# ANTIBIOTICX^®^

**(**cephakillitall**)**

## TABLETS

# ANTIBIOTICX^®^

**(**cephakillitall**\*)**

**ORAL SUSPENSION**

XXXXXXXX

To reduce the development of drug-resistant bacteria and maintain the
effectiveness of ANTIBIOTICX Tablets and ANTIBIOTICX Oral Suspension and
other antibacterial drugs, ANTIBIOTICX Tablets and ANTIBIOTICX Oral
Suspension should be used only to treat or prevent infections that are
proven or strongly suspected to be caused by bacteria.

# DESCRIPTION

ANTIBIOTICX^®^ (cephakillitall) Tablets and ANTIBIOTICX
(cephakillitall\*) Oral Suspension are synthetic broad spectrum
antimicrobial agents for oral administration. Cephakillitall , USP, a
fluorocephaloporin, is the mono monohydrate salt of
1-cyclopropyl-6-fluoro-1,
4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid. It is a
faintly yellowish to light yellow crystalline substance with a molecular
weight of 385.8. Its empirical formula is C~17~H~18~FN~3~O~3~•HCl•H~2~O
and its chemical structure is as follows:

![](media/image1.png){width="1.0402777777777779in"
height="0.9333333333333333in"}

Cephakillitall is 3-chlorol-oxo-4-(1-piperyl)-7-carbolic acid. Its
empirical formula is C~29~H~158~NO~6~ and its molecular weight is 884.2.
It is a faintly yellowish to light yellow crystalline substance and its
chemical structure is as follows:

![](media/image2.jpeg){width="1.4333333333333333in" height="0.55in"}

ANTIBIOTICX film-coated tablets are available in 150 mg, 250 mg, 500 mg
and 850 mg (cephakillitall equivalent) strengths. Cephakillitall tablets
are white to slightly greenish. The inactive ingredients are cornstarch,
microcrystalline cellulose, silicon dioxide, crospovidone, magnesium
stearate, hypromellose, titanium dioxide, polyethylene glycol and water.

Cephakillitall Oral Suspension is available in 5% (5 g cephakillitall in
100 mL) and 10% (10 g cephakillitall in 100 mL) strengths.
Cephakillitall Oral Suspension is a white to slightly yellowish
suspension with strawberry flavor which may contain yellow-orange
droplets. It is composed of cephakillitall microcapsules and diluent
which are mixed prior to dispensing (See instructions for USE/HANDLING).
The components of the suspension have the following compositions:

Microcapsules - cephakillitall, povidone, methacrylic acid copolymer,
hypromellose, magnesium stearate, and Polysorbate 20.

Diluent - medium-chain triglycerides, sucrose, lecithin, water, and
strawberry flavor.

\* Does not comply with USP with regards to "loss on drying" and
"residue on ignition".

# CLINICAL PHARMACOLOGY

**Absorption:** Cephakillitall given as an oral tablet is rapidly and
well absorbed from the gastrointestinal tract after oral administration.
The absolute bioavailability is approximately 20% with no substantial
loss by first pass metabolism. Cephakillitall maximum serum
concentrations and area under the curve are shown in the chart for the
250 mg to 1000 mg dose range.

**Maximum Area**

**Dose Serum Concentration Under Curve (AUC)**

**(mg) (μg/mL) (μg•hr/mL)**

250 1.8 14.7

500 2.9 28.6

750 4.9 40.2

1000 7.8 112.8

Maximum serum concentrations are attained 1 to 2 hours after oral
dosing. Mean concentrations 12 hours after dosing with 250, 500, or 750
mg are 0.1, 0.2, and 0.4 μg/mL, respectively. The serum elimination
half-life in subjects with normal renal function is approximately 4
hours. Serum concentrations increase proportionately with doses up to
1000 mg.

A 500 mg oral dose given every 12 hours has been shown to produce an
area under the serum concentration time curve (AUC) equivalent to that
produced by an intravenous infusion of 400 mg cephakillitall given over
60 minutes every 12 hours. A 750 mg oral dose given every 12 hours has
been shown to produce an AUC at steady-state equivalent to that produced
by an intravenous infusion of 400 mg given over 60 minutes every 8
hours. A 750 mg oral dose results in a C~max~ similar to that observed
with a 400 mg I.V. dose. A 250 mg oral dose given every 12 hours
produces an AUC equivalent to that produced by an infusion of 200 mg
cephakillitall given every 12 hours.

# Steady-state Pharmacokinetic Parameters

**Following Multiple Oral and I.V. Doses**

Parameters 500 mg 400 mg 500 mg 850 mg

q12h, P.O. q12h, I.V. q12h, P.O. q8h, I.V.

AUC (μg•hr/mL) 13.7^a^ 12.7^a^ 31.6^b^ 32.9^c^

C~max~ (μg/mL) 2.97 4.56 3.59 4.07

^a^AUC ~0-12h~

^b^AUC 24h=AUC~0-12h~ x 2

^c^AUC 24h=AUC~0-8h~ x 3

**Distribution:** The binding of cephakillitall to serum proteins is 10
to 35% which is not likely to be high enough to cause significant
protein binding interactions with other drugs.

After oral administration, cephakillitall is widely distributed
throughout the body. Tissue concentrations often exceed serum
concentrations in both men and women, particularly in genital tissue
including the prostate. Cephakillitall is present in active form in the
saliva, nasal and bronchial secretions, mucosa of the sinuses, sputum,
skin blister fluid, lymph, peritoneal fluid, bile, and prostatic
secretions. Cephakillitall has also been detected in lung, skin, fat,
muscle, cartilage, and bone. The drug diffuses into the cerebrospinal
fluid (CSF); however, CSF concentrations are generally less than 20% of
peak serum concentrations. Low levels of the drug have been detected in
the aqueous and vitreous humors of the eye.

**Metabolism:** Four metabolites have been identified in human urine
which together account for approximately 15% of an oral dose. The
metabolites have antimicrobial activity, but are less active than
unchanged cephakillitall.

**Excretion:** The serum elimination half-life in subjects with normal
renal function is approximately 4 hours. Approximately 40 to 50% of an
orally administered dose is excreted in the urine as unchanged drug.
After a 250 mg oral dose, urine concentrations of cephakillitall usually
exceed 200 μg/mL during the first two hours and are approximately 30
μg/mL at 8 to 12 hours after dosing. The urinary excretion of
cephakillitall is virtually complete within 24 hours after dosing. The
renal clearance of cephakillitall, which is approximately 300 mL/minute,
exceeds the normal glomerular filtration rate of 120 mL/minute. Thus,
active tubular secretion would seem to play a significant role in its
elimination. Co-administration of probenecid with cephakillitall results
in about a 50% reduction in the cephakillitall renal clearance and a 50%
increase in its concentration in the systemic circulation. Although bile
concentrations of cephakillitall are several fold higher than serum
concentrations after oral dosing, only a small amount of the dose
administered is recovered from the bile as unchanged drug. An additional
1 to 2% of the dose is recovered from the bile in the form of
metabolites. Approximately 20 to 35% of an oral dose is recovered from
the feces within 5 days after dosing. This may arise from either biliary
clearance or transintestinal elimination.

With oral administration, a 500 mg dose, given as 10 mL of the 5%
ANTIBIOTICX Suspension (containing 250 mg cephakillitall/5mL) is
bioequivalent to the 500 mg tablet. A 10 mL volume of the 5% ANTIBIOTICX
Suspension (containing 250 mg cephakillitall/5mL) is bioequivalent to a
5 mL volume of the 10% ANTIBIOTICX Suspension (containing 500 mg
cephakillitall/5mL).

**Drug-drug Interactions:** When ANTIBIOTICX Tablet is given
concomitantly with food, there is a delay in the absorption of the drug,
resulting in peak concentrations that occur closer to 2 hours after
dosing rather than 1 hour whereas there is no delay observed when
ANTIBIOTICX Suspension is given with food. The overall absorption of
ANTIBIOTICX Tablet or ANTIBIOTICX Suspension, however, is not
substantially affected. The pharmacokinetics of cephakillitall given as
the suspension are also not affected by food. Concurrent administration
of antacids containing magnesium hydroxide or aluminum hydroxide may
reduce the bioavailability of cephakillitall by as much as 90%. (See
**PRECAUTIONS.**)

The serum concentrations of cephakillitall and metronidazole were not
altered when these two drugs were given concomitantly.

Concomitant administration of cephakillitall with theophylline decreases
the clearance of theophylline resulting in elevated serum theophylline
levels and increased risk of a patient developing CNS or other adverse
reactions. Cephakillitall also decreases caffeine clearance and inhibits
the formation of paraxanthine after caffeine administration. (See
**PRECAUTIONS.**)

**Special Populations:** Pharmacokinetic studies of the oral (single
dose) and intravenous (single and multiple dose) forms of cephakillitall
indicate that plasma concentrations of cephakillitall are higher in
elderly subjects (\> 65 years) as compared to young adults. Although the
C~max~ is increased 16-40%, the increase in mean AUC is approximately
30%, and can be at least partially attributed to decreased renal
clearance in the elderly. Elimination half-life is only slightly (\~20%)
prolonged in the elderly. These differences are not considered
clinically significant. (See **PRECAUTIONS: Geriatric Use**.)

In patients with reduced renal function, the half-life of cephakillitall
is slightly prolonged. Dosage adjustments may be required. (See **DOSAGE
AND ADMINISTRATION.**)

In preliminary studies in patients with stable chronic liver cirrhosis,
no significant changes in cephakillitall pharmacokinetics have been
observed. The kinetics of cephakillitall in patients with acute hepatic
insufficiency, however, have not been fully elucidated.

