NDC 54868-4735 Augmentinxr

NDC Product Code 54868-4735

NDC 54868-4735-0

Package Description: 20 TABLET, FILM COATED, EXTENDED RELEASE in 1 BOTTLE, PLASTIC

NDC 54868-4735-1

Package Description: 40 TABLET, FILM COATED, EXTENDED RELEASE in 1 BOTTLE

NDC 54868-4735-2

Package Description: 28 TABLET, FILM COATED, EXTENDED RELEASE in 1 BOTTLE

This product is EXCLUDED from the official NDC directory because the listing data was inactivated by the FDA.

NDC Product Information

Augmentinxr with NDC 54868-4735 is a product labeled by Physicians Total Care, Inc.. The generic name of Augmentinxr is . The product's dosage form is and is administered via form.

Labeler Name: Physicians Total Care, Inc.

Dosage Form: -

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Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • CITRIC ACID MONOHYDRATE (UNII: 2968PHW8QP)
  • SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
  • HYPROMELLOSES (UNII: 3NXW29V3WO)
  • MAGNESIUM STEARATE (UNII: 70097M6I30)
  • CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)
  • POLYETHYLENE GLYCOL (UNII: 3WJQ0SDW1A)
  • SODIUM STARCH GLYCOLATE TYPE A POTATO (UNII: 5856J3G2A2)
  • TITANIUM DIOXIDE (UNII: 15FIX9V2JP)
  • XANTHAN GUM (UNII: TTV12P4NEE)

Product Labeler Information

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Labeler Name: Physicians Total Care, Inc.
Labeler Code: 54868
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Information for Patients

Amoxicillin and Clavulanic Acid

Amoxicillin and Clavulanic Acid is pronounced as (a mox i sil' in) (klav' yoo lan ic)

Why is amoxicillin and clavulanic acid medication prescribed?
The combination of amoxicillin and clavulanic acid is used to treat certain infections caused by bacteria, including infections of the ears, lungs, sinus, skin, and urina...
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Augmentinxr Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

Other

To reduce the development of drug-resistant bacteria and maintain
the effectiveness of AUGMENTIN XR (amoxicillin/clavulanate potassium) and other
antibacterial drugs, AUGMENTIN XR should be used only to treat or prevent
infections that are proven or strongly suspected to be caused by bacteria.

AUGMENTIN XR and AUGMENTIN are registered trademarks of GlaxoSmithKline.MAALOX is a registered trademark of Novartis Consumer Health,
Inc.GlaxoSmithKlineResearch Triangle Park, NC 27709©2010, GlaxoSmithKline. All rights reserved.September 2010                    AUX:11PIRelabeling and Repackaging by:Physicians Total Care, Inc.Tulsa, OK        74146

Description

AUGMENTIN XR is an oral antibacterial combination consisting of
the semisynthetic antibiotic amoxicillin (present as amoxicillin trihydrate and
amoxicillin sodium) 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 trihydrate molecular formula is C16H19N3O5S•3H2O, and the molecular weight is 419.45. Chemically, amoxicillin
trihydrate 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:The amoxicillin sodium molecular formula is C16H18N3NaO5S, and
the molecular weight is 387.39. Chemically, amoxicillin sodium is [2S-[2α,5α,6β(S
*)]]-6-[[Amino(4-hydroxyphenyl)acetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic
acid monosodium salt 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 C8H8KNO5, 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 IngredientsCitric acid, colloidal silicon dioxide, hypromellose, magnesium
stearate, microcrystalline cellulose, polyethylene glycol, sodium starch
glycolate, titanium dioxide, and xanthan gum.Each tablet of AUGMENTIN XR contains 12.6 mg (0.32 mEq) of potassium and
29.3 mg (1.27 mEq) of sodium.

