AMOXICILLIN

Main information

  • Trade name:
  • AMOXICILLIN - amoxicillin tablet, coated
  • Composition:
  • AMOXICILLIN 875 mg
  • Administration route:
  • ORAL
  • Prescription type:
  • PRESCRIPTION DRUG
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • AMOXICILLIN - amoxicillin tablet, coated
    United States
  • Language:
  • English

Therapeutic information

  • Therapeutic indications:
  • To reduce the development of drug-resistant bacteria and maintain the effectiveness of amoxicillin and other antibacterial drugs, amoxicillin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. Amoxicillin is indicated in the treatment of infections due to susceptible (ONLY α -lactamase-negative) strains of the designated microorganisms in the conditions listed below: Infections of the ear, nose and throat – due to Streptococcus spp. (α- and β –hemolytic strains only), S. 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. (α- and β -hemolytic strains only), Staphylococcus spp. or E. coli. Infections of the lower respiratory tract – due to Streptococcus spp. (α- and β –hemolytic strains only), S. pneumoniae, Staphylococcus spp., or H. influenzae. Gonorrhea, acute uncomplicated (ano-ge
  • Product summary:
  • Tablets of Amoxicillin: Amoxicillin Tablets USP, 875 mg are available as film-coated, capsule-shaped, pink tablets scored on one side and imprinted WW951 on the other side. They are available in bottles of 100 and 20. Store at 20°-25°C (68°-77°F) [See USP Controlled Room Temperature]. Dispense in a tight container.

Status

  • Source:
  • DailyMed - NLM - National Library of Medicine
  • Authorization status:
  • Abbreviated New Drug Application
  • Authorization number:
  • 67296-0628-1
  • Last update:
  • 24-05-2019

Summary of Product characteristics: dosage, interactions, side effects

AMOXICILLIN - amoxicillin tablet, coated

RedPharm Drug Inc.

----------

AMOXICILLIN TABLETS, USP 875 mg

Rx only

Revised: August 2008

To reduce the development of drug-resistant bacteria and maintain the effectiveness of amoxicillin and

other antibacterial drugs, amoxicillin should be used only to treat or prevent infections that are proven

or strongly suspected to be caused by bacteria.

DESCRIPTION

Formulation of amoxicillin tablets contain amoxicillin, 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 structural formula

The amoxicillin molecular formula is C

H N O S3H O, and the molecular weight is 419.45.

Tablets of amoxicillin are intended for oral administration.

Tablets: Each film coated tablet contains 875 mg amoxicillin as the trihydrate. Each film-coated,

capsule-shaped, pink tablet is scored on one side and imprinted WW951 on the other side. Inactive

ingredients: carmine, colloidal silicon dioxide, crospovidone, FD&C Red #40 Lake, magnesium

stearate, microcrystalline cellulose, polyvinyl alcohol-partially hydrolyzed, polyethylene glycol,

sodium starch glycolate, talc, and titanium dioxide.

CLINICAL PHARMACOLOGY

Amoxicillin is stable in the presence of gastric acid and is rapidly absorbed after oral administration.

The effect of food on the absorption of amoxicillin from the tablets and suspension of amoxicillin has

been partially investigated. The 400-mg and 875-mg formulations have been studied only when

administered at the start of a light meal. However, food effect studies have not been performed with the

200-mg and 500-mg formulations. Amoxicillin 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. In blood serum, amoxicillin is approximately 20% protein-

bound.

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 mcg/mL and 5.5 mcg/mL to 7.5

mcg/mL, respectively.

Mean amoxicillin pharmacokinetic parameters from an open, two-part, single-dose crossover

bioequivalence study in 27 adults comparing 875 mg of amoxicillin with Amoxicillin and Clavulanate

Potassium Tablets 875 mg/125 mg showed that the 875-mg tablet of amoxicillin produces an AUC -∞

of 35.4 ± 8.1 mcghr/mL and a C

of 13.8 ± 4.1 mg/mL. Dosing was at the start of a light meal

following an overnight fast.

Orally administered doses of amoxicillin suspension, 125 mg/5mL 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

mcg/mL to 5 mcg/mL, respectively.

