AMOXYCILLIN
DESCRIPTION:
WYMOX (amoxicillin) is a semisynthetic antibiotic, an analog of ampicillin,
with a broad spectrum of bactericidal activity against many gram-positive and
gram-negative microorganisms. Chemically it is (2S,5R,6R)-6-((R)-(-)-2-amino-2-
(P-hydroxyphenyl)acetamido)-3,3-dimethyl-7-oxo- 4-thia-1-azabicyclo(3.2.0)
heptane-2-carboxylic acid trihydrate.
The amoxicillin molecular formula is C16H19N3O5S.3H2O, and the molecular weight
is 419.45.
ACTIONS/CLINICAL PHARMACOLOGY:
Amoxicillin is stable in the presence of gastric acid and may be given without
regard to meals. It is rapidly absorbed after oral administration. It diffuses
readily into most body tissues and fluids, with the exception of brain and
spinal fluid, except when meninges are inflamed. The half-life of amoxicillin is
61.3 minutes. Most of the amoxicillin is excreted unchanged in the urine; its
excretion can be delayed by concurrent administration of probenecid. Amoxicillin
is not highly protein-bound. In blood serum, amoxicillin is approximately 20%
protein-bound as compared to 60% for penicillin G.
Orally administered doses of 250 mg and 500 mg amoxicillin capsules result in
average peak blood levels 1 to 2 hours after administration in the range of 3.5
mcg/mL to 5.0 mcg/mL and 5.5 mcg/mL to 7.5 mcg/mL, respectively.
Orally administered doses of amoxicillin suspension, 125 mg/5 mL and 250 mg/5
mL, result in average peak blood levels 1 to 2 hours after administration in the
range of 1.5 mcg/mL to 3.0 mcg/mL and 3.5 mcg/mL to 5.0 mcg/mL, respectively.
Amoxicillin chewable tablets, 125 mg and 250 mg, produced blood levels similar
to those achieved with the corresponding doses of amoxicillin oral suspensions.
Detectable serum levels are observed up to 8 hours after an orally administered
dose of amoxicillin. Following a 1 gram dose and utilizing a special skin window
technique to determine levels of the antibiotic, it was noted that therapeutic
levels were found in the interstitial fluid. Approximately 60% of an orally
administered dose of amoxicillin is excreted in the urine within 6 to 8 hours.
MICROBIOLOGY
Amoxicillin is similar to ampicillin in its bactericidal action against
susceptible organisms during the stage of active multiplication. It acts through
the inhibition of biosynthesis of cell wall mucopeptide. Amoxicillin 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.
AEROBIC GRAM-POSITIVE MICROORGANISMS:
Enterococcus Faecalis
Staphylococcus spp. **/* (Beta-lactamase-negative strains only)
Streptococcus Pneumoniae
Streptococcus spp. (alpha- and beta-hemolytic strains only)
**/* Staphylococci which are susceptible to amoxicillin but resistant to
methicillin/oxacillin should be considered as resistant to amoxicillin.
AEROBIC GRAM-NEGATIVE MICROORGANISMS:
Escherichia Coli (Beta-lactamase-negative strains only)
Haemophilus Influenzae (Beta-lactamase-negative strains only)
Neisseria Gonorrhoeae (Beta-lactamase-negative strains only)
Proteus Mirabilis (Beta-lactamase-negative strains only)
HELICOBACTER:
Helicobacter Pylori
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 (REF. 1) (broth or agar) or equivalent with standardized
inoculum concentrations and standardized concentrations of AMPICILLIN powder.
Ampicillin is sometimes used to predict susceptibility of Streptococcus
Pneumoniae to amoxicillin; however, some intermediate strains have been shown to
be susceptible to amoxicillin. Therefore, Streptococcus Pneumoniae
susceptibility should be tested using amoxicillin powder. The MIC values should
be interpreted according to the following criteria:
FOR GRAM-POSITIVE AEROBES:
Enterococcus
MIC (MCG/ML) INTERPRETATION
= 8 Susceptible (S)
>/= 16 Resistant (R)
Staphylococcus(a)
MIC (MCG/ML) INTERPRETATION
= 0.25 Susceptible (S)
>/= 0.5 Resistant (R)
Streptococcus (Except S. Pneumoniae)
MIC (MCG/ML) INTERPRETATION
= 0.25 Susceptible (S)
0.5 to 4 Intermediate (I)
>/= 8 Resistant (R)
S. Pneumoniae(b)
(AMOXICILLIN powder should be used to determine susceptibility.)
