Amoxicillin powder, for suspension

Rx only


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


Formulations of amoxicillin for oral suspension, USPcontain 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 (2 S,5 R,6 R)-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.It may be represented structurally as:
Structural Formula
The amoxicillin molecular formula is C 16H 19N 3O 5S3H 2O, and the molecular weight is 419.45.

Amoxicillin for oral suspension is intended for oral administration.

Each 5 mL of reconstituted suspension contains amoxicillin trihydrate equivalent to 200 mg or 400 mg anhydrous amoxicillin. Each 5 mL of the 200 mg and 400 mg reconstituted suspension contains 0.16 mEq (3.61 mg) of sodium.

Amoxicillin trihydrate for oral suspension 200 mg/5 mL and 400 mg/5 mL (reconstituted) are bubble-gum flavored light pink suspensions. Inactive ingredients: Sucrose, sodium citrate, sodium benzoate, edetate disodium, FD&C Red No. 3, xanthan gum, bubble-gum flavor, and colloidal silicon 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 mgformulation hasbeen studied only when administered at the start of a light meal. 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 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 mcg/mL and 3.5 mcg/mL to 5 mcg/mL, respectively.

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 vitroand in clinical infections as described in the INDICATIONS AND USAGEsection.

Aerobic Gram-Positive Microorganisms

Enterococcus faecalis
Staphylococcusspp.* (-lactamasenegative strains only)
Streptococcus pneumoniae
Streptococcus
spp. (- and -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
(-lactamasenegative strains only)
Haemophilus influenzae(-lactamasenegative strains only)
Neisseria gonorrhoeae(-lactamasenegative strains only)
Proteus mirabilis(-lactamasenegative 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 1(broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of ampicillinpowder. Ampicillin is sometimes used to predict susceptibility of S. pneumoniaeto amoxicillin; however, some intermediate strains have been shown to be susceptible to amoxicillin. Therefore, S. pneumoniaesusceptibility 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 bfrom non-meningitis sources.

( Amoxicillinpowder should be used to determine susceptibility.)

MIC (mcg/mL)

Interpretation

2

Susceptible(S)

4

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)

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 to 5% lysed horse blood.
c. These interpretive standards are applicable only to broth microdilution test with H. influenzaeusing HaemophilusTest Medium (HTM). 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 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 ampicillinpowder should provide the following MIC values:

Microorganism

MIC Range mcg/mL)

E. coliATCC 25922

2 to 8

E. faecalisATCC 29212

0.5 to 2

H. influenzaeATCC 49247 d

2 to 8

S. aureusATCC 29213

0.25 to 1

Using amoxicillinto determine susceptibility:

Microorganism

MIC Range (mcg/mL)

S. pneumoniaeATCC 49619 e

0.03 to 0.12

d. This quality control range is applicable to only H. influenzaeATCC 49247 tested by a broth microdilution procedure using HTM. 1
e. This quality control range is applicable to only S. pneumoniaeATCC 49619 tested by the broth microdilution procedure using
cation-adjusted Mueller-Hinton broth with 2 to 5% lysedhorse 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 2requires 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)
-hemolytic streptococci

Zone Diameter (mm)

Interpretation

26

Susceptible (S)

19 to 25

Intermediate(I)

18

Resistant (R)

NOTE:For streptococci (other than -hemolytic streptococci and S. pneumoniae), an ampicillin MIC should be determined.

S. pneumoniae

S. pneumoniaeshould 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. pneumoniaewith 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. influenzaeusing HaemophilusTest
Medium (HTM). 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 ampicillindisk should provide the following zone diameters in these laboratory test quality control strains:

Microorganism

Zone Diameter (mm)

E. coliATCC 25922

16 to 22

H. influenzaeATCC 49247 h

13 to 21

S. aureusATCC 25923

27 to 35

Using 1 mcg oxacillindisk:

Microorganism

Zone Diameter (mm)

S. pneumoniaeATCC 49619 i

8 to 12

h.This quality control range is applicable to only H. influenzaeATCC 49247 tested by a disk diffusion procedure using HTM. 2
i. This quality control range is applicable to only S. pneumoniaeATCC 49619 tested by a disk diffusion procedure using
Mueller-Hinton agar supplemented with 5%sheep blood and incubated in 5%CO 2.

