Amoxicillin and Clavulanate Potassium

Indications and Usage ( 1 ) 12/2024 Dosage and Administration, Dosage in Pediatric Patients ( 2.2 ) 12/2024 Warnings and Precautions, Drug-Induced Enterocolitis Syndrome (DIES) ( 5.3 ) 5/2024

1 INDICATIONS AND USAGE Amoxicillin and clavulanate potassium for oral suspension is a combination of amoxicillin, a penicillin-class antibacterial and clavulanate potassium, a beta-lactamase inhibitor, indicated for the treatment of infections caused by designated susceptible (confirmed or suspected) beta-lactamase-producing microorganisms ( 1 ): Lower Respiratory Tract Infections ( 1.1 ) Amoxicillin and Clavulanate Potassium for Oral Suspension: pediatric patients weighing less than 40 kg, and in adult and pediatric patients who cannot swallow tablets Acute Bacterial Sinusitis ( 1.3 ) Amoxicillin and Clavulanate Potassium for Oral Suspension: pediatric patients weighing less than 40 kg, and in adult and pediatric patients who cannot swallow tablets Acute Bacterial Otitis Media ( 1.4 ) Amoxicillin and Clavulanate Potassium for Oral Suspension: pediatric patients weighing less than 40 kg, and in adult and pediatric patients who cannot swallow tablets Skin and Skin Structure Infections ( 1.6 ) Amoxicillin and Clavulanate Potassium for Oral Suspension: pediatric patients weighing less than 40 kg, and in adult and pediatric patients who cannot swallow tablets Urinary Tract Infections ( 1.7 ) Amoxicillin and Clavulanate Potassium for Oral Suspension: pediatric patients weighing less than 40 kg, and in adult and pediatric patients who cannot swallow tablets Limitations of Use ( 1.8 ) Therapy may be initiated before bacteriological results are available when beta-lactamase-producing pathogens are suspected. When results show susceptibility to amoxicillin alone, amoxicillin and clavulanate potassium for oral suspension should not be used. Usage to Reduce Development of Drug-Resistant Bacteria ( 1.9 ) To reduce the development of drug-resistant bacteria and maintain the effectiveness of amoxicillin and clavulanate potassium for oral suspension and other antibacterial drugs, amoxicillin and clavulanate potassium for oral suspension should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. 1.1 Lower Respiratory Tract Infections Amoxicillin and clavulanate potassium for oral suspension is indicated for the treatment of lower respiratory tract infection due to confirmed or suspected beta-lactamase producing Haemophilus influenzae and Moraxella catarrhalis as follows [see Clinical Pharmacology (12.4) , Clinical Studies (14.1) ] : Amoxicillin and Clavulanate Pot assi um for Oral Suspension: pediatric patients weighing less than 40 kg, and in adult and pediatric patients who cannot swallow tablets 1.3 Acute Bacterial Sinusitis Amoxicillin and clavulanate potassium for oral suspension are indicated for the treatment of acute bacterial sinusitis due to confirmed or suspected beta-lactamase-producing Haemophilus influenzae and Moraxella catarrhalis as follows [see Clinical Pharmacology (12.4) , Clinical Studies (14.4) ]: Amoxicillin and Clavulanate Po tassi um for Oral Suspension: pediatric patients weighing less than 40 kg, and in adult and pediatric patients who cannot swallow tablets 1.4 Acute Bacterial Otitis Media Amoxicillin and clavulanate potassium for oral suspension is indicated for the treatment of acute bacterial otitis media due to confirmed or suspected beta-lactamase-producing Haemophilus influenzae and Moraxella catarrhalis as follows [see Use in Specific Populations (8.4) , Clinical Studies (14.5) ] : Amoxicillin and Clavulanate Pot assi um for Oral Suspension: pediatric patients weighing less than 40 kg, and in adult and pediatric patients who cannot swallow tablets 1.6 Skin and Skin Structure Infections Amoxicillin and clavulanate potassium for oral suspension is indicated for the treatment of skin and skin structure infections due to confirmed or suspected beta-lactamase-producing S. aureus , Escherichia coli , and Klebsiella species as follows [see Use in Specific Populations (8.4) ] : Amoxicillin and Clav ulana te Potassium for Oral Suspension: pediatric …