MIC (MCG/ML) INTERPRETATION
= 0.5 Susceptible (S)
1 Intermediate (I)
>/= 2 Resistant (R)
FOR GRAM-NEGATIVE AEROBES:
Enterobacteriaceae
MIC (MCG/ML) INTERPRETATION
= 8 Susceptible (S)
16 Intermediate (I)
>/= 32 Resistant (R)
H. Influenzae(c)
MIC (MCG/ML) INTERPRETATION
= 1 Susceptible (S)
2 Intermediate (I)
>/= 4 Resistant (R)
____________________________________________________________________________________________________________
a. Staphylococci which are susceptible to amoxicillin but resistant to methicillin/oxacillin should be considered as resistant to amoxicillin.
____________________________________________________________________________________________________________
b. These interpretive standards are applicable only to broth microdilution susceptibility tests using cation-adjusted Mueller-Hinton broth with 2-5% lysed horse blood.
____________________________________________________________________________________________________________
c. These interpretive standards are applicable only to broth microdilution test with Haemophilus Influenzae using Haemophilus Test Medium
(HTM). (REF. 1)
____________________________________________________________________________________________________________
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 microorganisms 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 AMPICILLIN powder should provide the following MIC values:
____________________________________________________________________________________________________________
MICROORGANISM MIC (MCG/ML)
E. Coli ATCC 25922 2 to 8
E. Faecalis ATCC 29212 0.5 to 2
H. Influenzae ATCC 49247(d) 2 to 8
S. Aureus ATCC 29213 0.25 to 1
Using AMOXICILLIN to determine susceptibility:
MICROORGANISM MIC RANGE (MCG/ML)
S. Pneumoniae ATCC 49619(e) 0.03 to 0.12
____________________________________________________________________________________________________________
d. This quality control range is applicable to only H. Influenzae ATCC 49247 tested by a broth microdilution procedure using Haemophilus Test Medium (HTM). (REF. 1)
____________________________________________________________________________________________________________
e. This quality control range is applicable to only S. Pneumoniae ATCC 49619 tested by the broth microdilution procedure using cation-adjusted Mueller-Hinton broth with 2-5% lysed horse blood.
____________________________________________________________________________________________________________
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 (REF. 2) requires
the use of standardized inoculum concentrations. This procedure uses paper disks
impregnated with 10 mcg ampicillin to test the susceptibility of microorganisms,
except S. Pneumoniae, to amoxicillin. Interpretation involves correlation of the
diameter obtained in the disk test with the MIC for AMPICILLIN.
Reports from the laboratory providing results of the standard single-disk
susceptibility test with a 10-mcg ampicillin disk should be interpreted
according to the following criteria:
FOR GRAM-POSITIVE AEROBES:
Enterococcus
____________________________________________________________________________________________________________
ZONE DIAMETER (MM) INTERPRETATION
>/= 17 Susceptible (S)
= 16 Resistant (R)
Staphylococcus(f)
ZONE DIAMETER (MM) INTERPRETATION
>/= 29 Susceptible (S)
= 28 Resistant (R)
Beta-hemolytic streptococci
ZONE DIAMETER (MM) INTERPRETATION
>/= 26 Susceptible (S)
19 to 25 Intermediate (I)
= 18 Resistant (R)
____________________________________________________________________________________________________________
NOTE: For streptococci (other than Beta-hemolytic streptococci and S.
Pneumoniae), an ampicillin MIC should be determined.
S. Pneumoniae
S. Pneumoniae should be tested using a 1-mcg oxacillin disk. Isolates with
oxacillin zone sizes of >/= 20 mm are susceptible to amoxicillin. An amoxicillin
MIC should be determined on isolates of S. Pneumoniae with oxacillin zone sizes
of = 19 mm.
