{"adverse_reactions":["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 tablets were (incidence ≥3%) diarrhea/loose stools, nausea, skin rash and urticaria ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp. at 1-800-706-5575 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 tablets 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 amoxicillin and clavulanate potassium tablets 875 mg/125 mg Tablets every 12 hours and amoxicillin and clavulanate potassium tablets 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 amoxicillin and clavulanate potassium tablets 875 mg/125 mg every 12 hours and 14% of patients receiving amoxicillin and clavulanate potassium tablets 500 mg/125 mg every 8 hours. The rate of severe diarrhea or discontinuation due to diarrhea was 1% versus 2%, respectively. 6.2 Postmarketing Experience The following adverse reactions have been identified during postmarketing use of amoxicillin and clavulanate potassium tablets. 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), 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 antibacterial treatment [see Warnings and Precautions ( 5.3 , 5.5 )] . Immune Hypersensitivity reactions, anaphylactic reactions (including shock), angioedema, serum sickness–like reactions (urticaria or skin rash accompanied by arthritis, arthralgia, myalgia, and frequently fever), hypersensitivity vasculitis [ see Warnings and Precautions ( 5.1 ) ]. Skin and Appendages Rashes, pruritus, urticaria, erythema multiforme, SJS, TEN, DRESS, AGEP, exfoliative dermatitis, and linear IgA bullous dermatosis [see Warnings and Precautions ( 5.1 , 5.2 , 5.6 )]. Liver A moderate rise in AST (SGOT) and/or ALT (SGPT) has been noted in patients treated with ampicillin-class antibacterials. Hepatic dysfunction, including hepatitis and cholestatic jaundice, increases in serum transaminases (AST and/or ALT), serum bilirubin, and/or alkaline phosphatase, has been reported with amoxicillin and clavulanate potassium tablets. 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 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. Deaths have been reported [see Contraindications ( 4.2 ), Warnings and Precautions ( 5.4 )]. Renal Interstitial nephritis and hematuria have been reported. Crystalluria has also been reported [ see Overdosage ( 10 ) ]. 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. There have been reports of increased prothrombin time in patients receiving amoxicillin and clavulanate potassium tablets and anticoagulant therapy concomitantly [ see Drug Interactions ( 7.2 ) ]. Central Nervous System Agitation, anxiety, behavioral changes, aseptic meningitis, confusion, convulsions, dizziness, insomnia, and reversible hyperactivity have been reported. Miscellaneous Tooth discoloration (brown, yellow, or gray staining) has been reported. Most reports occurred in pediatric patients. Discoloration was reduced or eliminated with brushing or dental cleaning in most cases."],"clinical_pharmacology":["12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Amoxicillin and clavulanate potassium tablets are an antibacterial drug [see Clinical Pharmacology ( 12.4 )]. 12.2 Pharmacodynamics The antibacterial activity of amoxicillin/clavulanate is primarily driven by the percentage of the dosing interval during which unbound (free) amoxicillin plasma concentrations exceed the minimum inhibitory concentration (%fT>MIC) of the target bacterial organism. Clavulanate inhibits β-lactamase enzymes and thereby restores activity of amoxicillin against certain β-lactamase–producing bacteria. 12.3 Pharmacokinetics Absorption Dosing in the fasted or fed state has minimal effect on the pharmacokinetics of amoxicillin. While amoxicillin clavulanate potassium tablets can be given without regard to meals, absorption of clavulanate potassium when taken with food is greater relative to the fasted state. In one study, the relative bioavailability of clavulanate was reduced when amoxicillin clavulanate potassium tablets was dosed at 30 and 150 minutes after the start of a high‑fat breakfast. Amoxicillin clavulanate potassium tablets Mean amoxicillin and clavulanate potassium pharmacokinetic parameters in healthy adult subjects following administration of amoxicillin and clavulanate potassium tablets are shown in Table 7 T able 7: Mean (±S.D.) Amoxicillin and Clavulanate Potassium Pharmacokinetic Parameters a,b with Amoxicillin and Clavulanate Potassium Tablets Dose and Regimen C max (mcg/mL) C max (mcg/mL) AUC 0 to 24 (mcg * hr/mL) AUC 0 to 24 (mcg * hr/mL) Amoxicillin/Clavulanate potassium Amoxicillin Clavulanate potassium Amoxicillin Clavulanate potassium 250/125 mg every 8 hours 3.3 ± 1.12 1.5 ± 0.70 26.7 ± 4.56 12.6 ± 3.25 500/125 mg every 12 hours 6.5 ± 1.41 1.8 ± 0.61 33.4 ± 6.76 8.6 ± 1.95 500/125 mg every 8 hours 7.2 ± 2.26 2.4 ± 0.83 53.4 ± 8.87 15.7 ± 3.86 875/125 mg every 12 hours 11.6 ± 2.78 2.2 ± 0.99 53.5 ± 12.31 10.2 ± 3.04 a Mean (± standard deviation) values of 14 healthy adult subjects (N =15 for clavulanate potassium in the low-dose regimens). Peak concentrations occurred ~ 1.5 hours after the dose. b administered at the start of a light meal. Distribution The protein binding of amoxicillin and clavulanic acid to human serum