AMOXICILLIN AND CLAVULANATE POTASSIUM - amoxicillin and clavulanate potassium suspension

United States - English - NLM (National Library of Medicine)

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Active ingredient:
AMOXICILLIN (UNII: 804826J2HU) (AMOXICILLIN ANHYDROUS - UNII:9EM05410Q9), CLAVULANATE POTASSIUM (UNII: Q42OMW3AT8) (CLAVULANIC ACID - UNII:23521W1S24)
Available from:
Physicians Total Care, Inc.
INN (International Name):
AMOXICILLIN
Composition:
AMOXICILLIN ANHYDROUS 600 mg in 5 mL
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Amoxicillin and Clavulanate Potassium for Oral Suspension USP, 600 mg/42.9 mg per 5 mL is indicated for the treatment of pediatric patients with recurrent or persistent acute otitis media due to S. pneumoniae (penicillin MICs ≤ 2 mcg/mL), H. influenzae (including β-lactamase-producing strains), or M. catarrhalis (including β-lactamase-producing strains) characterized by the following risk factors: • antibiotic exposure for acute otitis media within the preceding 3 months, and either of the following: See ( CLINICAL PHARMACOLOGY, Microbiology) . NOTE: Acute otitis media due to S. pneumoniae alone can be treated with amoxicillin. Amoxicillin and Clavulanate Potassium for Oral Suspension 600 mg/42/9 mg per 5 mL is not indicated for the treatment of acute otitis media due to S. pneumoniae with penicillin MIC ≥ 4 mcg /mL. Therapy may be instituted prior to obtaining the results from bacteriological studies when there is reason to believe the infection may involve both S. pneumoniae (penicillin MIC ≤
Product summary:
Amoxicillin and Clavulanate Potassium for Oral Suspension USP, 600 mg/42.9 mg per 5 mL: Each 5 mL of reconstituted suspension contains 600 mg amoxicillin and 42.9 mg clavulanic acid as the potassium salt. NDC 54868-5165-2    75 mL bottle NDC 54868-5165-0    125 mL bottle NDC 54868-5165-1    200 mL bottle Store reconstituted suspension under refrigeration. Discard unused suspension after 10 days. Store dry powder for oral suspension at 20º-25°C (68º-77°F) [see USP Controlled Room Temperature]. Dispense in original container. Two clinical studies were conducted in pediatric patients with acute otitis media. A non-comparative, open-label study assessed the bacteriologic and clinical efficacy of Amoxicillin and Clavulanate Potassium for Oral Suspension  USP, 600 mg/42.9 mg per 5 mL (90/6.4 mg/kg/day, divided every 12 hours) for 10 days in 521 pediatric patients (3 to 50 months) with acute otitis media. The primary objective was to assess bacteriological response in children with acute otitis media due to S. pneumoniae with amoxicillin/clavulanic acid MICs of 4 mcg/mL. The study sought the enrollment of patients with the following risk factors: Failure of antibiotic therapy for acute otitis media in the previous 3 months, history of recurrent episodes of acute otitis media, ≤ 2 years, or daycare attendance. Prior to receiving Amoxicillin and Clavulanate Potassium for Oral Suspension  USP, 600 mg/42.9 mg per 5 mL, all patients had tympanocentesis to obtain middle ear fluid for bacteriological evaluation. Patients from whom S. pneumoniae (alone or in combination with other bacteria) was isolated had a second tympanocentesis 4 to 6 days after the start of therapy. Clinical assessments were planned for all patients during treatment (4-6 days after starting therapy), as well as 2-4 days post-treatment and 15-18 days post-treatment. Bacteriological success was defined as the absence of the pretreatment pathogen from the on-therapy tympanocentesis specimen. Clinical success was defined as improvement or resolution of signs and symptoms. Clinical failure was defined as lack of improvement or worsening of signs and/or symptoms at any time following at least 72 hours of Amoxicillin and Clavulanate Potassium for Oral Suspension  USP, 600 mg/5 mL; patients who received an additional systemic antibacterial drug for otitis media after 3 days of therapy were considered clinical failures. Bacteriological eradication on therapy (day 4-6 visit) in the per protocol population is summarized in Table 5 . Table 5. Bacteriologic Eradication Rates in the Per Protocol Population Pathogen Bacteriologic Eradication on Therapy n/N % 95% CI* All S. pneumoniae 121/123 98.4 (94.3, 99.8) S. pneumoniae with penicillin MIC = 2 mcg/mL 19/19 100 (82.4, 100) S. pneumoniae with penicillin MIC = 4 mcg/mL 12/14 85.7 (57.2, 98.2) H. influenzae 75/81 92.6 (84.6, 97.2) M. catarrhalis 11/11 100 (71.5, 100) *CI = confidence intervals; 95% CIs are not adjusted for multiple comparisons. Clinical assessments were made in the per protocol population 2-4 days post-therapy and 15-18 days post-therapy. Patients who responded to therapy 2-4 days post-therapy were followed for 15-18 days post-therapy to assess them for acute otitis media. Nonresponders at 2-4 days post-therapy were considered failures at the latter timepoint. Table 6. Clinical Assessments in the Per Protocol Population (Includes S. pneumoniae Patients With Penicillin MICs = 2 or 4 mcg/mL*) Pathogen 2-4 Days Post-Therapy (Primary Endpoint) n/N % 95% CI†  All S. pneumoniae 122/137 89.1 (82.6, 93.7) S. pneumoniae with penicillin MIC = 2 mcg/mL 17/20 85 (62.1,96.8) S. pneumoniae with penicillin MIC = 4 mcg/mL 11/14 78.6 (49.2, 95.3) H. influenzae 141/162 87  (80.9, 91.8) M. catarrhalis 22/26 84.6 (65.1, 95.6) Pathogen 15-18 Days Post-Therapy‡ (Secondary Endpoint) n/N % 95% CI†  All S. pneumoniae 95/136 69.9 (61.4, 77.4) S. pneumoniae with penicillin MIC = 2 mcg/mL 11/20 55 (31.5, 76.9) S. pneumoniae with penicillin MIC = 4 mcg/mL 5/14 35.7 (12.8, 64.9) H. influenzae 106/156 67.9 (60, 75.2) M. catarrhalis 14/25 56 (34.9, 75.6) *S. pneumoniae strains with penicillin MICs of 2 or 4 mcg/mL are considered resistant to penicillin. †  CI = confidence intervals; 95% CIs are not adjusted for multiple comparisons. ‡ Clinical assessments at 15-18 days post-therapy may have been confounded by viral infections and new episodes of acute otitis media with time elapsed post-treatment. In the intent-to-treat analysis, overall clinical outcomes at 2-4 days and 15-18 days post-treatment in patients with S. pneumoniae with penicillin MIC = 2 mcg/mL and 4 mcg/mL were 29/41 (71%) and 17/41 (41.5%), respectively. In the intent-to-treat population of 521 patients, the most frequently reported adverse events were vomiting (6.9%), fever (6.1%), contact dermatitis (i.e., diaper rash) (6.1%), upper respiratory tract infection (4%), and diarrhea (3.8%). Protocol-defined diarrhea (i.e., 3 or more watery stools in one day or 2 watery stools per day for 2 consecutive days as recorded on diary cards) occurred in 12.9% of patients. A double-blind, randomized, clinical study compared Amoxicillin and Clavulanate Potassium for Oral Suspension 600 mg/42.9 mg per 5 mL (90/6.4 mg/kg/day, divided every 12 hours) to Amoxicillin and Clavulanate Potassium (45/6.4 mg/kg/day, divided every 12 hours) for 10 days in 450 pediatric patients (3 months to 12 years) with acute otitis media. The primary objective of the study was to compare the safety of Amoxicillin and Clavulanate Potassium for Oral Suspension USP, 600 mg/42.9 mg per 5 mL to Amoxicillin and Clavulanate Potassium. There was no statistically significant difference between treatments in the proportion of patients with 1 or more adverse events. The most frequently reported adverse events for Amoxicillin and Clavulanate Potassium for Oral Suspension USP, 600 mg/42.9 mg per 5 mL and the comparator of Amoxicillin and Clavulanate Potassium, were coughing (11.9% versus 6.8%), vomiting (6.5% versus 7.7%), contact dermatitis (i.e., diaper rash, 6% versus 4.8%), fever (5.5% versus 3.9%), and upper respiratory infection (3% versus 9.2%), respectively. The frequencies of protocol-defined diarrhea with Amoxicillin and Clavulanate Potassium for Oral Suspension USP, 600 mg/42.9 mg per 5 mL (11.1%) and Amoxicillin and Clavulanate Potassium (9.4%) were similar (95% confidence interval on difference: −4.2% to 7.7%). Only 2 patients in the group treated with Amoxicillin and Clavulanate Potassium for Oral Suspension USP, 600 mg/42.9 mg per 5 mL and 1 patient in the group treated with Amoxicillin and Clavulanate Potassium were withdrawn due to diarrhea. CLINITEST is a registered trademark of Miles, Inc. CLINISTIX is a registered trademark of Bayer Corporation. Manufactured in Slovenia by Lek Pharmaceuticals d.d. for Sandoz Inc., Princeton, NJ 08540 Rev. June 2012 Distributed by: Physicians Total Care, inc. Tulsa, OK     74146
Authorization status:
Abbreviated New Drug Application
Authorization number:
54868-5165-0, 54868-5165-1, 54868-5165-2