Clinical Pharmacology

Amoxicillin and clavulanate potassium are well absorbed from the
gastrointestinal tract after oral administration of AUGMENTIN XR.AUGMENTIN XR is an extended-release formulation which provides sustained
plasma concentrations of amoxicillin. Amoxicillin systemic exposure achieved
with AUGMENTIN XR is similar to that produced by the oral administration of
equivalent doses of amoxicillin alone. In a study of healthy adult volunteers,
the pharmacokinetics of AUGMENTIN XR were compared when administered in a fasted
state, at the start of a standardized meal (612 kcal, 89.3 g carb, 24.9 g fat,
and 14.0 g protein), or 30 minutes after a high-fat meal. When the systemic
exposure to both amoxicillin and clavulanate is taken into consideration,
AUGMENTIN XR is optimally administered at the start of a standardized meal.
Absorption of amoxicillin is decreased in the fasted state. AUGMENTIN XR is not
recommended to be taken with a high-fat meal, because clavulanate absorption is
decreased. The pharmacokinetics of the components of AUGMENTIN XR following
administration of two AUGMENTIN XR tablets at the start of a standardized meal
are presented in Table 1.Table 1. Mean (SD) Pharmacokinetic Parameters for Amoxicillin and
Clavulanate Following Oral Administration of Two AUGMENTIN XR Tablets
(2,000 mg/125 mg) to Healthy Adult Volunteers (n = 55) Fed a Standardized
MealParameter (units)AmoxicillinClavulanateAUC(0-inf) (mcg•hr/mL)71.6 (16.5)5.29 (1.55)Cmax
(mcg/mL)17.0 (4.0)2.05 (0.80)Tmax
(hours)a1.50 (1.00 - 6.00)1.03 (0.75 - 3.00)T½
(hours)1.27 (0.20)1.03
(0.17)a  Median (range).The half-life of amoxicillin after the oral administration of AUGMENTIN XR is
approximately 1.3 hours, and that of clavulanate is approximately 1.0 hour.Clearance of amoxicillin is predominantly renal, with approximately 60% to
80% of the dose being excreted unchanged in urine, whereas clearance of
clavulanate has both a renal (30% to 50%) and a non-renal component.Concurrent administration of probenecid delays amoxicillin excretion but does
not delay renal excretion of clavulanate.In a study of adults, the pharmacokinetics of amoxicillin and clavulanate
were not affected by administration of an antacid (MAALOX®), either simultaneously with or 2 hours after AUGMENTIN
XR.Neither component in AUGMENTIN XR is highly protein-bound; clavulanate has
been found to be approximately 25% bound to human serum and amoxicillin
approximately 18% bound.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.In a study of pediatric patients with acute bacterial sinusitis, 7 to 15
years of age, and weighing at least 40 kg, the pharmacokinetics of amoxicillin
and clavulanate were assessed following administration of AUGMENTIN XR
2000 mg/125 mg (as two 1000 mg/62.5 mg tablets) every 12 hours with food
(Table 2).Table 2. Mean (SD) Pharmacokinetic Parameters for Amoxicillin and
Clavulanate Following Oral Administration of Two AUGMENTIN XR Tablets
(2,000 mg/125 mg) Every 12 Hours With Food to Pediatric Patients (7 to 15 Years
of Age and Weighing ≥ 40kg) With Acute Bacterial SinusitisParameter (units)Amoxicillin(n=24)Clavulanate(n=23)AUC(0-τ) (mcg•hr/mL)57.8 (15.6)3.18 (1.37)Cmax
(mcg/mL)11.0 (3.34)1.17 (0.67)Tmax
(hours)a2.0 (1.0 – 5.0)2.0 (1.0 – 4.0)T½ (hours)3.32 (2.21)b0.94 (0.13)ca  Median (range).b  n=18.c  n=17.MicrobiologyAmoxicillin 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 AUGMENTIN XR 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.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 MicroorganismsStreptococcus pneumoniae (including
isolates with penicillin MICs ≤ 2 mcg/mL)Staphylococcus aureus (including
β-lactamase−producing isolates)NOTE: Staphylococci which are resistant to
methicillin/oxacillin must be considered resistant to amoxicillin/clavulanic
acid.Aerobic
Gram-Negative MicroorganismsHaemophilus influenzae (including
β-lactamase−producing isolates)Moraxella catarrhalis (including
β-lactamase−producing isolates)Haemophilus parainfluenzae (including
β-lactamase−producing isolates)Klebsiella pneumoniae (all known isolates are
β-lactamase−producing)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.1,2 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 MicroorganismsStreptococcus pyogenesAnaerobic
MicroorganismsBacteroides fragilis (including
β-lactamase−producing isolates)Fusobacterium nucleatum (including
β-lactamase−producing isolates)Peptostreptococcus magnusPeptostreptococcus microsNOTE:S. pyogenes, P. magnus, and P. micros do 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 MethodsWhen 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
TechniqueQuantitative 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.1,3
Standardized procedures are based on dilution methods (broth or agar; broth for
S. pneumoniae and 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
TechniqueQuantitative methods that require measurement of zone diameters
also provide reproducible estimates of the susceptibility of bacteria to
antimicrobials. One such standardized technique requires the use of a
standardized inoculum concentration.1,4 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 PotassiumMinimum Inhibitory Concentration(mcg/mL)Disk Diffusion (Zone
Diameter in mm)PathogenSIRSIRHaemophilus spp.≤ 4/2Not applicable (NA)≥ 8/4≥ 20NA≤ 19Klebsiella
pneumoniae≤ 8/416/8≥ 32/16≥ 1814 to 17≤ 13Staphylococcus spp.≤ 4/2NA≥ 8/4≥ 20NA≤ 19Streptococcus pneumoniae≤ 2/14/2≥ 8/4NANOTE: Susceptibility of S.
pneumoniae should be determined using a 1-mcg oxacillin disk. Isolates
with oxacillin zone sizes of ≥ 20 mm are susceptible to amoxicillin/clavulanate
acid. An amoxicillin/clavulanate acid MIC should be determined on isolates of
S. pneumoniae with oxacillin zone sizes of ≤
19 mm.NOTE: β-lactamase−negative, ampicillin-resistant
H. influenzae isolates 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.1,3,4 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
PotassiumQuality Control OrganismMinimum
Inhibitory Concentration Range (mcg/mL)Disk Diffusion (Zone
Diameter Range in mm)Escherichia coli ATCC®a 35218b(H.
influenzae quality control) 4/2 to 16/817 to 22Escherichia coli ATCC 259222/1 to 8/418 to 24Haemophilus influenzae ATCC 492472/1 to 16/815 to 23Staphylococcus aureus ATCC 292130.12/0.06 to 0.5/0.25Not applicable (NA)Staphylococcus aureus ATCC 25923NA28 to 36Streptococcus pneumoniae ATCC 496190.03/0.015 to 0.12/0.06NAa  ATCC is a trademark of the American Type Culture
Collection.b  When using Haemophilus
Test Medium (HTM).