is approximately 18% and 25%, respectively. Amoxicillin diffuses readily into most body tissues and fluids, with the exception of the brain and spinal fluid. Metabolism and Excretion The half-life of amoxicillin after the oral administration of amoxicillin and clavulanate potassium tablets is approximately 1.3 hours and that of clavulanic acid is approximately 1 hour. 12.4 Microbiology Mechanism of Action Amoxicillin binds to penicillin-binding proteins within the bacterial cell wall and inhibits bacterial cell wall synthesis. Clavulanic acid is a beta-lactam, structurally related to penicillin, that may inactivate certain beta‑lactamase enzymes. Resistance Resistance to penicillins may be mediated by destruction of the beta-lactam ring by a betalactamase, altered affinity of penicillin for target, or decreased penetration of the antibacterial drug to reach the target site. Amoxicillin alone is susceptible to degradation by beta‑lactamases, and therefore its spectrum of activity does not include bacteria that produce these enzymes. Antimicrobial Activity Amoxicillin and clavulanic acid has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections [see Indications and Usage ( 1 )]. Lower Respiratory Tract Infections G ram-negative bacteria H aemophilus influenzae Moraxella catarrhalis Acute Bacterial Sinusitis Gram-positive bacteria: Staphylococcus aureus (methicillin-susceptible) Streptococcus pneumoniae Gram-negative bacteria: Haemophilus influenzae Haemophilus parainfluenzae Klebsiella pneumoniae Moraxella catarrhalis Acute Bacterial Otitis Media, including Recurrent or Persistent Acute Otitis Media Gram-positive bacteria: Streptococcus pneumoniae Gram-negative bacteria: Haemophilus influenzae Moraxella catarrhalis Skin and Skin Structure Infections Gram-positive bacteria: Staphylococcus aureus (methicillin-susceptible) Gram-negative bacteria: E scherichia coli Klebsiella spp. Urinary Tract Infections Gram-negative bacteria (including beta-lactamase-producing strains): Escherichia coli Klebsiella spp. Enterobacter spp. The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for amoxicillin and clavulanic acid against isolates of similar genus or organism group. However, the efficacy of amoxicillin and clavulanic acid in treating clinical infections caused by these bacteria have not been established in adequate and well-controlled trials. Gram-positive bacteria: Enterococcus faecalis Staphylococcus epidermidis Staphylococcus saprophyticus Streptococcus pyogenes Viridans group Streptococcus Gram-negative Bacteria Eikenella corrodens Proteus mirabilis Anaerobic Bacteria Bacteroides species including Bacteroides fragilis Fusobacterium species Peptostreptococcus species Susceptibility Testing: For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see https://www.fda.gov/STIC ."],"clinical_pharmacology_table":["
Dose and RegimenCmax (mcg/mL)Cmax (mcg/mL)AUC0 to 24 (mcg * hr/mL)AUC0 to 24 (mcg * hr/mL)
Amoxicillin/Clavulanate potassiumAmoxicillinClavulanate potassiumAmoxicillinClavulanate potassium
250/125 mg every 8 hours3.3 ± 1.121.5 ± 0.7026.7 ± 4.5612.6 ± 3.25
500/125 mg every 12 hours6.5 ± 1.411.8 ± 0.6133.4 ± 6.768.6 ± 1.95
500/125 mg every 8 hours7.2 ± 2.262.4 ± 0.8353.4 ± 8.8715.7 ± 3.86
875/125 mg every 12 hours11.6 ± 2.782.2 ± 0.9953.5 ± 12.3110.2 ± 3.04
"],"clinical_studies":["14 CLINICAL STUDIES 14.1 Lower Respiratory Tract Infections in Adults Treated with Amoxicillin and Clavulanate Potassium Tablets A randomized, controlled trial was conducted in 562 adults with lower respiratory tract infections, comparing amoxicillin and clavulanate potassium tablets 875 mg/125 mg every 12 hours with amoxicillin and clavulanate potassium tablets 500 mg/125 mg every 8 hours. Comparable efficacy was demonstrated between the two regimens. 14.2 Complicated Urinary Tract Infections in Adults Treated with Amoxicillin and Clavulanate Potassium Tablets A randomized, controlled trial was conducted in adults with pyelonephritis (n=361) or complicated urinary tract infection (n=268), defined as urinary tract abnormalities that predispose to relapse after bacteriuria eradication. Patients were randomized 1:1 to receive amoxicillin and clavulanate potassium tablets 875 mg/125 mg every 12 hours (n=308) or amoxicillin and clavulanate potassium tablets 500 mg/125 mg every 8 hours (n=321). Among bacteriologically evaluable patients, bacteriologic success rates were comparable between the two dosing regimens when assessed immediately after therapy and at follow-up visits. Table 13: Bacteriologic Efficacy Rates in Complicated Urinary Tract Infections in Adults Time Post Therapy 875 mg every 12 hours % (n) 500 mg every 8 hours % (n) 2 to 4 days 81% (58) 80% (54) 5 to 9 days 58% (41) 52% (52) 2 to 4 weeks 52% (101) 55% (104)"],"clinical_studies_table":["
Time Post Therapy875 mg every 12 hours% (n)500 mg every 8 hours% (n)
2 to 4 days81% (58)80% (54)
5 to 9 days58% (41)52% (52)
2 to 4 weeks52% (101)55% (104)