Oral administration of single doses of 400-mg/5 mL suspension of amoxicillin to 24 adult volunteers

yielded the following pharmacokinetic data:

Dose

(mcghr/mL)

(mcg/mL)

Amoxicillin

Amoxicillin

(±S.D.)

Amoxicillin

(±S.D.)

400 mg (5 mL of suspension)

17.1 (3.1)

5.92 (1.62)

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 - 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.† (β -lactamase-negative strains only)

Streptococcus pneumoniae

Streptococcus spp. (α- and β -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 (β-lactamase -negative strains only)

Haemophilus influenzae (β-lactamase -negative strains only)

Neisseria gonorrhoeae (β-lactamase -negative strains only)

Proteus mirabilis (β-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

o-∞

bacteria to antimicrobial compounds. The MICs should be determined using a standardized procedure.

Standardized procedures are based on a dilution method (broth or agar) or equivalent with standardized

inoculum concentrations and standardized concentrations of ampicillin powder. Ampicillin is sometimes

used to predict susceptibility of S. pneumoniae to amoxicillin; however, some intermediate strains have

been shown to be susceptible to amoxicillin. Therefore, S. 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

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

(Amoxicillin powder should be used to determine susceptibility.)

(mcg/mL)

Interpretation

≤2

Susceptible (S)

Intermediate (I)

≥8

Resistant (R)

NOTE: These interpretive criteria are based on the recommended doses for respiratory tract

infections.

For Gram-Negative Aerobes:

Enterobacteriaceae

MIC (mcg/mL) Interpretation

≤8

Susceptible (S)

Intermediate (I)

≥32

Resistant (R)

H. influenzae

(mcg/mL)

Interpretation

≤1

Susceptible (S)

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 H. influenzae using

Haemophilus Test Medium (HTM).

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 ampicillin powder should provide the following MIC values:

Microorganism

MIC Range (mcg/mL)

E. coli ATCC 25922

2 to 8

E. faecalis ATCC 29212

0.5 to 2

H. influenzae ATCC 49247

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

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 HTM.

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 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

Zone Diameter

(mm)

Interpretation

≥29

Susceptible (S)

≤28

Resistant (R)

β -hemolytic streptococci

Zone Diameter

(mm)

Interpretation

≥26

Susceptible (S)

19 to 25

Intermediate (I)

≤18

Resistant (R)

NOTE: For streptococci (other than β -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

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) .

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

13 to 21

S. aureus ATCC 25923

27 to 35

Using 1-mcg oxacillin disk:

Microorganism

Zone Diameter

(mm)

S. pneumoniae ATCC 49619

8 to 12

h. This quality control range is applicable to only H. influenzae ATCC 49247 tested by a disk diffusion

procedure using HTM .

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% CO .

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

Amoxicillin is indicated in the treatment of infections due to susceptible (ONLY α -lactamase-negative)

strains of the designated microorganisms in the conditions listed below:

Infections of the ear, nose and throat – due to Streptococcus spp. (α- and β –hemolytic strains only), S.

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. (α- and β -hemolytic strains only),

Staphylococcus spp. or E. coli.

Infections of the lower respiratory tract – due to Streptococcus spp. (α- and β –hemolytic strains only),

S. pneumoniae, Staphylococcus spp., or H. influenzae.

Gonorrhea, acute uncomplicated (ano-genital and urethral infections) – due to N. gonorrhoeae

(males and females).

H. pylori eradication to reduce the risk of duodenal ulcer recurrence.

Triple Therapy: Amoxicillin/clarithromycin/lansoprazole

Amoxicillin, 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 1-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: Amoxicillin/lansoprazole

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 1-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.)

To reduce the development of drug-resistant bacteria and maintain the effectiveness of amoxicillin and

other antibacterial drugs, amoxicillin 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.

Indicated surgical procedures should be performed.

CONTRAINDICATIONS

A history of allergic reactions 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 AMOXICILLIN,

CAREFUL INQUIRY SHOULD BE MADE CONCERNING PREVIOUS HYPERSENSITIVITY

REACTIONS TO PENICILLINS, CEPHALOSPORINS, OR OTHER ALLERGENS. IF AN

ALLERGIC REACTION OCCURS, AMOXICILLIN 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.

