AUGMENTIN is an oral antibacterial combination consisting of amoxicillin and the beta‑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 16 H 19 N 3 O 5 S•3H 2 O, and the molecular weight is 419.46. Chemically, amoxicillin is (2 S ,5 R ,6 R )-6-[( R )-(-)-2-Amino-2-( p -hydroxyphenyl)acetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid trihydrate and may be represented structurally as: Clavulanic acid is produced by the fermentation of Streptomyces clavuligerus . It is a beta-lactam structurally related to the penicillins and possesses the ability to inactivate some beta‑lactamases by blocking the active sites of these enzymes. The clavulanate potassium molecular formula is C 8 H 8 KNO 5 , and the molecular weight is 237.25. Chemically, clavulanate potassium is potassium ( Z )(2 R ,5 R )-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]-heptane-2-carboxylate and may be represented structurally as: AUGMENTIN for Oral Suspension: 125 mg/31.25 mg : Following constitution, each 5 mL of oral suspension contains 125 mg of amoxicillin as the trihydrate, and 31.25 mg of clavulanic acid (equivalent to 37.23 mg of clavulanate potassium). 250 mg/62.5 mg : Following constitution, each 5 mL of oral suspension contains 250 mg of amoxicillin as the trihydrate, and 62.5 mg of clavulanic acid (equivalent to 74.5 mg of clavulanate potassium). Inactive Ingredients: AUGMENTIN for Oral Suspension, 125 mg/31.5 mg per 5mL and 250 mg/62.5 mg per 5mL - Colloidal silicon dioxide, flavorings, xanthan gum, mannitol, succinic acid, silica gel and sodium saccharin. • Each 5 mL of reconstituted 125 mg/31.5 mg oral suspension of AUGMENTIN contains 0.16 mEq potassium • Each 5 mL of reconstituted 250 mg/62.5 mg oral suspension of AUGMENTIN contains 0.32 mEq potassium structure-amoxicillin structure-clav-acid

AUGMENTIN is indicated for the treatment of infections in adults and pediatric patients, due to susceptible isolates of the designated bacteria in the conditions listed below: Lower Respiratory Tract Infections - caused by beta‑lactamase–producing isolates of Haemophilus influenzae and Moraxella catarrhalis . Acute Bacterial Otitis Media - caused by beta‑lactamase–producing isolates of H. influenzae and M. catarrhalis . Sinusitis - caused by beta‑lactamase–producing isolates of H. influenzae and M. catarrhalis . Skin and Skin Structure Infections - caused by beta‑lactamase–producing isolates of Staphylococcus aureus , Escherichia coli , and Klebsiella species. Urinary Tract Infections - caused by beta‑lactamase–producing isolates of E. coli , Klebsiella species, and Enterobacter species. AUGMENTIN is a combination of amoxicillin, a penicillin-class antibacterial and clavulanate potassium, a beta‑lactamase inhibitor indicated for treatment of the following infections in adults and pediatric patients: Lower respiratory tract infections Acute bacterial otitis media Sinusitis Skin and skin structure infections Urinary tract infections Limitations of Use When susceptibility test results show susceptibility to amoxicillin, indicating no beta-lactamase production, AUGMENTIN should not be used. Usage 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 bacteria. Limitations of Use When susceptibility test results show susceptibility to amoxicillin, indicating no beta-lactamase production, AUGMENTIN should not be used. Usage 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.

Augmentin for Oral Suspension, USP: 125 mg/31.25 mg per 5 mL : Banana-flavored powder for oral suspension (each 5 mL of reconstituted suspension contains 125 mg of amoxicillin as the trihydrate and 31.25 mg of clavulanic acid as the potassium salt). 250 mg/62.5 mg per 5 mL : Orange-flavored powder for oral suspension (each 5 mL of reconstituted suspension contains 250 mg of amoxicillin as the trihydrate and 62.5 mg of clavulanic acid as the potassium salt). For Oral Suspension: 125 mg/31.25 mg per 5 mL, 250 mg/62.5 mg per 5 mL