"],"contraindications":["4 CONTRAINDICATIONS History of a serious hypersensitivity reaction (e.g., anaphylaxis or Stevens-Johnson syndrome) to amoxicillin and clavulanate potassium tablets or to other beta-lactams (e.g., penicillins or cephalosporins) ( 4.1 ) History of cholestatic jaundice/hepatic dysfunction associated with amoxicillin and clavulanate potassium tablets. ( 4.2 ) 4.1 Serious Hypersensitivity Reactions Amoxicillin and clavulanate potassium tablets are 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 tablets are contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with treatment with amoxicillin/clavulanate potassium."],"description":["11 DESCRIPTION Amoxicillin and clavulanate potassium tablets, USP are an oral antibacterial combination consisting of the semisynthetic antibacterialamoxicillin and the beta-lactamase inhibitor, clavulanate potassium (the potassium salt of clavulanic acid). In amoxicillin and clavulanate potassium tablets, amoxicillin is present as amoxicillin trihydrate. Amoxicillin is an analog of ampicillin, derived from the basic penicillin nucleus, 6-aminopenicillanic acid. The amoxicillin trihydrate has a molecular formula of C 16 H 19 N 3 O 5 S•3H 2 O, and a molecular weight of 419.46 g/mol. Chemically, it is (2S,5R,6R)-6-[(R)-(-)-2-Amino-2-(p-hydroxyphenyl)acetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo [3.2.0]heptane-2-carboxylic acid trihydrate and may be represented structurally as: Clavulanic acid is produced by the fermentation of S treptomyces clavuligerus . It is a beta-lactam structurally related to the penicillins and possesses the ability to inactivate a wide variety of beta-lactamases by blocking the active sites of these enzymes. Clavulanic acid is particularly active against the clinically important plasmid-mediated beta-lactamases frequently responsible for transferred drug resistance to penicillins and cephalosporins. Clavulanate potassium has a molecular formula of C 8 H 8 KNO 5 , and a molecular weight of 237.25 g/mol. 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: Amoxicillin and Clavulanate Potassium Tablets, USP: 250 mg/125 mg: Each tablet contains 250 mg of amoxicillin (equivalent to 287 mg of amoxicillin trihydrate) and 125 mg of clavulanic acid (equivalent to 149 mg of clavulanate potassium). 500 mg/125 mg: Each tablet contains 500 mg of amoxicillin (equivalent to 574 mg of amoxicillin 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 (equivalent to 1004 mg of amoxicillin trihydrate) and 125 mg of clavulanic acid (equivalent to 149 mg of clavulanate potassium). Inactive Ingredients Colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, hydroxypropyl cellulose, methanol, polyethylene glycol, and titanium dioxide Amoxicillin and clavulanate potassium tablets meet USP Dissolution Test # 2"],"dosage_and_administration":["2 DOSAGE AND ADMINISTRATION Amoxicillin and clavulanate potassium tablets may be taken without regard to meals; however, absorption of clavulanate potassium is enhanced when amoxicillin and clavulanate potassium tablets, USP are administered at the start of a meal. To minimize the potential for gastrointestinal intolerance, amoxicillin and clavulanate potassium tablets should be taken at the start of a meal. Recommended dosage and administration for the various formulations of amoxicillin and clavulanate potassium tablets depends on the indication, patient age, weight, and ability to swallow tablets. Therefore, carefully follow the recommended dosage and administration instructions specified below. Adults and Pediatric Patients Weighing 40 kg or More ( 2.2 ) Infection Type Frequency Dose Formulation Strength Amoxicillin and Clavulanate Potassium Tablets Mild to Moderate Infections Every 12 hours One tablet 500 mg/125 mg Every 12 hours One tablet 250 mg/125 mg Severe Infections Every 12 hours One tablet 875 mg/125 mg Every 8 hours One tablet 500 mg/125 mg Adjust dose for severe renal impairment (GFR less than 30 mL/min) and in patients on hemodialysis. ( 2.6 , 8.6 , 12.3 ) 2.1 Important Administration Instructions The recommended dosage and administration of amoxicillin and clavulanate potassium tablets), depends on the indication, patient age, weight, and ability to swallow tablets. Therefore, carefully follow the recommended dosage and administration instructions specified below [see Dosage and Administration ( 2.2 to 2.8 )] . Amoxicillin and clavulanate potassium tablets should only be used in adults and pediatric patients weighing 40 kg or more who can swallow tablets whole [see Indications and Usage ( 1 ), Dosage and Administration ( 2.2 ), Use in Specific Populations ( 8.4 )]. Pediatric patients weighing 40 kg or more who can swallow tablets should receive the adult dose [see Indications and Usage ( 1 ), Dosage and Administration ( 2.2 ), Use in Specific Populations ( 8.4 )] . Substitution among amoxicillin and clavulanate potassium tablet formulations should only occur when the amoxicillin to-clavulanic acid ratio is matched; certain amoxicillin and clavulanate potassium tablets strengths are substitutable. [see Dosage and Administration ( 2.8 )] . 