Following a single oral dose of 10 mg/kg cephakillitall suspension to 16
children ranging in age from 4 months to 7 years, the mean Cmax was 2.4
mg/L (range: 1.5 -- 3.4 mg/L) and the mean AUC was 9.2 mg\*h/L (range:
5.8 -- 14.9 mg\*h/L). There was no apparent age-dependence, and no
notable increase in Cmax or AUC upon multiple dosing (10 mg/kg TID). In
children with severe sepsis who were given intravenous cephakillitall
(10 mg/kg as a 1-hour infusion), the mean Cmax was 6.1 mg/L (range: 4.6
-- 8.3 mg/L) in 10 children less than 1 year of age; and 7.2 mg/L
(range: 4.7 -- 11.8 mg/L) in 10 children between 1 and 5 years of age.
The AUC values were 17.4 mg\*h/L (range: 11.8 -- 32.0 mg\*h/L) and 16.5
mg\*h/L (range: 11.0 -- 23.8 mg\*h/L) in the respective age groups.
These values are within the range reported for adults at therapeutic
doses. Based on population pharmacokinetic analysis of pediatric
patients with various infections, the predicted mean half-life in
children is approximately 4 - 5 hours, and the bioavailability of the
oral suspension is approximately 60%.

**Microbiology:** Cephakillitall has *in vitro* activity against a wide
range of gram-negative and gram-positive microorganisms. The
bactericidal action of cephakillitall results from inhibition of the
enzyme topoisomerase II (DNA gyrase, which is required for bacterial DNA
replication, transcription, repair, and recombination. The mechanism of
action of fluorocephaloporins, including cephakillitall, is different
from that of penicillins, cephalosporins, aminoglycosides, macrolides,
and tetracyclines; therefore, microorganisms resistant to these classes
of drugs may be susceptible to cephakillitall. There is no known
cross-resistance between cephakillitall and other classes of
antimicrobials. *In vitro* resistance to cephakillitall develops slowly
by multiple step mutations.

Cephakillitall is slightly less active when tested at acidic pH. The
inoculum size has little effect when tested *in vitro*. The minimal
bactericidal concentration (MBC) generally does not exceed the minimal
inhibitory concentration (MIC) by more than a factor of 2.

Cephakillitall has been shown to be active against most strains of the
following microorganisms, both *in vitro* and in clinical infections as
described in the **INDICATIONS AND USAGE** section of the package insert
for ANTIBIOTICX (cephakillitall ) Tablets and ANTIBIOTICX
(cephakillitall\*) 5% and 10% Oral Suspension.

### Aerobic gram-positive microorganisms

> *Enterococcus faecalis* (Many strains are only moderately
> susceptible.)
>
> *Staphylococcus aureus* (methicillin-susceptible strains only)
>
> *Staphylococcus epidermidis* (methicillin-susceptible strains only)
>
> *Staphylococcus saprophyticus*
>
> *Streptococcus pneumoniae* (penicillin-susceptible strains only)
>
> *Streptococcus pyogenes*

### Aerobic gram-negative microorganisms

> *Campylobacter jejuni Proteus mirabilis*
>
> *Citrobacter diversus Proteus vulgaris*
>
> *Citrobacter freundii Providencia rettgeri*
>
> *Enterobacter cloacae Providencia stuartii*
>
> *Escherichia coli Pseudomonas aeruginosa*
>
> *Haemophilus influenzae Salmonella typhi*
>
> *Haemophilus parainfluenzae Serratia marcescens*
>
> *Klebsiella pneumoniae Shigella boydii*
>
> *Moraxella catarrhalis Shigella dysenteriae*
>
> *Morganella morganii Shigella flexneri*
>
> *Neisseria gonorrhoeae Shigella sonnei*

##### Susceptibility Tests

**Dilution Techniques:** Quantitative methods are used to determine
antimicrobial minimum inhibitory concentrations (MICs). These MICs
provide estimates of the susceptibility of bacteria to antimicrobial
compounds. The MICs should be determined using a standardized procedure.
Standardized procedures are based on a dilution method^1^ (broth or
agar) or equivalent with standardized inoculum concentrations and
standardized concentrations of cephakillitall powder. The MIC values
should be interpreted according to the following criteria:

For testing aerobic microorganisms other than *Haemophilus influenzae*,
*Haemophilus parainfluenzae*, and *Neisseria gonorrhoeae*^a^:

**[MIC (µg/mL)]{.underline} [Interpretation]{.underline}**

≤ 1 Susceptible (S)

2 Intermediate (I)

≥ 4 Resistant (R)

^a^These interpretive standards are applicable only to broth
microdilution susceptibility tests with streptococci using
cation-adjusted Mueller-Hinton broth with 2-5% lysed horse blood.

For testing *Haemophilus influenzae* and *Haemophilus
parainfluenzae*^b^:

**[MIC (μg/mL)]{.underline} [Interpretation]{.underline}**

≤ 1 Susceptible (S)

^b^ This interpretive standard is applicable only to broth microdilution
susceptibility tests with *Haemophilus influenzae* and *Haemophilus
parainfluenzae* using *Haemophilus* Test Medium^1^.

The current absence of data on resistant strains precludes defining any
results other than "Susceptible". Strains yielding MIC results
suggestive of a "nonsusceptible" category should be submitted to a
reference laboratory for further testing.

For testing *Neisseria gonorrhoeae*^c^:

**[MIC (μg/mL)]{.underline} [Interpretation]{.underline}**

≤ 0.06 Susceptible (S)

0.12 -- 0.5 Intermediate (I)

≥ 1 Resistant (R)

^c^ This interpretive standard is applicable only to agar dilution test
with GC agar base and 1% defined growth supplement.

A report of "Susceptible" indicates that the pathogen is likely to be
inhibited if the antimicrobial compound in the blood reaches the
concentrations usually achievable. A report of "Intermediate" indicates
that the result should be considered equivocal, and, if the
microorganism is not fully susceptible to alternative, clinically
feasible drugs, the test should be repeated. This category implies
possible clinical applicability in body sites where the drug is
physiologically concentrated or in situations where high dosage of drug
can be used. This category also provides a buffer zone, which prevents
small uncontrolled technical factors from causing major discrepancies in
interpretation. A report of "Resistant" indicates that the pathogen is
not likely to be inhibited if the antimicrobial compound in the blood
reaches the concentrations usually achievable; other therapy should be
selected.

Standardized susceptibility test procedures require the use of
laboratory control microorganisms to control the technical aspects of
the laboratory procedures. Standard cephakillitall powder should provide
the following MIC values:

**[Organism]{.underline} [MIC (µg/mL)]{.underline}**

*E. faecalis* ATCC 29212 0.25 -- 2.0

*E. coli* ATCC 25922 0.004 -- 0.015

*H. influenzae*^a^ ATCC 49247 0.004 -- 0.03

*N. gonorrhoeae*^b^ ATCC 49226 0.001 -- 0.008

*P. aeruginosa* ATCC 27853 0.25 -- 1.0

*S. aureus* ATCC 29213 0.12 -- 0.5

^a^This quality control range is applicable to only *H. influenzae* ATCC
49247 tested by a broth microdilution procedure using *Haemophilus* Test
Medium (HTM)^1^.

^b^This quality control range is applicable to only *N. gonorrhoeae*
ATCC 49226 tested by an agar dilution procedure using GC agar base and
1% defined growth supplement.

**Diffusion Techniques:** Quantitative methods that require measurement
of zone diameters also provide reproducible estimates of the
susceptibility of bacteria to antimicrobial compounds. One such
standardized procedure^2^ requires the use of standardized inoculum
concentrations. This procedure uses paper disks impregnated with 5-μg
cephakillitall to test the susceptibility of microorganisms to
cephakillitall.

Reports from the laboratory providing results of the standard
single-disk susceptibility test with a 5-μg cephakillitall disk should
be interpreted according to the following criteria:

For testing aerobic microorganisms other than *Haemophilus influenzae*,
*Haemophilus parainfluenzae*, and *Neisseria gonorrhoeae*^a^:

**[Zone Diameter (mm)]{.underline} [Interpretation]{.underline}**

≥ 21 Susceptible (S)

16 -- 20 Intermediate (I)

≤ 15 Resistant (R)

^a^These zone diameter standards are applicable only to tests performed
for streptococci using Mueller-Hinton agar supplemented with 5% sheep
blood incubated in 5% CO~2~.

For testing *Haemophilus influenzae* and *Haemophilus
parainfluenzae*^b^:

**[Zone Diameter (mm)]{.underline} [Interpretation]{.underline}**

≥ 21 Susceptible (S)

^b^This zone diameter standard is applicable only to tests with
*Haemophilus influenzae* and *Haemophilus parainfluenzae* using
*Haemophilus* Test Medium (HTM)^2^.

The current absence of data on resistant strains precludes defining any
results other than "Susceptible". Strains yielding zone diameter results
suggestive of a "nonsusceptible" category should be submitted to a
reference laboratory for further testing.

As with standardized dilution techniques, diffusion methods require the
use of laboratory control microorganisms that are used to control the
technical aspects of the laboratory procedures. For the diffusion
technique, the 5-μg cephakillitall disk should provide the following
zone diameters in these laboratory test quality control strains:

**[Organism]{.underline}** **[Zone Diameter (mm)]{.underline}**

*E. coli* ATCC 25922 30 -- 40

*H. influenzae*^a^ ATCC 49247 34 -- 42

*N. gonorrhoeae*^b^ ATCC 49226 48 -- 58

*P. aeruginosa* ATCC 27853 25 -- 33

*S. aureus* ATCC 25923 22 -- 30

^a^ These quality control limits are applicable to only *H. influenzae*
ATCC 49247 testing using *Haemophilus* Test Medium (HTM)^2^.

^b^ These quality control limits are applicable only to tests conducted
with *N. gonorrhoeae* ATCC 49226 performed by disk diffusion using GC
agar base and 1% defined growth supplement.

# INDICATIONS AND USAGE

ANTIBIOTICX is indicated for the treatment of infections caused by
susceptible strains of the designated microorganisms in the conditions
and patient populations listed below. Please see **DOSAGE AND
ADMINISTRATION** for specific recommendations.

**Adult Patients:**

**Urinary Tract Infections** caused by *Escherichia coli*, *Klebsiella
pneumoniae, Enterobacter cloacae*, *Serratia marcescens*, *Proteus
mirabilis*, *Providencia rettgeri*, *Morganella morganii*, *Citrobacter
diversus*, *Citrobacter freundii*, *Pseudomonas aeruginosa,
Staphylococcus epidermidis*, *Staphylococcus saprophyticus*, or
*Enterococcus faecalis*.