2 DOSAGE AND ADMINISTRATION 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 amoxicillin component. ( 2.2 , 2.3 ) 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. ( 2.3 ) 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/31.25 mg per 5 mL oral suspension is recommended. ( 2.3 ) 2.1 Important Administration Instructions Amoxicillin and clavulanate potassium for oral suspension may be taken without regard to meals; however, absorption of clavulanate potassium is enhanced when amoxicillin and clavulanate potassium for oral suspension is administered at the start of a meal. To minimize the potential for gastrointestinal intolerance, amoxicillin and clavulanate potassium for oral suspension should be taken at the start of a meal. 2.2 Adult Patients See dosing regimens of amoxicillin and clavulanate potassium (based on the amoxicillin component) provided in Table 1 below. Table 1. Dosing Regimens of Amoxicillin and Clavulanate Potassium in Adult Patients TYPE OF INFECTION DOSING REGIMEN OF AMOXICILLIN AND CLAVULANATE POTASSIUM Severe infections and infections of the respiratory tract one 875 mg/125 mg tablet a of amoxicillin and clavulanate potassium every 12 hours or one 500 mg/125 mg tablet b,c of amoxicillin and clavulanate potassium every 8 hours Less severe infections one 500 mg/125 mg tablet b,c of amoxicillin and clavulanate potassium every 12 hours or one 250 mg/125 mg tablet d of amoxicillin and clavulanate potassium every 8 hours a Adults who have difficulty swallowing may be given the amoxicillin and clavulanate potassium 200 mg/28.5 mg per 5 mL suspension or the amoxicillin and clavulanate potassium 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 amoxicillin and clavulanate potassium 125 mg/31.25 mg per 5 mL or amoxicillin and clavulanate potassium 250 mg/62.5 mg per 5 mL suspension in place of the 500 mg/125 mg tablet. c Two amoxicillin and clavulanate potassium 250 mg/125 mg tablets are NOT substitutable with one 500 mg/125 mg amoxicillin and clavulanate potassium tablet [see Dosage and Administration (2.6) ] . d Amoxicillin and clavulanate potassium 250 mg/125 mg tablet is NOT substitutable with amoxicillin and clavulanate potassium 250 mg/62.5 mg chewable tablet [see Dosage and Administration (2.6) ]. 2.3 Pediatric Patients Based on the amoxicillin component, amoxicillin and clavulanate potassium for oral suspension should be dosed as follows: Neonates and Infants Aged less than 12 weeks (less than 3 months) : See dosing regimens of amoxicillin and clavulanate potassium for oral suspension provided in Table 2 below. Table 2: Dosing Regimens of Amoxicillin and Clavulanate Potassium for Oral Suspension in Neonates and Infants Aged Less than 12 Weeks (Less than 3 Months) PATIENT POPULATION DOSING REGIMEN Amoxicillin and clavulanate potassium 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 amoxicillin and clavulanate potassium for oral suspension 200 mg/28.5 mg per 5 mL formulation in this age group is limited, and thus, use of the amoxicillin and clavulanate potassium 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 [see Clinical Studies (14.2) ] . 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 20 …