2.2 Recommended Dosage of Amoxicillin and Clavulanate Potassium tablets in Adults and Pediatric Patients Weighing 40 kg or More Who Are Able to Swallow Tablets The recommended dosage for adults and pediatric patients weighing 40 kg or more who are able to swallow tablets are provided in Table 1. Amoxicillin and clavulanate potassium tablets Amoxicillin and clavulanate potassium tablets may be taken without regard to meals; however, absorption of clavulanate is enhanced when amoxicillin and clavulanate potassium tablet are administered at the start of a meal. To minimize the potential for gastrointestinal intolerance, amoxicillin and clavulanate potassium tablets should be taken at the start of a meal. Table 1. Recommended Dosage for Amoxicillin and Clavulanate Potassium Tablets in Adult and Pediatric Patients Weighing 40 kg or More Infection Type Frequency Dose Formulation Strength Amoxicillin and Clavulanate Potassium Tablets Mild to Moderate Infection Every 12 hours One tablet 500 mg/125 mg Every 8 hours One tablet 250 mg/125 mg Severe Infections Every 12 hours One tablet 875 mg/125 mg Every 8 hours One tablet 500 mg/125 mg a Recommended duration of therapy is 7 to 10 days b Recommended duration of therapy is 10 days 2.3 Recommended Dosage of Amoxicillin and Clavulanate Potassium in Pediatric Patients Less Than 3 Months of Age The recommended dosage for pediatric patients less than 3 months of age, based on the amoxicillin component, is 30 mg/kg/day orally divided into two doses every 12 hours. 2.6 Recommended Dosage in Patients with Renal Impairment Amoxicillin and Clavulanate Potassium Tablets A reduced dosage is recommended in patients with severe renal impairment (see Table 4). No dosage adjustment is recommended in patients with mild to moderate renal impairment. Table 4. Recommended Dosage of Amoxicillin and Clavulanate Potassium Tablets in Patients with Severe Renal Impairment Patients with Renal Impairment Dosage GFR 10 mL/min to less than 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 the severity of the infection Hemodialysis 500 mg or 250 mg every 24 hours, depending on the severity of the infection Administer an additional dose both during and at the end of dialysis Patients with a GFR of less than 30 mL/min should not receive the 875 mg/125 mg dose of amoxicillin and clavulanate potassium tablets 2.8 Switching between Dosage Forms and between Strengths Amoxicillin and clavulanate potassium tablets Substitution among amoxicillin and clavulanate potassium tablets formulations should only occur when the amoxicillin-to clavulanic acid ratio is matched. and certain amoxicillin and clavulanate potassium tablet strengths are substitutable. Amoxicillin and clavulanate potassium tablets should not be used in pediatric patients weighing less than 40 kg [see Indications and Usage ( 1 ), Use in Specific Populations ( 8.4 )]."],"dosage_and_administration_table":["
Infection TypeFrequencyDoseFormulation Strength
Amoxicillin and Clavulanate Potassium Tablets
Mild to Moderate InfectionsEvery 12 hoursOne tablet500 mg/125 mg
Every 12 hoursOne tablet250 mg/125 mg
Severe InfectionsEvery 12 hoursOne tablet875 mg/125 mg
Every 8 hoursOne tablet500 mg/125 mg
","
Infection TypeFrequencyDoseFormulation Strength
Amoxicillin and Clavulanate Potassium Tablets
Mild to Moderate InfectionEvery 12 hoursOne tablet500 mg/125 mg
Every 8 hoursOne tablet250 mg/125 mg
Severe InfectionsEvery 12 hoursOne tablet875 mg/125 mg
Every 8 hoursOne tablet500 mg/125 mg
","
Patients with Renal ImpairmentDosage
GFR 10 mL/min to less than 30 mL/min500 mg or 250 mg every 12 hours, depending on the severity of the infection
GFR less than 10 mL/min500 mg or 250 mg every 24 hours, depending on the severity of the infection
Hemodialysis500 mg or 250 mg every 24 hours, depending on the severity of the infection Administer an additional dose both during and at the end of dialysis
"],"dosage_forms_and_strengths":["3 DOSAGE FORMS AND STRENGTHS 250-mg/125-mg Tablets : white, oval, biconvex, film-coated tablets, engraved “APO” on one side, “250-125” on the other, contains 250 mg of amoxicillin (as amoxicillin trihydrate) and 125 mg of clavulanic acid as the potassium salt. 500-mg/125-mg Tablets : white, oval, biconvex, film-coated tablets, engraved “APO” on one side, “500-125” on the other, contains 500 mg of amoxicillin (as amoxicillin trihydrate)and 125 mg of clavulanic acid as the potassium salt. 875-mg/125-mg Tablets : white, capsule-shaped, biconvex, film-coated tablets, engraved “APO” on one side, engraved “A” bisect “C” on the other, contains 875 mg of amoxicillin (as amoxicillin trihydrate) and 125 mg of clavulanic acid as the potassium salt. Amoxicillin and clavulanate potassium tablets: 250 mg/125 mg, 500 mg/125 mg and 875 mg/125 mg tablets are scored ( 3 )."],"drug_interactions":["7 DRUG INTERACTIONS Concomitant use with probenecid is not recommended. ( 7.1 ) Concomitant use with oral anticoagulants may increase the prolongation of prothrombin time. ( 7.2 ) Concomitant use with allopurinol increases the risk of rash. ( 7.3) 7.1 Probenecid Probenecid decreases the renal tubular secretion of amoxicillin. Concurrent use with amoxicillin and clavulanate potassium tablets may result in increased and prolonged blood levels of amoxicillin. Co-administration of probenecid is not recommended. 7.2 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. 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. Discontinue allopurinol at the first appearance of skin rash when used concomitantly with amoxicillin and clavulanate potassium tablets. 