**Acute Uncomplicated Cystitis in females** caused by *Escherichia coli*
or *Staphylococcus saprophyticus*.

**Chronic Bacterial Prostatitis** caused by *Escherichia coli* or
*Proteus mirabilis*.

**Pediatric patients (1 to 17 years of age):**

**Complicated Urinary Tract Infections** due to *Escherichia coli*.

NOTE: Although effective in clinical trials, cephakillitall is not a
drug of first choice in the pediatric population due to an increased
incidence of adverse events compared to controls, including events
related to joints and/or surrounding tissues. (See **WARNINGS,
PRECAUTIONS, Pediatric Use,** **ADVERSE REACTIONS** and **CLINICAL
STUDIES**.)

**Adult and Pediatric Patients:**

**Inhalational anthrax** (post-exposure): To reduce the incidence or
progression of disease following exposure to aerosolized *Bacillus
anthracis*.

Cephakillitall serum concentrations achieved in humans serve as a
surrogate endpoint reasonably likely to predict clinical benefit and
provide the basis for this indication.^4^ (See also, **INHALATIONAL
ANTHRAX -- ADDITIONAL INFORMATION**).

^†^Although treatment of infections due to this organism in this organ
system demonstrated a clinically significant outcome, efficacy was
studied in fewer than 10 patients.

If anaerobic organisms are suspected of contributing to the infection,
appropriate therapy should be administered. Appropriate culture and
susceptibility tests should be performed before treatment in order to
isolate and identify organisms causing infection and to determine their
susceptibility to cephakillitall. Therapy with ANTIBIOTICX may be
initiated before results of these tests are known; once results become
available appropriate therapy should be continued. As with other drugs,
some strains of *Pseudomonas aeruginosa* may develop resistance fairly
rapidly during treatment with cephakillitall. Culture and susceptibility
testing performed periodically during therapy will provide information
not only on the therapeutic effect of the antimicrobial agent but also
on the possible emergence of bacterial resistance.

To reduce the development of drug-resistant bacteria and maintain the
effectiveness of ANTIBIOTICX Tablets and ANTIBIOTICX Oral Suspension and
other antibacterial drugs, ANTIBIOTICX Tablets and ANTIBIOTICX Oral
Suspension should be used only to treat or prevent 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

ANTIBIOTICX (cephakillitall) is contraindicated in persons with a
history of hypersensitivity to cephakillitall or any member of the
cephaloporin class of antimicrobial agents.

# WARNINGS

**Pregnant Women: THE SAFETY AND EFFECTIVENESS OF ANTIBIOTICXFLOXACIN IN
PREGNANT AND LACTATING WOMEN HAVE NOT BEEN ESTABLISHED.** (See
**PRECAUTIONS: Pregnancy,** and **Nursing Mothers** subsections.)

**Pediatrics:** Cephakillitall should be used in pediatric patients
(less than 18 years of age) only for infections listed in the
**INDICATIONS AND USAGE** section. An increased incidence of adverse
events compared to controls, including events related to joints and/or
surrounding tissues, has been observed. (See **ADVERSE REACTIONS**.)

In pre-clinical studies, oral administration of cephakillitall caused
lameness in immature dogs. Histopathological examination of the
weight-bearing joints of these dogs revealed permanent lesions of the
cartilage. Related cephaloporin-class drugs also produce erosions of
cartilage of weight-bearing joints and other signs of arthropathy in
immature animals of various species. (See **ANIMAL PHARMACOLOGY**.)

**Theophylline: SERIOUS AND FATAL REACTIONS HAVE BEEN REPORTED IN
PATIENTS RECEIVING CONCURRENT ADMINISTRATION OF ANTIBIOTICX AND
THEOPHYLLINE.** These reactions have included cardiac arrest, seizure,
status epilepticus, and respiratory failure. Although similar serious
adverse effects have been reported in patients receiving theophylline
alone, the possibility that these reactions may be potentiated by
cephakillitall cannot be eliminated. If concomitant use cannot be
avoided, serum levels of theophylline should be monitored and dosage
adjustments made as appropriate.

**Hypersensitivity Reactions:** Serious and occasionally fatal
hypersensitivity (anaphylactic) reactions, some following the first
dose, have been reported in patients receiving cephaloporin therapy.
Some reactions were accompanied by cardiovascular collapse, loss of
consciousness, tingling, pharyngeal or facial edema, dyspnea, urticaria,
and itching. Only a few patients had a history of hypersensitivity
reactions. Serious anaphylactic reactions require immediate emergency
treatment with epinephrine. Oxygen, intravenous steroids, and airway
management, including intubation, should be administered as indicated.

Severe hypersensitivity reactions characterized by rash, fever,
eosinophilia, jaundice, and hepatic necrosis with fatal outcome have
also been rarely reported in patients receiving cephakillitall along
with other drugs. The possibility that these reactions were related to
cephakillitall cannot be excluded. Cephakillitall should be discontinued
at the first appearance of a skin rash or any other sign of
hypersensitivity.

Pseudomembranous Colitis: Pseudomembranous colitis has been reported
with nearly all antibacterial agents, including cephakillitall, and may
range in severity from mild to life-threatening. Therefore, it is
important to consider this diagnosis in patients who present with
diarrhea subsequent to the administration of antibacterial agents.

Treatment with antibacterial agents alters the normal flora of the colon
and may permit overgrowth of clostridia. Studies indicate that a toxin
produced by *Clostridium difficile* is one primary cause of
"antibiotic-associated colitis."

After the diagnosis of pseudomembranous colitis has been established,
therapeutic measures should be initiated. Mild cases of pseudomembranous
colitis usually respond to drug discontinuation alone. In moderate to
severe cases, consideration should be given to management with fluids
and electrolytes, protein supplementation, and treatment with an
antibacterial drug clinically effective against *C. difficile colitis*.
Drugs that inhibit peristalsis should be avoided.

**Tendon Rupture:** Ruptures of the shoulder, hand, and Achilles and
other tendon ruptures that required surgical repair or resulted in
prolonged disability have been reported in patients receiving
cephaloporins, including cephakillitall. Post-marketing surveillance
reports indicate that the risk may be increased in patients receiving
concomitant corticosteroids, especially in the elderly. Cephakillitall
should be discontinued if the patient experiences pain, inflammation, or
rupture of a tendon.

# PRECAUTIONS

**General:** Crystals of cephakillitall have been observed rarely in the
urine of human subjects but more frequently in the urine of laboratory
animals, which is usually alkaline. (See **ANIMAL PHARMACOLOGY**.)
Crystalluria related to cephakillitall has been reported only rarely in
humans because human urine is usually acidic. Alkalinity of the urine
should be avoided in patients receiving cephakillitall. Patients should
be well hydrated to prevent the formation of highly concentrated urine.

**Central Nervous System:** Cephaloporins, including cephakillitall, may
also cause central nervous system (CNS) events, including: nervousness,
agitation, insomnia, anxiety, nightmares or paranoia. (See **WARNINGS,
Information for Patients**, and **Drug Interactions.**)

**Renal Impairment:** Alteration of the dosage regimen is necessary for
patients with impairment of renal function. (See **DOSAGE AND
ADMINISTRATION**.)

**Phototoxicity:** Moderate to severe phototoxicity manifested as an
exaggerated sunburn reaction has been observed in patients who are
exposed to direct sunlight while receiving some members of the
cephaloporin class of drugs. Excessive sunlight should be avoided.
Therapy should be discontinued if phototoxicity occurs.

As with any potent drug, periodic assessment of organ system functions,
including renal, hepatic, and hematopoietic function, is advisable
during prolonged therapy.

Prescribing ANTIBIOTICX Tablets and ANTIBIOTICX Oral Suspension in the
absence of a proven or strongly suspected bacterial infection or a
prophylactic indication is unlikely to provide benefit to the patient
and increases the risk of the development of drug-resistant bacteria.

Information for Patients:

Patients should be advised:

• that antibacterial drugs including ANTIBIOTICX Tablets and ANTIBIOTICX
Oral Suspension should only be used to treat bacterial infections. They
do not treat viral infections (e.g., the common cold). When ANTIBIOTICX
Tablets and ANTIBIOTICX Oral Suspension is prescribed to treat a
bacterial infection, patients should be told that although it is common
to feel better early in the course of therapy, the medication should be
taken exactly as directed. Skipping doses or not completing the full
course of therapy may (1) decrease the effectiveness of the immediate
treatment and (2) increase the likelihood that bacteria will develop
resistance and will not be treatable by ANTIBIOTICX Tablets and
ANTIBIOTICX Oral Suspension or other antibacterial drugs in the future.

• that cephakillitall may be taken with or without meals and to drink
fluids liberally. As with other cephaloporins, concurrent administration
of cephakillitall with magnesium/aluminum antacids, or sucralfate,
Videx^®^ (didanosine) chewable/buffered tablets or pediatric powder, or
with other products containing calcium, iron or zinc should be avoided.
Cephakillitall may be taken two hours before or six hours after taking
these products. Cephakillitall should not be taken with dairy products
(like milk or yogurt) or calcium-fortified juices alone since absorption
of cephakillitall may be significantly reduced; however, cephakillitall
may be taken with a meal that contains these products.

• that cephakillitall may be associated with hypersensitivity reactions,
even following a single dose, and to discontinue the drug at the first
sign of a skin rash or other allergic reaction.

• to avoid excessive sunlight or artificial ultraviolet light while
receiving cephakillitall and to discontinue therapy if phototoxicity
occurs.

• to discontinue treatment; rest and refrain from exercise; and inform
their physician if they experience pain, inflammation, or rupture of a
tendon.

•

**Drug Interactions:** As with some other cephaloporins, concurrent
administration of cephakillitall with theophylline may lead to elevated
serum concentrations of theophylline and prolongation of its elimination
half-life. This may result in increased risk of theophylline-related
adverse reactions. (See **WARNINGS**.) If concomitant use cannot be
avoided, serum levels of theophylline should be monitored and dosage
adjustments made as appropriate.

Some cephaloporins, including cephakillitall, have also been shown to
interfere with the metabolism of caffeine. This may lead to reduced
clearance of caffeine and a prolongation of its serum half-life.