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial

agents, including amoxicillin, and may range in severity from mild diarrhea to fatal colitis. Treatment

with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin

producing strains of C. difficile cause increased morbidity and mortality, as these infections can be

refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients

who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD

has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to

be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic

treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

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.

A high percentage of patients with mononucleosis who receive ampicillin develop an erythematous skin

rash. This, ampicillin-class antibiotics should not be administered to patients with mononucleosis.

Prescribing amoxicillin in the absence of 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.

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 of amoxicillin and

probenecid may result in increased and prolonged blood levels of amoxicillin.

Chloramphenicol, macrolides, 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.

In common with other antibiotics, amoxicillin may affect the gut flora, leading to lower estrogen

reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives.

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®, 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®) 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.

Amoxicillin and potassium clavulanate mixture was non-mutagenic in the Ames bacterial mutation assay,

and the yeast gene conversion assay. Amoxicillin and potassium clavulanate mixture 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. Amoxicillin and potassium

clavulanate mixture 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 500

mg/kg (approximately 3 times the human dose in mg/m ).

Pregnancy: Teratogenic Effects.

Pregnancy Category B. Reproduction studies have been performed in mice and rats at doses up to 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 have shown

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 the 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 Amoxicillin should be modified in pediatric patients 12 weeks

or younger (≤3 months). (See DOSAGE AND ADMINISTRATION – Neonates and Infants).

Geriatric Use

An analysis of clinical studies of amoxicillin was conducted to determine whether subjects aged 65 and

over respond differently from younger subjects. Of the 1,811 subjects treated with capsules of

amoxicillin, 85% were <60 years old, 15% were ≥61 years old and 7% were ≥71 years old. This

analysis and other reported clinical experience have not identified differences in responses between the

elderly and younger patients, but a greater sensitivity of some older individuals cannot be ruled out.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug

may be greater in patients with impaired renal function. Because elderly patients are more likely to have

decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal

function.

Information for Patients

Amoxicillin may be taken every 8 hours or every 12 hours, depending on the strength of the product

prescribed.

Patients should be counseled that antibacterial drugs, including amoxicillin, should only be used to treat

bacterial infections. They do not treat viral infections (e.g. the common cold). When amoxicillin 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

amoxicillin or other antibacterial drugs in the future.

Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is

discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody

stools (with or without stomach cramps and fever) even as late as 2 or more months after having taken

the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

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:

Infections and Infestations: Mucocutaneous candidiasis.

Gastrointestinal: Nausea, vomiting, diarrhea, black hairy tongue, and hemorrhagic/pseudomembranous

colitis.

Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment. (See

WARNINGS.)

Hypersensitivity Reactions: Anaphylaxis (See WARNINGS) Serum sickness-like reactions,

erythematous maculopapular rashes, erythema multiforme, Stevens-Johnson Syndrome, exfoliative

dermatitis, toxic epidermal necrolysis, acute generalized exanthematous pustulosis, hypersensitivity

vasculitis 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) and/or ALT (SGPT) has been noted, but the significance of this

finding is unknown. Hepatic dysfunction, including cholestatic jaundice, hepatic cholestasis and acute

cytolytic hepatitis have been reported.

Renal: Crystalluria has also been reported (see OVERDOSAGE).

Hemic and Lymphatic Systems: Anemia, including hemolytic 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,

convulsions, behavioral changes, and/or dizziness have been reported rarely.

Miscellaneous: Tooth discoloration (brown, yellow or gray staining) has been rarely reported. Most

reports occurred in pediatric patients. Discoloration was reduced or eliminated with brushing or dental

cleaning in most cases.

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 for patients who

received amoxicillin three times daily plus lansoprazole three times daily dual therapy were diarrhea

(8%) and headache (7%). No treatment-emergent adverse events were observed at significantly higher

rates with amoxicillin three times daily plus lansoprazole three times daily 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.