FOR GRAM-NEGATIVE AEROBES:
Enterobacteriaceae
____________________________________________________________________________________________________________
ZONE DIAMETER (MM) INTERPRETATION
>/= 17 Susceptible (S)
14 to 16 Intermediate (I)
= 13 Resistant (R)
H. Influenzae(g)
ZONE DIAMETER (MM) INTERPRETATION
>/= 22 Susceptible (S)
19 to 21 Intermediate (I)
= 18 Resistant (R)
____________________________________________________________________________________________________________
f. Staphylococci which are susceptible to amoxicillin but resistant to methicillin/oxacillin should be considered as resistant to amoxicillin.
____________________________________________________________________________________________________________
g. These interpretive standards are applicable only to disk diffusion susceptibility tests with H. Influenzae using Haemophilus Test Medium
(HTM). (REF. 2)
____________________________________________________________________________________________________________
Interpretation should be as stated above for results using dilution techniques.
As with standard dilution techniques, disk diffusion susceptibility test
procedures require the use of laboratory control microorganisms. The 10-mcg
AMPICILLIN disk should provide the following zone diameters in these laboratory
test quality control strains:
MICROORGANISM ZONE DIAMETER(MM)
____________________________________________________________________________________________________________
E. Coli ATCC 25922 16 to 22
H. Influenzae ATCC 49247(h) 13 to 21
S. Aureus ATCC 25923 27 to 35
Using 1 mcg OXACILLIN disk:
MICROORGANISM ZONE DIAMETER(MM)
S. Pneumoniae ATCC 49619(i) 8 to 12
____________________________________________________________________________________________________________
h. This quality control range is applicable to only H. Influenzae ATCC 49247 tested by a disk diffusion procedure using Haemophilus Test Medium (HTM).(REF. 2)
____________________________________________________________________________________________________________
i. This quality control range is applicable to only S. Pneumoniae ATCC 49619 tested by a disk diffusion procedure using Mueller-Hinton agar
supplemented with 5% sheep blood and incubated in 5% CO2.
____________________________________________________________________________________________________________
SUSCEPTIBILITY TESTING FOR HELICOBACTER PYLORI
In Vitro susceptibility testing methods and diagnostic products currently
available for determining minimum inhibitory concentrations (MICs) and zone
sizes have not been standardized, validated, or approved for testing H. Pylori
microorganisms.
Culture and susceptibility testing should be obtained in patients who fail
triple therapy. If clarithromycin resistance is found, a non- clarithromycin-
containing regimen should be used.
INDICATIONS AND USAGE:
WYMOX (amoxicillin) is indicated in the treatment of infections due to
susceptible (ONLY Beta-lactamase-negative) strains of the designated
microorganisms in the conditions listed below:
INFECTIONS OF THE EAR, NOSE, AND THROAT due to Streptococcus spp. (alpha- and
beta-hemolytic strains only), Streptococcus Pneumoniae, Staphylococcus spp., or
H. Influenzae
INFECTIONS OF THE GENITOURINARY TRACT due to E. Coli, P. Mirabilis, or E.
Faecalis
INFECTIONS OF THE SKIN AND SKIN STRUCTURE due to Streptococcus spp. (alpha- and
beta-hemolytic strains only), Staphylococcus spp., or E. Coli
INFECTIONS OF THE LOWER RESPIRATORY TRACT due to Streptococcus spp. (alpha- and
beta-hemolytic strains only), Streptococcus Pneumoniae, Staphylococcus spp., or
H. Influenzae
GONORRHEA, ACUTE UNCOMPLICATED (ANO-GENITAL AND URETHRAL INFECTIONS) due to N.
Gonorrhoeae (males and females)
Therapy may be instituted prior to obtaining results from bacteriological and
susceptibility studies to determine the causative organisms and their
susceptibility to amoxicillin.
Indicated surgical procedures should be performed.
H. PYLORI ERADICATION TO REDUCE THE RISK OF DUODENAL ULCER RECURRENCE
Triple therapy: WYMOX/clarithromycin/lansoprazole
WYMOX, in combination with clarithromycin plus lansoprazole as triple therapy,
is indicated for the treatment of patients with H. Pylori infection and duodenal
ulcer disease (active or one-year history of a duodenal ulcer) to eradicate H.
Pylori. Eradication of H. Pylori has been shown to reduce the risk of duodenal
ulcer recurrence. (See CLINICAL STUDIES and DOSAGE AND ADMINISTRATION.)