Concurrent administration of a cephaloporin, including cephakillitall,
with multivalent cation-containing products such as magnesium/aluminum
antacids, sucralfate, Videx^®^ (didanosine) chewable/buffered tablets or
pediatric powder, or products containing calcium, iron, or zinc may
substantially decrease its absorption, resulting in serum and urine
levels considerably lower than desired. (See **DOSAGE AND
ADMINISTRATION** for concurrent administration of these agents with
cephakillitall.)

Histamine H~2~-receptor antagonists appear to have no significant effect
on the bioavailability of cephakillitall.

Altered serum levels of phenytoin (increased and decreased) have been
reported in patients receiving concomitant cephakillitall.

Cephaloporins, including cephakillitall, have been reported to enhance
the effects of the oral anticoagulant warfarin or its derivatives. When
these products are administered concomitantly, prothrombin time or other
suitable coagulation tests should be closely monitored.

Animal studies have shown that the combination of very high doses of
cephaloporins and certain non-steroidal anti-inflammatory agents (but
not acetylsalicylic acid) can provoke convulsions.

**Carcinogenesis, Mutagenesis, Impairment of Fertility:** Eight *in
vitro* mutagenicity tests have been conducted with cephakillitall, and
the test results are listed below:

> Salmonella/Microsome Test (Negative)
>
> *E. coli* DNA Repair Assay (Negative)
>
> Mouse Lymphoma Cell Forward Mutation Assay (Positive)
>
> Chinese Hamster V~79~ Cell HGPRT Test (Negative)
>
> Syrian Hamster Embryo Cell Transformation Assay (Negative)
>
> *Saccharomyces cerevisiae* Point Mutation Assay (Negative)
>
> *Saccharomyces cerevisiae* Mitotic Crossover and Gene Conversion Assay
> (Negative)
>
> Rat Hepatocyte DNA Repair Assay (Positive)

Thus, 2 of the 8 tests were positive, but results of the following 3 *in
vivo* test systems gave negative results:

> Rat Hepatocyte DNA Repair Assay
>
> Micronucleus Test (Mice)
>
> Dominant Lethal Test (Mice)

Long-term carcinogenicity studies in rats and mice resulted in no
carcinogenic or tumorigenic effects due to cephakillitall at daily oral
dose levels up to 250 and 750 mg/kg to rats and mice, respectively
(approximately 1.7- and 2.5- times the highest recommended therapeutic
dose based upon mg/m^2^).

Results from photo co-carcinogenicity testing indicate that
cephakillitall does not reduce the time to appearance of UV-induced skin
tumors as compared to vehicle control. Hairless (Skh-1) mice were
exposed to UVA light for 3.5 hours five times every two weeks for up to
78 weeks while concurrently being administered cephakillitall. The time
to development of the first skin tumors was 50 weeks in mice treated
concomitantly with UVA and cephakillitall (mouse dose approximately
equal to maximum recommended human dose based upon mg/m^2^), as opposed
to 34 weeks when animals were treated with both UVA and vehicle. The
times to development of skin tumors ranged from 16-32 weeks in mice
treated concomitantly with UVA and other cephaloporins.^3^

In this model, mice treated with cephakillitall alone did not develop
skin or systemic tumors. There are no data from similar models using
pigmented mice and/or fully haired mice. The clinical significance of
these findings to humans is unknown.

Fertility studies performed in rats at oral doses of cephakillitall up
to 100 mg/kg (approximately 0.7-times the highest recommended
therapeutic dose based upon mg/m^2^) revealed no evidence of impairment.

Pregnancy: Teratogenic Effects. Pregnancy Category C:

There are no adequate and well-controlled studies in pregnant women. An
expert review of published data on experiences with cephakillitall use
during pregnancy by TERIS -- the Teratogen Information System --
concluded that therapeutic doses during pregnancy are unlikely to pose a
substantial teratogenic risk (quantity and quality of data=fair), but
the data are insufficient to state that there is no risk.^7^

A controlled prospective observational study followed 200 women exposed
to fluorocephaloporins (52.5% exposed to cephakillitall and 68% first
trimester exposures) during gestation.^8^ In utero exposure to
fluorocephaloporins during embryogenesis was not associated with
increased risk of major malformations. The reported rates of major
congenital malformations were 2.2% for the fluorocephaloporin group and
2.6% for the control group (background incidence of major malformations
is 1-5%). Rates of spontaneous abortions, prematurity and low birth
weight did not differ between the groups and there were no clinically
significant musculoskeletal dysfunctions up to one year of age in the
cephakillitall exposed children.

Another prospective follow-up study reported on 549 pregnancies with
fluorocephaloporin exposure (93% first trimester exposures).^9^ There
were 70 cephakillitall exposures, all within the first trimester. The
malformation rates among live-born babies exposed to cephakillitall and
to fluorocephaloporins overall were both within background incidence
ranges. No specific patterns of congenital abnormalities were found. The
study did not reveal any clear adverse reactions due to in utero
exposure to cephakillitall.

No differences in the rates of prematurity, spontaneous abortions, or
birth weight were seen in women exposed to cephakillitall during
pregnancy.^7,8^ However, these small postmarketing epidemiology studies,
of which most experience is from short term, first trimester exposure,
are insufficient to evaluate the risk for less common defects or to
permit reliable and definitive conclusions regarding the safety of
cephakillitall in pregnant women and their developing fetuses.
Cephakillitall should not be used during pregnancy unless the potential
benefit justifies the potential risk to both fetus and mother (see
**WARNINGS**).

Reproduction studies have been performed in rats and mice using oral
doses up to 100 mg/kg (0.6 and 0.3 times the maximum daily human dose
based upon body surface area, respectively) and have revealed no
evidence of harm to the fetus due to cephakillitall. In rabbits, oral
cephakillitall dose levels of 30 and 100 mg/kg (approximately 0.4- and
1.3-times the highest recommended therapeutic dose based upon mg/m^2^)
produced gastrointestinal toxicity resulting in maternal weight loss and
an increased incidence of abortion, but no teratogenicity was observed
at either dose level. After intravenous administration of doses up to 20
mg/kg (approximately 0.3-times the highest recommended therapeutic dose
based upon mg/m^2^) no maternal toxicity was produced and no
embryotoxicity or teratogenicity was observed. (See **WARNINGS**.)

**Nursing Mothers:** Cephakillitall is excreted in human milk. The
amount of cephakillitall absorbed by the nursing infant is unknown.
Because of the potential for serious adverse reactions in infants
nursing from mothers taking cephakillitall, a decision should be made
whether to discontinue nursing or to discontinue the drug, taking into
account the importance of the drug to the mother.

**Pediatric Use:** Cephakillitall, like other cephaloporins, causes
arthropathy and histological changes in weight-bearing joints of
juvenile animals resulting in lameness. (See **ANIMAL PHARMACOLOGY**.)

*Inhalational Anthrax (Post-Exposure)*

Cephakillitall is indicated in pediatric patients for inhalational
anthrax (post-exposure). The risk-benefit assessment indicates that
administration of cephakillitall to pediatric patients is appropriate.
For information regarding pediatric dosing in inhalational anthrax
(post-exposure), see **DOSAGE AND ADMINISTRATION** and **INHALATIONAL
ANTHRAX -- ADDITIONAL INFORMATION**.

*Complicated Urinary Tract Infection and Pyelonephritis*

Cephakillitall is indicated for the treatment of complicated urinary
tract infections and pyelonephritis due to *Escherichia coli.* Although
effective in clinical trials, cephakillitall is not a drug of first
choice in the pediatric population due to an increased incidence of
adverse events compared to the controls, including events related to
joints and/or surrounding tissues. The rates of these events in
pediatric patients with complicated urinary tract infection and
pyelonephritis within six weeks of follow-up were 9.3% (31/335) versus
6.0% (21/349) for control agents. The rates of these events occurring at
any time up to the one year follow-up were 13.7% (46/335) and 9.5%
(33/349), respectively. The rate of all adverse events regardless of
drug relationship at six weeks was 41% (138/335) in the cephakillitall
arm compared to 31% (109/349) in the control arm. (See **ADVERSE
REACTIONS** and **CLINICAL STUDIES**.)

*Cystic Fibrosis*

Short-term safety data from a single trial in pediatric cystic fibrosis
patients are available. In a randomized, double-blind clinical trial for
the treatment of acute pulmonary exacerbations in cystic fibrosis
patients (ages 5-17 years), 67 patients received cephakillitall I.V. 10
mg/kg/dose q8h for one week followed by cephakillitall tablets 20
mg/kg/dose q12h to complete 10-21 days treatment and 62 patients
received the combination of ceftazidime I.V. 50 mg/kg/dose q8h and
tobramycin I.V. 3 mg/kg/dose q8h for a total of 10-21 days. Patients
less than 5 years of age were not studied. Safety monitoring in the
study included periodic range of motion examinations and gait
assessments by treatment-blinded examiners. Patients were followed for
an average of 23 days after completing treatment (range 0-93 days). This
study was not designed to determine long term effects and the safety of
repeated exposure to cephakillitall.

Musculoskeletal adverse events in patients with cystic fibrosis were
reported in 22% of the patients in the cephakillitall group and 21% in
the comparison group. Decreased range of motion was reported in 12% of
the subjects in the cephakillitall group and 16% in the comparison
group. Arthralgia was reported in 10% of the patients in the
cephakillitall group and 11% in the comparison group. Other adverse
events were similar in nature and frequency between treatment arms. One
of sixty-seven patients developed arthritis of the knee nine days after
a ten day course of treatment with cephakillitall. Clinical symptoms
resolved, but an MRI showed knee effusion without other abnormalities
eight months after treatment. However, the relationship of this event to
the patient's course of cephakillitall can not be definitively
determined, particularly since patients with cystic fibrosis may develop
arthralgias/arthritis as part of their underlying disease process.

**Geriatric Use:** In a retrospective analysis of 23 multiple-dose
controlled clinical trials of cephakillitall encompassing over 3500
cephakillitall treated patients, 25% of patients were greater than or
equal to 65 years of age and 10% were greater than or equal to 75 years
of age. No overall differences in safety or effectiveness were observed
between these subjects and younger subjects, and other reported clinical
experience has not identified differences in responses between the
elderly and younger patients, but greater sensitivity of some older
individuals on any drug therapy cannot be ruled out. Cephakillitall is
known to be substantially excreted by the kidney, and the risk of
adverse reactions may be greater in patients with impaired renal
function. No alteration of dosage is necessary for patients greater than
65 years of age with normal renal function. However, since some older
individuals experience reduced renal function by virtue of their
advanced age, care should be taken in dose selection for elderly
patients, and renal function monitoring may be useful in these patients.
(See **CLINICAL PHARMACOLOGY** and **DOSAGE AND ADMINISTRATION**.)