Indications And Usage

AUGMENTIN XR Extended Release Tablets are indicated for the
treatment of patients with community-acquired pneumonia or acute bacterial
sinusitis due to confirmed, or suspected β-lactamase−producing pathogens (i.e.,
H. influenzae, M. catarrhalis, H.
parainfluenzae, K. pneumoniae, or
methicillin-susceptible S. aureus) and S. pneumoniae with reduced susceptibility to penicillin
(i.e., penicillin MICs = 2 mcg/mL). AUGMENTIN XR is not indicated for the
treatment of infections due to S. pneumoniae with
penicillin MICs ≥ 4 mcg/mL. Data are limited with regard to infections due to
S. pneumoniaewith penicillin MICs ≥ 4 mcg/mL (see
CLINICAL STUDIES).Of the common epidemiological risk factors for patients with resistant
pneumococcal infections, only age > 65 years was studied. Patients with other
common risk factors for resistant pneumococcal infections (e.g., alcoholism,
immune-suppressive illness, and presence of multiple co-morbid conditions) were
not studied.In patients with community-acquired pneumonia in whom
penicillin-resistant S. pneumoniae is suspected,
bacteriological studies should be performed to determine the causative organisms
and their susceptibility when AUGMENTIN XR is prescribed.Acute bacterial sinusitis or community-acquired pneumonia due to a
penicillin-susceptible strain of S. pneumoniae plus a
β-lactamase−producing pathogen can be treated with another AUGMENTIN® (amoxicillin/clavulanate potassium) product containing lower
daily doses of amoxicillin (i.e., 500 mg every 8 hours or 875 mg every 12
hours). Acute bacterial sinusitis or community-acquired pneumonia due to S. pneumoniae alone can be treated with amoxicillin.To reduce the development of drug-resistant bacteria and maintain the
effectiveness of AUGMENTIN XR and other antibacterial drugs, AUGMENTIN XR 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

AUGMENTIN XR 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 treatment with amoxicillin/clavulanate potassium.AUGMENTIN XR is contraindicated in patients with severe renal impairment
(creatinine clearance < 30 mL/min.) and in hemodialysis patients.