Adults and Pediatric Patients greater than 40 kg: 500 or 875 mg every 12 hours or 250 or 500 mg every 8 hours, based on the amoxicillin component. Pediatric patients aged 12 weeks (3 months) and older: 25 to 45 mg/kg/day every 12 hours or 20 to 40 mg/kg/day every 8 hours, up to the adult dose. Neonates and infants less than 12 weeks of age: 30 mg/kg/day divided every 12 hours, based on the amoxicillin component. Use of the 125 mg/5 mL oral suspension is recommended

Important Administration Instructions AUGMENTIN may be taken without regard to meals; however, absorption of clavulanate potassium is enhanced when AUGMENTIN is administered at the start of a meal. To minimize the potential for gastrointestinal intolerance, AUGMENTIN should be taken at the start of a meal

Adult Patients See dosing regimens of AUGMENTIN (based on the amoxicillin component) provided in Table 1 below. Table 1. Dosing Regimens of AUGMENTIN in Adult Patients TYPE OF INFECTION DOSING REGIMEN OF Amoxicillin and Clavulanate Potassium Severe infections and infections of the respiratory tract one 875 mg tablet a of AUGMENTIN every 12 hours or one 500 mg tablet b,c of AUGMENTIN every 8 hours Less severe infections one 500 mg tablet b,c of AUGMENTIN every 12 hours or one 250 mg tablet d of AUGMENTIN every 8 hours a Adults who have difficulty swallowing may be given the AUGMENTIN 200 mg/28.5 mg per 5 mL suspension or the AUGMENTIN 400 mg/57 mg per 5 mL suspension may be used in place of the 875 mg/125 mg tablet. b Adults who have difficulty swallowing may be given the AUGMENTIN 125 mg/31.25 mg per 5 mL or AUGMENTIN 250 mg/62.5 mg per 5 mL suspension in place of the 500 mg/125 mg tablet. c Two AUGMENTIN 250 mg/125 mg tablets are NOT substitutable with one 500 mg/125 mg AUGMENTIN tablet . d AUGMENTIN 250 mg/125 mg tablet is NOT substitutable with AUGMENTIN 250 mg/62.5 mg chewable tablet 2.3 Pediatric Patients Based on the amoxicillin component, AUGMENTIN should be dosed as follows: Neonates and Infants Aged less than 12 weeks (less than 3 months) : See dosing regimens of AUGMENTIN provided in Table 2 below. Table 2: Dosing Regimens of AUGMENTIN in Neonates and Infants Aged Less than 12 Weeks (Less than 3 Months) PATIENT POPULATION DOSING REGIMEN AUGMENTIN 125 mg/31.25 mg per 5 mL for oral suspension a Neonates and Infants aged less than 12 weeks (less than 3 months) 30 mg/kg/day every 12 hours a Experience with the AUGMENTIN 200 mg/28.5 mg per 5 mL formulation in this age group is limited, and thus, use of the AUGMENTIN 125 mg/31.25 mg per 5 mL for oral suspension is recommended. Patients Aged 12 weeks (3 months) and Older and Weighing Less than 40 kg: See dosing regimens provided in Table 3 below. The every 12 hour regimen is recommended as it is associated with significantly less diarrhea . The Amoxicillin and Clavulanate Potassium 200 mg/28.5 mg per 5 mL and Amoxicillin and Clavulanate Potassium 400 mg/57 mg per 5 mL) for oral suspension and Amoxicillin and Clavulanate Potassium 200 mg/28.5 mg and Amoxicillin and Clavulanate Potassium 400 mg/57 mg chewable tablets contain aspartame and should not be used by phenylketonurics. . Table 3: Dosing in Patients Aged 12 Weeks (3 Months) and Older and Weighing Less than 40 kg Table Patients Weighing 40 kg or More : Pediatric patients weighing 40 kg or more should be dosed according to adult recommendations. The 250 mg/125 mg tablet of AUGMENTIN should NOT be used until the child weighs at least 40 kg, due to the different amoxicillin to clavulanic acid ratios in the 250 mg/125 mg tablet of AUGMENTIN versus the 250 mg/62.5 mg chewable tablet of AUGMENTIN