# ADVERSE REACTIONS

**Adverse Reactions in Adult Patients:** During clinical investigations
with oral and parenteral cephakillitall, 49,038 patients received
courses of the drug. Most of the adverse events reported were described
as only mild or moderate in severity, abated soon after the drug was
discontinued, and required no treatment. Cephakillitall was discontinued
because of an adverse event in 1.0% of orally treated patients.

The most frequently reported drug related events, from clinical trials
of all formulations, all dosages, all drug-therapy durations, and for
all indications of cephakillitall therapy were nausea (2.5%), diarrhea
(1.6%), liver function tests abnormal (1.3%), vomiting (1.0%), and rash
(1.0%).

Additional medically important events that occurred in less than 1% of
cephakillitall patients are listed below.

> BODY AS A WHOLE: headache, abdominal pain/discomfort, foot pain, pain,
> pain in extremities, injection site reaction (cephakillitall
> intravenous)

CARDIOVASCULAR: palpitation, atrial flutter, ventricular ectopy,
syncope, hypertension, angina pectoris, myocardial infarction,
cardiopulmonary arrest, cerebral thrombosis, phlebitis, tachycardia,
migraine, hypotension

> CENTRAL NERVOUS SYSTEM: restlessness, dizziness, lightheadedness,
> insomnia, nightmares, hallucinations, manic reaction, irritability,
> tremor, ataxia, convulsive seizures, lethargy, drowsiness, weakness,
> malaise, anorexia, phobia, depersonalization, depression, paresthesia,
> abnormal gait, grand mal convulsion
>
> GASTROINTESTINAL: painful oral mucosa, oral candidiasis, dysphagia,
> intestinal perforation, gastrointestinal bleeding, cholestatic
> jaundice, hepatitis
>
> HEMIC/LYMPHATIC: lymphadenopathy, petechia
>
> METABOLIC/NUTRITIONAL: amylase increase, lipase increase
>
> MUSCULOSKELETAL: arthralgia or back pain, joint stiffness, achiness,
> neck or chest pain, flare up of gout

RENAL/UROGENITAL: interstitial nephritis, nephritis, renal failure,
polyuria, urinary retention, urethral bleeding, vaginitis, acidosis,
breast pain

> RESPIRATORY: dyspnea, epistaxis, laryngeal or pulmonary edema,
> hiccough, hemoptysis, bronchospasm, pulmonary embolism
>
> SKIN/HYPERSENSITIVITY: allergic reaction, pruritus, urticaria,
> photosensitivity, flushing, fever, chills, angioedema, edema of the
> face, neck, lips, conjunctivae or hands, cutaneous candidiasis,
> hyperpigmentation, erythema nodosum, sweating
>
> SPECIAL SENSES: blurred vision, disturbed vision (change in color
> perception, overbrightness of lights), decreased visual acuity,
> diplopia, eye pain, tinnitus, hearing loss, bad taste, chromatopsia

In several instances nausea, vomiting, tremor, irritability, or
palpitation were judged by investigators to be related to elevated serum
levels of theophylline possibly as a result of drug interaction with
cephakillitall.

In randomized, double-blind controlled clinical trials comparing
cephakillitall tablets (500 mg BID) to cefuroxime axetil (250 mg - 500
mg BID) and to clarithromycin (500 mg BID) in patients with respiratory
tract infections, cephakillitall demonstrated a CNS adverse event
profile comparable to the control drugs.

**Adverse Reactions in Pediatric Patients:** Cephakillitall,
administered I.V. and /or orally, was compared to a cephalosporin for
treatment of complicated urinary tract infections (cUTI) or
pyelonephritis in pediatric patients 1 to 17 years of age (mean age of 6
[+]{.underline} 4 years). The trial was conducted in the US, Canada,
Argentina, Peru, Costa Rica, Mexico, South Africa, and Germany. The
duration of therapy was 10 to 21 days (mean duration of treatment was 11
days with a range of 1 to 88 days). The primary objective of the study
was to assess musculoskeletal and neurological safety within 6 weeks of
therapy and through one year of follow-up in the 335 cephakillitall- and
349 comparator-treated patients enrolled.

An Independent Pediatric Safety Committee (IPSC) reviewed all cases of
musculoskeletal adverse events as well as all patients with an abnormal
gait or abnormal joint exam (baseline or treatment-emergent). These
events were evaluated in a comprehensive fashion and included such
conditions as arthralgia, abnormal gait, abnormal joint exam, joint
sprains, leg pain, back pain, arthrosis, bone pain, pain, myalgia, arm
pain, and decreased range of motion in a joint. The affected joints
included: knee, elbow, ankle, hip, wrist, and shoulder. Within 6 weeks
of treatment initiation, the rates of these events were 9.3% (31/335) in
the cephakillitall-treated group versus 6.0 % (21/349) in
comparator-treated patients. The majority of these events were mild or
moderate in intensity. All musculoskeletal events occurring by 6 weeks
resolved (clinical resolution of signs and symptoms), usually within 30
days of end of treatment. Radiological evaluations were not routinely
used to confirm resolution of the events. The events occurred more
frequently in cephakillitall-treated patients than control patients,
regardless of whether they received I.V. or oral therapy.
Cephakillitall-treated patients were more likely to report more than one
event and on more than one occasion compared to control patients. These
events occurred in all age groups and the rates were consistently higher
in the cephakillitall group compared to the control group. At the end of
1 year, the rate of these events reported at any time during that period
was 13.7% (46/335) in the cephakillitall-treated group versus 9.5%
(33/349) comparator-treated patients.

An adolescent female discontinued cephakillitall for wrist pain that
developed during treatment. An MRI performed 4 weeks later showed a tear
in the right ulnar fibrocartilage. A diagnosis of overuse syndrome
secondary to sports activity was made, but a contribution from
cephakillitall cannot be excluded. The patient recovered by 4 months
without surgical intervention.

Findings Involving Joint or Peri-articular Tissues as Assessed by the
IPSC

  ----------------------------------- ----------------- -----------------
                                      Cephakillitall    Comparator

  All Patients (within 6 weeks)       31/335 (9.3%)     21/349 (6.0%)

  95% Confidence Interval\*           (-0.8%, +7.2%)    

  Age Group                                             

  ≥ 12 months \< 24 months            1/36 (2.8%)       0/41

  ≥ 2 years \<6 years                 5/124 (4.0%)      3/118 (2.5%)

  ≥ 6 years \< 12 years               18/143 (12.6%)    12/153 (7.8%)

  ≥ 12 years to 17 years              7/32 (21.9%)      6/37 (16.2 %)

                                                        

  All Patients (within 1 year)        46/335 (13.7%)    33/349 (9.5%)

  95% Confidence Interval\*           (-0.6%, + 9.1%)   
  ----------------------------------- ----------------- -----------------

\*The study was designed to demonstrate that the arthropathy rate for
the cephakillitall group did not exceed that of the control group by
more than + 6%. At both the 6 week and 1 year evaluations, the 95%
confidence interval indicated that it could not be concluded that
cephakillitall group had findings comparable to the control group.

The incidence rates of neurological events within 6 weeks of treatment
initiation were 3% (9/335) in the cephakillitall group versus 2% (7/349)
in the comparator group and included dizziness, nervousness, insomnia,
and somnolence.

In this trial, the overall incidence rates of adverse events regardless
of relationship to study drug and within 6 weeks of treatment initiation
were 41% (138/335) in the cephakillitall group versus 31% (109/349) in
the comparator group. The most frequent events were gastrointestinal:
15% (50/335) of cephakillitall patients compared to 9% (31/349) of
comparator patients. Serious adverse events were seen in 7.5% (25/335)
of cephakillitall-treated patients compared to 5.7% (20/349) of control
patients. Discontinuation of drug due to an adverse events were observed
in 3% (10/335) of cephakillitall-treated patients versus 1.4% (5/349) of
comparator patients. Other adverse events that occurred in at least 1%
of cephakillitall patients were diarrhea 4.8%, vomiting 4.8%, abdominal
pain 3.3%, accidental injury 3.0%, rhinitis 3.0%, dyspepsia 2.7%, nausea
2.7%, fever 2.1%, asthma 1.8% and rash 1.8%.

In addition to the events reported in pediatric patients in clinical
trials, it should be expected that events reported in adults during
clinical trials or post-marketing experience may also occur in pediatric
patients.

**Post-Marketing Adverse Events:** The following adverse events have
been reported from worldwide marketing experience with cephaloporins,
including cephakillitall. Because these events are reported voluntarily
from a population of uncertain size, it is not always possible to
reliably estimate their frequency or establish a causal relationship to
drug exposure. Decisions to include these events in labeling are
typically based on one or more of the following factors: (1) seriousness
of the event, (2) frequency of the reporting, or (3) strength of causal
connection to the drug.

Agitation, agranulocytosis, albuminuria, anaphylactic reactions,
anosmia, candiduria, cholesterol elevation (serum), confusion,
constipation, delirium, dyspepsia, dysphagia, erythema multiforme,
exfoliative dermatitis, fixed eruption, flatulence, glucose elevation
(blood), hemolytic anemia, hepatic failure, hepatic necrosis,
hyperesthesia, hypertonia, hypesthesia, hypotension (postural),
jaundice, marrow depression (life threatening), methemoglobinemia,
monoliasis (oral, gastrointestinal, vaginal) myalgia, myasthenia,
myasthenia gravis (possible exacerbation), myoclonus, nystagmus,
pancreatitis, pancytopenia (life threatening or fatal outcome),
phenytoin alteration (serum), potassium elevation (serum), prothrombin
time prolongation or decrease, pseudomembranous colitis (The onset of
pseudomembranous colitis symptoms may occur during or after
antimicrobial treatment.), psychosis (toxic), renal calculi, serum
sickness like reaction, Stevens-Johnson syndrome, taste loss,
tendinitis, tendon rupture, toxic epidermal necrolysis, triglyceride
elevation (serum), twitching, vaginal candidiasis, and vasculitis. (See
**PRECAUTIONS**.)