AMOXICILLIN AND CLAVULANATE POTASSIUM - amoxicillin and clavulanate

potassium suspension

Physicians Total Care, Inc.

----------

AMOXICILLIN AND CLAVULANATE POTASSIUM FOR ORAL SUSPENSION, USP

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

Clavulanate Potassium for Oral Suspension 600 mg/42.9 mg per 5 mL and other antibacterial drugs,

Amoxicillin and Clavulanate Potassium for Oral Suspension 600 mg/ 42.9 mg per 5 mL should be used

only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

DESCRIPTION

Amoxicillin and Clavulanate Potassium for Oral Suspension 600 mg/42.9 mg per 5 mL is an oral

antibacterial combination consisting of the semisynthetic antibiotic amoxicillin and the β-lactamase

inhibitor, clavulanate potassium (the potassium salt of clavulanic acid). Amoxicillin is an analog of

ampicillin, derived from the basic penicillin nucleus, 6-aminopenicillanic acid. The amoxicillin

molecular formula is C

H N O S 3H O, and the molecular weight is 419.46. Chemically,

amoxicillin 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 and may be represented structurally as:

Clavulanic acid is produced by the fermentation of Streptomyces clavuligerus. It is a β-lactam structurally

related to the penicillins and possesses the ability to inactivate a wide variety of β-lactamases by

blocking the active sites of these enzymes. Clavulanic acid is particularly active against the clinically

important plasmid-mediated β-lactamases frequently responsible for transferred drug resistance to

penicillins and cephalosporins. The clavulanate potassium molecular formula is C H KNO and the

molecular weight is 237.25. Chemically, clavulanate potassium is potassium (Z)-(2R,5R)-3-(2-

hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]-heptane-2-carboxylate and may be represented

structurally as:

Inactive Ingredients: Powder for Oral Suspension—Caramel flavor, carboxymethyl cellulose sodium,

citric acid, colloidal silicon dioxide, microcrystalline cellulose, orange flavor, raspberry flavor,

saccharin sodium, silicon dioxide, sodium citrate, and xanthan gum.

Each 5 mL of reconstituted Amoxicillin and Clavulanate Potassium for Oral Suspension 600 mg/42.9

mg per 5 mL contains 600 mg amoxicillin as the trihydrate and 42.9 mg clavulanic acid as the potassium

salt (clavulanate potassium). The potassium content per 5 mL is 0.23 mEq (equivalent to 9 mg).

Color and appearance of the dry powder: White to yellowish white crystalline powder

Color and appearance of the suspension: Almost white to yellow, homogeneous suspension.

CLINICAL PHARMACOLOGY

The pharmacokinetics of amoxicillin and clavulanate were determined in a study of 19 pediatric patients,

8 months to 11 years, given Amoxicillin and Clavulanate Potassium for Oral Suspension 600 mg/42.9

mg per 5 mL at an amoxicillin dose of 45 mg/kg every 12 hours with a snack or meal. The mean plasma

amoxicillin and clavulanate pharmacokinetic parameter values are listed in the following table.

Table 1. Mean (±SD) Plasma Amoxicillin and Clavulanate Pharmacokinetic Parameter Values

Following Administration of 45 mg/kg of Amoxicillin and Clavulanate Potassium for Oral

Suspension 600 mg/42.9 mg per 5 mL Every 12 Hours to Pediatric Patients.

