SUPRAX TABLET

Canada - English - Health Canada

Buy It Now

Active ingredient:
CEFIXIME
Available from:
ODAN LABORATORIES LTD
ATC code:
J01DD08
INN (International Name):
CEFIXIME
Dosage:
400MG
Pharmaceutical form:
TABLET
Composition:
CEFIXIME 400MG
Administration route:
ORAL
Units in package:
7/10
Prescription type:
Prescription
Therapeutic area:
THIRD GENERATION CEPHALOSPORINS
Product summary:
Active ingredient group (AIG) number: 0122105003; AHFS: 08:12.06.12
Authorization status:
APPROVED
Authorization number:
00868981
Authorization date:
2006-05-04

Documents

PRODUCT MONOGRAPH

Pr

SUPRAX

®

Cefixime tablets, Mfr. Std., 400 mg

Cefixime for oral suspension, Mfr. Std., 100 mg/5 mL

Antibiotic

ODAN LABORATORIES LTD.

325 Stillview Ave.,

Pointe-Claire, Québec

H9R 2Y6

Date of Revision:

March 17, 2020

Submission Control No. : 233967

www.odanlab.com

Page 2 of 30

PRODUCT MONOGRAPH

Pr

SUPRAX

®

Cefixime tablets, Mfr. Std., 400 mg

Cefixime for oral suspension, Mfr. Std., 100 mg/5 mL

THERAPEUTIC CLASSIFICATION

Antibiotic

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

in vivo

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

S. pyogenes

Middle Ear:

Otitis media caused by

S. pneumoniae, H. influenzae

(beta-lactamase positive and negative

strains),

M. catarrhalis

(former

B. catarrhalis

) (beta-lactamase positive and negative strains)

S. pyogenes

Paranasal sinuses

Sinusitis caused by

S. pneumoniae, H. influenzae

(beta-lactamase positive and negative strains),

M. catarrhalis

(former

B. catarrhalis

) (beta-lactamase positive and negative strains).

Lower Respiratory Tract:

Acute

bronchitis

caused

S. pneumoniae,

M.

catarrhalis

(former

B.

catarrhalis

(beta-lactamase positive and negative strains) and

H. influenzae

(beta-lactamase positive and

negative strains).

Page 3 of 30

Urinary Tract:

Acute uncomplicated cystitis and urethritis caused by

E. coli, P. mirabilis

, and

Klebsiella

species.

Uncomplicated Gonorrhea:

Uncomplicated

gonorrhea (cervical/urethral and rectal) caused by

Neisseria gonorrhoeae

including

penicillinase

(beta-lactamase-positive)

nonpenicillinase

(beta-lactamase-

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.

reduce

development

drug-resistant

bacteria

maintain

effectiveness

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.

CONTRAINDICATIONS

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.

WARNINGS

Hypersensitivity:

IN

PENICILLIN-SENSITIVE

PATIENTS,

SUPRAX

(CEFIXIME)

SHOULD

BE

ADMINISTERED

CAUTIOUSLY.

PATIENTS

MAY

BE

SENSITIVE

TO

PENICILLINS

AND

NOT

TO

CEPHALOSPORINS

SUCH

AS

SUPRAX

OR

BE

SENSITIVE TO BOTH. MEDICAL LITERATURE INDICATES THAT PATIENTS

SENSITIVE

TO

CEPHALOSPORINS

ARE

VERY

LIKELY

TO

BE

PENICILLIN

SENSITIVE.

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

Page 4 of 30

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:

Clostridium

difficile

-associated

disease

(CDAD)

been

reported

with

many

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

overgrowth of

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

directed against

Clostridium difficile

. 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

Clostridium difficile

. Surgical evaluation

should be instituted as clinically indicated, as surgical intervention may be required in certain

severe cases

Hemolytic Anemia:

SUPRAX

SHOULD

NOT

BE

USED

IN

PATIENTS

WITH

A

HISTORY

OF

CEPHALOSPORIN-ASSOCIATED

HEMOLYTIC

ANEMIA

SINCE

THE

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:

with

other

cephalosporins,

SUPRAX

cause

acute

renal

failure

including

tubulointerstitial nephritis. When acute renal failure occurs, SUPRAX should be discontinued

and appropriate therapy and/or measures should be taken.