Patients with Renal Impairment Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. Renal impairment patients with a glomerular filtration rate (GFR) of less than 30 mL/min should NOT receive the 875 mg dose (based on the amoxicillin component) of AUGMENTIN. See dosing regimens in patients with severe renal impairment provided in Table 4. Table 4. Dosing Regimens of AUGMENTIN in Patients with Severe Renal Impairment Patients with Renal Impairment Dosing Regimen GFR 10 mL/min to 30 mL/min 500 mg or 250 mg every 12 hours, depending on the severity of the infection GFR less than 10 mL/min 500 mg or 250 mg every 24 hours, depending on severity of the infection Hemodialysis 500 mg or 250 mg every 24 hours, depending on severity of the infection Administer an additional dose both during and at the end of dialysis 2.5 Directions for Mixing Amoxicillin and Clavulanate Potassium for Oral Suspension Prepare AUGMENTIN for oral suspension at time of dispensing as follows: Tap bottle until all powder flows freely. Measure a total OF WATER. Add approximately 2/3 of the water to the powder. Replace cap and shake VIGOROUSLY. Add remaining water. Replace cap and shake VIGOROUSLY. Table 5: Amount of Water for Mixing AUGMENTIN for Oral Suspension Strength of AUGMENTIN Oral Suspension Bottle Size Amount of Water for Reconstitution Contents of Each Teaspoonful (5 mL) 125 mg/31.25 mg per 5 mL 75 mL 100 mL 150 mL 67 mL 90 mL 134 mL 125 mg of amoxicillin and 31.25 mg of clavulanic acid as the potassium salt 250 mg/62.5 mg per 5 mL 75 mL 100 mL 150 mL 65 mL 87 mL 130 mL 250 mg of amoxicillin and 62.5 mg of clavulanic acid as the potassium salt Shake oral suspension well before using. Reconstituted suspension must be stored under refrigeration and discarded after 10 days. Some color change is normal during dosing period

Switching between Dosage Forms and between Strengths AUGMENTIN 250 mg/125 mg Tablet is NOT Substitutable with AUGMENTIN 250 mg/62.5 mg Chewable Tablet The 250 mg/125 mg tablet of AUGMENTIN and the 250 mg/62.5 mg chewable tablet of AUGMENTIN should NOT be substituted for each other and the 250 mg/125 mg tablet of AUGMENTIN should NOT be used in pediatric patients weighing less than 40 kg . The 250 mg tablet of AUGMENTIN and the 250 mg chewable tablet of AUGMENTIN do not contain the same amount of clavulanic acid. The 250 mg tablet of AUGMENTIN contains 125 mg of clavulanic acid whereas the 250 mg chewable tablet of AUGMENTIN contains 62.5 mg of clavulanic acid. Two AUGMENTIN 250 mg/125 mg Tablets are NOT Substitutable with One 500 mg/125 mg AUGMENTIN Tablet Two 250 mg/125 mg tablets of AUGMENTIN should NOT be substituted for one 500 mg/125 mg tablet of AUGMENTIN. Since both the 250 mg and 500 mg tablets of AUGMNTIN contain the same amount of clavulanic acid (125 mg, as the potassium salt), two 250 mg tablets of AUGMENTIN are not equivalent to one 500 mg tablet of AUGMENTIN.

Serious (including fatal) hypersensitivity reactions: Discontinue AUGMENTIN if a reaction occurs. Severe Cutaneous Adverse Reactions (SCAR): Monitor closely. Discontinue if rash progresses. Drug-induced enterocolitis syndrome (DIES) has been reported with use of Amoxicillin, A componet of Augmentin. If this occures, discontinue AUGMENIN and institute appropriate therapy Hepatic dysfunction and cholestatic jaundice: Discontinue if signs/symptoms of hepatitis occur. Monitor liver function tests in patients with hepatic impairment. Clostridioides difficile -associated diarrhea (CDAD): Evaluate patients if diarrhea occurs. Patients with mononucleosis who receive AUGMENTIN develop skin rash. Avoid AUGMENTIN use in these patients. ( 5.6 Overgrowth: The possibility of superinfections with fungal or bacterial pathogens should be considered during therapy. 5.1 Hypersensitivity Reactions Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam antibacterials, including AUGMENTIN. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. Before initiating therapy with AUGMENTIN, careful inquiry should be made regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, AUGMENTIN should be discontinued, and appropriate therapy instituted