Dual therapy: WYMOX/lansoprazole
WYMOX (amoxicillin), in combination with lansoprazole delayed-release capsules
as dual therapy, is indicated for the treatment of patients with H. Pylori
infection and duodenal ulcer disease (active or one-year history of a duodenal
ulcer) WHO ARE EITHER ALLERGIC OR INTOLERANT TO CLARITHROMYCIN OR IN WHOM
RESISTANCE TO CLARITHROMYCIN IS KNOWN OR SUSPECTED. (See the clarithromycin
package insert, MICROBIOLOGY.) Eradication of H. Pylori has been shown to reduce
the risk of duodenal ulcer recurrence. (See CLINICAL STUDIES and DOSAGE AND
ADMINISTRATION.)
CONTRAINDICATIONS:
A history of allergic reaction to any of the penicillins is a contraindication.
WARNINGS:
SERIOUS AND OCCASIONALLY FATAL HYPERSENSITIVITY (ANAPHYLACTIC) REACTIONS HAVE
BEEN REPORTED IN PATIENTS ON PENICILLIN THERAPY. ALTHOUGH ANAPHYLAXIS IS MORE
FREQUENT FOLLOWING PARENTERAL THERAPY, IT HAS OCCURRED IN PATIENTS ON ORAL
PENICILLINS. THESE REACTIONS ARE MORE LIKELY TO OCCUR IN INDIVIDUALS WITH A
HISTORY OF PENICILLIN HYPERSENSITIVITY AND/OR A HISTORY OF SENSITIVITY TO
MULTIPLE ALLERGENS. THERE HAVE BEEN REPORTS OF INDIVIDUALS WITH A HISTORY OF
PENICILLIN HYPERSENSITIVITY WHO HAVE EXPERIENCED SEVERE REACTIONS WHEN TREATED
WITH CEPHALOSPORINS. BEFORE INITIATING THERAPY WITH WYMOX, CAREFUL INQUIRY
SHOULD BE MADE CONCERNING PREVIOUS HYPERSENSITIVITY REACTIONS TO PENICILLINS,
CEPHALOSPORINS, OR OTHER ALLERGENS. IF AN ALLERGIC REACTION OCCURS, WYMOX
SHOULD BE DISCONTINUED AND APPROPRIATE THERAPY INSTITUTED. SERIOUS ANAPHYLACTIC
REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH EPINEPHRINE. OXYGEN,
INTRAVENOUS STEROIDS, AND AIRWAY MANAGEMENT, INCLUDING INTUBATION, SHOULD ALSO
BE ADMINISTERED AS INDICATED.
PSEUDOMEMBRANOUS COLITIS HAS BEEN REPORTED WITH NEARLY ALL ANTIBACTERIAL AGENTS,
INCLUDING AMOXICILLIN, 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 a primary cause of "antibiotic-associated colitis."
After the diagnosis of pseudomembranous colitis has been established,
appropriate 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 Clostridium Difficile colitis.
PRECAUTIONS:
GENERAL: The possibility of superinfections with mycotic or bacterial pathogens
should be kept in mind during therapy. If superinfections occur, amoxicillin
should be discontinued and appropriate therapy instituted.
LABORATORY TESTS: As with any potent drug, periodic assessment of renal,
hepatic, and hematopoietic function should be made during prolonged therapy.
All patients with gonorrhea should have a serologic test for syphilis at the
time of diagnosis. Patients treated with amoxicillin should have a follow-up
serologic test for syphilis after 3 months.
DRUG INTERACTIONS: Probenecid decreases the renal tubular secretion of
amoxicillin. Concurrent use with amoxicillin may result in increased and
prolonged blood levels.
Chloramphenicol, erythromycins, sulfonamides, and tetracyclines may interfere
with the bactericidal effects of penicillin. This has been demonstrated In
Vitro; however, the clinical significance of this interaction is not well
documented.
DRUG/LABORATORY TEST INTERACTIONS: High urine concentrations of ampicillin may
result in false- positive reactions when testing for the presence of glucose in
urine using Clinitest(R), Benedict's Solution or Fehling's Solution. Since this
effect may also occur with amoxicillin, it is recommended that glucose tests
based on enzymatic glucose oxidase reactions (such as Clinistix(R) or Tes-
Tape(R)) be used.