Warnings

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 AUGMENTIN XR, CAREFUL INQUIRY SHOULD BE MADE CONCERNING
PREVIOUS HYPERSENSITIVITY REACTIONS TO PENICILLINS, CEPHALOSPORINS, OR OTHER
ALLERGENS. IF AN ALLERGIC REACTION OCCURS, AUGMENTIN XR 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.Clostridium difficile associated diarrhea (CDAD)
has been reported with use of nearly all antibacterial agents, including
AUGMENTIN XR, and may range in severity from mild diarrhea to fatal colitis.
Treatment with antibacterial agents alters the normal flora of the colon leading
to overgrowth of C. difficile.C. difficile produces toxins A and B which
contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as
these infections can be refractory to antimicrobial therapy and may require
colectomy. CDAD must be considered in all patients who present with diarrhea
following antibiotic use. Careful medical history is necessary since CDAD has
been reported to occur over two months after the administration of antibacterial
agents.If CDAD is suspected or confirmed, ongoing antibiotic use not directed
against C. difficile may need to be discontinued.
Appropriate fluid and electrolyte management, protein supplementation,
antibiotic treatment of C. difficile, and surgical
evaluation should be instituted as clinically indicated.AUGMENTIN XR 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

GeneralWhile amoxicillin/clavulanate potassium 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 spp. or Candida spp.), the drug should be discontinued and/or
appropriate therapy instituted.Prescribing AUGMENTIN XR 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 PatientsAUGMENTIN XR 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.Patients should be counseled that antibacterial drugs, including
AUGMENTIN XR, should only be used to treat bacterial infections. They do not
treat viral infections (e.g., the common cold). When AUGMENTIN XR 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 AUGMENTIN XR or other antibacterial drugs in the future. Discard
any unused medicine.Drug InteractionsProbenecid decreases the renal tubular secretion of amoxicillin.
Concurrent use with AUGMENTIN XR may result in increased and prolonged blood
levels of amoxicillin. Coadministration 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. In controlled clinical trials of AUGMENTIN XR, 25
patients received concomitant allopurinol and AUGMENTIN XR. No rashes were
reported in these patients. However, this sample size is too small to allow for
any conclusions to be drawn regarding the risk of rashes with concomitant
AUGMENTIN XR and allopurinol use.In common with other broad-spectrum antibiotics, AUGMENTIN XR may reduce the
efficacy of oral contraceptives.Drug/Laboratory Test InteractionsOral administration of AUGMENTIN XR 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
AUGMENTIN XR, 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, AUGMENTIN XR. Carcinogenesis, Mutagenesis, Impairment of
FertilityLong-term studies in animals have not been performed to evaluate
carcinogenic potential. The mutagenic potential of AUGMENTIN 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. AUGMENTIN at oral doses of up to 1,200 mg/kg/day (1.9 times the
maximum human dose of amoxicillin and 15 times the maximum human dose of
clavulanate 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.PregnancyTeratogenic
EffectsPregnancy Category B. Reproduction studies performed in pregnant
rats and mice given AUGMENTIN at oral doses up to 1,200 mg/kg/day revealed no
evidence of harm to the fetus due to AUGMENTIN. In terms of body surface area,
the doses in rats were 1.6 times the maximum human oral dose of amoxicillin and
13 times the maximum human dose for clavulanate. For mice, these doses were 0.9
and 7.4 times the maximum human oral dose of amoxicillin and clavulanate,
respectively. 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 DeliveryOral 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 AUGMENTIN XR 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 AUGMENTIN may be associated with an increased risk of necrotizing
enterocolitis in neonates.Nursing MothersAmpicillin-class antibiotics are excreted in the milk; therefore,
caution should be exercised when AUGMENTIN XR is administered to a nursing
woman.Pediatric UseThe safety and effectiveness of AUGMENTIN XR have been
established for pediatric patients weighing ≥ 40 kg who are able to swallow
tablets. Use of AUGMENTIN XR in these pediatric patients is supported by
evidence from adequate and well-controlled trials of adults with acute bacterial
sinusitis and community-acquired pneumonia with additional data from a pediatric
pharmacokinetic study.A pharmacokinetic study in pediatric patients (7 to 15 years of age and
weighing ≥ 40 kg) was conducted (see CLINICAL PHARMACOLOGY).The adverse event profile in 44 pediatric patients who received at least one
dose of AUGMENTIN XR was consistent with the established adverse event profile
for the product in adults.Geriatric UseOf the total number of subjects in clinical studies of AUGMENTIN
XR, 18.4% were 65 years or older and 7.2% were 75 years or older. No overall
differences in safety and effectiveness were observed between these subjects and
younger subjects, and other clinical experience has not reported 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 dose-dependent 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, it may be useful to monitor renal function.Each tablet of AUGMENTIN XR contains 29.3 mg (1.27 mEq) of sodium.