Page 5 of 30

Neurologic:

Several

cephalosporins,

including

cefixime,

have

been

implicated

triggering

seizures,

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

given

clinically

indicated

(see

DOSAGE

ADMINISTRATION

OVERDOSAGE).

Susceptibility/Resistance:

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.

PRECAUTIONS

General:

If an allergic reaction to SUPRAX (cefixime) occurs, the drug should be discontinued, and, if

necessary,

patient

should

treated

with

appropriate

agents,

e.g.,

pressor

amines,

antihistamines, or corticosteroids.

The possibility of the emergence of resistant organisms, which might result in overgrowth,

should

kept

mind,

particularly

during

prolonged

treatment.

such

use,

careful

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

Staphylococcus aureus

as this strain of staphylococcus is resistant

to cefixime.

Renal Impairment:

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

renal

impairment (i.e., creatinine clearance of < 40 mL/min) (see PHARMACOLOGY and DOSAGE

AND ADMINISTRATION).

Page 6 of 30

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

clinical

trial

experience

with

suspension

only

available

(see

DOSAGE

ADMINISTRATION).

Drug/Drug Interactions:

SUPRAX

should

administered

with

caution

patients

receiving

coumarin-type

anticoagulants

such

warfarin

potassium.

Since

SUPRAX

enhance

effects

anticoagulants,

prolonged

prothrombin

time

with

without

bleeding

occur

(see

ADVERSE REACTIONS and PHARMACOLOGY).

Drug/Laboratory 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 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

drug.

Usage in Pregnancy:

The safety of SUPRAX in the treatment of infection in pregnant women has not been

established.

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.

Page 7 of 30

Nursing Mothers:

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

woman.

Usage in Children:

Safety and effectiveness of SUPRAX in children less than six months old have not been

established.

ADVERSE REACTIONS

Clinical Trials:

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

commonly

seen

adverse

reactions

clinical

trials

tablet

formulation

were

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

children

treated,

incidence

adverse

reactions

pediatric

patients

receiving

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

discontinued.

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%.

Page 8 of 30

Clinical Trial and Post-Market Adverse Drug Reactions:

The following adverse reactions have been observed during clinical trial studies and/or during

marketed use.

Blood and lymphatic system disorders:

Thrombocytopenia,

thrombocytosis,

leucopenia,

eosinophilia,

neutropenia,

agranulocytosis,

immune hemolytic anemia (see WARNINGS, Hemolytic Anemia).

Gastrointestinal disorders:

Diarrhea, stool changes, nausea, abdominal pain, dyspepsia, flatulence, vomiting.

General disorders and administration site conditions:

Drug fever, face oedema.

Hepatobiliary disorders:

Jaundice (cholestatic and/or hepatocellular).

Immune system disorders:

Serum sickness-like reaction, anaphylactic reactions (urticaria and angioedema).

Infections and infestations:

Vaginitis, candidiasis, pseudomembranous colitis.

Investigations:

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:

Genital pruritus.

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-

Johnson syndrome).

Page 9 of 30

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

cephalosporin-class

antibiotics:

superinfection,

renal

dysfunction,

toxic

nephropathy,

hepatic

dysfunction

including

cholestasis,

aplastic

anemia,

hemorrhage,

elevated

lactate

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

Adults:

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.

treatment

uncomplicated

gonococcal

infections,

single

oral

dose

400 mg

recommended.

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

WEIGHT

(Kg)

DOSE/DAY

(mg)

DOSE/DAY

(mL)

12.5

10.0

14.0

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

been established.

Page 10 of 30

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:

Bottle:

SIZE

50 mL

RECONSTITUTION DIRECTIONS

Suspend with 33 mL water.

Method:

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.

After

mixing,

suspension

kept

days

room

temperature

under

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

Streptococcus pyogenes

, a therapeutic dose of SUPRAX

should be administered for at least 10 days.