7.4 Interference of Amoxicillin and Clavulanate Potassium Tablets with Glucose 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. Therefore, it is recommended that glucose tests based on enzymatic glucose oxidase reactions be used."],"effective_time":"20260812","how_supplied":["16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Table 19 Amoxicillin and Clavulanate Potassium Tablets Tablets Strength Description NDC Package Amoxicillin and Clavulanate Potassium Tablets 250 mg/125 mg Each white, oval, biconvex, film-coated tablets, engraved “APO” on one side, “250-125” on the other. Each tablet contains 250 mg of amoxicillin as the trihydrate and 125 mg of clavulanic acid as the potassium salt (equivalent to 149 mg of clavulanate potassium). 60505-2539-2 60505-2539-3 60505-2539-5 Bottles of 20 Bottles of 30 Bottles of 500 Amoxicillin and Clavulanate Potassium Tablets 500 mg/125 mg Each white, oval, biconvex, film-coated tablets, engraved “APO” on one side, “500-125” on the other. Each tablet contains 500 mg of amoxicillin as the trihydrate and 125 mg of clavulanic acid as the potassium salt (equivalent to 149 mg of clavulanate potassium). 60505-2540-2 60505-2540-3 60505-2540-5 Bottles of 20 Bottles of 30 Bottles of 500 Amoxicillin and Clavulanate Potassium Tablets 875 mg/125 mg Each white, capsule-shaped, biconvex, film-coated tablets, engraved “APO” on one side, engraved “A” bisect “C” on the other. Each tablet contains 875 mg of amoxicillin as the trihydrate and 125 mg of clavulanic acid as the potassium salt (equivalent to 149 mg of clavulanate potassium). 60505-2541-2 60505-2541-3 60505-2541-5 Bottles of 20 Bottles of 30 Bottles of 500 Storage Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Dispense in a tight container. Keep out of the reach of children."],"how_supplied_table":["
TabletsStrengthDescriptionNDCPackage
Amoxicillin and Clavulanate Potassium Tablets250 mg/125 mg Each white, oval, biconvex, film-coated tablets, engraved “APO” on one side, “250-125” on the other. Each tablet contains 250 mg of amoxicillin as the trihydrate and 125 mg of clavulanic acid as the potassium salt (equivalent to 149 mg of clavulanate potassium).60505-2539-2 60505-2539-3 60505-2539-5Bottles of 20 Bottles of 30 Bottles of 500
Amoxicillin and Clavulanate Potassium Tablets500 mg/125 mgEach white, oval, biconvex, film-coated tablets, engraved “APO” on one side, “500-125” on the other. Each tablet contains 500 mg of amoxicillin as the trihydrate and 125 mg of clavulanic acid as the potassium salt (equivalent to 149 mg of clavulanate potassium).60505-2540-2 60505-2540-3 60505-2540-5Bottles of 20 Bottles of 30 Bottles of 500
Amoxicillin and Clavulanate Potassium Tablets875 mg/125 mgEachwhite, capsule-shaped, biconvex, film-coated tablets, engraved “APO” on one side, engraved “A” bisect “C” on the other. Each tablet contains 875 mg of amoxicillin as the trihydrate and 125 mg of clavulanic acid as the potassium salt (equivalent to 149 mg of clavulanate potassium).60505-2541-2 60505-2541-3 60505-2541-5Bottles of 20 Bottles of 30 Bottles of 500
"],"id":"f95e9c05-74d0-d78a-8560-49b7b8175edb","indications_and_usage":["1 INDICATIONS AND USAGE Amoxicillin and clavulanate potassium tablets are 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 tablets: adults and pediatric patients weighing 40 kg or more Acute Bacterial Sinusitis ( 1.3 ) Amoxicillin and clavulanate potassium tablets: adults and pediatric patients weighing 40 kg or more Acute bacterial otitis media ( 1.4 ) Amoxicillin and clavulanate potassium tablets: adults and pediatric patients weighing 40 kg or more Urinary tract infections ( 1.7 ) Amoxicillin and clavulanate potassium tablets: adults and pediatric patients weighing 40 kg or more Limitations of Use 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 tablets 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 tablets, and other antibacterial drugs, amoxicillin and clavulanate potassium tablets, 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 tablets are 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 potassium tablets: adults and pediatric patients weighing greater than or equal to 40 kg 1.3 Acute Bacterial Sinusitis Amoxicillin and clavulanate potassium tablets, 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 )]: Amoxicillin and clavulanate potassium tablets: adults and pediatric patients weighing greater than or equal to 40 kg 1.4 Acute Bacterial Otitis Media Amoxicillin and clavulanate potassium tablets are 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 )]: Amoxicillin and clavulanate potassium tablets: adults and pediatric patients weighing greater than or equal to 40 kg 1.6 Skin and Skin Structure Infections Amoxicillin and clavulanate potassium tablets are 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 clavulanate potassium tablets: adults and pediatric patients weighing greater than or equal to 40 kg 1.7 Urinary Tract Infections Amoxicillin and clavulanate potassium tablets are indicated for the treatment of urinary tract infections due to confirmed or suspected beta-lactamase-producing E. coli, Klebsiella species, and Enterobacter species as follows [see Use in Specific Populations ( 8.4 ), Clinical Studies ( 14.2 )]: Amoxicillin and clavulanate potassium tablets: adults and pediatric patients weighing greater than or equal to 40 kg 1.8 Limitations of Use Therapy may be initiated before bacteriological results are available when betalactamase-producing pathogens are suspected. When results show susceptibility to amoxicillin alone, amoxicillin and clavulanate potassium tablets should not be used. 1.9 Usage to Reduce Development if Drug-Resistant Bacteria To reduce the development of drug-resistant bacteria and maintain the effectiveness of amoxicillin and clavulanate potassium tablets and other antibacterial drugs, amoxicillin and clavulanate potassium tablets 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."],"nonclinical_toxicology":["13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Long-term studies in animals have not been performed to evaluate carcinogenic potential. Mutagenesis Amoxicillin and clavulanate (4:1 ratio formulation of amoxicillin: clavulanate) was non-mutagenic in the Ames bacterial mutation assay, and the yeast gene conversion assay. Amoxicillin and clavulanate were weakly positive in the mouse lymphoma assay, but the trend toward increased mutation frequencies in this assay occurred at concentrations that were also associated with decreased cell survival. Amoxicillin and clavulanate was negative in the mouse micronucleus test, and in the dominant lethal assay in mice. Clavulanate potassium alone was tested in the Ames bacterial mutation assay and in the mouse micronucleus test and was negative in each of these assays. Impairment of Fertility Amoxicillin and clavulanate (2:1 ratio formulation of amoxicillin: clavulanate) at oral doses of up to 1,200 mg/kg/day were found to have no effect on fertility and reproductive performance in rats. Based on body surface area comparisons, these doses correspond to approximately 4 times the MHRD for adults for amoxicillin trihydrate and 10 times the MRHD for clavulanate potassium."],"openfda":{},"overdosage":["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 tablets, treat symptomatically, and institute supportive measures as required. 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 . Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations. 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."],"package_label_principal_display_panel":["PRINCIPAL DISPLAY PANEL - 250 mg/125 mg BOTTLE APOTEX CORP. NDC 60505-2539-3 AMOXICILLIN AND CLAVULANATE POTASSIUM TABLETS, USP 250 mg/125 mg * Rx only 30 bottle count","PRINCIPAL DISPLAY PANEL - 500 mg/125 mg BOTTLE APOTEX CORP. NDC 60505-2540-3 AMOXICILLIN AND CLAVULANATE POTASSIUM TABLETS, USP 500 mg/125 mg * Rx only 30 bottle count","PRINCIPAL DISPLAY PANEL - 875 mg/125 mg BOTTLE APOTEX CORP. NDC 60505-2541-3 AMOXICILLIN AND CLAVULANATE POTASSIUM TABLETS , USP 875 mg/125 mg * Rx only 30 bottle count"],"patient_medication_information":["17 PATIENT COUNSELING INFORMATION Administration Instructions Advise patients or caregivers that when dosing a child with amoxicillin and clavulanate potassium tablets may be taken every 8 hours or every 12 hours, depending on the dose prescribed. Each dose should be taken with a meal or snack to reduce the possibility of gastrointestinal upset. Allergic Reactions Counsel patients that amoxicillin and clavulanate potassium tablets contain a penicillin class drug product that can cause allergic reactions in some individuals [see Warnings and Precautions ( 5.1 , 5.3 )]. Severe Cutaneous Adverse Reactions (SCAR) Advise patients about the signs and symptoms of serious skin manifestations. Instruct patients to stop taking amoxicillin and clavulanate potassium tablets immediately and promptly report the first signs or symptoms of skin rash, mucosal lesions, or any other sign of hypersensitivity [ see Warnings and Precautions ( 5.2 )]. Diarrhea ounsel patients that diarrhea is a common problem caused by antibacterial drugs, including amoxicillin and clavulanate potassium tablets, which and it usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterial drugs, 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 their last dose of the antibacterial drug. If this occurs, patients should contact their physician as soon as possible. If diarrhea develops and is severe or lasts more than 2 or 3 days, advise patients to call their doctor [see Warnings and Precautions ( 5.5 )] . Antibacterial Resistance Patients should be counseled that antibacterial drugs, including amoxicillin and clavulanate potassium tablets, should only be used to treat bacterial infections. Antibacterial drugs do not treat viral infections (e.g., the common cold). When amoxicillin and clavulanate potassium tablets are prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may: (1) decrease the effectiveness of the immediate treatment, and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by amoxicillin and clavulanate potassium tablets or other antibacterial drugs in the future [see Warnings and Precautions ( 5.9 )] . Manufactured by: Manufactured for: Apotex Inc. Apotex Corp. Toronto, Ontario Weston, Florida Canada M9L 1T9 33326 Revised: August 2026 Rev. 17 CLINITEST is a registered trademark of Miles, Inc."],"patient_medication_information_table":["
Manufactured by: Manufactured for:
Apotex Inc. Apotex Corp.