3 DOSAGE FORMS AND STRENGTHS Tablets : • 250 ‐ mg/125-mg Tablets: Each white oval film-coated tablet, debossed with AUGMENTIN on one side and 250/125 on the other side, contains 250 mg of amoxicillin and 125 mg clavulanic acid as the potassium salt. • 500 ‐ mg/125-mg Tablets : Each white oval film-coated tablet, debossed with AUGMENTIN on one side and 500/125 on the other side, contains 500 mg amoxicillin and 125 mg of clavulanic acid as the potassium salt. • 875 ‐ mg/125-mg Tablets : Each scored white capsule‐shaped tablet, debossed with AUGMENTIN 875 on one side and scored on the other side, contains 875 mg amoxicillin and 125 mg clavulanic acid as the potassium salt. Powder for Oral Suspension: • 125 mg/31.25 mg per 5 mL : Banana-flavored powder for oral suspension (each 5 mL of reconstituted suspension contains 125 mg amoxicillin and 31.25 mg of clavulanic acid as the potassium salt). • 200 mg/28.5 mg per 5 mL : Orange-favored powder for oral suspension (each 5 mL of reconstituted suspension contains 200 mg amoxicillin and 28.5 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 amoxicillin and 62.5 mg of clavulanic acid as the potassium salt). • 400 mg/57 mg per 5 mL Orange-flavored powder for oral suspension (each 5 mL of reconstituted suspension contains 400 mg amoxicillin and 57.0 mg of clavulanic acid as the potassium salt). Chewable Tablets: • 125-mg/31.25-mg Chewable Tablets : Each mottled yellow, round, lemon-lime-flavored tablet, debossed with BMP 189 contains 125 mg amoxicillin and 31.25 mg clavulanic acid as the potassium salt. • 200-mg/28.5 mg Chewable Tablets : Each mottled pink, round, biconvex cherry-banana-flavored tablet, debossed with PL over C20 contains 200 mg amoxicillin and 28.5 mg clavulanic acid as the potassium salt. • 250-mg/62.5-mg Chewable Tablets : Each mottled yellow, round, lemon-lime-flavored tablet, debossed with BMP 190 contains 250 mg amoxicillin and 62.5 mg clavulanic acid as the potassium salt. • 400-mg/57-mg Chewable Tablets : Each mottled pink, round, biconvex cherry-banana-flavored tablet, debossed with PL over C40 contains 400 mg amoxicillin and 57.0 mg clavulanic acid as the potassium salt. The 250-mg tablet of Amoxicillin and Clavulanate Potassium and the 250-mg chewable tablet should NOT be substituted for each other, as they are not interchangeable and the 250-mg tablet should not be used in children weighing less than 40 kg. The 250-mg tablet of Amoxicillin and Clavulanate Potassium and the 250-mg chewable tablet do not contain the same amount of clavulanic acid. The 250-mg tablet of Amoxicillin and Clavulanate Potassium contains 125 mg of clavulanic acid whereas the 250-mg chewable tablet contains 62.5 mg of clavulanic acid. Two 250 mg tablets of Amoxicillin and Clavulanate Potassium should NOT be substituted for one 500 mg tablet of Amoxicillin and Clavulanate Potassium. Since both the 250 mg and 500 mg tablets of Amoxicillin and Clavulanate Potassium contain the same amount of clavulanic acid (125 mg, as the potassium salt), two 250 mg tablets of Amoxicillin and Clavulanate Potassium are not equivalent to one 500 mg tablet of Amoxicillin and Clavulanate Potassium. Formulations and amoxicillin/clavulanate content are: Tablets: 250 mg/125 mg, 500 mg/125 mg, 875 mg/125 mg; 875 mg/125 mg tablets are scored. (3) Powder for Oral Suspension: 125 mg/31.25 mg per 5 mL, 200 mg/28.5 mg per 5 mL, 250 mg/62.5 mg per 5 mL, 400 mg/57 mg per 5 mL (3) Chewable Tablets: 125 mg/31.25 mg, 200 mg/28.5 mg, 250 mg/62.5 mg, 400 mg/57 mg (3)