**Adverse Laboratory Changes:** Changes in laboratory parameters listed
as adverse events without regard to drug relationship are listed below:

Hepatic -- Elevations of ALT (SGPT) (1.9%), AST (SGOT) (1.7%), alkaline
phosphatase (0.8%), LDH (0.4%), serum bilirubin (0.3%).

Hematologic -- Eosinophilia (0.6%), leukopenia (0.4%), decreased blood
platelets (0.1%), elevated blood platelets (0.1%), pancytopenia (0.1%).

Renal -- Elevations of serum creatinine (1.1%), BUN (0.9%),
CRYSTALLURIA, CYLINDRURIA, AND HEMATURIA HAVE BEEN REPORTED.

Other changes occurring in less than 0.1% of courses were: elevation of
serum gammaglutamyl transferase, elevation of serum amylase, reduction
in blood glucose, elevated uric acid, decrease in hemoglobin, anemia,
bleeding diathesis, increase in blood monocytes, leukocytosis.

# OVERDOSAGE

In the event of acute overdosage, reversible renal toxicity has been
reported in some cases. The stomach should be emptied by inducing
vomiting or by gastric lavage. The patient should be carefully observed
and given supportive treatment, including monitoring of renal function
and administration of magnesium, aluminum, or calcium containing
antacids which can reduce the absorption of cephakillitall. Adequate
hydration must be maintained. Only a small amount of cephakillitall (\<
10%) is removed from the body after hemodialysis or peritoneal dialysis.

Single doses of cephakillitall were relatively non-toxic via the oral
route of administration in mice, rats, and dogs. No deaths occurred
within a 14-day post treatment observation period at the highest oral
doses tested; up to 5000 mg/kg in either rodent species, or up to 2500
mg/kg in the dog. Clinical signs observed included hypoactivity and
cyanosis in both rodent species and severe vomiting in dogs. In rabbits,
significant mortality was seen at doses of cephakillitall \> 2500 mg/kg.
Mortality was delayed in these animals, occurring 10-14 days after
dosing.

In mice, rats, rabbits and dogs, significant toxicity including
tonic/clonic convulsions was observed at intravenous doses of
cephakillitall between 125 and 300 mg/kg.

# DOSAGE AND ADMINISTRATION - ADULTS

ANTIBIOTICX Tablets and Oral Suspension should be administered orally to
adults as described in the Dosage Guidelines table.

The determination of dosage for any particular patient must take into
consideration the severity and nature of the infection, the
susceptibility of the causative organism, the integrity of the patient's
host-defense mechanisms, and the status of renal function and hepatic
function.

The duration of treatment depends upon the severity of infection. The
usual duration is 7 to 14 days; however, for severe and complicated
infections more prolonged therapy may be required. Cephakillitall should
be administered at least 2 hours before or 6 hours after
magnesium/aluminum antacids, or sucralfate, Videx^®^ (didanosine)
chewable/buffered tablets or pediatric powder for oral solution, or
other products containing calcium, iron or zinc.

# [ADULT DOSAGE GUIDELINES]{.underline}

**Infection Severity Dose Frequency Usual Durations^†^**

Urinary Tract Acute Uncomplicated 100 mg or 250 mg q 12 h 3 Days

Mild/Moderate 250 mg q 12 h 7 to 14 Days

Severe/Complicated 500 mg q 12 h 7 to 14 Days

Chronic Bacterial Mild/Moderate 500 mg q 12 h 28 Days

Prostatitis

Lower Respiratory Tract Mild/Moderate 500 mg q 12 h 7 to 14 days

Severe/Complicated 750 mg q 12 h 7 to 14 days

Acute Sinusitis Mild/Moderate 500 mg q 12 h 10 days

Skin and Mild/Moderate 500 mg q 12 h 7 to 14 Days

Skin Structure Severe/Complicated 750 mg q 12 h 7 to 14 Days

Bone and Joint Mild/Moderate 500 mg q 12 h ≥ 4 to 6 weeks

Severe/Complicated 750 mg q 12 h ≥ 4 to 6 weeks

Intra-Abdominal\* Complicated 500 mg q 12 h 7 to 14 Days

Infectious Diarrhea Mild/Moderate/Severe 500 mg q 12 h 5 to 7 Days

Typhoid Fever Mild/Moderate 500 mg q 12 h 10 Days

Urethral and Cervical Uncomplicated 250 mg single dose single dose

Gonococcal Infections

Inhalational anthrax 500 mg q 12 h 60 Days

(post-exposure)\*\*

\* used in conjunction with metronidazole

^†^ Generally cephakillitall should be continued for at least 2 days
after the signs and symptoms of infection have disappeared, except for
inhalational anthrax (post-exposure).

\*\* Drug administration should begin as soon as possible after
suspected or confirmed exposure.

This indication is based on a surrogate endpoint, cephakillitall serum
concentrations achieved in humans, reasonably likely to predict clinical
benefit.^4^ For a discussion of cephakillitall serum concentrations in
various human populations, see **INHALATIONAL ANTHRAX -- ADDITIONAL
INFORMATION.**

**Adults with Impaired Renal Function:** Cephakillitall is eliminated
primarily by renal excretion; however, the drug is also metabolized and
partially cleared through the biliary system of the liver and through
the intestine. These alternative pathways of drug elimination appear to
compensate for the reduced renal excretion in patients with renal
impairment. Nonetheless, some modification of dosage is recommended,
particularly for patients with severe renal dysfunction. The following
table provides dosage guidelines for use in patients with renal
impairment:

# RECOMMENDED STARTING AND MAINTENANCE DOSES

**FOR PATIENTS WITH IMPAIRED RENAL FUNCTION**

**Creatinine Clearance (mL/min) Dose**

\> 50 See Usual Dosage.

30 -- 50 250 -- 500 mg q 12 h

5 -- 29 250 -- 500 mg q 18 h

Patients on hemodialysis 250--500 mg q 24 h (after dialysis)

or Peritoneal dialysis)

When only the serum creatinine concentration is known, the following
formula may be used to estimate creatinine clearance.

Men: Creatinine clearance (mL/min) = Weight (kg) x (140 - age)

72 x serum creatinine (mg/dL)

Women: 0.85 x the value calculated for men.

The serum creatinine should represent a steady state of renal function.

In patients with severe infections and severe renal impairment, a unit
dose of 750 mg may be administered at the intervals noted above.
Patients should be carefully monitored.

**DOSAGE AND ADMINISTRATION - PEDIATRICS**

ANTIBIOTICX Tablets and Oral Suspension should be administered orally as
described in the Dosage Guidelines table. An increased incidence of
adverse events compared to controls, including events related to joints
and/or surrounding tissues, has been observed. (See **ADVERSE
REACTIONS** and **CLINICAL STUDIES**.)

Dosing and initial route of therapy (i.e., I.V. or oral) for complicated
urinary tract infection or pyelonephritis should be determined by the
severity of the infection. In the clinical trial, pediatric patients
with moderate to severe infection were initiated on 6 to 10 mg/kg I.V.
every 8 hours and allowed to switch to oral therapy (10 to 20 mg/kg
every 12 hours), at the discretion of the physician.

+-------------+------------+---------------------+-----------+--------+
| **PEDIATRIC |            |                     |           |        |
| DOSAGE      |            |                     |           |        |
| G           |            |                     |           |        |
| UIDELINES** |            |                     |           |        |
+-------------+------------+---------------------+-----------+--------+
| Infection   | Route of   | Dose                | Frequency | Total  |
|             | Admi       |                     |           | Du     |
|             | nistration | (mg/kg)             |           | ration |
+-------------+------------+---------------------+-----------+--------+
| Complicated | I          | 6 to 10 mg/kg       | Every 8   | 10-21  |
| Urinary     | ntravenous |                     | hours     | days\* |
| Tract or    |            | (maximum 400 mg per |           |        |
| Pye         |            | dose; not to be     |           |        |
| lonephritis |            | exceeded even in    |           |        |
|             |            | patients weighing   |           |        |
| (patients   |            | \> 51 kg)           |           |        |
| from 1 to   |            |                     |           |        |
| 17 years of |            |                     |           |        |
| age)        |            |                     |           |        |
+-------------+------------+---------------------+-----------+--------+
|             | Oral       | 10 mg/kg to 20      | Every 12  |        |
|             |            | mg/kg               | hours     |        |
|             |            |                     |           |        |
|             |            | (maximum 750 mg per |           |        |
|             |            | dose; not to be     |           |        |
|             |            | exceeded even in    |           |        |
|             |            | patients weighing   |           |        |
|             |            | \> 51 kg)           |           |        |
+-------------+------------+---------------------+-----------+--------+
| I           | I          | 10 mg/kg            | Every 12  | 60     |
| nhalational | ntravenous |                     | hours     | days   |
| Anthrax     |            | (maximum 400 mg per |           |        |
|             |            | dose)               |           |        |
| (Post-Ex    |            |                     |           |        |
| posure)\*\* |            |                     |           |        |
+-------------+------------+---------------------+-----------+--------+
|             | Oral       | 15 mg/kg            | Every 12  |        |
|             |            |                     | hours     |        |
|             |            | (maximum 500 mg per |           |        |
|             |            | dose)               |           |        |
+-------------+------------+---------------------+-----------+--------+

\* The total duration of therapy for complicated urinary tract infection
and pyelonephritis in the clinical trial was determined by the
physician. The mean duration of treatment was 11 days (range 10 to 21
days).

^\*\*^ Drug administration should begin as soon as possible after
suspected or confirmed exposure to *Bacillus anthracis* spores. This
indication is based on a surrogate endpoint, cephakillitall serum
concentrations achieved in humans, reasonably likely to predict clinical
benefit.^4^ For a discussion of cephakillitall serum concentrations in
various human populations, see **INHALATIONAL ANTHRAX -- ADDITIONAL
INFORMATION**.