Renal Impairment:

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.

NOTE:

Neither hemodialysis, nor peritoneal dialysis remove significant amounts of SUPRAX

from the body.

Page 11 of 30

PHARMACEUTICAL INFORMATION

Chemistry:

Trade Name:

SUPRAX

Proper Name:

Cefixime

Chemical Name:

(6R, 7R)-7-[[(Z)-2-(2-aminothiazol-4-yl)-2-

[(carboxymethoxy)imino]acetyl]amino]-3-ethenyl-8-oxo-

5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

trihydrate.

Structural Formula:

Molecular Formula:

Molecular Weight:

507.50

Description:

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

Composition:

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.

Inactive Ingredients:

Tablets:

tablets

contain:

Calcium

phosphate

dibasic

dihydrate,

hydroxypropyl

methylcellulose,

light

mineral

oil,

magnesium

stearate,

microcrystalline

cellulose,

pregelatinized starch, sodium lauryl sulfate and titanium dioxide.

Page 12 of 30

Powder for Oral Suspension:

The powder for oral suspension contains artificial strawberry flavour, sodium benzoate, sucrose

and xanthan gum.

AVAILABILITY

Tablets:

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

powder.

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).

Storage:

The tablets and powder for oral suspension should be stored at controlled room temperature

15 - 30

Page 13 of 30

MICROBIOLOGY

In vitro

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

Organism

Number of

isolates

MIC

50

a

(µg/mL)

MIC

90

(µg /mL)

GRAM-NEGATIVE

Acinetobacter calcoaceticus

9.07

19.41

Moraxella catarrhalis

0.14

0.40

(formerly Branhamella catarrhalis)

Campylobacter jejuni

1.60

1.60

Citrobacter amalonaticus

0.32

1.54

Citrobacter diversus

0.12

0.16

Citrobacter Freundii

2.01

57.40

Enterobacter aerogenes

0.85

38.30

Enterobacter agglomerans

0.40

25.70

Enterobacter cloacae

1532

2.48

48.40

Enterobacter

species

3.27

20.00

Escherichia coli

6190

0.19

0.71

Haemophilus influenzae

0.04

0.13

H. influenzae

Ampicillin-susceptible

2236

0.03

0.12

H. influenzae

Ampicillin-resistant

0.08

0.08

H. influenzae

Beta-lactamase-negative

0.05

0.05

H. influenzae

Beta-lactamase-positive

0.03

0.06

H. parainfluenzae

0.05

0.05

Klebsiella oxytoca

0.04

0.06

Klebsiella pneumoniae

2760

0.06

0.10

Klebsiella

species

0.08

0.34

Morganella morganii

0.74

17.00

Neisseria gonorrhoeae

0.15

0.15

Neisseria gonorrhoeae

Beta-lactamase-negative

0.008

0.015

Neisseria gonorrhoeae

Beta-lactamase-positive

0.008

0.03

Neisseria gonorrhoeae

Tetracycline-resistant

0.008

0.015

Table 2- Activity of cefixime against clinical isolates of bacteria (cont’d)

Organism

Number of

isolates

MIC

50

a

(µg/mL)

MIC

90

(µg /mL)

GRAM-NEGATIVE

Neisseria gonorrhoeae

Chromasomally-resistan

t

0.015

0.06

Neisseria meningitis

0.06

0.06

Pasteurella multocida

0.06

0.06

Proteus mirabilis

1983

0.05

0.06

Page 14 of 30

Proteus vulgaris

0.03

0.10

Proteus

, indole-positive

0.06

5.91

Proteus

species

0.25

0.25

Providencia rettgeri

0.05

0.37

Providencia stuartii

0.10

0.67

Providencia

species

0.40

2.15

Pseudomonas aerugin

2003

47.00

53.10

Pseudomonas cepacia

2.42

6.87

Salmonella enteriditis

0.17

0.34

Salmonella

species

0.09

0.21

Serratia marcescens

1552

0.71

12.90

Shigella

species

0.12

0.48

Yersinia enterocolitica

0.37

1.62

GRAM-POSITIVE

Enterococcus faecalis

65.60

100.00

Enterococcus

species

33.00

33.00

Staphylococcus aureus

1949

17.50

36.50

Staphylococcus epidermidis

10.80

61.80

Streptococcus agalactiae

0.21

0.32

Streptococcus pyogenes

0.11

0.16

Streptococcus

Group B

0.17

0.22

Streptococcus pneumoniae

0.13

0.29

Streptococcus viridans

0.84

26.70

Geometric mean MIC for 50% and 90% of the isolates.