Interstitial nephritis resulting in oliguric renal failure has been reported in a small number of patients

after overdosage with amoxicillin. Crystalluria, in some cases leading to renal failure, has also been

reported after amoxicillin overdosage in adult and pediatric patients. In case of overdosage, adequate

fluid intake and diuresis should be maintained to reduce the risk of amoxicillin crystalluria.

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 the circulation by hemodialysis.

DOSAGE AND ADMINISTRATION

The 875-mg tablet has been studied only when administered at the start of a light meal. However, food

effect studies have not been performed with the 200-mg and 500-mg formulations.

Neonates and Infants Aged ≤12 weeks (≤3 months): Due to incompletely developed renal function

affecting elimination of amoxicillin in this age group, the recommended upper dose of Amoxicillin is

30 mg/kg/day divided q12h.

Adults and Pediatric Patients > 3 Months:

Infection

Severity

Usual Adult Dosage

Usual Dose for Children > 3

Months

Ear/Nose/

Throat

Mild/ Moderate

500 mg every 12 hours or 250

mg every 8 hours

25 mg/kg/day in divided doses

every 12 hours or 20 mg/kg/day in

divided doses every 8 hours

Severe

875 mg every 12 hours or 500

mg every 8 hours

45 mg/kg/day in divided doses

every 12 hours or 40 mg/kg/day in

divided doses every 8 hours

Lower

Respiratory

Tract

Mild/ Moderate

or Severe

875 mg every 12 hours or 500

mg every 8 hours

45 mg/kg/day in divided doses every

12 hours

40 mg/kg/day in divided doses every

8 hours

Skin/Skin

Structure

Mild/ Moderate

500 mg every 12 hours or 250

mg every 8 hours

25 mg/kg/day in divided doses

every 12 hours or 20 mg/kg/day in

divided doses every 8 hours

Severe

875 mg every 12 hours or 500

mg every 8 hours

45 mg/kg/day in divided doses

every 12 hours or 40 mg/kg/day in

divided doses every 8 hours

Genitourinary

Tract

Mild/ Moderate

500 mg every 12 hours or 250

mg every 8 hours

25 mg/kg/day in divided doses

every 12 hours or 20 mg/kg/day in

divided doses every 8 hours

Severe

875 mg every 12 hours or 500

mg every 8 hours

45 mg/kg/day in divided doses

every 12 hours or 40 mg/kg/day in

divided doses every 8 hours

Gonorrhea

Acute,

Uncomplicated

Ano-genital and

urethral

infections in

males and

females

3 grams as single oral dose

Prepubertal children: 50 mg/kg

Amoxicillin combined with 25

mg/kg probenecid as single dose.

NOTE: SINCE PROBENICID IS

CONTRAINDICATED IN

CHILDREN UNDER 2 YEARS,

DO NOT USE THIS REGIMEN

IN THESE CASES.

All patients with gonorrhea should be evaluated for syphilis. (See PRECAUTIONS – Laboratory

T ests).

Larger doses may be required for stubborn or severe infections.

General: 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 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.

H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence: Triple therapy:

Amoxicillin/clarithromycin/ lansoprazole

The recommended adult oral dose is 1 gram amoxicillin, 500 mg clarithromycin, and 30 mg

lansoprazole, all given twice daily (q12h) for 14 days. (See INDICATIONS AND USAGE).

Dual therapy: Amoxicillin/lansoprazole

The recommended adult oral dose is 1 gram amoxicillin 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.

Dosing Recommendations for Adults with Impaired Renal Function: Patients with impaired renal

function do not generally require a reduction in dose unless the impairment is severe. Severely impaired

patients with a glomerular filtration rate of <30 mL/min. should not receive the 875 mg tablet. Patients

with a glomerular filtration rate of 10 to 30 mL/min. should receive 500 mg or 250 mg every 12 hours,

depending on the severity of the infection. Patients with a less than 10 mL/min. glomerular filtration rate

should receive 500 mg or 250 mg every 24 hours, depending on the severity of the infection.

Hemodialysis patients should receive 500 mg or 250 mg every 24 hours, depending on the severity of

the infection. They should receive an additional dose both during and at the end of dialysis.

There are currently no dosing recommendations for pediatric patients with impaired renal

function.