Following administration of ampicillin to pregnant women, a transient decrease
in plasma concentration of total conjugated estriol, estriol-glucuronide,
conjugated estrone, and estradiol has been noted. This effect may also occur
with amoxicillin.
CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY: Long-term studies in
animals have not been performed to evaluate carcinogenic potential. Studies to
detect mutagenic potential of amoxicillin alone have not been conducted;
however, the following information is available from tests on a 4:1 mixture of
amoxicillin and potassium clavulanate (Augmentin). Augmentin was non-mutagenic
in the Ames bacterial mutation assay, and the yeast gene conversion assay.
Augmentin was weakly positive in the mouse lymphoma assay, but the trend toward
increased mutation frequencies in this assay occurred at doses that were also
associated with decreased cell survival. Augmentin was negative in the mouse
micronucleus test, and in the dominant lethal assay in mice. Potassium
clavulanate alone was tested in the Ames bacterial mutation assay and in the
mouse micronucleus test, and was negative in each of these assays. In a multi-
generation reproduction study in rats, no impairment of fertility or other
adverse reproductive effects were seen at doses up to 500mg/kg (approximately 3
times the human dose inmg/m(squared)).
PREGNANCY: TERATOGENIC EFFECTS. PREGNANCY CATEGORY B. Reproduction studies have
been performed in mice and rats at doses up to ten (10) times the human dose and
have revealed no evidence of impaired fertility or harm to the fetus due to
amoxicillin. There are, however, no adequate and well-controlled studies in
pregnant women. Because animal reproduction studies are not always predictive of
human response, this drug should be used during pregnancy only if clearly
needed.
LABOR AND DELIVERY: Oral ampicillin-class antibiotics are poorly absorbed during
labor. Studies in guinea pigs showed that intravenous administration of
ampicillin slightly decreased the uterine tone and frequency of contractions but
moderately increased the height and duration of contractions. However, it is not
known whether use of amoxicillin in humans during labor or delivery has
immediate or delayed adverse effects on the fetus, prolongs the duration of
labor, or increases the likelihood that forceps delivery or other obstetrical
intervention or resuscitation of the newborn will be necessary.
NURSING MOTHERS: Penicillins have been shown to be excreted in human milk.
Amoxicillin use by nursing mothers may lead to sensitization of infants. Caution
should be exercised when amoxicillin is administered to a nursing woman.
PEDIATRIC USE: Because of incompletely developed renal function in neonates and
young infants, the elimination of amoxicillin may be delayed. Dosing of WYMOX
(amoxicillin) should be modified in pediatric patients 12 weeks or younger (=
months). (See DOSAGE AND ADMINISTRATION-Neonates and infants.)
DRUG INTERACTIONS:
DRUG INTERACTIONS: Probenecid decreases the renal tubular secretion of
amoxicillin. Concurrent use with amoxicillin may result in increased and
prolonged blood levels.
Chloramphenicol, erythromycins, sulfonamides, and tetracyclines may interfere
with the bactericidal effects of penicillin. This has been demonstrated In
Vitro; however, the clinical significance of this interaction is not well
documented.
DRUG/LABORATORY TEST INTERACTIONS: High urine concentrations of ampicillin may
result in false- positive reactions when testing for the presence of glucose in
urine using Clinitest(R), Benedict's Solution or Fehling's Solution. Since this
effect may also occur with amoxicillin, it is recommended that glucose tests
based on enzymatic glucose oxidase reactions (such as Clinistix(R) or Tes-
Tape(R)) be used.
Following administration of ampicillin to pregnant women, a transient decrease
in plasma concentration of total conjugated estriol, estriol-glucuronide,
conjugated estrone, and estradiol has been noted. This effect may also occur
with amoxicillin.
(See also PRECAUTIONS.)
ADVERSE REACTIONS:
As with other penicillins, it may be expected that untoward reactions will be
essentially limited to sensitivity phenomena. They are more likely to occur in
individuals who have previously demonstrated hypersensitivity to penicillins and
in those with a history of allergy, asthma, hay fever, or urticaria. The
following adverse reactions have been reported as associated with the use of
penicillins:
Gastrointestinal: Nausea, vomiting, diarrhea, and pseudomembranous colitis.