Abbreviation: MIC, minimal inhibitory concentration.

The following organisms are resistant to cefixime:

Pseudomonas

species

strains of group D streptococci (including enterococci)

Listeria

monocytogenes

most strains of staphylococci (including methicillin-resistant strains)

most strains of

Enterobacter

most strains of

Bacteroides fragilis

Clostridia

Susceptibility testing:

Susceptibility Tests: Diffusion Techniques:

Quantitative methods that require measurement of zone diameters give an estimate of antibiotic

susceptibility.

such

procedure

been

recommended

with

disks

test

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

Page 15 of 30

Organisms

Resistant

Moderately Resistant

Susceptible

Neisseria gonorrhoeae

> 31 mm

All other organisms

< 15 mm

16-18 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

achievable

blood

levels.

report

"Moderately

Susceptible"

indicates

that

inhibitory

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

Organism

Zone Diameter (mm)

E. coli

ATCC 25922

23-27

N. gonorrhoeae

ATCC 49226

37-45

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

in

vitro

testing of isolates.

Dilution Techniques:

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)

Organisms

Resistant

Moderately Resistant

Susceptible

Neisseria gonorrhoeae

< 0.25

All other organisms

> 4

< 1

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.

Organism

MIC Range

(µg

/mL)

E. coli

ATCC 25922

0.25

S. aureus

ATCC 29213

- 32

N. gonorrhoeae

ATCC 49226

0.004 - 0.03

Page 16 of 30

PHARMACOLOGY

Animal Pharmacology:

Tissue Distribution/Accumulation:

In rats,

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

C-labelled cefixime.

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

administered dose.

Human Pharmacokinetics:

Absorption:

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)

DOSE

1hr

2hr

4hr

6hr

8hr

12hr

24hr

100 mg*

200 mg

0.03

400 mg

0.04

* ½ x 200 mg tablets

Page 17 of 30

Table 8 - Serum Levels of Cefixime in Adults after Administration of Oral Suspension

(µg/mL)

DOSE

1hr

2hr

4hr

6hr

8hr

12hr

24hr

100 mg

0.02

200 mg

0.07

400 mg

0.07

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.

Metabolism:

There is no evidence of metabolism of cefixime

in vivo

Excretion:

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

DOSE

24-h Urinary Recovery of

Cefixime (% of

administered dose)

Maximum Concentration of

Cefixime in Urine (µg/mL)

200 mg

20.0

400 mg

16.1

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:

RENAL

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.

Page 18 of 30

AGE (CHILDREN)

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

single

time

point

after

administration

(3.5

hours)

increased

with

dose

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

were

2.2 to 2.6 µg/mL.

serum

concentrations

after

mg/kg

doses

were

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)

DOSE

0.5 to 2

> 2 to < 6

6

All Patients

4 mg/kg

2.56

2.51

2.22

2.44

6 mg/kg

4.48

2.51

4.82

4.07

8 mg/kg

3.40

3.55

4.79

3.91

AGE (ELDERLY PATIENTS)

adults

given

same

dosage

regimen

SUPRAX

regardless

age.

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

urine

samples

were

obtained

frequent

intervals.

Table

shows

mean

serum

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

GROUP

AGE

(yrs)

C

max

(µg/mL)

T

max

(h)

AUC

0-inf.

(µg.h/mL

T

1/2

(h)

fe

(% dose)

Young

20-32

4.74

34.9

20.2

Elderly

65-74

5.68

49.5

24.6

Abbreviations:

peak serum concentration;

time to reach maximum serum concentration;

area under the serum concentration versus time curve;

serum half-life;

urinary recovery of cefixime expressed as a fraction of the administered

dose.

