Chemotherapy l988; l:
amoxicillin in the treatment of respiratory tract infections. American Journal of Medicine
l988; 85: 6-l3.
36. Krepel, C.J., Schopf, L.R., Gordon, R.C., Edmiston, C.E. Comparative
Current Therapeutic Research l988; 43: 296-302.
37. Kuhlwein, A., Hies, B.A. Efficacy and safety of a single 400 mg oral dose of cefixime in
the treatment of uncomplicated gonorrhea. Eur J Clin Microbial Infect Dis 1989; 8:261-
38. Kumar, A., Kelly, K.J.
activity of cefixime (CL 284635) and other antimicrobial
isolates from pediatric patients. Chemotherapy l988, 34: 30-35,
amoxicillin for treatment of acute otitis media with effusion. Pediatric Infectious Disease
l987; 6: 997-l00l.
40. Nakashima, M., Uematsu, T., Takiguchi, Y., Kanamaru, M. Phase l study of cefixime, a
new oral cephalosporin. Journal of Clinical Pharmacology l987; 27: 425-43l.
cephalosporin, cefixime. Pediatric Infectious Disease l987; 6: 958-962.
42. Neu, H.C., Chin, N.X., Labthavikul, P. Comparative
activity and beta-lactamase
Chemotherapy l984; 26: l74-l80.
43. Powell, M., Kentsia-Carouzou, C., Voutsinas, D., Williams, J.D. A comparison of the
activity of ampicillin and cefixime against 2458 clinical isolates of
. Workshop, l5th International Congress of Chemotherapy, July, l987. Advances
in Experimental and Clinical Chemotherapy l988; l: l5-l7.
multicentre trial of cefixime for treatment of bacterial pharyngitis, cystitis, pneumonia in
pediatric patients. Pediatric Infectious Disease l987; 6: l002-l006.
Page 26 of 30
45. Silber, D.M., Bohaychuk, W., Stout, M., Haynes, J.D., Schneider, J., Woodward, D.L.,
Look, Z.M., Weiss, A.I., Yacobi, A., Faulkner, R.D. Pharmacokinetics of cefixime in young
and elderly volunteers. Workshop, l5th International Congress of Chemotherapy, July l987.
Advances in Experimental and Clinical Chemotherapy l988; l: l8-20.
46. Smith, S.M., Eng, R.H.K. Activity of Cefixime (FK027) for resistant gram-negative bacilli.
Chemotherapy l988; 34: 455-46l.
pharmacokinetics and tissue penetration. Journal of Antimicrobial Chemotherapy l989; 23:
48. Tally, F.P., Desjardins, R.E., McCarthy, E.F., Cartwright, K. Safety profile of cefixime.
Pediatric Infectious Disease l987; 6: 976-980.
Page 27 of 30
PATIENT MEDICATION INFORMATION
Cefixime tablets, Mfr. Std., 400 mg
Cefixime for oral suspension, Mfr. Std., 100 mg/5 mL
Read this carefully before you start taking
and each time you get a refill. This leaflet is a summary and
will not tell you everything about this drug. Talk to your healthcare professional about your medical condition and
treatment and ask if there is any new information about
What is SUPRAX used for?
Antibacterial drugs like SUPRAX treat only bacterial infections. They do not treat viral infections such as the
SUPRAX is used to treat infections caused by bacteria. These include infections of the:
Upper respiratory tract
Sinuses that surround the nasal cavity
Lower respiratory tract
It is also used to treat
How does SUPRAX work?
SUPRAX is an antibiotic. It is used to treat certain types of bacterial infections. SUPRAX is from a class of
antibiotics called cephalosporins. It kills bacteria by interfering with their cell wall.
What are the ingredients in SUPRAX?
Tablets: Calcium phosphate dibasic dihydrate, hydroxypropyl methylcellulose, light mineral oil, magnesium
stearate, microcrystalline cellulose, pregelatinized starch, sodium lauryl sulfate and titanium dioxide.
Powder for Oral Suspension: artificial strawberry flavour, sodium benzoate, sucrose and xanthan gum.
SUPRAX comes in the following dosage forms:
Powder for Oral Suspension:
100 mg / 5 mL when reconstituted
Do not use SUPRAX if:
You are allergic to the cephalosporin or any of the ingredients in SUPRAX.
You are allergic to penicillin.
To help avoid side effects and ensure proper use, talk to your healthcare professional before you take
SUPRAX. Talk about any health conditions or problems you may have, including if you:
have or have had gastrointestinal disease (diseases of the stomach or gut)
have had a condition called hemolytic anemia (loss of red blood cells) after taking an antibiotic
have kidney problems
have had an allergic reaction in the past, including to a medicine
are pregnant or planning to become pregnant
are breastfeeding or planning to breastfeed
Page 28 of 30
Tell your healthcare professional
about all the medicines you take, including any drugs, vitamins, minerals,
natural supplements or alternative medicines.