Adverse Reactions

In clinical trials, 5,643 patients have been treated with
AUGMENTIN XR. The majority of side effects observed in clinical trials were of a
mild and transient nature; 2% of patients discontinued therapy because of
drug-related side effects. The most frequently reported adverse effects which
were suspected or probably drug-related were diarrhea (14.5%), vaginal mycosis
(3.3%) nausea (2.1%), and loose stools (1.6%). AUGMENTIN XR had a higher rate of
diarrhea which required corrective therapy (3.8% versus 2.6% for AUGMENTIN XR
and all comparators, respectively).The following adverse reactions have been reported for ampicillin-class
antibiotics:GastrointestinalDiarrhea, 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 ReactionsSkin 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. 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).LiverA 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 AUGMENTIN or AUGMENTIN XR. 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.RenalInterstitial nephritis and hematuria have been reported rarely.
Crystalluria has also been reported (see OVERDOSAGE).Hemic and Lymphatic SystemsAnemia, 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. There have been reports of increased prothrombin time in patients
receiving AUGMENTIN and anticoagulant therapy concomitantly.Central Nervous SystemAgitation, anxiety, behavioral changes, confusion, convulsions,
dizziness, headache, insomnia, and reversible hyperactivity have been reported
rarely.MiscellaneousTooth 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 AUGMENTIN XR, 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.5Interstitial 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 (see DOSAGE AND ADMINISTRATION).

Dosage And Administration

AUGMENTIN XR should be taken at the start of a meal to enhance
the absorption of amoxicillin and to minimize the potential for gastrointestinal
intolerance. Absorption of the amoxicillin component is decreased when AUGMENTIN
XR is taken on an empty stomach (see CLINICAL PHARMACOLOGY).The recommended dose of AUGMENTIN XR is 4,000 mg/250 mg daily according to
the following table:IndicationDoseDurationAcute bacterial sinusitis2 tablets q12h10 daysCommunity-acquired
pneumonia2 tablets q12h7-10
daysTablets of AUGMENTIN (250 mg or 500 mg) CANNOT be used to
provide the same dosages as AUGMENTIN XR Extended Release Tablets. This is
because AUGMENTIN XR contains 62.5  mg of clavulanic acid, while the AUGMENTIN
250-mg and 500-mg tablets each contain 125 mg of clavulanic acid. In addition,
the Extended Release Tablet provides an extended time course of plasma
amoxicillin concentrations compared to immediate-release Tablets. Thus, two
AUGMENTIN 500-mg tablets are not equivalent to one AUGMENTIN XR tablet.Scored AUGMENTIN XR Extended Release Tablets are available for greater
convenience for adult patients who have difficulty swallowing. The scored tablet
is not intended to reduce the dosage of medication taken; as stated in the table
above, the recommended dose of AUGMENTIN XR is two tablets twice a day (every 12
hours).Renally Impaired PatientsThe pharmacokinetics of AUGMENTIN XR have not been studied in
patients with renal impairment. AUGMENTIN XR is contraindicated in patients with
a creatinine clearance of < 30 mL/min. and in hemodialysis patients (see
CONTRAINDICATIONS).Hepatically Impaired PatientsHepatically impaired patients should be dosed with caution and
hepatic function monitored at regular intervals (see WARNINGS).Pediatric UsePediatric patients who weigh 40 kg or more and can swallow
tablets should receive the adult dose.Geriatric UseNo dosage adjustment is required for the elderly (see
PRECAUTIONS, Geriatric Use).