Parameter*

Amoxicillin

Clavulanate

(mcg/mL)

15.7 ± 7.7

1.7 ± 0.9

(hr)

2 (1-4)

1.1(1-4)

(mcghr/mL)

59.8 ± 20

4 ± 1.9

T (hr)

1.4 ± 0.3

1.1 ± 0.3

CL/F (L/hr/kg)

0.9 ± 0.4

1.1 ± 1.1

*Arithmetic mean ± standard deviation, except T

values which are medians (ranges).

The effect of food on the oral absorption of Amoxicillin and Clavulanate Potassium for Oral

Suspension 600 mg/42.9 mg per 5 mL has not been studied.

Approximately 50% to 70% of the amoxicillin and approximately 25% to 40% of the clavulanic acid are

excreted unchanged in urine during the first 6 hours after administration of 10 mL of 250 mg/62.5 mg

per 5 mL suspension of Amoxicillin and Clavulanate Potassium.

Concurrent administration of probenecid delays amoxicillin excretion but does not delay renal excretion

of clavulanic acid.

Neither component in Amoxicillin and Clavulanate Potassium for Oral Suspension 600 mg/42.9 mg per

5 mL is highly protein-bound; clavulanic acid has been found to be approximately 25% bound to human

serum and amoxicillin approximately 18% bound.

Oral administration of a single dose of Amoxicillin and Clavulanate Potassium for Oral Suspension at

45 mg/kg (based on the amoxicillin component) to pediatric patients, 9 months to 8 years, yielded the

following pharmacokinetic data for amoxicillin in plasma and middle ear fluid (MEF):

Table 2. Amoxicillin Concentrations in Plasma and Middle Ear Fluid Following Administration of

45 mg/kg of Amoxicillin and Clavulanate Potassium for Oral Suspensionto Pediatric Patients

Timepoint

Amoxicillin Concentration in

Plasma (mcg/mL)

Amoxicillin Concentration in

MEF (mcg/mL)

1 hour

mean

median

range

1.5-14

(n=5)

0.2-5.5

(n=4)

2 hour

mean

15.7

median

range

11-25

(n = 7)

1.9-6

(n = 5)

3 hour

mean

median

range

5.5-21

(n = 5)

3.9-7.4

(n = 5)

Dose administered immediately prior to eating.

Amoxicillin diffuses readily into most body tissues and fluids with the exception of the brain and spinal

fluid. The results of experiments involving the administration of clavulanic acid to animals suggest that

this compound, like amoxicillin, is well distributed in body tissues.

Microbiology

Amoxicillin is a semisynthetic antibiotic with a broad spectrum of bactericidal activity against many

gram-positive and gram-negative microorganisms. Amoxicillin is, however, susceptible to degradation

by β-lactamases, and therefore, its spectrum of activity does not include organisms which produce these

enzymes. Clavulanic acid is a β-lactam, structurally related to penicillin, which possesses the ability to

inactivate a wide range of β-lactamase enzymes commonly found in microorganisms resistant to

penicillins and cephalosporins. In particular, it has good activity against the clinically important

plasmid-mediated β-lactamases frequently found responsible for transferred drug resistance.

The clavulanic acid component of Amoxicillin and Clavulanate Potassium for Oral Suspension 600

mg/42.9 mg per 5 mL protects amoxicillin from degradation by β-lactamase enzymes and effectively

extends the antibiotic spectrum of amoxicillin to include many bacteria normally resistant to amoxicillin

and other β-lactam antibiotics. Thus, Amoxicillin and Clavulanate Potassium for Oral Suspension 600

mg/42.9 mg per 5 mL possesses the distinctive properties of a broad-spectrum antibiotic and a β-

lactamase inhibitor.

Amoxicillin/clavulanic acid has been shown to be active against most isolates of the following

microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND

USAGE section.

Aerobic Gram-Positive Microorganisms:

Streptococcus pneumoniae(including isolates with penicillin MICs ≤ 2 mcg/mL)

Aerobic Gram-Negative Microorganisms:

Haemophilusinfluenzae(including β-lactamase–producing isolates)

Moraxella catarrhalis(including β-lactamase–producing isolates)

The following in vitro data are available, but their clinical significance is unknown.

At least 90% of the following microorganisms exhibit in vitro minimum inhibitory concentrations

(MICs) less than or equal to the susceptible breakpoint for amoxicillin/clavulanic acid. However, the

safety and efficacy of amoxicillin/clavulanic acid in treating infections due to these microorganisms

have not been established in adequate and well-controlled trials.

Aerobic Gram-Positive Microorganisms:

Staphylococcus aureus(including β-lactamase–producing isolates)

NOTE: Staphylococci which are resistant to methicillin/oxacillin must be considered resistant to

amoxicillin/clavulanic acid.

Streptococcus pyogenes

NOTE: S. pyogenesdo not produce β-lactamase, and therefore, are susceptible to amoxicillin alone.

Adequate and well-controlled clinical trials have established the effectiveness of amoxicillin alone in

treating certain clinical infections due to S. pyogenes.

Susceptibility Test Methods

When available, the clinical microbiology laboratory should provide cumulative results of in vitro

susceptibility test results for antimicrobial drugs used in local hospitals and practice areas to the

physician as periodic reports that describe the susceptibility profile of nosocomial and community-

acquired pathogens. These reports should aid the physician in selecting the most effective

antimicrobial.

Dilution Technique

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 dilution

methods (broth for S. pneumoniaeand H. influenzae) or equivalent with standardized inoculum

concentration and standardized concentrations of amoxicillin/clavulanate potassium powder.

The recommended dilution pattern utilizes a constant amoxicillin/clavulanate potassium ratio of 2 to 1 in

all tubes with varying amounts of amoxicillin. MICs are expressed in terms of the amoxicillin

concentration in the presence of clavulanic acid at a constant 2 parts amoxicillin to 1 part clavulanic

acid. The MIC values should be interpreted according to criteria provided in Table 3.

Diffusion Technique

Quantitative methods that require measurement of zone diameters also provides reproducible estimates

of the susceptibility of bacteria to antimicrobials. One such standardized technique requires the use of a

standardized inoculum concentration.

