Inactive Ingredients

Colloidal silicon dioxide, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, sodium starch glycolate, and titanium dioxide.

Each tablet of AUGMENTIN contains 0.63 mEq potassium.

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, the spectrum of activity does not include organisms which produce these enzymes. Clavulanic acid is a β-lactam, structurally related to the penicillins, which possesses the ability to inactivate a wide range ofβ-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 responsible for transferred drug resistance.

The formulation of amoxicillin and clavulanic acid in AUGMENTIN 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, AUGMENTIN possesses the properties of a broad-spectrum antibiotic and a β-lactamase inhibitor.

Amoxicillin/clavulanic acid has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in INDICATIONS AND USAGE.

Susceptibility Testing

For Gram-Negative Enteric Aerobes

For Staphylococcus** and Haemophilus species

** Staphylococci which are susceptible to amoxicillin/clavulanic acid but resistant to methicillin/oxacillin must be considered as resistant.

For S. pneumoniae from non-meningitis sources

Isolates should be tested using amoxicillin/clavulanic acid and the following criteria should be used:

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

A report of “Susceptible” indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentration usually achievable. A report of “Intermediate” indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone, which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected.

Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standard amoxicillin/clavulanate potassium powder should provide the following MIC values:

MicroorganismMIC Range (mcg/mL)††

Escherichia coli ATCC 25922 2 to 8

Escherichia coli ATCC 35218 4 to 16

Enterococcus faecalis ATCC 29212 0.25 to 1.0

Haemophilus influenzae ATCC 49247 2 to 16

Staphylococcus aureus ATCC 29213 0.12 to 0.5

Streptococcus pneumoniae ATCC 49619 0.03 to 0.12

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

For Staphylococcus ‡‡ species and H. influenzaea

For Other Organisms Except S. pneumoniae and N. gonorrhoea

‡‡ Staphylococci which are resistant to methicillin/oxacillin must be considered as resistant to amoxicillin/clavulanic acid.

a A broth microdilution method should be used for testing H. influenzae. Beta-lactamase−negative, ampicillin-resistant strains must be considered resistant to amoxicillin/clavulanic acid.

b 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/clavulanic acid. An amoxicillin/clavulanic acid MIC should be determined on isolates of S. pneumoniae with oxacillin zone sizes of ≤19 mm.

c A broth microdilution method should be used for testing N. gonorrhoeae and interpreted according to penicillin breakpoints.

Interpretation should be as stated above for results using dilution techniques. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for amoxicillin/clavulanic acid.

As with standardized dilution techniques, diffusion methods require the use of laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. For the diffusion technique, the 30-mcg amoxicillin/clavulanate potassium (20-mcg amoxicillin plus 10-mcg clavulanate potassium) disk should provide the following zone diameters in these laboratory quality control strains:

MicroorganismZone Diameter (mm)

Escherichia coli ATCC 25922 19 to 25

Escherichia coli ATCC 35218 18 to 22

Staphylococcus aureus ATCC 25923 28 to 36

Lower Respiratory Tract Infections

− caused by β-lactamase−producing strains of H. influenzae and M. catarrhalis.

Otitis Media

− caused by β-lactamase−producing strains of H. influenzae and M. catarrhalis.

Sinusitis

− caused by β-lactamase−producing strains of H. influenzae and M. catarrhalis.

Skin and Skin Structure Infections

− caused by β-lactamase−producing strains of S. aureus, E. coli, and Klebsiella spp.

Urinary Tract Infections

− caused by β-lactamase−producing strains of E. coli, Klebsiella spp., and Enterobacter spp.

While AUGMENTIN is indicated only for the conditions listed above, infections caused by ampicillin-susceptible organisms are also amenable to treatment with AUGMENTIN due to its amoxicillin content; therefore, mixed infections caused by ampicillin-susceptible organisms and β-lactamase−producing organisms susceptible to AUGMENTIN should not require the addition of another antibiotic. Because amoxicillin has greater in vitro activity against S. pneumoniae than does ampicillin or penicillin, the majority of S. pneumoniae strains with intermediate susceptibility to ampicillin or penicillin are fully susceptible to amoxicillin and AUGMENTIN. (See Microbiology.)

To reduce the development of drug-resistant bacteria and maintain the effectiveness of AUGMENTIN and other antibacterial drugs, AUGMENTIN 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.

Bacteriological studies, to determine the causative organisms and their susceptibility to AUGMENTIN, should be performed together with any indicated surgical procedures.

General

While AUGMENTIN 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 during prolonged therapy.

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 AUGMENTIN 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.

Drug Interactions

Probenecid decreases the renal tubular secretion of amoxicillin. Concurrent use with AUGMENTIN may result in increased and prolonged blood levels of amoxicillin. Coadministration of probenecid cannot be recommended.

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 AUGMENTIN and allopurinol administered concurrently.

In common with other broad-spectrum antibiotics, AUGMENTIN may reduce the efficacy of oral contraceptives.

Drug/Laboratory Test Interactions

Oral administration of AUGMENTIN 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, 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.

Information for Patients

 Patients should be counseled that antibacterial drugs including AUGMENTIN, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When AUGMENTIN 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 or other antibacterial drugs in the future.

Carcinogenesis, Mutagenesis, Impairment of Fertility

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

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 AUGMENTIN 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 Mothers

Ampicillin-class antibiotics are excreted in the milk; therefore, caution should be exercised when AUGMENTIN is administered to a nursing woman.

Pediatric Use

 Pediatric patients weighing 40 kg or more should be dosed according to the adult recommendations (see DOSAGE AND ADMINISTRATION: Pediatric Patients). Safety and effectiveness of AUGMENTIN Tablets in pediatric patients weighing less than 40 kg have not been established. (See prescribing information for AUGMENTIN Powder for Oral Suspension and Chewable Tablets.)