The following may interact with SUPRAX:
carbamazepine, a medicine used to treat seizures
medicines used to thin your blood and prevent clots such as warfarin
How to take SUPRAX:
Swallow SUPRAX tablets with water.
The SUPRAX oral suspension should be taken by mouth.
Take SUPRAX exactly how your healthcare professional has told you to.
Take SUPRAX for the full number of days that your healthcare professional has told you to.
Although you may feel better early in treatment, SUPRAX should be used exactly as directed.
Misuse or overuse of SUPRAX could lead to the growth of bacteria that will not be killed by SUPRAX
(resistance). This is means that SUPRAX may not work for you in the future.
Do not share your medicine.
The pharmacist will usually provide you the reconstituted suspension. If product was not previously reconstituted
by the pharmacist and provided in powder form, reconstitute as follows for 50 mL of suspension (provides 20
Tap the bottle several times to loosen powder contents
Add a total volume of 33 mL of water. The total volume of water (33 mL) should be split into TWO
SEPARATE PORTIONS when added to the powder.
Mix well after each addition
Your healthcare professional will decide how much SUPRAX you should take and for how long you
should take it.
Adults: 400 mg tablet once a day
Children (6 months or older): 8 mg/kg/day once a day or 4 mg/kg/day twice a day
Children weighing more than 50 kg or those older than 12 years should be treated with the recommended
If you think you have taken too much SUPRAX, contact your healthcare professional, hospital emergency
department or regional poison control centre immediately, even if there are no symptoms.
If you miss a dose of SUPRAX by a few hours, take it as soon as you remember.
However, if it is nearly time for the next dose, skip the missed dose.
Do not take a double dose to make up for a forgotten dose.
What are possible side effects from using SUPRAX?
These are not all the possible side effects you may feel when taking SUPRAX. If you experience any side effects
not listed here, contact your healthcare professional.
Side effects may include:
Page 29 of 30
Serious side effects and what to do about them
Symptom / effect
Talk to your healthcare
Stop taking drug
Only if severe
In all cases
Kidney problems, including kidney failure:
abdominal or back pain, changes in your urine,
confusion, fatigue, irregular heartbeat, nausea,
shortness of breath, swelling, weakness.
Severe allergic reaction:
hives, itching, skin rash, swelling of your tongue or
Severe skin reactions such as Stevens-Johnson
syndrome, toxic epidermal necrolysis and erythema
multiforma: blistering, hives, itching blistering,
inflamed, peeling, red and dying skin and severe
Clostridium difficile colitis (inflamed bowel), fever,
severe diarrhea (bloody or watery) and stomach
pain or tenderness.
Blood problems such as: decreased blood platelets
(thrombocytopenia) leads to increased bleeding ,
decreased red blood cells (hemolytic anemia) leads
to fatigue, shortness of breath and decreased white
blood cells ( neutropenia, leucopenia,
agranulocytosis) leads to increased infection
Liver problems with symptoms such as: abdominal
pain, dark urine, fatigue, loss of appetite, nausea,
vomiting, yellowing of the skin or eyes (jaundice).
Breathing problems including asthma: difficulty
breathing, shortness of breath, wheezing.
Severe Cutaneous Adverse Reactions (SCAR)
(severe skin reactions that may also affect other
Skin peeling, scaling, or blistering (with or
without pus) which may also affect your eyes,
mouth, nose or genitals, itching, severe rash,
bumps under the skin, skin pain, skin color
changes (redness, yellowing, purplish)
Swelling and redness of eyes or face
Flu-like feeling, fever, chills, body aches,
swollen glands, cough
Shortness of breath, chest pain or discomfort
If you have a troublesome symptom or side effect that is not listed here or becomes bad enough to interfere with
your daily activities, talk to your healthcare professional.
Page 30 of 30
Reporting Side Effects
You can report any suspected side effects associated with the use of health products to Health Canada by:
Visiting the Web page Adverse reaction reporting
for more for
information on how to report online, by mail or by fax; or
Call toll-free at 1-866-234-2345.
NOTE: Contact your health professional if you need information about how to manage your side effects. The
Canada Vigilance Program does not provide medical advice.
Store tablets or dry powder at room temperature between15°C and 30°C.
Store reconstituted oral suspension at room temperate between 15°C and 30°C; or refrigerate for up to 14 days.
Discard unused portion after 14 days.
Keep out of reach and sight of children
If you want more information about SUPRAX:
Talk to your healthcare professional
Find the full product monograph that is prepared for healthcare professionals and includes this Patient
Medication Information by visiting the Health Canada website (http://hc-sc.gc.ca/index-eng.php ); or
by calling the manufacturer at 1-800-387-9342.
This leaflet was prepared by Odan Laboratories Ltd., Montreal, Canada, H9R 2Y6
Date of Revision:
March 17, 2020