Severe Cutaneous Adverse Reactions AUGMENTIN may cause severe cutaneous adverse reactions (SCAR), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). If patients develop a skin rash, they should be monitored closely, and AUGMENTIN discontinued if lesions progress

Drug-Induced Enterocolitis Syndrome (DIES) Drug-induced enterocolitis syndrome (DIES) has been reported with use of amoxicillin, a componet of AUGMENTIN , with most cases occurring in pediatric patients < 18 years of age. DIES is a non IgE mediated hypersensitivity reaction characterized by protracted vomiting occuring 1 to 4 hours after drug ingestion in the absence of skin or respiratory symptoms. DIES may be associated with pallor, lethargy, hypotension, shock, diarrhea within 24 hours of ingesting amoxicillin, and leukocytosis with neutrophilia. If DIES occurs, discontinue AUGMENTIN and institute appropriate therapy

Hepatic Dysfunction Hepatic dysfunction, including hepatitis and cholestatic jaundice has been associated with the use of AUGMENTIN. Hepatic toxicity is usually reversible; however, deaths have been reported. Hepatic function should be monitored at regular intervals in patients with hepatic impairment

Clostridioides difficile Associated Diarrhea (CDAD) Clostridioides difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including AUGMENTIN, 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 antibacterial use. Careful medical history is necessary since CDAD has been reported to occur over 2 months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated

Skin Rash in Patients with Mononucleosis A high percentage of patients with mononucleosis who receive amoxicillin develop an erythematous skin rash. Thus, AUGMENTIN should not be administered to patients with mononucleosis

Potential for Microbial Overgrowth The possibility of superinfections with fungal or bacterial pathogens should be considered during therapy. If superinfection occurs, amoxicillin and clavulanate potassium should be discontinued and appropriate therapy instituted

Phenylketonurics AUGMENTIN Chewable tablets and AUGMENTIN for Oral Suspension contain aspartame which contains phenylalanine. Each 200 mg chewable tablet of AUGMENTIN contains 2.1 mg phenylalanine; each 400 mg chewable tablet contains 4.2 mg phenylalanine; each 5 mL of either the 200 mg/5 mL or 400 mg/5 mL oral suspension contains 7 mg phenylalanine. The other formulations of AUGMENTIN do not contain phenylalanine

Development of Drug-Resistant Bacteria 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.

Co‑administration with probenecid is not recommended. Concomitant use of AUGMENTIN and oral anticoagulants may increase the prolongation of prothrombin time.( 7.2 ) Co-administration with allopurinol increases the risk of rash. AUGMENTIN may reduce efficacy of oral contraceptives

Probenecid Probenecid decreases the renal tubular secretion of amoxicillin but does not delay renal excretion of clavulanic acid. Concurrent use with AUGMENTIN may result in increased and prolonged blood concentrations of amoxicillin. Co-administration of probenecid is not recommended

Oral Anticoagulants Abnormal prolongation of prothrombin time (increased international normalized ratio [INR]) has been reported in patients receiving amoxicillin and oral anticoagulants. Appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently with AUGMENTIN. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation

Allopurinol The concurrent administration of allopurinol and amoxicillin increases the incidence of rashes in patients receiving both drugs as compared to patients receiving amoxicillin alone. It is not known whether this potentiation of amoxicillin rashes is due to allopurinol or the hyperuricemia present in these patients

Oral Contraceptives AUGMENTIN may affect intestinal flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives

Effects on Laboratory Tests High urine concentrations of amoxicillin 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 AUGMENTIN, it is recommended that glucose tests based on enzymatic glucose oxidase reactions be used. Following administration of amoxicillin to pregnant women, a transient decrease in plasma concentration of total conjugated estriol, estriol-glucuronide, conjugated estrone, and estradiol has been noted.