Page 19 of 30

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

men. C

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.

DRUG INTERACTION

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,

phenytoin,

ibuprofen,

furosemide

diazepam

their

reported

maximum

therapeutic

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.

open-label,

randomized,

crossover

study

healthy

found

that

concomitant

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.

TOXICOLOGY

Single-Dose Toxicity:

Oral LD

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,

respectively,

mice

(5-10/sex/group),

5, 8

g/kg,

respectively

rats

(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

rate, emesis,

electrocardiogram abnormalities.

Page 20 of 30

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 Toxicity:

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

conducted

rats

(10/sex/group)

dogs

(2/sex/group)

assess

effects

daily

intravenous

administration

cefixime.

8-day

study

dogs

(3/sex/group)

utilizing

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

aging

rats

exacerbated

following

administration

high

doses

cefixime

(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

young animals.

Mutagenicity:

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

in vitro

cytogenetics test. Two investigational

product (IP) doses of 100 to 3200 mg/kg were given to mice in an

in vivo

micronucleus test.

Reproductive Toxicity:

Page 21 of 30

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

teratogenic.

these

studies

mice

rats,

cefixime

affect

postnatal

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

teratogenic

this

species.

Toxic

responses

(abortions

and/or

maternal

deaths)

typically

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

fetuses (F

) were not affected.

Antigenicity:

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.

Carcinogenesis:

Lifetime studies in animals to evaluate carcinogenic potential have not been conducted.

Page 22 of 30

BIBLIOGRAPHY

Asmar, B., Barone, J., Clark, P., Simpkins, D. A comparative trial of cefixime and

amoxicillin

treatment

acute

otitis

media

with

effusion.

Workshop,

l5th

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.

Beumer,

H.M.

Cefixime

versus

amoxicillin/clavulanic

acid

lower

respiratory

tract

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

resistant

Haemophilus

influenzae

including

beta-lactam

tolerant

strains.

Journal

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;

14: 132-136.

Bialer, M., Wu, W.H., Faulkner, R.D., Silbert, B.M., Yacobi, A.

In vitro

protein binding

interaction studies involving cefixime. Biopharmaceutics and Drug Disposition l988; 9:

3l5-320.

Bowie, W.R., Shaw, C.E., Chan, D.G.W., Boyd, J., Black, W.A.

In vitro

activity of

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

characteristics

oral

cefixime.

Clinical

Pharmacology

Therapeutics

l985;

590-594.

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

N. gonorrhoeae

United States; 1988 and 1989. MMWR 1990; 39:284-293.

11. Counts, G.W., Baugher, L.K., Ulness, B.K., Hamilton, D.J. Comparative

in vitro

activity of

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

plasmid

chromosomally

mediated

beta-lactamases.

Workshop,

l5th

International

Congress

Chemotherapy,

July

l987.

Advances

Experimental

Clinical

Chemotherapy l985; l: 9-14.

13. Dornbusch, K. Kronvall, G., Goransson, E. Comparative

in vitro

antibacterial activity and

beta-lactamase

stability

cefixime.

Workshop,

l5th

International

Congress

Chemotherapy, July l987. Advances in Experimental and Clinical Chemotherapy l988;

l: 1-8.

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.

Neisseria gonorrhoeae

: a versatile pathogen. J. Clin Pathol

1987; 40:1088-1097.

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.,

Silber,

B.M.

Pharmacokinetics

cefixime

young

elderly.

Journal

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,

E.H.

In vitro

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

23. Greene,

Anslow,

Bohaychuk,

Faulkner,

Silber,

Woodward, D,

Dabrowski,

Kibbe,

Pharmacokinetics

cefixime

fasted

state.

Workshop,

l5th

International

Congress

Chemotherapy,

July,

l987.

Advances

Experimental and Clinical Chemotherapy l988; l: 2l-23.