HOW SUPPLIED

Tablets of Amoxicillin: Amoxicillin Tablets USP, 875 mg are available as film-coated, capsule-

shaped, pink tablets scored on one side and imprinted WW951 on the other side. They are available in

bottles of 100 and 20.

Store at 20°-25°C (68°-77°F) [See USP Controlled Room Temperature].

Dispense in a tight container.

CLINICAL STUDIES

H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence:

Randomized, double-blind clinical studies performed in the United States 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 twice daily/clarithromycin 500 mg twice daily/lansoprazole 30 mg

twice daily.

Dual therapy: Amoxicillin 1 gram three times daily/lansoprazole 30 mg three times daily.

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

Intent-to-Treat Analysis

Study 1

[80 – 97.7]

(n = 48)

[73.3 – 93.5]

(n = 55)

Study 2

[75.7 – 93.6]

(n = 66)

[72 – 90.8]

(n = 70)

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

(p<0.05) versus lansoprazole/amoxicillin and lansoprazole/ clarithromycin dual therapy.

(p<0.05) versus clarithromycin/amoxicillin dual therapy.

[62.5 – 87.2]

(n = 51)

[56.8 – 81.2]

(n = 60)

Study 2

[51.9 – 77.5]

(n = 58)

[48.5 – 72.9]

(n = 67)

REFERENCES

National Committee for Clinical Laboratory Standards. Methods for Dilution Antimicrobial

Susceptibility Tests for Bacteria that Grow Aerobically – Fourth Edition; Approved Standard.

NCCLS Document M7-A4, Vol. 17, No. 2. NCCLS, Wayne, PA, January 1997.

National Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial

Disk Susceptibility Tests – Sixth Edition; Approved Standard. NCCLS Document M2-A6, Vol. 17,

No. 1. NCCLS, Wayne, PA, January 1997.

Swanson-Biearman B, Dean BS, Lopez G, Krenzelok EP. The effects of penicillin and

cephalosporin ingestions in children less than six years of age. Vet Hum Toxicol 1988;30:66-67.

CLINITEST is a registered trademark of Miles, Inc.

CLINISTIX is a registered trademark of Bayer Corporation.

CLOtest is a registered trademark of Kimberly-Clark Corporation.

Manufactured by:

Hikma Pharmaceuticals

P.O. Box 182400

Amman 11118 - Jordan

Distributed by:

West-ward Pharmaceutical Corp.

Eatontown, NJ 07724

Revised: August 2008

copy of label

AMOXICILLIN

(p<0.05) versus lansoprazole alone.

(p<0.05) versus lansoprazole alone or amoxicillin alone.

amoxicillin tablet, coated

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:6 729 6 -0 6 28 (NDC:0 143-9 9 51)

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

AMO XICILLIN (UNII: 8 0 48 26 J2HU) (AMOXICILLIN ANHYDROUS - UNII:9 EM0 5410 Q9 )

AMOXICILLIN

8 75 mg

Inactive Ingredients

Ingredient Name

Stre ng th

CO LLO IDAL SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

CRO SPO VIDO NE (UNII: 6 8 40 19 6 0 MK)

FD&C RED NO . 4 0 (UNII: WZB9 127XOA)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

CELLULO SE, MICRO CRYSTALLINE (UNII: OP1R32D6 1U)

PO LYVINYL ALCO HO L (UNII: 532B59 J9 9 0 )

PO LYETHYLENE GLYCO L (UNII: 3WJQ0 SDW1A)

SO DIUM STARCH GLYCO LATE TYPE A PO TATO (UNII: 58 56 J3G2A2)

TALC (UNII: 7SEV7J4R1U)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

Product Characteristics

Color

pink

S core

2 pieces

S hap e

OVAL (capsule-shaped)

S iz e

9 mm

Flavor

Imprint Code

WW;9 51

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:6 729 6 -0 6 28 -1

20 in 1 BOTTLE

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 6 5255

0 3/29 /20 0 6

Labeler -

RedPharm Drug Inc. (008039641)

Establishment

RedPharm Drug Inc.

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Hikma Pharmaceutical

5346 6 16 45

MANUFACTURE

Revised: 7/2011