Onset of pseudomembranous colitis symptoms may occur during or after antibiotic
treatment. (See WARNINGS.)
Hypersensitivity Reactions: Erythematous maculopapular rashes, erythema
multiforme, Stevens-Johnson Syndrome, toxic epidermal necrolysis, and urticaria
have been reported.
NOTE: These hypersensitivity reactions may be controlled with antihistamines
and, if necessary, systemic corticosteroids. Whenever such reactions occur,
amoxicillin should be discontinued unless, in the opinion of the physician, the
condition being treated is life-threatening and amenable only to amoxicillin
therapy.
Liver: A moderate rise in AST (SGOT) has been noted, but the significance of
this finding is unknown.
Hemic And Lymphatic Systems: Anemia, thrombocytopenia, thrombocytopenic purpura,
eosinophilia, leukopenia, and agranulocytosis have been reported during therapy
with penicillins. These reactions are usually reversible on discontinuation of
therapy and are believed to be hypersensitivity phenomena.
Central Nervous System: Reversible hyperactivity, agitation, anxiety, insomnia,
confusion, behavioral changes, and/or dizziness have been reported rarely.
Combination Therapy With Clarithromycin And Lansoprazole:
In clinical trials using combination therapy with amoxicillin plus
clarithromycin and lansoprazole, and amoxicillin plus lansoprazole, no adverse
reactions peculiar to these drug combinations were observed. Adverse reactions
that have occurred have been limited to those that had been previously reported
with amoxicillin, clarithromycin, or lansoprazole.
Triple Therapy: Amoxicillin/Clarithromycin/Lansoprazole:
The most frequently reported adverse events for patients who received triple
therapy were diarrhea (7%), headache (6%), and taste perversion (5%). No
treatment-emergent adverse events were observed at significantly higher rates
with triple therapy than with any dual therapy regimen.
Dual Therapy: Amoxicillin/Lansoprazole
The most frequently reported adverse events of patients who received amoxicillin
t.i.d. plus lansoprazole t.i.d. dual therapy were diarrhea (8%) and headache
(7%). No treatment-emergent adverse events were observed at significantly higher
rates with amoxicillin t.i.d. plus lansoprazole t.i.d. dual therapy than with
lansoprazole alone.
For more information on adverse reactions with clarithromycin or lansoprazole,
refer to their package inserts, ADVERSE REACTIONS.
OVERDOSAGE:
In case of overdosage, discontinue medication, treat symptomatically, and
institute supportive measures as required. If the overdosage is very recent and
there is no contraindication, an attempt at emesis or other means of removal of
drug from the stomach may be performed. A prospective study of 51 pediatric
patients at a poison-control center suggested that overdosages of less than 250
mg/kg of amoxicillin are not associated with significant clinical symptoms and
do not require gastric emptying. (REF. 3)
Interstitial nephritis resulting in oliguric renal failure has been reported in
a small number of patients after overdosage with amoxicillin. Renal impairment
appears to be reversible with cessation of drug administration. High blood
levels may occur more readily in patients with impaired renal function because
of decreased renal clearance of amoxicillin. Amoxicillin may be removed from
circulation by hemodialysis.
DOSAGE AND ADMINISTRATION:
NEONATES AND INFANTS AGES = 12 WEEKS = 3 MONTHS)/ Due to incompletely
developed renal function affecting elimination of amoxicillin in this age group,
the recommended upper dose of WYMOX (amoxicillin) is 30 mg/kg/ day divided
q12h.
INFECTION USUAL ADULT DOSE USUAL DOSE FOR
CHILDREN >3
MONTHS**
------------------------------------------------------------------------------------------------------------------------
Ear/nose/throat 250 mg every 8 20 mg/kg/day in
hours divided doses
every 8 hours
Lower respiratory 500 mg every 8 40 mg/kg/day in
tract hours divided doses
every 8 hours
Skin/skin 250 mg every 8 20 mg/kg/day in
structure hours divided doses
every 8 hours
Genitourinary 250 mg every 8 20 mg/kg/day in
tract hours divided doses
every 8 hours
Gonorrhea; 3 grams as single PREPUBERTAL
acute, oral dose children: 50 mg/kg
uncomplicated WYMOX, combined
ano-genital and with 25 mg/kg
urethral probenecid as a
infections in single dose.
males and NOTE: SINCE
females PROBENECID IS
CONTRAINDICATED
IN CHILDREN
UNDER 2 YEARS,
DO NOT USE
THIS REGIMEN IN
THESE CASES.