Susceptibility Testing for Helicobacter pylori

In vitrosusceptibility 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. pylorimicroorganisms.

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


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. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Amoxicillin is indicated in the treatment of infections due to susceptible (ONLY -lactamasenegative) strains of the designated microorganisms in the conditions listed below:

Infections of the ear, nose, and throat
due to Streptococcusspp. (- and -hemolytic strains only), S. pneumoniae, Staphylococcusspp., 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 Streptococcusspp. (- and -hemolytic strains only), Staphylococcusspp., or E. coli.

Infections of the lower respiratory tract
due to Streptococcusspp. (- and -hemolytic strains only), S. pneumoniae, Staphylococcusspp., or H. influenzae.

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

H. pylorieradication 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. pyloriinfection and duodenal ulcer disease (active or 1-year history of a duodenal ulcer) to eradicate H. pylori. Eradication of H. pylorihas been shown to reduce the risk of duodenal ulcer recurrence. (See CLINICAL STUDIESand 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. pyloriinfection 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. pylorihas been shown to reduce the risk of duodenal ulcer recurrence. (See CLINICAL STUDIESand DOSAGE AND ADMINISTRATION.)

Indicated surgical procedures should be performed.

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 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 difficileassociated 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. difficileproduces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficilecause 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. difficilemay 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. Thus, ampicillin-class antibiotics should not be administered to patients with mononucleosis.

Prescribing amoxicillin 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


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.

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.

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 clavulanic acid mixture was non-mutagenic in the Ames bacterial mutation assay, and the yeast gene conversion assay. Amoxicillin and clavulanic acid 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 clavulanic acid 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 2).

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 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 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.

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 sicknesslike 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. 3

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 circulation by hemodialysis.

Dosage and administration


Oral suspensions of amoxicillin may be given without regard to meals. The 400 mg suspensionhas been studied only when administered at the start of a light meal.

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
* Dosing for infections caused by less susceptible organisms should follow the recommendationsfor
severe infections.
The childrens dosage is intended for individuals whose weight is less than 40 kg. Children weighing 40 kg
or more should bedosed according to the adult recommendations.

Infection

Severity*

Usual Adult Dose

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
or

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 andfemales



3 grams as single oral
dose

Prepubertalchildren:
50 mg/kg amoxicillin,
combined with 25 mg/kg
probenecid as a single
dose.
NOTE: SINCE
PROBENECID IS
CONTRAINDICATED
IN CHILDREN UNDER
2 YEARS, DO NOT USE
THIS REGIMEN IN
THESE CASES.

After reconstitution, the required amount of suspension should be placed directly on the childs 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.

All patients with gonorrhea should be evaluated for syphilis. (See PRECAUTIONS: Laboratory Tests.)

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 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 pyogenesto 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.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 severity of the infection.

Hemodialysis patients should receive 500 mg or 250 mg every 24 hours, depending on 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.


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.

200 mg/5 mL

Amount of Water
Bottle Size Required for Reconstitution
50 mL 35 mL
75 mL 52 mL
100 mL 69 mL

Each teaspoonful (5 mL) will contain 200 mg amoxicillin.

400 mg/5 mL

Amount of Water
Bottle Size Required for Reconstitution
50 mL 35 mL
75 mL 52 mL
100 mL 69 mL

Each teaspoonful (5 mL) will contain 400 mg amoxicillin.

NOTE:
SHAKE ORAL SUSPENSION 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.

How supplied

Amoxicillin for Oral Suspension, USP:Each 5 mL of reconstituted bubble-gum-flavored pink suspension contains 200 or 400 mg amoxicillin as the trihydrate.


Amoxicillinis supplied as follows:

NDC Strength Quantity/Form
55045-2992-2 400 mg/5 mL 100 mL


Store dry powder at 20 to 25C (68 to 77F); excursions permitted to 15 to 30C (59 to 86F) [see USP Controlled Room Temperature].