Toronto, Ontario Weston, Florida
Canada M9L 1T9 33326
"],"pharmacodynamics":["12.2 Pharmacodynamics The antibacterial activity of amoxicillin/clavulanate is primarily driven by the percentage of the dosing interval during which unbound (free) amoxicillin plasma concentrations exceed the minimum inhibitory concentration (%fT>MIC) of the target bacterial organism. Clavulanate inhibits β-lactamase enzymes and thereby restores activity of amoxicillin against certain β-lactamase–producing bacteria."],"recent_major_changes":["RECENT MAJOR CHANGES Indications and Usage ( 1 ) 7/2026 Dosage and Administration ( 2 ) 7/2026 Contraindications, Renal Impairment (4.3) removed 7/2026"],"references":["15 REFERENCES 1. Swanson-Biearman B, Dean BS, Lopez G, Krenzelok EP. The effects of penicillin and cephalosporin ingestions in children less than six years of age. Vet Hum Toxicol. 1988; 30: 66-67."],"set_id":"73dc6199-aadd-15bb-ee2c-2f7d049f7b2b","spl_product_data_elements":["Amoxicillin and Clavulanate Potassium Amoxicillin and Clavulanate Potassium AMOXICILLIN AMOXICILLIN ANHYDROUS CLAVULANATE POTASSIUM CLAVULANIC ACID SILICON DIOXIDE CROSCARMELLOSE SODIUM MAGNESIUM STEARATE HYDROXYPROPYL CELLULOSE (1600000 WAMW) METHYL ALCOHOL POLYETHYLENE GLYCOL 8000 TITANIUM DIOXIDE APO;250;125 Amoxicillin and Clavulanate Potassium Amoxicillin and Clavulanate Potassium AMOXICILLIN AMOXICILLIN ANHYDROUS CLAVULANATE POTASSIUM CLAVULANIC ACID SILICON DIOXIDE CROSCARMELLOSE SODIUM MAGNESIUM STEARATE HYDROXYPROPYL CELLULOSE (1600000 WAMW) METHYL ALCOHOL POLYETHYLENE GLYCOL 8000 TITANIUM DIOXIDE APO;500;125 Amoxicillin and Clavulanate Potassium Amoxicillin and Clavulanate Potassium AMOXICILLIN AMOXICILLIN ANHYDROUS CLAVULANATE POTASSIUM CLAVULANIC ACID SILICON DIOXIDE CROSCARMELLOSE SODIUM MAGNESIUM STEARATE HYDROXYPROPYL CELLULOSE (1600000 WAMW) METHYL ALCOHOL POLYETHYLENE GLYCOL 8000 TITANIUM DIOXIDE APO;A;C amox-clav-01 amox-clav-02 250mg-30sbtl 500mg-30sbtl 875mg-30sbtl"],"use_in_specific_populations":["8 USE IN SPECIFIC POPULATIONS Renal Impairment: Dosage adjustment is recommended for severe renal impairment (GFR < 30mL/min). ( 2.4 , 8.6 ) See 17 for PATIENT COUNSELING INFORMATION 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 tablets based on body surface area, revealed no evidence of fetal harm ( see Dat a). 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) 6-15). 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 (2:1 ratio 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 tablets 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 tablets and any potential adverse effects on the breastfed child from amoxicillin and clavulanate potassium tablets or from the underlying maternal condition. 8.4 Pediatric Use Lower Respiratory Tract Infections The safety and effectiveness of amoxicillin and clavulanate potassium tablets have been established for the treatment of lower respiratory tract infections due to confirmed or suspected beta-lactamase producing isolates of Haemophilus influenzae and Moraxella catarrhalis as follows [see Indications and Usage ( 1.1 ), Clinical Pharmacology ( 12.3 ), Clinical Studies ( 14.1 )]: Amoxicillin clavulanate potassium tablets: pediatric patients weighing greater than or equal to 40 kg. Effectiveness is supported by adequate and well-controlled studies in adults, with pediatric pharmacokinetic data demonstrating comparable amoxicillin and clavulanate exposures, and under the assumption that disease course and response are sufficiently similar in these pediatric patients to adults. Acute Bacterial Sinusitis The safety and effectiveness of amoxicillin clavulanate potassium tablets have been established for the treatment of acute bacterial sinusitis due to confirmed or suspected beta-lactamase-producing Haemophilus influenzae and Moraxella catarrhalis as follows [see Indications and Usage ( 1.3 ), Clinical Pharmacology ( 12.3 )]: Amoxicillin and clavulanate potassium tablets: pediatric patients weighing greater than or equal to 40 kg. Effectiveness is supported by adequate and well-controlled studies in adults, with pediatric pharmacokinetic data demonstrating comparable amoxicillin and clavulanate exposures, and under the assumption that disease course and response are sufficiently similar in these pediatric patients to adults. Acute Bacterial Otitis Media The safety and effectiveness of amoxicillin and clavulanate potassium tablets have been established for the treatment of acute bacterial otitis media due to confirmed or suspected beta-lactamase-producing Haemophilus influenzae and Moraxella catarrhalis as follows [see Indications and Usage ( 1.4 ), Clinical Pharmacology ( 12.3 )] : Amoxicillin and clavulanate potassium tablets: pediatric patients weighing greater than or equal to 40 kg. Effectiveness is supported by adequate and well-controlled studies in adults, with pediatric pharmacokinetic data demonstrating comparable amoxicillin and clavulanate exposures, and under the assumption that disease course and response are sufficiently similar in these pediatric patients to adults. Skin and Skin Structure Infections The safety and effectiveness of amoxicillin and clavulanate potassium tablets have been established 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 Indications and Usage ( 1.6 ), Clinical Pharmacology ( 12.3 )] : Amoxicillin and clavulanate potassium tablets: pediatric patients weighing greater than or equal to 40 kg. Effectiveness is supported by adequate and well-controlled studies in adults, with pediatric pharmacokinetic data demonstrating comparable amoxicillin and clavulanate exposures, and under the assumption that disease course and response are sufficiently similar in these pediatric patients to adults. Urinary Tract Infections The safety and effectiveness of amoxicillin and clavulanate potassium tablets have been established for the treatment of urinary tract infections due to confirmed or suspected beta-lactamase-producing E. coli, Klebsiella species, and Enterobacter species as follows [see Indications and Usage ( 1.7 ), Clinical Pharmacology ( 12.3 ), Clinical Studies ( 14.2 )]: Amoxicillin and clavulanate potassium tablets: pediatric patients weighing greater than or equal to 40 kg. Effectiveness is supported by adequate and well-controlled studies in adults, with pediatric pharmacokinetic data demonstrating comparable amoxicillin and clavulanate exposures, and under the assumption that disease course and response are sufficiently similar in these pediatric patients to adults. Data are insufficient to support extrapolation in these age groups due to developmental differences in renal function. Elimination of amoxicillin may be delayed, while clavulanate elimination is not altered. Dosage should be modified in pediatric patients less than 12 weeks (3 months) [see Dosage and Administration ( 2.3 )] . 