----------------------------------------------------------------------------------------------------------------------------------
** Children weighing 40 kg or more should be dosed according to the adult
recommendations.
In severe ear, nose, throat, genitourinary, skin and skin structure infections,
or those caused by less susceptible organisms:
Adults: 500 mg every 8 hours
Children: 40 mg/kg/day in divided doses every 8 hours
All patients with gonorrhea should be evaluated for syphilis. (See PRECAUTIONS -
Laboratory Tests.)
Larger doses may be required for stubborn or severe infections.
H. PYLORI ERADICATION TO REDUCE THE RISK OF DUODENAL ULCER RECURRENCE
Triple Therapy: WYMOX/Clarithromycin/Lansoprazole
The recommended adult oral dose is 1 gram WYMOX, 500 mg clarithromycin, and 30
mg lansoprazole, all given twice daily (q12h) for 14 days. (See INDICATIONS AND
USAGE.)
Dual Therapy: WYMOX/Lansoprazole
The recommended adult oral dose is 1 gram WYMOX and 30 mg lansoprazole, each
given three times daily (q8h) for 14 days. (See INDICATIONS AND USAGE.)
Please refer to clarithromycin and lansoprazole full prescribing information for
CONTRAINDICATIONS and WARNINGS, and for information regarding dosing in elderly
and renally impaired patients.
GENERAL: The children's dosage is intended for individuals whose weight will not
cause a dosage to be calculated greater than that recommended for adults.
It should be recognized that in the treatment of chronic urinary tract
infections, frequent bacteriological and clinical appraisals are necessary.
Smaller doses than those recommended above should not be used. Even higher doses
may be needed at times. In stubborn infections, therapy may be required for
several weeks. It may be necessary to continue clinical and/or bacteriological
follow-up for several months after cessation of therapy. Except for gonorrhea,
treatment should be continued for a minimum of 48 to 72 hours beyond the time
that the patient becomes asymptomatic or evidence of bacterial eradication has
been obtained. It is recommended that there be at least 10 days' treatment for
any infection caused by Streptococcus Pyogenes to prevent the occurrence of
acute rheumatic fever.
After reconstitution, the required amount of suspension should be placed
directly on the child's tongue for swallowing. Alternate means of administration
are to add the required amount of suspension to formula, milk, fruit juice,
water, ginger ale, or cold drinks. These preparations should then be taken
immediately. To be certain the child is receiving full dosage, such preparations
should be consumed in entirety.
DIRECTIONS FOR MIXING ORAL SUSPENSION
Prepare suspension at time of dispensing as follows: Tap bottle until all powder
flows freely. Add approximately 1/3 of the total amount of water for
reconstitution (see table below) and shake vigorously to wet powder. Add
remainder of the water and again shake vigorously.
DIRECTIONS FOR MIXING PEDIATRIC DROPS
Prepare pediatric drops at time of dispensing as follows: Add the required
amount of water (see table below) to the bottle and shake vigorously. Each mL of
suspension will then contain amoxicillin trihydrate equivalent to 50 mg
amoxicillin.
AMOUNT OF WATER
BOTTLE SIZE REQUIRED FOR RECONSTITUTION
15 mL 12 mL
30 mL 23 mL
NOTE: SHAKE BOTH ORAL SUSPENSION AND PEDIATRIC DROPS WELL BEFORE USING. Keep
bottle tightly closed. Any unused portion of the reconstituted suspension must
be discarded after 14 days. Refrigeration preferable, but not required.
CLINICAL STUDIES:
H. PYLORI ERADICATION TO REDUCE THE RISK OF DUODENAL ULCER RECURRENCE
Randomized, double-blind clinical studies performed in the U.S. in patients with
H. Pylori and duodenal ulcer disease (defined as an active ulcer or history of
an ulcer within one year) evaluated the efficacy of lansoprazole in combination
with amoxicillin capsules and clarithromycin tablets as triple 14-day therapy,
or in combination with amoxicillin capsules as dual 14-day therapy, for the
eradication of H. Pylori. Based on the results of these studies, the safety and
efficacy of two different eradication regimens were established:
Triple Therapy: amoxicillin 1 gram b.i.d./clarithromycin 500 mg
b.i.d./lansoprazole 30 mg b.i.d.