This procedure uses paper disks impregnated with 30 mcg

amoxicillin/clavulanate potassium (20 mcg amoxicillin plus 10 mcg clavulanate potassium) to test

susceptibility of microorganisms to amoxicillin/clavulanate potassium. Disk diffusion zone sizes should

be interpreted according to criteria provided in Table 3.

Table 3. Susceptibility Test Result Interpretive Criteria for Amoxicillin/Clavulanate Potassium

Pathogen

Minimum Inhibitory Concentration

(mcg/mL)

Disk Diffusion

(Zone Diameter in mm)

S

I

R

S

I

R

Streptococcus pneumoniae

(non-meningitis isolates)

≤ 2/1

≥ 8/4

Not applicable (NA)

Haemophilusinfluenzae

≤ 4/2

≥ 8/4

≥ 20

≤ 19

NOTE: Susceptibility of S. pneumoniaeshould be determined using a 1-mcg oxacillin disk. Isolates with

oxacillin zone sizes of ≥ 20 mm are susceptible to amoxicillin/clavulanic acid. An

amoxicillin/clavulanic acid MIC should be determined on isolates of S. pneumoniaewith oxacillin zone

sizes of ≤ 19 mm.

NOTE: β-lactamase-negative, ampicillin-resistant H. influenzaeisolates must be considered resistant to

amoxicillin/clavulanic acid.

A report of S ("Susceptible") indicates that the antimicrobial is likely to inhibit growth of the pathogen

if the antimicrobial compound in the blood reaches the concentration usually achievable. A report of I

("Intermediate") indicates that the result should be considered equivocal, and, if the microorganism is

not fully susceptible to alternative, clinically feasible antimicrobials, 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 doses of antimicrobial can be used. This category also

provides a buffer zone that prevents small uncontrolled technical factors from causing major

discrepancies in interpretation. A report of R ("Resistant") indicates that the antimicrobial is not likely to

inhibit growth of the pathogen if the antimicrobial compound in the blood reaches the concentration

usually achievable; other therapy should be selected.

Standardized susceptibility test procedures require the use of quality control microorganisms to

determine the performance of the test procedures.

Standard amoxicillin/clavulanate potassium powder

should provide the MIC ranges for the quality control organisms in Table 4. For the disk diffusion

technique, the 30 mcg-amoxicillin/clavulanate potassium disk should provide the zone diameter ranges

for the quality control organisms in Table 4.

Table 4. Acceptable Quality Control Ranges for Amoxicillin/Clavulanate Potassium

Quality Control Organism

Minimum Inhibitory

Concentration Range

(mcg/mL)

Disk Diffusion (Zone

Diameter Range in mm)

Escherichia coli ATCC

35218 (H.

influenzae quality control)

4/2 to 16/8

17 to 22

HaemophilusinfluenzaeATCC 49247

2/1 to 16/8

15 to 23

Streptococcus pneumoniaeATCC 49619

0.03/0.016 to 0.12/0.06

ATCC is a trademark of the American Type Culture Collection.

When using HaemophilusTest Medium (HTM).

INDICATIONS AND USAGE

Amoxicillin and Clavulanate Potassium for Oral Suspension USP, 600 mg/42.9 mg per 5 mL is indicated

for the treatment of pediatric patients with recurrent or persistent acute otitis media due to S.

pneumoniae(penicillin MICs ≤ 2 mcg/mL), H. influenzae(including β-lactamase-producing strains), or M.

catarrhalis(including β-lactamase-producing strains) characterized by the following risk factors:

antibiotic exposure for acute otitis media within the preceding 3 months, and either of the following:

See ( CLINICAL PHARMACOLOGY, Microbiology).

NOTE: Acute otitis media due to S. pneumoniaealone can be treated with amoxicillin. Amoxicillin and

Clavulanate Potassium for Oral Suspension 600 mg/42/9 mg per 5 mL is not indicated for the treatment

of acute otitis media due to S. pneumoniaewith penicillin MIC ≥ 4 mcg /mL.

Therapy may be instituted prior to obtaining the results from bacteriological studies when there is

reason to believe the infection may involve both S. pneumoniae(penicillin MIC ≤ 2 mcg/mL) and the β-

lactamase-producing organisms listed above.

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

Clavulanate Potassium for Oral Suspension 600 mg/42.9 mg per 5 mL and other antibacterial drugs,

Amoxicillin and Clavulanate Potassium for Oral Suspension 600 mg/42.9 mg per 5 mL should be used

only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible

bacteria. When culture and susceptibility information are available, they should be considered in

selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and

susceptibility patterns may contribute to the empiric selection of therapy.

CONTRAINDICATIONS

Amoxicillin and Clavulanate Potassium for Oral Suspension 600 mg/42.9 mg per 5 mL is

contraindicated in patients with a history of allergic reactions to any penicillin. It is also contraindicated

in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with

Amoxicillin and Clavulanate Potassium.

WARNINGS

- age ≤ 2 years

- daycare attendance

SERIOUS AND OCCASIONALLY FATAL HYPERSENSITIVITY (ANAPHYLACTIC)

REACTIONS HAVE BEEN REPORTED IN PATIENTS ON PENICILLIN THERAPY. 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

AND CLAVULANATE POTASSIUM FOR ORAL SUSPENSION, 600 mg/42.9 mg per 5 mL

CAREFUL INQUIRY SHOULD BE MADE CONCERNING PREVIOUS HYPERSENSITIVITY

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

ALLERGIC REACTION OCCURS, AMOXICILLIN AND CLAVULANATE POTASSIUM FOR

ORAL SUSPENSION 600 mg /42.9 mg per 5 mL SHOULD BE DISCONTINUED AND THE

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/clavulanate potassium, and has ranged 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 difficileis one 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 C. difficile colitis.

Amoxicillin and Clavulanate Potassium for Oral Suspension 600 mg/42.9 mg per 5 mL should be used

with caution in patients with evidence of hepatic dysfunction. Hepatic toxicity associated with the use

of amoxicillin/clavulanate potassium is usually reversible. On rare occasions, deaths have been

reported (less than 1 death reported per estimated 4 million prescriptions worldwide). These have

generally been cases associated with serious underlying diseases or concomitant medications. (See

CONTRAINDICATIONS and ADVERSE REACTIONS— Liver.)

PRECAUTIONS

General

While amoxicillin/clavulanate possesses the characteristic low toxicity of the penicillin group of

antibiotics, periodic assessment of organ system functions, including renal, hepatic, and hematopoietic

function, is advisable if therapy is for longer than the drug is approved for administration.