How Supplied

AUGMENTIN XR Extended Release TabletsEach white, oval film-coated bilayer scored tablet, debossed with
AUGMENTIN XR, contains amoxicillin trihydrate and amoxicillin sodium equivalent
to a total of 1,000 mg of amoxicillin and clavulanate potassium equivalent to
62.5 mg of clavulanic acid.NDC 54868-4735-0     Bottles of 20NDC 54868-4735-2     Bottles of 28 (7 day XR pack)NDC 54868-4735-1     Bottles of 40 (10 day XR pack)

Storage

Store tablets at or below 25°C (77°F). Dispense in original
container.

Clinical Studies

Acute Bacterial SinusitisAdults with a diagnosis of acute bacterial sinusitis (ABS) were
evaluated in 3 clinical studies. In one study, 363 patients were randomized to
receive either AUGMENTIN XR 2,000 mg/125 mg orally every 12 hours or
levofloxacin 500 mg orally daily for 10 days in a double-blind, multicenter,
prospective trial. These patients were clinically and radiologically evaluated
at the test of cure (day 17-28) visit. The combined clinical and radiological
responses were 83.7% for AUGMENTIN XR and 84.3% for levofloxacin at the test of
cure visit in clinically evaluable patients (95% CI for the treatment difference
= -9.4, 8.3). The clinical response rates at the test of cure were 87.0% and
88.6%, respectively.The other 2 trials were non-comparative, multicenter studies designed to
assess the bacteriological and clinical efficacy of AUGMENTIN XR (2,000
mg/125 mg orally every 12 hours for 10 days) in the treatment of 2288 patients
with ABS. Evaluation timepoints were the same as in the prior study. Patients
underwent maxillary sinus puncture for culture prior to receiving study
medication. At test of cure, the clinical success rates were 87.5% and 86.6%
(intention-to-treat) and 92.5% and 92.1% (per protocol populations).Patients with acute bacterial sinusitis due to S.
pneumoniae with reduced susceptibility to penicillin were accrued through
enrollment in these 2 open-label non-comparative clinical trials. Microbiologic
eradication rates for key pathogens in these studies are shown in the following
table:Clinical
Outcome for ABS Penicillin MICs of S. pneumoniae
IsolatesIntent-To-TreatClinically
Evaluablen/Na%95% CIbn/Na%95% CIbAll S.
pneumoniae344/37093.0—318/32697.5—  MIC ≥ 2.0 mcg/mLc35/3697.285.5, 99.930/3195.883.3, 99.9  MIC = 2.0 mcg/mL23/2495.878.9, 99.919/2095.075.1, 99.9  MIC ≥ 4.0 mcg/mLd12/1210073.5, 10011/1110071.5, 100H.
influenzae265/30586.9—242/25993.4—M.
catarrhalis94/10589.5—86/9095.6—a  n/N = patients with pathogen eradicated or presumed
eradicated/total number of patients.b  Confidence limits calculated using exact
probabilities.c  S. pneumoniae strains
with penicillin MICs of ≥ 2 mcg/mL are considered resistant to penicillin.d  Includes one patient each with S. pneumoniae penicillin MICs of 8 and 16 mcg/mL.Community-Acquired PneumoniaFour randomized, controlled, double-blind clinical studies and
one non-comparative study were conducted in adults with community-acquired
pneumonia (CAP). In comparative studies, 904 patients received AUGMENTIN XR at a
dose of 2,000 mg/125 mg orally every 12 hours for 7 or 10 days. In the
non-comparative study to assess both clinical and bacteriological efficacy,
1,122 patients received AUGMENTIN XR 2,000 mg/125 mg orally every 12 hours for
7 days. In the 4 comparative studies, the combined clinical success rate at test
of cure ranged from 86.3% to 94.7% in clinically evaluable patients who received
AUGMENTIN XR; in the non-comparative study, the clinical success rate was
85.6%.Data on the efficacy of AUGMENTIN XR in the treatment of community-acquired
pneumonia due to S. pneumoniae with reduced
susceptibility to penicillin were accrued from the 4 controlled clinical studies
and the 1 non-comparative study. The majority of these cases were accrued from
the non-comparative study.Clinical
Outcome for CAP due to S. pneumoniaePenicillin MICs of S. pneumoniae
IsolatesIntent-To-TreatClinically
Evaluablen/Na%95% CIbn/Na%95% CIbAll S.
pneumoniae318/36786.6—275/29792.6—  MIC ≥ 2.0 mcg/mLc30/3585.769.7, 95.224/2596.079.6, 99.9  MIC = 2.0 mcg/mL22/2491.773.0, 99.018/1810081.5, 100  MIC ≥ 4.0 mcg/mLd8/1172.739.0, 94.06/785.742.1, 99.6a  n/N = patients with pathogen eradicated or presumed
eradicated/total number of patients.b  Confidence limits calculated using exact
probabilities.c  S. pneumoniae strains
with penicillin MICs of ≥ 2 mcg/mL are considered resistant to penicillin.d  Includes one patient each with S. pneumoniae penicillin MICs of 8 and 16 mcg/mL in the
Intent-To-Treat group only.SafetyIn 2 randomized, double-blind, multicenter studies, AUGMENTIN XR
(2,000 mg/125 mg orally every 12 hours, n = 577) was compared to AUGMENTIN
(875 mg/125 mg orally every 12 hours, n = 570), administered for 7 days for the
treatment of community-acquired pneumonia. Adverse events, regardless of
relationship to test drug, were reported by 44.4% of patients who received
AUGMENTIN XR (versus 46.3% in comparator group). Treatment-related adverse
events were reported in 21.7% of patients who received AUGMENTIN XR (versus
21.2% in comparator group); most were mild and transient in nature. Adverse
events which led to withdrawal were reported by 2.8% of patients who received
AUGMENTIN XR (versus 5.3% in comparator group). In each group, the most
frequently reported adverse events were diarrhea (14.4% versus 13.0%, p = 0.47),
nausea (3.5 % versus 4.4%), and headache (3.5% versus 3.2%). Only 2 patients
(0.3%) who received AUGMENTIN XR and 3 patients (0.5%) in the comparator group
withdrew due to diarrhea. Serious adverse events considered suspected or
probably related to test drug were reported in 0.3% of patients (versus 0.5% in
comparator).