Dual Therapy: amoxicillin 1 gram t.i.d./lansoprazole 30 mg t.i.d.
All treatments were for 14 days. H. Pylori eradication was defined as two
negative tests (culture and histology) at 4 to 6 weeks following the end of
treatment.
Triple therapy was shown to be more effective than all possible dual therapy
combinations. Dual therapy was shown to be more effective than both
monotherapies. Eradication of H. Pylori has been shown to reduce the risk of
duodenal ulcer recurrence.
H. PYLORI ERADICATION RATES - TRIPLE THERAPY
(AMOXICILLIN/CLARITHROMYCIN/LANSOPRAZOLE)
PERCENT OF PATIENTS CURED
(95% CONFIDENCE INTERVAL)
(NUMBER OF PATIENTS)
---------------------------------------------------------------------------------------------------------------------
TRIPLE THERAPY TRIPLE THERAPY
--------------------------------------------------------------------------------------------------------------------
STUDY EVALUABLE ANALYSIS(I) INTENT-TO-TREAT
ANALYSIS(II)
--------------------------------------------------------------------------------------------------------------------
Study 1 92(III) 86(I)
(80.0-97.7) (73.3-93.5)
(n=48) (n=55)
-------------------------------------------------------------------------------------------------------------------
Study 2 86(**) 83(**)
(75.7-93.6) (72.0-90.8)
(n=66) (n=70)
------------------------------------------------------------------------------------------------------------------
(I) This analysis was based on evaluable patients with confirmed duodenal
ulcer (active or within one year) and H. Pylori infection at baseline
defined as at least two of three positive endoscopic tests from
CLOtest(R) (Delta West Ltd., Bentley, Australia), histology and/or
culture. Patients were included in the analysis if they completed the
study. Additionally, if patients dropped out of the study due to an
adverse event related to the study drug, they were included in the
analysis as failures of therapy.
(II) Patients were included in the analysis if they had documented H.
Pylori infection at baseline as defined above and had a confirmed
duodenal ulcer (active or within one year). All dropouts were included
as failures of therapy.
(III) (P<0.05) versus lansoprazole/amoxicillin and lansoprazole/clarithromycin
dual therapy.
(**) (P<0.05) versus clarithromycin/amoxicillin dual therapy.
H. PYLORI ERADICATION RATES - DUAL THERAPY
(AMOXICILLIN/LANSOPRAZOLE)
PERCENT OF PATIENTS CURED
(95% CONFIDENCE INTERVAL)
(NUMBER OF PATIENTS)
------------------------------------------------------------------------------------------------------------------
DUAL THERAPY DUAL THERAPY
------------------------------------------------------------------------------------------------------------------
STUDY EVALUABLE ANALYSIS(##) INTENT-TO-TREAT
ANALYSIS(#)
------------------------------------------------------------------------------------------------------------------
Study 1 77(###) 70(###)
(62.5-87.2) (56.8-81.2)
(n=51) (n=60)
-----------------------------------------------------------------------------------------------------------------
Study 2 66(IIII) 61(IIII)
(51.9-77.5) (48.5-72.9)
(n=58) (n=67)
-----------------------------------------------------------------------------------------------------------------
(#) This analysis was based on evaluable patients with confirmed duodenal
ulcer (active or within one year) and H. Pylori infection at baseline
defined as at least two of three positive endoscopic tests from
CLOtest(R), histology and/or culture. Patients were included in the
analysis if they completed the study. Additionally, if patients dropped
out of the study due to an adverse event related to the study drug,
they were included in the analysis as failures of therapy.
(##) Patients were included in the analysis if they had documented H. Pylori
infection at baseline as defined above and had a confirmed duodenal
ulcer (active or within one year). All dropouts were included as
failures of therapy.
(###) (P<0.05) versus lansoprazole alone.
(IIII) (P<0.05) versus lansoprazole alone or amoxicillin alone.
************************************************************************