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.

The possibility of superinfections with mycotic or bacterial pathogens should be kept in mind during

therapy. If superinfections occur (usually involving Pseudomonas or Candida), the drug should be

discontinued and/or appropriate therapy instituted.

Prescribing Amoxicillin and Clavulanate Potassium for Oral Suspension 600 mg/42.9 mg per 5 mL 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.

to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Information for the Patient

Amoxicillin and Clavulanate Potassium for Oral Suspension 600 mg /42.9 mg per 5 mL should be taken

every 12 hours with a meal or snack to reduce the possibility of gastrointestinal upset. If diarrhea

develops and is severe or lasts more than 2 or 3 days, call your doctor.

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.

Keep suspension refrigerated. Shake well before using. When dosing a child with the suspension

(liquid) of Amoxicillin and Clavulanate Potassium for Oral Suspension, 600 mg/42.9 mg per 5 mL use a

dosing spoon or medicine dropper. Be sure to rinse the spoon or dropper after each use. Bottles of

suspension of Amoxicillin and Clavulanate Potassium for Oral Suspension 600 mg /42.9 mg per 5 mL

may contain more liquid than required. Follow your doctor's instructions about the amount to use and the

days of treatment your child requires. Discard any unused medicine.

Patients should be counseled that antibacterial drugs including Amoxicillin and Clavulanate Potassium

for Oral Suspension, 600 mg/42.9 mg per 5 mL should only be used to treat bacterial infections. They

do not treat viral infections (e.g., the common cold). When Amoxicillin and Clavulanate Potassium for

Oral Suspension 600 mg/42.9 mg per 5 mL 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 and Clavulanate Potassium for Oral Suspension 600

mg/42.9 mg per 5 mL or other antibacterial drugs in the future.

Drug Interactions

Probenecid decreases the renal tubular secretion of amoxicillin. Concurrent use with Amoxicillin and

Clavulanate Potassium for Oral Suspension 600 mg/42.9 mg per 5 mL may result in increased and

prolonged blood levels of amoxicillin. Co-administration of probenecid cannot be recommended.

Abnormal prolongation of prothrombin time (increased international normalized ratio [INR]) has been

reported rarely in patients receiving amoxicillin and oral anticoagulants. Appropriate monitoring should

be undertaken when anticoagulants are prescribed concurrently. Adjustments in the dose of oral

anticoagulants may be necessary to maintain the desired level of anticoagulation.

The concurrent administration of allopurinol and ampicillin increases substantially the incidence of

rashes in patients receiving both drugs as compared to patients receiving ampicillin alone. It is not

known whether this potentiation of ampicillin rashes is due to allopurinol or the hyperuricemia present

in these patients. There are no data with Amoxicillin and Clavulanate Potassium for Oral Suspension

600 mg/42.9 mg per 5 mL and allopurinol administered concurrently.

In common with other broad-spectrum antibiotics, amoxicillin/clavulanate may reduce the efficacy of

oral contraceptives.

Drug/Laboratory Test Interactions

Oral administration of Amoxicillin and Clavulanate Potassium will result in high urine concentrations of

amoxicillin. 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 and therefore Amoxicillin and Clavulanate Potassium

for Oral Suspension 600 mg/42.9 mg per 5 mL, 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 and therefore Amoxicillin and Clavulanate Potassium for Oral

Suspension, 600 mg/42.9 mg per 5 mL.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals have not been performed to evaluate carcinogenic potential. The

mutagenic potential of Amoxicillin and Clavulanate Potassium was investigated in vitro with an Ames

test, a human lymphocyte cytogenetic assay, a yeast test, and a mouse lymphoma forward mutation assay,

and in vivo with mouse micronucleus tests and a dominant lethal test. All were negative apart from the in

vitro mouse lymphoma assay where weak activity was found at very high, cytotoxic concentrations.

Amoxicillin and Clavulanate Potassium at oral doses of up to 1,200 mg/kg/day (5.7 times the maximum

adult human dose based on body surface area) was found to have no effect on fertility and reproductive

performance in rats, dosed with a 2:1 ratio formulation of amoxicillin:clavulanate.

Teratogenic Effects

Pregnancy (Category B). Reproduction studies performed in pregnant rats and mice given Amoxicillin

and Clavulanate Potassium at oral dosages up to 1,200 mg/kg/day (4.9 and 2.8 times the maximum adult

human oral dose based on body surface area, respectively), revealed no evidence of harm to the fetus

due to Amoxicillin and Clavulanate Potassium. 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 generally poorly absorbed during labor. Studies in guinea pigs

have shown that intravenous administration of ampicillin decreased the uterine tone, frequency of

contractions, height of contractions, and duration of contractions. However, it is not known whether the

use of Amoxicillin and Clavulanate Potassium 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. In a

single study in women with premature rupture of fetal membranes, it was reported that prophylactic

treatment with Amoxicillin and Clavulanate Potassium may be associated with an increased risk of

necrotizing enterocolitis in neonates.

Nursing Mothers

Ampicillin-class antibiotics are excreted in human milk; therefore, caution should be exercised when

Amoxicillin and Clavulanate Potassium is administered to a nursing woman.

Pediatric Use

Safety and efficacy of Amoxicillin and Clavulanate Potassium for Oral Suspension 600 mg/42.9 mg per

5 mL in infants younger than 3 months have not been established. Safety and efficacy of Amoxicillin and

Clavulanate Potassium for Oral Suspension 600 mg/42.9 mg per 5 mL have been demonstrated for

treatment of acute otitis media in infants and children 3 months to 12 years (see Description of Clinical

Studies).

The safety and effectiveness of Amoxicillin and Clavulanate Potassium for Oral Suspension 600

mg/42.9 mg per 5 mL have been established for the treatment of pediatric patients (3 months to 12 years)

with acute bacterial sinusitis. This use is supported by evidence from adequate and well-controlled

studies of Amoxicillin and Clavulanate Potassium Extended Release Tablets 1000 mg/62.5 mg in adults

with acute bacterial sinusitis, studies of Amoxicillin and Clavulanate Potassium for Oral Suspension

600 mg/42.9 mg per 5 mL in pediatric patients with acute otitis media, and by similar pharmacokinetics

of amoxicillin and clavulanate in pediatric patients taking Amoxicillin and Clavulanate Potassium for

Oral Suspension 600 mg/42.9 mg per 5 mL (see CLINICAL PHARMACOLOGY) and adults taking

Amoxicillin and Clavulanate Potassium Extended Release Tablets 1000 mg/62.5 mg.