4 CONTRAINDICATIONS • History of a serious hypersensitivity reaction (e.g., anaphylaxis or Stevens-Johnson syndrome) to amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL or to other beta-lactams (e.g., penicillins or cephalosporins). ( 4.1 ) • History of cholestatic jaundice/hepatic dysfunction associated with amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL. ( Error! Hyperlink reference not valid. ) 4.1 Serious Hypersensitivity Reactions Amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mLis contraindicated in patients with a history of serious hypersensitivity reactions (e.g., anaphylaxis or Stevens-Johnson syndrome) to amoxicillin, clavulanate or to other beta-lactam antibacterial drugs (e.g., penicillins and cephalosporins). 4.2 Cholestatic Jaundice/Hepatic Dysfunction Amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL is contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with treatment with amoxicillin/clavulanate potassium.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Serious Allergic Reactions, including Anaphylaxis [see Warnings and Precautions (5.1) ] Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.2) ] Drug-Induced Enterocolitis Syndrome (DIES) [see Warnings and Precautions (5.3) ] Hepatic Dysfunction [see Warnings and Precautions (5.4) ] Clostridioides difficile -associated diarrhea (CDAD) [see Warnings and Precautions (5.5) ] Skin Rash in Patients with Mononucleosis [see Warnings and Precautions (5.6) ] The most frequently reported adverse reactions with amoxicillin and clavulanate potassium for oral suspension were (incidence ≥3%) diarrhea/loose stools, nausea, skin rash, and urticaria. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Amoxicillin and Clavulanate Potassium for Oral Suspension The most frequently reported adverse reactions in clinical trials were diarrhea/loose stools (9%), nausea (3%), skin rash and urticaria (3%), vomiting (1%) and vaginitis (1%). Less than 3% of patients discontinued therapy due to adverse reactions. The overall incidence of adverse reactions, particularly diarrhea, increased with higher recommended doses. Other less frequently reported adverse reactions (<1%) included abdominal discomfort, flatulence, and headache. In two pivotal trials in adults with lower respiratory tract or urinary tract infections , the overall incidence of adverse reactions was similar between AUGMENTIN 875 mg/125 mg Tablets every 12 hours and AUGMENTIN 500 mg/125 mg Tablets every 8 hours [see Clinical Studies (14.1 , 14.2) ] . The most common adverse reaction was diarrhea, reported in 15% of patients receiving AUGMENTIN 875 mg/125 mg every 12 hours and 14% of patients receiving AUGMENTIN 500 mg/125 mg every 8 hours. The rate of severe diarrhea or discontinuation due to diarrhea was 1% versus 2%, respectively. In a controlled clinical trial of pediatric patients aged 2 months to 12 years with acute otitis media [see Clinical Studies (14.5) ], diarrhea was defined in the protocol as ≥3 watery stools or ≥4 loose/watery stools in 1 day, or ≥2 watery stools or ≥3 loose/watery stools per day for 2 consecutive days, as recorded on diary cards. The incidence of diarrhea was significantly lower in patients treated with amoxicillin and clavulanate potassium for oral suspension 45 mg/kg/day divided every 12 hours (14%) compared to patients treated with amoxicillin and clavulanate potassium for oral suspension 40 mg/kg/day divided every 8 hours (34%). It is not known whether the statistically significant reduction in diarrhea with the oral suspension dosed every 12 hours, versus suspensions dosed every 8 hours, can be extrapolated to the chewable tablets, all of which contain mannitol . The presence of mannitol in the chewable tablets may contribute to a different diarrhea profile. Severe diarrhea or discontinuation due to diarrhea occurred in 3% and 8% of patients, respectively. Allergic reactions leading to discontinuation occurred in 1% and <1% of patients, and candidal infection of the diaper area was reported in 4% and 6% of patients, respectively. 6.2 Postmarketing Experience The following adverse reactions have been identified during postmarketing use of amoxicillin and clavulanate potassium product. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Gastrointestinal: Drug-induced enterocolitis syndrome (DIES …

7 DRUG INTERACTIONS • Coadministration with probenecid is not recommended. ( 7.1 ) • Concomitant use of amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL with oral anticoagulants may increase the prolongation of prothrombin time. ( 7.2 ) • Coadministration with allopurinol increases the risk of rash. ( 7.3 ) • Amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL may reduce efficacy of oral contraceptives. ( 7.4 ) 7.1 Probenecid 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. Coadministration of probenecid is not recommended. 7.2 Oral Anticoagulants Abnormal prolongation of prothrombin time (increased international normalized ratio [INRI) has been reported 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. 7.3 Allopurinol The concurrent administration of allopurinol and amoxicillin increases substantially 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. There are no data with amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL and allopurinol administered concurrently. 7.4 Oral Contraceptives Amoxicillin and clavulanate potassium for oral suspension, 600 mg/42.9 mg per 5 mL may affect intestinal flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives. 7.5 Effects on Laboratory Test 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 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 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.