8.5 Geriatric Use Of the 3,119 patients included clinical studies of amoxicillin and clavulanate potassium tablets,32% were 65 years of age, and 14% were 75 years of age and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other clinical experience has not identified differences in responses between elderly and younger patients. Amoxicillin and clavulanate potassium tablets substantially excreted by the kidney, and the risk of adverse reactions to amoxicillin and clavulanate potassium tablets may be greater in patients with renal impairment than in patients with normal renal function. Because geriatric patients are more likely to have renal impairment, monitor for adverse reactions. Dosage adjustment is recommended in patients with severe renal impairment [see Dosage and Administration ( 2.6 ), Use in Specific Populations ( 8.6 )] . 8.6 Renal Impairment Amoxicillin is primarily eliminated by the kidney. Both amoxicillin and clavulanate are removed from the circulation by hemodialysis. Amoxicillin and clavulanate potassium tablets No dosage adjustment is recommended in patients with mild to moderate renal impairment. A reduced dosage is recommended in patients with severe renal impairment (GFR less than 30 mL/min). Patients with a GFR of less than 30 mL/min should not receive the 875 mg/125 mg dose of amoxicillin and clavulanate potassium tablets [see Dosage and Administration ( 2.6 )]. 8.7 Hepatic Impairment Monitor hepatic function as appropriate during therapy with amoxicillin and clavulanate potassium tablets [see Contraindications ( 4.2 ), Warnings and Precautions ( 5.4 )] ."],"version":"12","warnings_and_cautions":["5 WARNINGS AND PRECAUTIONS Serious (including fatal) hypersensitivity reactions: Discontinue amoxicillin and clavulanate potassium tablets if a reaction occurs and institute appropriate therapy. ( 5.1 ) Severe Cutaneous Adverse Reactions (SCAR): Monitor closely. Discontinue if rash progresses. ( 5.2 ) Drug-induced enterocolitis syndrome (DIES): has been reported with amoxicillin, a component of amoxicillin and clavulanate potassium tablets. If this occurs, discontinue amoxicillin and clavulanate potassium tablets and institute appropriate therapy. ( 5.3 ) Hepatic dysfunction and cholestatic jaundice: Discontinue if signs/symptoms of hepatitis occur. Monitor liver function tests in patients with hepatic impairment. ( 5.4 ) Clostridioides difficile -associated diarrhea (CDAD): Evaluate patients if diarrhea occurs. ( 5.5 ) Patients with mononucleosis: Increased risk of skin rash. Avoid amoxicillin and clavulanate potassium tablets use in these patients. ( 5.6 ) 5.1 Serious Allergic Reactions including Anaphylaxis Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam antibacterials. 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 amoxicillin and clavulanate potassium tablets, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. Amoxicillin and clavulanate potassium tablets are contraindicated in patients with a history of serious hypersensitivity reactions to amoxicillin, clavulanate, or to other beta-lactam antibacterial drugs [see Contraindications ( 4.1 )] . If an allergic reaction occurs, discontinue amoxicillin and clavulanate potassium tablets and institute appropriate therapy. 5.2 Severe Cutaneous Adverse Reactions (SCAR) Amoxicillin and clavulanate potassium tablets 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 amoxicillin and clavulanate potassium tablets discontinued if lesions progress. 5.3 Drug-Induced Enterocolitis Syndrome (DIES) Drug-induced enterocolitis syndrome (DIES) has been reported with use of amoxicillin a component of amoxicillin and clavulanate potassium tablets [see Adverse Reactions ( 6.2 )] , with most cases occurring in pediatric patients. DIES is a non-IgE mediated hypersensitivity reaction characterized by protracted vomiting occurring 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 after ingesting amoxicillin, and leukocytosis with neutrophilia. If DIES occurs, discontinue amoxicillin and clavulanate potassium tablets and institute appropriate therapy. 5.4 Hepatic Dysfunction Hepatic dysfunction, including hepatitis and cholestatic jaundice has been associated with the use of amoxicillin and clavulanate potassium tablets. Hepato-toxicity is usually reversible; however, deaths have been reported. These cases have generally been associated with serious underlying diseases or concomitant medications. Amoxicillin clavulanate potassium tablets are contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with treatment with amoxicillin and clavulanate potassium [see Contraindications ( 4.2 ), Use in Specific Populations ( 8.7 ), Adverse Reactions ( 6.2 )] . 5.5 Clostridioides difficile Associated Diarrhea (CDAD) Clostridioides difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including amoxicillin and clavulanate potassium tablets, 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 drug 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 drug 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. 5.6 Skin Rash in Patients with Mononucleosis A high percentage of patients with mononucleosis who receive amoxicillin develop an erythematous skin rash. Avoid amoxicillin and clavulanate potassium tablet use in patients with mononucleosis [see Adverse Reactions ( 6.2 )]. 5.7 Potential for Microbial Overgrowth The possibility of superinfections with mycotic or bacterial pathogens should be considered during therapy. If superinfections occur (commonly involving Pseudomonas spp. or Candida spp.), discontinue amoxicillin and clavulanate potassium tablets and institute appropriate therapy. 5.9 Development of Drug-Resistant Bacteria Prescribing amoxicillin and clavulanate potassium tablets 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."]}