24. Hegran, D.W., Lefebvre, K., Willetts, V., Bowie, W.R. Single-dose oral cefixime versus

amoxicillin

plus

probenecid

treatment

uncomplicated

gonorrhea

men.

Antimicrob Agents Chemother 1990; 34:355-357.

25. Hook,

E.W.

III,

Holmes,

K.K.,

Hansfield,

H.H.

Division

Infectious

Diseases,

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.

27. Iravani,

Richard,

G.A.,

Johnson,

Bryant,

double-blind,

multicenter

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

data.

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.

In vitro

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.,

l985.

31. Kamimura, T., Kojo, H., Matsumoto, Y., Mine, Y., Goto S., Kuwahara, S.

In vitro

in

vivo

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

distributions

clinical

results

with

cefixime

infections.

Workshop,

l5th

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:

38-43.

35. Kiani,

Johnson,

Nelson

Comparative

multicentre

studies

cefixime

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

in vitro

activity of

cefixime

with

eight

other

antimicrobials

against

Enterobacteriaceae,

streptococci

Haemophilus influenzae.

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-

262.

38. Kumar, A., Kelly, K.J.

In vitro

activity of cefixime (CL 284635) and other antimicrobial

agents against

Haemophilus

isolates from pediatric patients. Chemotherapy l988, 34: 30-35,

39. McLinn,

S.E.

Randomized,

open

label,

multicenter

trial

cefixime

compared

with

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.

41. Neu,

H.C.

In

vitro

activity

broad

spectrum

beta-lactamase-stable

oral

cephalosporin, cefixime. Pediatric Infectious Disease l987; 6: 958-962.

42. Neu, H.C., Chin, N.X., Labthavikul, P. Comparative

in vitro

activity and beta-lactamase

stability

l7027,

orally

active

cephalosporin.

Antimicrobial

Agents

Chemotherapy l984; 26: l74-l80.

43. Powell, M., Kentsia-Carouzou, C., Voutsinas, D., Williams, J.D. A comparison of the

in

vitro

activity of ampicillin and cefixime against 2458 clinical isolates of

Haemophilus

influenzae

. Workshop, l5th International Congress of Chemotherapy, July, l987. Advances

in Experimental and Clinical Chemotherapy l988; l: l5-l7.

44. Risser,

W.L.,

Barone,

J.S.,

Clark,

P.A.,

Simpkins,

D.L.

Noncomparative

open

label

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.

47. Stone,

J.W.,

Liong,

Andrews,

J.M.,

Wise,

Cefixime,

in

vitro

activity,

pharmacokinetics and tissue penetration. Journal of Antimicrobial Chemotherapy l989; 23:

22l-228.

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

Pr

SUPRAX

®

Cefixime tablets, Mfr. Std., 400 mg

Cefixime for oral suspension, Mfr. Std., 100 mg/5 mL

Read this carefully before you start taking

SUPRAX

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

SUPRAX

What is SUPRAX used for?

Antibacterial drugs like SUPRAX treat only bacterial infections. They do not treat viral infections such as the

common cold.

SUPRAX is used to treat infections caused by bacteria. These include infections of the:

Upper respiratory tract

Middle ear

Sinuses that surround the nasal cavity

Lower respiratory tract

Urinary tract

It is also used to treat

uncomplicated gonorrhea.

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?

Medicinal ingredient:

Cefixime

Non-medicinal ingredients:

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:

Tablets:

400 mg.

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

mg/mL):

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

Usual dose:

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

adult dose

Overdose:

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.

Missed Dose:

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:

diarrhea

nausea

vomiting

upset stomach

headache

dizziness

Page 29 of 30

Serious side effects and what to do about them

Symptom / effect

Talk to your healthcare

professional

Stop taking drug

and get

immediate

medical help

Only if severe

In all cases

Seizures

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:

difficulty breathing,

hives, itching, skin rash, swelling of your tongue or

throat, weakness.

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

rash

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

organs):

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

https://www.canada.ca/en/health-

canada/services/drugs-health-products/medeffect-canada/adverse-reaction-reporting.html

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.

Storage:

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

Similar products

Search alerts related to this product

Share this information