Geriatric Use

 An analysis of clinical studies of AUGMENTIN was conducted to determine whether subjects aged 65 and over respond differently from younger subjects. Of the 3,119 patients in this analysis, 68% were <65 years old, 32% were ≥65 years old and 14% were ≥75 years old. This analysis and other reported clinical experience have not identified differences in responses between the elderly and younger patients, but a greater sensitivity of some older individuals cannot be ruled out.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Gastrointestinal

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, 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 increases in serum transaminases (AST and/or ALT), serum bilirubin, and/or alkaline phosphatase, has been infrequently reported with AUGMENTIN. 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 AUGMENTIN. There have been reports of increased prothrombin time in patients receiving AUGMENTIN and anticoagulant therapy concomitantly.

Central Nervous System

Agitation, anxiety, behavioral changes, confusion, convulsions, dizziness, insomnia, and reversible hyperactivity have been reported rarely.

Miscellaneous

Tooth discoloration (brown, yellow, or gray staining) has been rarely reported. Most reports occurred in pediatric patients. Discoloration was reduced or eliminated with brushing or dental cleaning in most cases.

Adults

 The usual adult dose is one 500-mg tablet of AUGMENTIN every 12 hours or one 250-mg tablet of AUGMENTIN every 8 hours. For more severe infections and infections of the respiratory tract, the dose should be one 875-mg tablet of AUGMENTIN every 12 hours or one 500-mg tablet of AUGMENTIN every 8 hours.

Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. Severely impaired patients with a glomerular filtration rate of <30 mL/min. should not receive the 875-mg tablet. Patients with a glomerular filtration rate of 10 to 30 mL/min. should receive 500 mg or 250 mg every 12 hours, depending on the severity of the infection. Patients with a less than 10 mL/min. glomerular filtration rate should receive 500 mg or 250 mg every 24 hours, depending on severity of the infection.

Hemodialysis patients should receive 500 mg or 250 mg every 24 hours, depending on severity of the infection. They should receive an additional dose both during and at the end of dialysis.

Hepatically impaired patients should be dosed with caution and hepatic function monitored at regular intervals. (See WARNINGS.)

Pediatric Patients

Pediatric patients weighing 40 kg or more should be dosed according to the adult recommendations.

Due to the different amoxicillin to clavulanic acid ratios in the 250-mg tablet of AUGMENTIN (250/125) versus the 250-mg chewable tablet of AUGMENTIN (250/62.5), the 250-mg tablet of AUGMENTIN should not be used until the pediatric patient weighs at least 40 kg or more.

AUGMENTIN 250-mg Tablets

Each white oval filmcoated tablet, debossed with AUGMENTIN on 1 side and 250/125 on the other side, contains 250 mg amoxicillin as the trihydrate and 125 mg clavulanic acid as the potassium salt.

NDC 0029-6075-27 bottles of 30

NDC 0029-6075-31 Unit Dose (10x10) 100 tablets

AUGMENTIN 500-mg Tablets

Each white oval filmcoated tablet, debossed with AUGMENTIN on 1 side and 500/125 on the other side, contains 500 mg amoxicillin as the trihydrate and 125 mg clavulanic acid as the potassium salt.

NDC 0029-6080-12 bottles of 20

NDC 0029-6080-31 Unit Dose (10x10) 100 tablets

AUGMENTIN 875-mg Tablets

Each scored white capsule-shaped tablet, debossed with AUGMENTIN 875 on 1 side and scored on the other side, contains 875 mg amoxicillin as the trihydrate and 125 mg clavulanic acid as the potassium salt.

NDC 0029-6086-12 bottles of 20

NDC 0029-6086-21 Unit Dose (10x10) 100 tablets

AUGMENTIN is Also Supplied as

AUGMENTIN 125 mg/5 mL (125 mg amoxicillin/31.25 mg clavulanic acid) For Oral Suspension:

NDC 0029-6085-39 75 mL bottle

NDC 0029-6085-23 100 mL bottle

NDC 0029-6085-22 150 mL bottle

AUGMENTIN 200 mg/5 mL (200 mg amoxicillin/28.5 mg clavulanic acid) For Oral Suspension:

NDC 0029-6087-29 50 mL bottle

NDC 0029-6087-39 75 mL bottle

NDC 0029-6087-51 100 mL bottle

AUGMENTIN 250 mg/5 mL (250 mg amoxicillin/62.5 mg clavulanic acid) For Oral Suspension:

NDC 0029-6090-39 75 mL bottle

NDC 0029-6090-23 100 mL bottle

NDC 0029-6090-22 150 mL bottle

AUGMENTIN 400 mg/5 mL (400 mg amoxicillin/57 mg clavulanic acid) For Oral Suspension:

NDC 0029-6092-29 50 mL bottle

NDC 0029-6092-39 75 mL bottle

NDC 0029-6092-51 100 mL bottle

AUGMENTIN 125 mg (125 mg amoxicillin/31.25 mg clavulanic acid) Chewable Tablets:

NDC 0029-6073-47 carton of 30 (5x6) tablets

AUGMENTIN 200 mg (200 mg amoxicillin/28.5 mg clavulanic acid) Chewable Tablets:

NDC 0029-6071-12 carton of 20 tablets

AUGMENTIN 250 mg (250 mg amoxicillin/62.5 mg clavulanic acid) Chewable Tablets:

NDC 0029-6074-47 carton of 30 (5x6) tablets

AUGMENTIN 400 mg (400 mg amoxicillin/57.0 mg clavulanic acid) Chewable Tablets:

NDC 0029-6072-12 carton of 20 tablets

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