ADVERSE REACTIONS

Amoxicillin and Clavulanate Potassium for Oral Suspension 600 mg/42.9 mg per 5 mL is generally well

tolerated. The majority of side effects observed in pediatric clinical trials of acute otitis media were

either mild or moderate, and transient in nature; 4.4% of patients discontinued therapy because of drug-

related side effects. The most commonly reported side effects with probable or suspected relationship

to Amoxicillin and Clavulanate Potassium for Oral Suspension 600 mg/42.9 mg per 5 mL were contact

dermatitis, i.e., diaper rash (3.5%), diarrhea (2.9%), vomiting (2.2%), moniliasis (1.4%), and rash (1.1%).

The most common adverse experiences leading to withdrawal that were of probable or suspected

relationship to Amoxicillin and Clavulanate Potassium for Oral Suspension 600 mg/42.9 mg per 5 mL

were diarrhea (2.5%) and vomiting (1.4%).

The following adverse reactions have been reported for ampicillin-class antibiotics:

Gas trointes tinal

Diarrhea, nausea, vomiting, indigestion, gastritis, stomatitis, glossitis, black "hairy" tongue,

mucocutaneous candidiasis, enterocolitis, and hemorrhagic/pseudomembranous colitis. Onset of

pseudomembranous colitis symptoms may occur during or after antibiotic treatment (see WARNINGS).

Hypersensitivity Reactions

Skin rashes, pruritus, urticaria, angioedema, serum sickness-like reactions (urticaria or skin rash

accompanied by arthritis, arthralgia, myalgia, and frequently fever), erythema multiforme (rarely

Stevens-Johnson syndrome), acute generalized exanthematous pustulosis, hypersensitivity vasculitis,

and an occasional case of exfoliative dermatitis (including toxic epidermal necrolysis) have been

reported. These reactions may be controlled with antihistamines and, if necessary, systemic

corticosteroids. Whenever such reactions occur, the drug should be discontinued, unless the opinion of

the physician dictates otherwise. Serious and occasional fatal hypersensitivity (anaphylactic) reactions

can occur with oral penicillin (see WARNINGS).

Liver

A moderate rise in AST (SGOT) and/or ALT (SGPT) has been noted in patients treated with ampicillin-

class antibiotics, but the significance of these findings is unknown. Hepatic dysfunction, including

hepatitis and cholestatic jaundice, (see CONTRAINDICATIONS), increases in serum transaminases

(AST and/or ALT), serum bilirubin, and/or alkaline phosphatase, has been infrequently reported with

Amoxicillin and Clavulanate Potassium. It has been reported more commonly in the elderly, in males, or

in patients on prolonged treatment. The histologic findings on liver biopsy have consisted of

predominantly cholestatic, hepatocellular, or mixed cholestatic-hepatocellular changes. The onset of

signs/symptoms of hepatic dysfunction may occur during or several weeks after therapy has been

discontinued. The hepatic dysfunction, which may be severe, is usually reversible. On rare occasions,

deaths have been reported (less than 1 death reported per estimated 4 million prescriptions worldwide).

These have generally been cases associated with serious underlying diseases or concomitant

medications.

Renal

Interstitial nephritis and hematuria have been reported rarely. 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. A

slight thrombocytosis was noted in less than 1% of the patients treated with Amoxicillin and Clavulanate

Potassium. There have been reports of increased prothrombin time in patients receiving Amoxicillin and

Clavulanate Potassium and anticoagulant therapy concomitantly.

Central Nervous System

Agitation, anxiety, behavioral changes, confusion, convulsions, dizziness, insomnia, and reversible

hyperactivity have been reported rarely.

Mis cellaneous

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.

OVERDOSAGE

Following overdosage, patients have experienced primarily gastrointestinal symptoms including

stomach and abdominal pain, vomiting, and diarrhea. Rash, hyperactivity, or drowsiness have also been

observed in a small number of patients.

In the case of overdosage, discontinue Amoxicillin and Clavulanate Potassium for Oral Suspension, 600

mg/42.9 mg per 5 mL 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

both amoxicillin and clavulanate. Both amoxicillin and clavulanate are removed from the circulation by

hemodialysis.

DOSAGE AND ADMINISTRATION

Amoxicillin and Clavulanate Potassium for Oral Suspension, 600 mg/42.9 mg per 5 mL, does not

contain the same amount of clavulanic acid (asthe potassium salt) as any of the other

suspensions of Amoxicillin and Clavulanate Potassium. Amoxicillin and Clavulanate Potassium

for Oral Suspension, 600 mg/42.9 mg per 5 mL contains 42.9 mg of clavulanic acid per 5 mL,

whereas the 200 mg/28.5 mg per 5 mL suspension ofAmoxicillin and Clavulanate Potassium

contains 28.5 mg of clavulanic acid per 5 mL and the 400 mg/57 mg per 5 mL suspension

contains 57 mg of clavulanic acid per 5 mL. Therefore, the 200 mg/28.5 mg per 5 mL and 400

mg/57 mg per 5 mL suspensions of Amoxicillin and Clavulanate Potassium should not be

substituted for Amoxicillin and Clavulanate Potassium for Oral Suspension, 600 mg/42.9 mg per

5 mL as they are not interchangeable.

Dos age

Pediatric Patients 3 Months and Older

Based on the amoxicillin component (600 mg per 5 mL), the recommended dose of Amoxicillin and

Clavulanate Potassium for Oral Suspension 600 mg/42.9 mg per 5 mL is 90 mg/kg/day divided every 12

hours, administered for 10 days (see chart below).

Body Weight (kg)

Volume of Amoxicillin and Clavulanate Potassium for Oral

Suspension 600 mg/42.9 mg per 5 mL Providing 90

mg/kg/day

3 mL twice daily

4.5 mL twice daily

6 mL twice daily

7.5 mL twice daily

9 mL twice daily

10.5 mL twice daily

12 mL twice daily

13.5 mL twice daily

Pediatric Patients Weighing 40 kg and More

Experience with Amoxicillin and Clavulanate Potassium for Oral Suspension (600 mg/42.9 mg per 5 mL

formulation) in this group is not available.