8 USE IN SPECIFIC POPULATIONS Renal Impairment: Dosage adjustment is recommended for severe renal impairment (GFR <30 mL/min). ( 2.6 , 8.6 ) 8.1 Pregnancy Risk Summary Available data from published epidemiologic studies and pharmacovigilance case reports over several decades of use with amoxicillin and clavulanate during pregnancy have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal outcomes. A study in women with preterm prelabor rupture of membranes (PPROM) reported that prophylactic treatment with amoxicillin and clavulanate may be associated with an increased risk of necrotizing enterocolitis in neonates (see Data) . Reproduction studies conducted in pregnant rats, given doses greater than or equal to 4 and 10 times the Maximum Recommended Human Dose (MRHD) of amoxicillin trihydrate and clavulanate respectively in amoxicillin and clavulanate potassium based on body surface area, revealed no evidence of fetal harm (see Data) . The background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Human Data One randomized, controlled trial included 4,826 pregnant women with premature rupture of fetal membranes who were randomly assigned to 250 mg erythromycin (n=1,197), 250 mg amoxicillin and 125 mg clavulanate (n=1,212), amoxicillin and clavulanate plus erythromycin (n=1,192), or placebo (n=1,225) four times daily for 10 days or until delivery. Amoxicillin and clavulanate was associated with a significantly increased rate of proven neonatal necrotizing enterocolitis: 1.9% (n=24) in the amoxicillin and clavulanate only group versus 0.5% (n=6) in the placebo group (p=0.001), and 1.8% (n=44) in the any amoxicillin and clavulanate group versus 0.7% (n=17) in the no amoxicillin and clavulanate group (p=0.0005). Animal Data In an embryofetal developmental study in pregnant rats, amoxicillin and clavulanate (2:1 ratio formulation of amoxicillin:clavulanate) were administered at oral doses up to 1,200 mg/kg/day during the period of organogenesis (gestation days (GD) 6 to 15). No evidence of fetal harm was observed. Based on body surface area comparisons, the dose corresponds to approximately 4 times the MRHD for amoxicillin trihydrate and 10 times the MRHD for clavulanate potassium. In a pre-and postnatal developmental study in pregnant rats, amoxicillin and clavulanate (2:1ratio formulation of amoxicillin:clavulanate) were administered at oral doses up to 1,200 mg/kg/day beginning from GD 15 through Day 21 of lactation. No effects on maternal reproductive function or on developmental and reproductive parameters of the offspring were observed up to the highest dose, corresponding to approximately 4 times the MRHD for amoxicillin trihydrate and 10 times the MRHD for clavulanate potassium, based on body surface area comparisons. 8.2 Lactation Risk Summary Data from a published clinical lactation study report that amoxicillin is present in human milk. There are reports of diarrhea, irritability, and rash in infants exposed to amoxicillin and clavulanate through breast milk; therefore, infants exposed to amoxicillin and clavulanate potassium should be monitored for these symptoms. There are no data on the effects of amoxicillin and clavulanate on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for amoxicillin and clavulanate potassium and any potential adverse effects on the breastfed child from amoxicillin and clavulanate potassium or from the underlying maternal condition. 8.4 Pediatric Use The five amoxicillin and clavulanate potassium dosage forms (tablets, chewable tablets, oral suspension, XR tablets, an …

12.1 Mechanism of Action Amoxicillin and clavulanate potassium tablets, amoxicillin and clavulanate potassium for oral suspension, and amoxicillin and clavulanate potassium tablets (chewable) are antibacterial drugs [see Microbiology ( 12.4 )] .