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. pyloriand duodenal ulcer disease (defined as an active ulcer or history of an ulcer within 1 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 2 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. pylorieradication was defined as 2 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. pylorihas been shown to reduce the risk of duodenal ulcer recurrence.

H. pyloriEradication Rates Triple Therapy (amoxicillin/clarithromycin/lansoprazole)
Percent of Patients Cured [95%Confidence Interval] (Number of Patients)


* This analysis was based on evaluable patients with confirmed duodenal ulcer
(active or within 1 year) and H. pyloriinfection at baseline defined as at least
2 of 3 positive endoscopic tests from CLOtest ®, (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.
Patients were included in the analysis if they had documented H. pyloriinfection
at baseline as defined above and had a confirmed duodenal ulcer (active or within
1 year). All dropouts were included as failures of therapy.
(p<0.05) versus lansoprazole/amoxicillin and lansoprazole/clarithromycin dual therapy.
(p<0.05) versus clarithromycin/amoxicillin dual therapy.

Study

Triple Therapy

Triple Therapy

Evaluable Analysis *

Intent-to-Treat Analysis

Study 1

92
[80 - 97.7]
(n = 48)

86
[73.3 - 93.5]
(n = 55)

Study 2

86
[75.7 - 93.6]
(n = 66)

83
[72 - 90.8]
(n = 70)

H. pyloriEradication Rates Dual Therapy (amoxicillin/lansoprazole)
Percent of Patients Cured [95% Confidence Interval] (Number of Patients)


* This analysis was based on evaluable patients with confirmed duodenal ulcer
(active or within 1 year) and H. pyloriinfection at baseline defined as at least 2 of 3
positive endoscopic tests from CLOtest ®, 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. pyloriinfection at
baseline as defined above and had a confirmed duodenal ulcer (active or within 1 year).
All dropouts were included as failures of therapy.
(p<0.05) versus lansoprazole alone.
(p<0.05) versus lansoprazole alone or amoxicillin alone.

Study

Dual Therapy

Dual Therapy

Evaluable Analysis*

Intent-to-Treat Analysis

Study 1

77
[62.5 - 87.2]
(n = 51)

70
[56.8 - 81.2]
(n = 60)

Study 2

66
[51.9 - 77.5]
(n = 58)

61
[48.5 - 72.9]
(n = 67)

References



  1. 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.
  2. 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.
  3. 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.

Manufacturer information

Manufactured By:

Aurobindo Pharma Limited
Hyderabad-500 072, India

Manufactured for:

Aurobindo Pharma USA, Inc.
2400 Route 130 North
Dayton, NJ 08810


As NDC:

65862-0071-01 For 55045-2992-2 Amoxicillin 400 mg

Repackaged By:

Dispensing Solutions Inc.
3000 West Warner Ave
Santa Ana, CA 92704
United States

Ingredients and appearance - Product information

Amoxicillin powder, for suspension- Amoxicillin

Product information

Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC: 55045-2992
Route of Administration Oral

Active Ingredient/Active Moiety

Ingredient Name Strength
Amoxicillin ( UNII: 804826J2HU)( Amoxicillin - UNII: 804826J2HU ) 400 mgin 5 mL

Inactive Ingredients

Ingredient Name Code
Sucrose ( UNII: C151H8M554)
Sodium citrate ( UNII: 1Q73Q2JULR)
Sodium benzoate ( UNII: OJ245FE5EU)
Edetate disodium ( UNII: 7FLD91C86K)
Fd&c red no. 3 ( UNII: PN2ZH5LOQY)
Xanthan gum ( UNII: TTV12P4NEE)
Colloidal silicon dioxide ( UNII: ETJ7Z6XBU4)

Product Characteristics

Marketing Information

Marketing Category Application Number or Monograph Citation Territorial Authority Marketing Start Date
ANDA ANDA065334 USA

Labeler - Dispensing Solutions Inc.( 066070785)

Establishment

Name ID/FEI Business Operations
Dispensing Solutions Inc. 066070785 repack(), relabel()

Package label.principal display panel