Adults

Experience with Amoxicillin and Clavulanate Potassium for Oral Suspension (600 mg/5 mL

formulation) in adults is not available and adults who have difficulty swallowing should not be given

Amoxicillin and Clavulanate Potassium for Oral Suspension (600 mg/42.9 mg per 5 mL) in place of the

500 mg/125 mg or 875 mg/125 mg tablet of Amoxicillin and Clavulanate Potassium.

Hepatically impaired patients should be dosed with caution and hepatic function monitored at regular

intervals (see WARNINGS).

Directions for Mixing Oral Suspension

Prepare a suspension at time of dispensing as follows: Tap bottle until all the powder flows freely. Add

approximately 2/3 of the total amount of water for reconstitution (see table below) and shake vigorously

to suspend powder. Add remainder of the water and again shake vigorously.

Amoxicillin and Clavulanate Potassium for Oral Suspension (600 mg/42.9 mg per 5 mL

Sus pens ion)

Bottle Size

Amount of Water Required for Reconstitution

75 mL

62 mL

125 mL

103 mL

200 mL

165 mL

Each teaspoonful (5 mL) will contain 600 mg amoxicillin as the trihydrate and 42.9 mg of clavulanic

acid as the potassium salt.

NOTE: SHAKE ORAL SUSPENSION WELL BEFORE USING.

Adminis tration

To minimize the potential for gastrointestinal intolerance, Amoxicillin and Clavulanate Potassium for

Oral Suspension USP, 600 mg/42.9 mg per 5 mL should be taken at the start of a meal. Absorption of

clavulanate potassium may be enhanced when Amoxicillin and Clavulanate Potassium for Oral

Suspension USP, 600 mg/42.9 mg per 5 mL is administered at the start of a meal.

HOW SUPPLIED

Amoxicillin and Clavulanate Potassium for Oral Suspension USP, 600 mg/42.9 mg per 5 mL:

Each 5 mL of reconstituted suspension contains 600 mg amoxicillin and 42.9 mg clavulanic acid as the

potassium salt.

NDC 54868-5165-2 75 mL bottle

NDC 54868-5165-0 125 mL bottle

NDC 54868-5165-1 200 mL bottle

STORAGE

Store reconstituted suspension under refrigeration. Discard unused suspension after 10 days. Store dry

powder for oral suspension at 20º-25°C (68º-77°F) [see USP Controlled Room Temperature].

Dispense in original container.

Description of Clinical Studies

Two clinical studies were conducted in pediatric patients with acute otitis media.

A non-comparative, open-label study assessed the bacteriologic and clinical efficacy of Amoxicillin

and Clavulanate Potassium for Oral Suspension USP, 600 mg/42.9 mg per 5 mL (90/6.4 mg/kg/day,

divided every 12 hours) for 10 days in 521 pediatric patients (3 to 50 months) with acute otitis media.

The primary objective was to assess bacteriological response in children with acute otitis media due to

S. pneumoniaewith amoxicillin/clavulanic acid MICs of 4 mcg/mL. The study sought the enrollment of

patients with the following risk factors: Failure of antibiotic therapy for acute otitis media in the

previous 3 months, history of recurrent episodes of acute otitis media, ≤ 2 years, or daycare attendance.

Prior to receiving Amoxicillin and Clavulanate Potassium for Oral Suspension USP, 600 mg/42.9 mg

per 5 mL, all patients had tympanocentesis to obtain middle ear fluid for bacteriological evaluation.

Patients from whom S. pneumoniae(alone or in combination with other bacteria) was isolated had a

second tympanocentesis 4 to 6 days after the start of therapy. Clinical assessments were planned for all

patients during treatment (4-6 days after starting therapy), as well as 2-4 days post-treatment and 15-18

days post-treatment. Bacteriological success was defined as the absence of the pretreatment pathogen

from the on-therapy tympanocentesis specimen. Clinical success was defined as improvement or

resolution of signs and symptoms. Clinical failure was defined as lack of improvement or worsening of

signs and/or symptoms at any time following at least 72 hours of Amoxicillin and Clavulanate Potassium

for Oral Suspension USP, 600 mg/5 mL; patients who received an additional systemic antibacterial drug

for otitis media after 3 days of therapy were considered clinical failures. Bacteriological eradication

on therapy (day 4-6 visit) in the per protocol population is summarized in Table 5.

Table 5. Bacteriologic Eradication Rates in the Per Protocol Population

Pathogen

Bacteriologic Eradication on Therapy

n/N

%

95% CI*

All S. pneumoniae

121/123

98.4

(94.3, 99.8)

S. pneumoniaewith penicillin

MIC = 2 mcg/mL

19/19

(82.4, 100)

S. pneumoniaewith penicillin

MIC = 4 mcg/mL

12/14

85.7

(57.2, 98.2)

H. influenzae

75/81

92.6

(84.6, 97.2)

M. catarrhalis

11/11

(71.5, 100)

*CI = confidence intervals; 95% CIs are not adjusted for multiple comparisons.

Clinical assessments were made in the per protocol population 2-4 days post-therapy and 15-18 days

post-therapy. Patients who responded to therapy 2-4 days post-therapy were followed for 15-18 days

post-therapy to assess them for acute otitis media. Nonresponders at 2-4 days post-therapy were

considered failures at the latter timepoint.

Table 6. Clinical Assessments in the Per Protocol Population (Includes S. pneumoniae Patients

With Penicillin MICs = 2 or 4 mcg/mL*)

Pathogen

2-4 Days Post-Therapy (Primary Endpoint)

n/N

%

95% CI

All S. pneumoniae

122/137

89.1

(82.6, 93.7)

S. pneumoniaewith penicillin MIC

= 2 mcg/mL

17/20

(62.1,96.8)

S. pneumoniaewith penicillin MIC

= 4 mcg/mL

11/14

78.6

(49.2, 95.3)

H. influenzae

141/162

(80.9, 91.8)

M. catarrhalis

22/26

84.6

(65.1, 95.6)

Pathogen

15-18 Days Post-Therapy (Secondary Endpoint)

n/N

%

95% CI

All S. pneumoniae

95/136

69.9

(61.4, 77.4)

S. pneumoniaewith penicillin MIC

= 2 mcg/mL

11/20

(31.5, 76.9)

S. pneumoniaewith penicillin MIC

= 4 mcg/mL

5/14

35.7

(12.8, 64.9)

H. influenzae

106/156

67.9

(60, 75.2)

M. catarrhalis

14/25

(34.9, 75.6)

*S. pneumoniaestrains with penicillin MICs of 2 or 4 mcg/mL are considered resistant to penicillin.