11 DESCRIPTION Amoxicillin and clavulanate potassium tablets, amoxicillin and clavulanate potassium for oral suspension, and amoxicillin and clavulanate potassium tablets (chewable) are oral antibacterial combinations consisting of the semisynthetic antibiotic amoxicillin, USP and the beta–lactamase inhibitor, clavulanate potassium, USP (the potassium salt of clavulanic acid). Amoxicillin, USP is an analog of ampicillin, derived from the basic penicillin nucleus, 6–aminopenicillanic acid. Chemically, amoxicillin, USP 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 has the following structural formula: C 16 H 19 N 3 O 5 S•3H 2 O M.W. 419.45 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. Chemically, clavulanate potassium, USP is potassium ( Z )-(2 R ,5 R )-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]-heptane-2-carboxylate, and has the following structural formula: C 8 H 8 KNO 5 M.W. 237.25 Amoxicillin and Clavulanate Potassium Tablets, USP: 500 mg/125 mg: Each tablet contains 500 mg of amoxicillin, USP as the trihydrate, and 125 mg of clavulanic acid (equivalent to 149 mg of clavulanate potassium). 875 mg/125 mg: Each tablet contains 875 mg of amoxicillin, USP as the trihydrate, and 125 mg of clavulanic acid (equivalent to 149 mg of clavulanate potassium). Amoxicillin and Clavulanate Potassium for Oral Suspension, USP: 200 mg/28.5 mg per 5 mL: Following reconstitution, each 5 mL of oral suspension contains 200 mg of amoxicillin, USP as the trihydrate, and 28.5 mg of clavulanic acid (equivalent to 34 mg of clavulanate potassium). 400 mg/28.5 mg per 5 mL: Following reconstitution, each 5 mL of oral suspension contains 400 mg of amoxicillin, USP as the trihydrate, and 57 mg of clavulanic acid (equivalent to 68 mg of clavulanate potassium). Amoxicillin and Clavulanate Potassium Tablets, USP (Chewable): 200 mg/28.5 mg: Each chewable tablet contains 200 mg of amoxicillin, USP as the trihydrate, and 28.5 mg of clavulanic acid (equivalent to 34 mg of clavulanate potassium). 400 mg/57 mg: Each chewable tablet contains 400 mg of amoxicillin, USP as the trihydrate, and 57 mg of clavulanic acid (equivalent to 68 mg of clavulanate potassium). Inactive Ingredients: Amoxicillin and Clavulanate Potassium Tablets, USP - colloidal silicon dioxide, hypromellose, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, sodium starch glycolate, titanium dioxide, and triacetin. Each tablet of amoxicillin and clavulanate potassium tablets, USP contains 0.63 mEq potassium. Amoxicillin and Clavulanate Potassium for Oral Suspension, USP - artificial raspberry powder, aspartame, citric acid, colloidal silicon dioxide, mannitol, hypromellose, natural orange flavor, sodium citrate, sodium saccharin and xanthan gum [see Warnings and Precautions ( 5.8 ] . Each 5 mL of reconstituted 200 mg/28.5 mg oral suspension of amoxicillin and clavulanate potassium contains 0.14 mEq potassium Each 5 mL of reconstituted 400 mg/57 mg oral suspension of amoxicillin and clavulanate potassium contains 0.29 mEq potassium Amoxicillin and Clavulanate Potassium Tablets, USP (Chewable) - aspartame, colloidal silicon dioxide, FD&C Red #40 lake, magnesium stearate, mannitol, microcrystalline cellulose, SA84 artificial ripe banana flavor, and artificial cherry flavor powder [see Warnings and Precautions ( 5.8 ] . Each 200 mg/28.5 mg chewable tablet of amoxicillin and clavulanate potassium contains 0.14 mEq potassium Each 400 mg/57 mg chewable tablet of amoxicillin and clavulanate potassium contains 0.29 mEq potassium amoxicillin structural formula clavulanic acid structural formula

10 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. 1 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 [see Dosage and Administration ( 2 )].

16 HOW SUPPLIED/STORAGE AND HANDLING Amoxicillin and clavulanate potassium tablets, USP are supplied as follows: 500 mg/125 mg: White, oblong–shaped, biconvex, film–coated, unscored tablets, debossed 93 on one side and 2274 on the other side. Each tablet contains 500 mg amoxicillin, USP as the trihydrate and 125 mg clavulanic acid as the potassium salt. They are available in bottles of 20 tablets (NDC 0093–2274–34). 875 mg/125 mg: White, capsule–shaped, biconvex, film–coated, scored tablets, debossed 93 on one side and 22 score line 75 on the other side. Each tablet contains 875 mg amoxicillin, USP as the trihydrate and 125 mg clavulanic acid as the potassium salt. They are available in bottles of 20 tablets (NDC 0093–2275–34). Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Amoxicillin and clavulanate potassium for oral suspension, USP is supplied as follows: 200 mg/28.5 mg per 5 mL: White to off–white powder – Each 5 mL of reconstituted orange–raspberry–flavored suspension contains 200 mg amoxicillin, USP and 28.5 mg clavulanic acid as the potassium salt. It is available in bottles of 100 mL (NDC 0093–2277–73). 400 mg/57 mg per 5 mL: White to off–white powder – Each 5 mL of reconstituted orange–raspberry–flavored suspension contains 400 mg amoxicillin, USP and 57 mg clavulanic acid as the potassium salt. It is available in bottles of 100 mL (NDC 0093–2279–73). Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Dispense in original containers. Store reconstituted suspension under refrigeration. Discard unused suspension after 10 days. Amoxicillin and clavulanate potassium tablets, USP (chewable) are supplied as follows: 200 mg/28.5 mg: Mottled pink, oval, biconvex, unscored tablets, debossed 93 on one side and 2270 on the other. They are available in bottles of 20 tablets (NDC 0093–2270–34). 400 mg/57 mg: Mottled pink, oval, biconvex, unscored tablets, debossed 93 on one side and 2272 on the other. They are available in bottles of 20 tablets (NDC 0093–2272–34). Store at 20o to 25oC (68o to 77oF) [See USP Controlled Room Temperature]. Dispense in a tight, light–resistant container as defined in the USP, with a child–resistant closure (as required). Keep this and all medications out of the reach of children.