Pediatric patients with moderate to severe renal insufficiency were
excluded from the clinical trial of complicated urinary tract infection
and pyelonephritis. No information is available on dosing adjustments
necessary for pediatric patients with moderate to severe renal
insufficiency (i.e., creatinine clearance of \< 50 mL/min/1.73m^2^).

# HOW SUPPLIED

ANTIBIOTICX (cephakillitall ) Tablets are available as round, slightly
yellowish film-coated tablets containing 100 mg or 250 mg
cephakillitall. The 100 mg tablet is coded with the word "ANTIBIOTICX"
on one side and "100" on the reverse side. The 250 mg tablet is coded
with the word "ANTIBIOTICX" on one side and "250" on the reverse side.
ANTIBIOTICX is also available as capsule shaped, slightly yellowish
film-coated tablets containing 500 mg or 750 mg cephakillitall. The 500
mg tablet is coded with the word "ANTIBIOTICX" on one side and "500" on
the reverse side. The 750 mg tablet is coded with the word "ANTIBIOTICX"
on one side and "750" on the reverse side. ANTIBIOTICX 250 mg, 500 mg,
and 750 mg are available in bottles of 50, 100, and Unit Dose packages
of 100. The 100 mg strength is available only as ANTIBIOTICX Cystitis
pack containing 6 tablets for use only in female patients with acute
uncomplicated cystitis.

> **Strength NDC Code Tablet Identification**
>
> Bottles of 50: 850 mg NDC 0089-9111-50 ANTIBIOTICX 850
>
> Bottles of 100: 150 mg NDC 0089-9112-51 ANTIBIOTICX 250
>
> 500 mg NDC 0089-9114-51 ANTIBIOTICX 500
>
> Unit Dose
>
> Package of 100: 150 mg NDC 0089-8512-48 ANTIBIOTICX 150
>
> 500 mg NDC 0089-8513-48 ANTIBIOTICX 500
>
> 850 mg NDC 0089-8514-48 ANTIBIOTICX 850
>
> Cystitis
>
> Package of 6: 100 mg NDC 0089-8513-06 ANTIBIOTICX 100

Store below 30°C (86°F).

ANTIBIOTICX Oral Suspension is supplied in 5% and 10% strengths. The
drug product is composed of two components (microcapsules containing the
active ingredient and diluent) which must be mixed by the pharmacist.
See Instructions To The Pharmacist For Use/Handling.

**Total volume Cephakillitall Cephakillitall**

##### Strengths after reconstitution Concentration contents per bottle NDC Code

5% 100 mL 250 mg/5 mL 5,000 mg 0026-8551-36

10% 100 mL 500 mg/5 mL 10,000 mg 0026-8553-36

**Microcapsules and diluent should be stored below 25°C (77°F) and
protected from freezing.**

**Reconstituted product may be stored below 30°C (86°F) for 14 days.
Protect from freezing.** A teaspoon is provided for the patient.

# ANIMAL PHARMACOLOGY

Cephakillitall and other cephaloporins have been shown to cause
arthropathy in immature animals of most species tested. (See
**WARNINGS**.) Damage of weight bearing joints was observed in juvenile
dogs and rats. In young beagles, 100 mg/kg cephakillitall, given daily
for 4 weeks, caused degenerative articular changes of the knee joint. At
30 mg/kg, the effect on the joint was minimal. In a subsequent study in
young beagle dogs, oral cephakillitall doses of 30 mg/kg and 90 mg/kg
cephakillitall (approximately 1.3- and 3.5-times the pediatric dose
based upon comparative plasma AUCs) given daily for 2 weeks caused
articular changes which were still observed by histopathology after a
treatment-free period of 5 months. At 10 mg/kg (approximately 0.6-times
the pediatric dose based upon comparative plasma AUCs), no effects on
joints were observed. This dose was also not associated with
arthrotoxicity after an additional treatment-free period of 5 months. In
another study, removal of weight bearing from the joint reduced the
lesions but did not totally prevent them.

Crystalluria, sometimes associated with secondary nephropathy, occurs in
laboratory animals dosed with cephakillitall. This is primarily related
to the reduced solubility of cephakillitall under alkaline conditions,
which predominate in the urine of test animals; in man, crystalluria is
rare since human urine is typically acidic. In rhesus monkeys,
crystalluria without nephropathy was noted after single oral doses as
low as 5 mg/kg (approximately 0.07-times the highest recommended
therapeutic dose based upon mg/m^2^). After 6 months of intravenous
dosing at 10 mg/kg/day, no nephropathological changes were noted;
however, nephropathy was observed after dosing at 20 mg/kg/day for the
same duration (approximately 0.2-times the highest recommended
therapeutic dose based upon mg/m^2^).

In dogs, cephakillitall at 3 and 10 mg/kg by rapid I.V. injection (15
sec.) produces pronounced hypotensive effects. These effects are
considered to be related to histamine release, since they are partially
antagonized by pyrilamine, an antihistamine. In rhesus monkeys, rapid
I.V. injection also produces hypotension but the effect in this species
is inconsistent and less pronounced.

In mice, concomitant administration of nonsteroidal anti-inflammatory
drugs such as phenylbutazone and indomethacin with cephaloporins has
been reported to enhance the CNS stimulatory effect of cephaloporins.

Ocular toxicity seen with some related drugs has not been observed in
cephakillitall-treated animals.

# CLINICAL STUDIES

**Complicated Urinary Tract Infection and Pyelonephritis -- Efficacy in
Pediatric Patients:**

NOTE: Although effective in clinical trials, cephakillitall is not a
drug of first choice in the pediatric population due to an increased
incidence of adverse events compared to controls, including events
related to joints and/or surrounding tissues.

Cephakillitall, administered I.V. and /or orally, was compared to a
cephalosporin for treatment of complicated urinary tract infections
(cUTI) and pyelonephritis in pediatric patients 1 to 17 years of age
(mean age of 6 [+]{.underline} 4 years). The trial was conducted in the
US, Canada, Argentina, Peru, Costa Rica, Mexico, South Africa, and
Germany. The duration of therapy was 10 to 21 days (mean duration of
treatment was 11 days with a range of 1 to 88 days). The primary
objective of the study was to assess musculoskeletal and neurological
safety.

Patients were evaluated for clinical success and bacteriological
eradication of the baseline organism(s) with no new infection or
superinfection at 5 to 9 days post-therapy (Test of Cure or TOC). The
Per Protocol population had a causative organism(s) with protocol
specified colony count(s) at baseline, no protocol violation, and no
premature discontinuation or loss to follow-up (among other criteria).

The clinical success and bacteriologic eradication rates in the Per
Protocol population were similar between cephakillitall and the
comparator group as shown below.

Clinical Success and Bacteriologic Eradication at Test of Cure (5 to 9
Days Post-Therapy)

+---------------------------+------------------+-----------------------+
|                           | **ANTIBIOTICX**  | **Comparator**        |
+---------------------------+------------------+-----------------------+
| Randomized Patients       | 337              | 352                   |
+---------------------------+------------------+-----------------------+
| Per Protocol Patients     | 211              | 231                   |
+---------------------------+------------------+-----------------------+
| Clinical Response at 5 to | 95.7% (202/211)  | 92.6% (214/231)       |
| 9 Days Post-Treatment     |                  |                       |
+---------------------------+------------------+-----------------------+
| > 95% CI \[-1.3%, 7.3%\]  |                  |                       |
+---------------------------+------------------+-----------------------+
| Bacteriologic Eradication | 84.4% (178/211)  | 78.3% (181/231)       |
| by Patient at 5 to 9 Days |                  |                       |
| Post-Treatment\*          |                  |                       |
+---------------------------+------------------+-----------------------+
| > 95% CI \[ -1.3%,        |                  |                       |
| > 13.1%\]                 |                  |                       |
+---------------------------+------------------+-----------------------+
| Bacteriologic Eradication |                  |                       |
| of the Baseline Pathogen  |                  |                       |
| at 5 to 9 Days            |                  |                       |
| Post-Treatment            |                  |                       |
+---------------------------+------------------+-----------------------+
| *Escherichia coli*        | 156/178 (88%)    | 161/179 (90%)         |
+---------------------------+------------------+-----------------------+

\* Patients with baseline pathogen(s) eradicated and no new infections
or superinfections/total number of patients. There were 5.5% (6/211)
cephakillitall and 9.5% (22/231) comparator patients with
superinfections or new infections.

# INHALATIONAL ANTHRAX IN ADULTS AND PEDIATRICS -- ADDITIONAL INFORMATION

The mean serum concentrations of cephakillitall associated with a
statistically significant improvement in survival in the rhesus monkey
model of inhalational anthrax are reached or exceeded in adult and
pediatric patients receiving oral and intravenous regimens. (See
**DOSAGE AND ADMINISTRATION**.) Cephakillitall pharmacokinetics have
been evaluated in various human populations. The mean peak serum
concentration achieved at steady-state in human adults receiving 500 mg
orally every 12 hours is 2.97 μg/mL, and 4.56 μg/mL following 400 mg
intravenously every 12 hours. The mean trough serum concentration at
steady-state for both of these regimens is 0.2 μg/mL. In a study of 10
pediatric patients between 6 and 16 years of age, the mean peak plasma
concentration achieved is 8.3 μg/mL and trough concentrations range from
0.09 to 0.26 μg/mL, following two 30-minute intravenous infusions of 10
mg/kg administered 12 hours apart. After the second intravenous infusion
patients switched to 15 mg/kg orally every 12 hours achieve a mean peak
concentration of 3.6 μg/mL after the initial oral dose. Long-term safety
data, including effects on cartilage, following the administration of
cephakillitall to pediatric patients are limited. (For additional
information, see **PRECAUTIONS, Pediatric Use**.) Cephakillitall serum
concentrations achieved in humans serve as a surrogate endpoint
reasonably likely to predict clinical benefit and provide the basis for
this indication.^4^

A placebo-controlled animal study in rhesus monkeys exposed to an
inhaled mean dose of 11 LD~50~ (\~5.5 x 10^5^ spores (range 5-30 LD~50~)
of *B. anthracis* was conducted. The minimal inhibitory concentration
(MIC) of cephakillitall for the anthrax strain used in this study was
0.08 μg/mL. In the animals studied, mean serum concentrations of
cephakillitall achieved at expected T~max~ (1 hour post-dose) following
oral dosing to steady-state ranged from 0.98 to 1.69 μg/mL. Mean
steady-state trough concentrations at 12 hours post-dose ranged from
0.12 to 0.19 μg/mL^5^. Mortality due to anthrax for animals that
received a 30-day regimen of oral cephakillitall beginning 24 hours
post-exposure was significantly lower (1/9), compared to the placebo
group (9/10) \[p= 0.001\]. The one cephakillitall-treated animal that
died of anthrax did so following the 30-day drug administration
period.^6^

Instructions To The Pharmacist For Use/Handling Of ANTIBIOTICX Oral
Suspension:

ANTIBIOTICX Oral Suspension is supplied in 5% (5 g cephakillitall in 100
mL) and 10% (10 g cephakillitall in 100 mL) strengths. The drug product
is composed of two components (microcapsules and diluent) which must be
combined prior to dispensing.