CI = confidence intervals; 95% CIs are not adjusted for multiple comparisons.

Clinical assessments at 15-18 days post-therapy may have been confounded by viral infections and new

episodes of acute otitis media with time elapsed post-treatment.

In the intent-to-treat analysis, overall clinical outcomes at 2-4 days and 15-18 days post-treatment in

patients with S. pneumoniaewith penicillin MIC = 2 mcg/mL and 4 mcg/mL were 29/41 (71%) and 17/41

(41.5%), respectively.

In the intent-to-treat population of 521 patients, the most frequently reported adverse events were

vomiting (6.9%), fever (6.1%), contact dermatitis (i.e., diaper rash) (6.1%), upper respiratory tract

infection (4%), and diarrhea (3.8%). Protocol-defined diarrhea (i.e., 3 or more watery stools in one day

or 2 watery stools per day for 2 consecutive days as recorded on diary cards) occurred in 12.9% of

patients.

A double-blind, randomized, clinical study compared Amoxicillin and Clavulanate Potassium for Oral

Suspension 600 mg/42.9 mg per 5 mL (90/6.4 mg/kg/day, divided every 12 hours) to Amoxicillin and

Clavulanate Potassium (45/6.4 mg/kg/day, divided every 12 hours) for 10 days in 450 pediatric patients

(3 months to 12 years) with acute otitis media. The primary objective of the study was to compare the

safety of Amoxicillin and Clavulanate Potassium for Oral Suspension USP, 600 mg/42.9 mg per 5 mL to

Amoxicillin and Clavulanate Potassium. There was no statistically significant difference between

treatments in the proportion of patients with 1 or more adverse events. The most frequently reported

adverse events for Amoxicillin and Clavulanate Potassium for Oral Suspension USP, 600 mg/42.9 mg

per 5 mL and the comparator of Amoxicillin and Clavulanate Potassium, were coughing (11.9% versus

6.8%), vomiting (6.5% versus 7.7%), contact dermatitis (i.e., diaper rash, 6% versus 4.8%), fever (5.5%

versus 3.9%), and upper respiratory infection (3% versus 9.2%), respectively. The frequencies of

protocol-defined diarrhea with Amoxicillin and Clavulanate Potassium for Oral Suspension USP, 600

mg/42.9 mg per 5 mL (11.1%) and Amoxicillin and Clavulanate Potassium (9.4%) were similar (95%

confidence interval on difference: −4.2% to 7.7%). Only 2 patients in the group treated with Amoxicillin

and Clavulanate Potassium for Oral Suspension USP, 600 mg/42.9 mg per 5 mL and 1 patient in the

group treated with Amoxicillin and Clavulanate Potassium were withdrawn due to diarrhea.

REFERENCES

CLINITEST is a registered trademark of Miles, Inc.

CLINISTIX is a registered trademark of Bayer Corporation.

Manufactured in Slovenia by Lek Pharmaceuticals d.d.

for Sandoz Inc., Princeton, NJ 08540

Rev. June 2012

Distributed by:

Physicians Total Care, inc.

Tulsa, OK 74146

PRINCIPAL DISPLAY PANEL

Amoxicillin and Clavulanate Potassium for Oral Suspension, USP

*600 mg/ 42.9 mg per 5 mL

*When reconstituted, each 5 mL contains AMOXICILLIN, 600 mg as the trihydrate

CLAVULANIC ACID, 42.9 mg as clavulanate potassium.

125 mL (when reconstituted)

Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial

Susceptibility Testing – 21

Informational Supplement. CSLI Document M100-S21. CLSI, 940

West Valley Rd., Suite 1400, Wayne, PA 19087, 2011.

Clinical and Laboratory Standards Institute (CLSI). Methods for Antimicrobial Susceptibility

Testing of Anaerobic Bacteria – Approved Standard 7

ed. CSLI Document M11-A7. CLSI, 940

West Valley Rd., Suite 1400, Wayne, PA 19087, 2007.

Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial

Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard – 8

ed. CLSI

Document M07-A8. CLSI, 940 West Valley Rd., Suite 1400, Wayne, PA 19087, 2009.

Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Disk

Susceptibility Test; Approved Standard – 10

ed. CLSI Document M02-A10. CLSI, 940 West

Valley Rd., Suite 1400, Wayne, PA 19087, 2009.

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.

AMOXICILLIN AND CLAVULANATE POTASSIUM

amoxicillin and clavulanate potassium suspension

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:548 6 8 -516 5(NDC:0 78 1-6 139 )

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

ANHYDROUS

6 0 0 mg

in 5 mL

CLAVULANATE PO TASSIUM (UNII: Q42OMW3AT8 ) (CLAVULANIC ACID -

UNII:23521W1S24)

CLAVULANIC ACID

42.9 mg

in 5 mL

Inactive Ingredients

Ingredient Name

Stre ng th

CARBO XYMETHYLCELLULO SE SO DIUM (UNII: K6 79 OBS311)

CITRIC ACID MO NO HYDRATE (UNII: 29 6 8 PHW8 QP)

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

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

SACCHARIN SO DIUM DIHYDRATE (UNII: SB8 ZUX40 TY)

SO DIUM CITRATE (UNII: 1Q73Q2JULR)

XANTHAN GUM (UNII: TTV12P4NEE)

CARAMEL (UNII: T9 D9 9 G2B1R)

O RANGE (UNII: 5EVU0 4N5QU)

RASPBERRY (UNII: 4N14V5R27W)

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:548 6 8 -516 5-0

125 mL in 1 BOTTLE, DISPENSING

2

NDC:548 6 8 -516 5-1

20 0 mL in 1 BOTTLE, DISPENSING

3

NDC:548 6 8 -516 5-2

75 mL in 1 BOTTLE, DISPENSING

Marketing Information

Physicians Total Care, Inc.

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 6 5358

10 /13/20 0 8

Labeler -

Physicians T otal Care, Inc. (194123980)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Physicians To tal Care, Inc.

19 41239 8 0

re la be l(548 6 8 -516 5)

Revised: 2/2013

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