References

  • Clinical and Laboratory Standards Institute (CLSI) (formerly the National
  • Committee for Clinical Laboratory Standards). Performance Standards for
  • Antimicrobial Susceptibility Testing − Twentieth Informational Supplement. CSLI
  • Document M100-S20, Vol. 30, No. 1. CLSI, Wayne, PA, 2010.Clinical and Laboratory Standards Institute (CLSI) (formerly the National
  • Committee for Clinical Laboratory Standards). Methods for Antimicrobial
  • Susceptibility Testing of Anaerobic Bacteria − Seventh Edition. Approved
  • Standard CSLI Document M11-A7, Vol. 27, No. 2. CLSI, Wayne, PA, 2007.Clinical and Laboratory Standards Institute (CLSI) (formerly the National
  • Committee for Clinical Laboratory Standards). Methods for Dilution Antimicrobial
  • Susceptibility Tests for Bacteria that Grow Aerobically − Eighth Edition.
  • Approved Standard CLSI Document M7-A8, Vol. 29, No. 2. CLSI, Wayne, PA,
  • 2009.Clinical and Laboratory Standards Institute (CLSI) (formerly the National
  • Committee for Clinical Laboratory Standards). Performance Standards for
  • Antimicrobial Disk Susceptibility Tests − Tenth Edition. Approved Standard CLSI
  • Document M2-A10, Vol. 29, No. 1. CLSI, Wayne, PA, 2009.Swanson-Biearman B, Dean BS, Lopez G, Krenzelok EP. The effects of
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  • Vet Hum Toxicol 1988; 30: 66-67.

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