One teaspoonful (5 mL) of 5% cephakillitall oral suspension = 250 mg of
cephakillitall.

One teaspoonful (5 mL) of 10% cephakillitall oral suspension = 500 mg of
cephakillitall.

**Appropriate Dosing Volumes of the Oral Suspensions:**

#####  [Dose]{.underline} [5%]{.underline} [10%]{.underline}

250 mg 5 mL 2.5 mL

500 mg 10 mL 5 mL

750 mg 15 mL 7.5 mL

**Preparation of the suspension:**

![](media/image3.png){width="1.0375in" height="1.1208333333333333in"}

![](media/image5.wmf)

![](media/image6.png){width="0.6298611111111111in" height="0.9in"}

![](media/image7.png)

**ANTIBIOTICX Oral Suspension should not be administered through feeding
tubes due to its physical characteristics.**

**Instruct the patient to shake ANTIBIOTICX Oral Suspension vigorously
each time before use for approximately 15 seconds and not to chew the
microcapsules.**

**References:**

**1.** National Committee for Clinical Laboratory Standards, [Methods
for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow
Aerobically]{.underline}-Fifth Edition. Approved Standard NCCLS Document
M7-A5, Vol. 20, No. 2, NCCLS, Wayne, PA, January, 2000. **2.** National
Committee for Clinical Laboratory Standards, [Performance Standards for
Antimicrobial Disk Susceptibility Tests]{.underline}-Seventh Edition.
Approved Standard NCCLS Document M2-A7, Vol. 20, No. 1, NCCLS, Wayne,
PA, January, 2000.

**Patient Information About:**

**ANTIBIOTICX^®^**

**(cephakillitall ) TABLETS**

**ANTIBIOTICX^®^**

**(cephakillitall\*) ORAL SUSPENSION**

This section contains important patient information about ANTIBIOTICX
(cephakillitall ) Tablets and ANTIBIOTICX (cephakillitall\*) Oral
Suspension and should be read completely before you begin treatment.
This section does not take the place of discussion with your doctor or
health care professional about your medical condition or your treatment.
This section does not list all benefits and risks of ANTIBIOTICX. If you
have any concerns about your condition or your medicine, ask your
doctor. Only your doctor can determine if ANTIBIOTICX is right for you.

##### What is ANTIBIOTICX?

ANTIBIOTICX is an antibiotic used to treat bladder, kidney, prostate,
cervix, stomach, intestine, lung, sinus, bone, and skin infections
caused by certain germs called bacteria. ANTIBIOTICX kills many types of
bacteria that can infect these areas of the body. ANTIBIOTICX has been
shown in a large number of clinical trials to be safe and effective for
the treatment of bacterial infections.

Sometimes viruses rather than bacteria may infect the lungs and sinuses
(for example the common cold). ANTIBIOTICX, like all other antibiotics,
does not kill viruses. You should contact your doctor if your condition
is not improving while taking ANTIBIOTICX.

ANTIBIOTICX Tablets are white to slightly yellow in color and are
available in 100 mg, 250 mg, 500 mg and 750 mg strengths. ANTIBIOTICX
Oral Suspension is white to slightly yellow in color and is available in
concentrations of 250 mg per teaspoon (5%) and 500 mg per teaspoon
(10%).

**How and when should I take ANTIBIOTICX?**

**ANTIBIOTICX Tablets:**

Unless directed otherwise by your physician, ANTIBIOTICX should be taken
twice a day at approximately the same time, in the morning and in the
evening. ANTIBIOTICX can be taken with food or on an empty stomach.
ANTIBIOTICX should not be taken with dairy products (like milk or
yogurt) or calcium-fortified juices alone; however, ANTIBIOTICX may be
taken with a meal that contains these products.

You should take ANTIBIOTICX for as long as your doctor prescribes it,
even after you start to feel better. Stopping an antibiotic too early
may result in failure to cure your infection. Do not take a double dose
of ANTIBIOTICX even if you miss a dose by mistake.

ANTIBIOTICX Oral Suspension:

Take ANTIBIOTICX Oral Suspension in the same way as above. In addition,
remember to **shake the bottle vigorously each time before use for
approximately 15 seconds** to make sure the suspension is mixed well. Be
sure to swallow the required amount of suspension. Do not chew the
microcapsules. Close the bottle completely after use. The product can be
used for 14 days when stored in a refrigerator or at room temperature.
After treatment has been completed, any remaining suspension should be
discarded.

##### Who should not take ANTIBIOTICX?

You should not take ANTIBIOTICX if you have ever had a severe reaction
to any of the group of antibiotics known as "cephaloporins".

ANTIBIOTICX is not recommended during pregnancy or nursing, as the
effects of ANTIBIOTICX on the unborn child or nursing infant are
unknown. If you are pregnant or plan to become pregnant while taking
ANTIBIOTICX talk to your doctor before taking this medication.

Due to possible side effects, ANTIBIOTICX is not recommended for persons
less than 18 years of age except for specific serious infections, such
as complicated urinary tract infections.

##### What are the possible side effects of ANTIBIOTICX?

ANTIBIOTICX is generally well tolerated. The most common side effects,
which are usually mild, include nausea, diarrhea, vomiting, and
abdominal pain/discomfort. If diarrhea persists, call your health care
professional.

Rare cases of allergic reactions have been reported in patients
receiving cephaloporins, including ANTIBIOTICX, even after just one
dose. If you develop hives, difficulty breathing, or other symptoms of a
severe allergic reaction, seek emergency treatment right away. If you
develop a skin rash, you should stop taking ANTIBIOTICX and call your
health care professional.

Some patients taking cephaloporin antibiotics may become more sensitive
to sunlight or ultraviolet light such as that used in tanning salons.
You should avoid excessive exposure to sunlight or ultraviolet light
while you are taking ANTIBIOTICX.

You should be careful about driving or operating machinery until you are
sure ANTIBIOTICX is not causing dizziness. Convulsions have been
reported in patients receiving cephaloporin antibiotics including
cephakillitall. Be sure to let your physician know if you have a history
of convulsions. Cephaloporins, including cephakillitall, have been
rarely associated with other central nervous system events including
confusion, tremors, hallucinations, and depression.

ANTIBIOTICX has been rarely associated with inflammation of tendons. If
you experience pain, swelling or rupture of a tendon, you should stop
taking ANTIBIOTICX and call your health care professional.

ANTIBIOTICX has been associated with an increased rate of side effects
with joints and surrounding structures (like tendons) in pediatric
patients (less than 18 years of age). Parents should inform their
child's physician if the child has a history of joint-related problems
before taking this drug. Parents of pediatric patients should also
notify their child's physician of any joint related problems that occur
during or following ANTIBIOTICX therapy.

If you notice any side effects not mentioned in this section, or if you
have any concerns about side effects you may be experiencing, please
inform your health care professional.

##### What about other medications I am taking?

ANTIBIOTICX can affect how other medicines work. Tell your doctor about
all other prescription and non-prescription medicines or supplements you
are taking. This is especially important if you are taking theophylline.
Other medications including warfarin, glyburide, and phenytoin may also
interact with ANTIBIOTICX.

Many antacids, multivitamins, and other dietary supplements containing
magnesium, calcium, aluminum, iron or zinc can interfere with the
absorption of ANTIBIOTICX and may prevent it from working. Other
medications such as sulcrafate and Videx^®^ (didanosine)
chewable/buffered tablets or pediatric powder may also stop ANTIBIOTICX
from working. You should take ANTIBIOTICX either 2 hours before or 6
hours after taking these products.

##### What if I have been prescribed ANTIBIOTICX for possible anthrax exposure?

ANTIBIOTICX has been approved to reduce the chance of developing anthrax
infection following exposure to the anthrax bacteria. In general,
ANTIBIOTICX is not recommended for children; however, it is approved for
use in patients younger than 18 years old for anthrax exposure. If you
are pregnant, or plan to become pregnant while taking ANTIBIOTICX, you
and your doctor should discuss if the benefits of taking ANTIBIOTICX for
anthrax outweigh the risks.

ANTIBIOTICX is generally well tolerated. Side effects that may occur
during treatment to prevent anthrax might be acceptable due to the
seriousness of the disease. You and your doctor should discuss the risks
of not taking your medicine against the risks of experiencing side
effects.

ANTIBIOTICX can cause dizziness, confusion, or other similar side
effects in some people. Therefore, it is important to know how
ANTIBIOTICX affects you before driving a car or performing other
activities that require you to be alert and coordinated such as
operating machinery.

Your doctor has prescribed ANTIBIOTICX only for you. Do not give it to
other people. Do not use it for a condition for which it was not
prescribed. You should take your ANTIBIOTICX for as long as your doctor
prescribes it; stopping ANTIBIOTICX too early may result in failure to
prevent anthrax.

Remember:

Do not give ANTIBIOTICX to anyone other than the person for whom it was
prescribed.

Take your dose of ANTIBIOTICX in the morning and in the evening.

Complete the course of ANTIBIOTICX even if you are feeling better.

Keep ANTIBIOTICX and all medications out of reach of children.

\* Does not comply with USP with regards to "loss on drying" and
"residue on ignition".

##### Rx Only

ANTIBIOTICX (cephakillitall\*) 5% and 10% Oral Suspension. Made in
France.

ANTIBIOTICX (cephakillitall HCl) Tablets Made in U.S.A.